1
Comparative Study AJR Am J Roentgenol
. 2020 Jun;214(6):1280-1286. doi: 10.2214/AJR.20.22954. Epub 2020 Mar 4.
Coronavirus Disease 2019 (COVID-19): Role of Chest CT in Diagnosis and Management
Yan Li 1, Liming Xia 1
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PMID: 32130038 DOI: 10.2214/AJR.20.22954
Abstract
OBJECTIVE. The objective of our study was to determine the misdiagnosis rate of radiologists for coronavirus disease 2019 (COVID-19) and evaluate the performance of chest CT in the diagnosis and management of COVID-19. The CT features of COVID-19 are reported and compared with the CT features of other viruses to familiarize radiologists with possible CT patterns. MATERIALS AND METHODS. This study included the first 51 patients with a diagnosis of COVID-19 infection confirmed by nucleic acid testing (23 women and 28 men; age range, 26-83 years) and two patients with adenovirus (one woman and one man; ages, 58 and 66 years). We reviewed the clinical information, CT images, and corresponding image reports of these 53 patients. The CT images included images from 99 chest CT examinations, including initial and follow-up CT studies. We compared the image reports of the initial CT study with the laboratory test results and identified CT patterns suggestive of viral infection. RESULTS. COVID-19 was misdiagnosed as a common infection at the initial CT study in two inpatients with underlying disease and COVID-19. Viral pneumonia was correctly diagnosed at the initial CT study in the remaining 49 patients with COVID-19 and two patients with adenovirus. These patients were isolated and obtained treatment. Ground-glass opacities (GGOs) and consolidation with or without vascular enlargement, interlobular septal thickening, and air bronchogram sign are common CT features of COVID-19. The The "reversed halo" sign and pulmonary nodules with a halo sign are uncommon CT features. The CT findings of COVID-19 overlap with the CT findings of adenovirus infection. There are differences as well as similarities in the CT features of COVID-19 compared with those of the severe acute respiratory syndrome. CONCLUSION. We found that chest CT had a low rate of missed diagnosis of COVID-19 (3.9%, 2/51) and may be useful as a standard method for the rapid diagnosis of COVID-19 to optimize the management of patients. However, CT is still limited for identifying specific viruses and distinguishing between viruses.

Keywords: CT; SARS-CoV-2; coronavirus disease 2019 (COVID-19); infectious diseases; lung disease.

Cited by 7 articles
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2
Review Antimicrob Agents Chemother
. 2020 May 21;64(6):e00483-20. doi: 10.1128/AAC.00483-20. Print 2020 May 21.
Updated Approaches Against SARS-CoV-2
Haiou Li 1 2, Yunjiao Zhou 1 2, Meng Zhang 1 2, Haizhou Wang 1 2, Qiu Zhao 1 2, Jing Liu 3 2
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PMID: 32205349 DOI: 10.1128/AAC.00483-20
Abstract
Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lies behind the ongoing outbreak of coronavirus disease 2019 (COVID-19). There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. However, no anti-SARS-CoV-2 drug or vaccine has been officially approved due to the absence of adequate evidence. Scientists are racing to develop a treatment for COVID-19. Recent studies have revealed many attractive therapeutic options, even if some of them remain to be further confirmed in rigorous preclinical models and clinical trials. In this minireview, we aim to summarize the updated potential approaches against SARS-CoV-2. We emphasize that further efforts are warranted to develop the safest and most effective approach.

Keywords: COVID-19; SARS-CoV-2; antiviral drugs; treatment; vaccines.

Copyright © 2020 American Society for Microbiology.

Cited by 3 articles
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3
Review Clin Microbiol Infect
. 2020 Jun;26(6):729-734. doi: 10.1016/j.cmi.2020.03.026. Epub 2020 Mar 28.
COVID-19, SARS and MERS: Are They Closely Related?
N Petrosillo 1, G Viceconte 2, O Ergonul 3, G Ippolito 4, E Petersen 5
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PMID: 32234451 PMCID: PMC7176926 DOI: 10.1016/j.cmi.2020.03.026
Free PMC article
Abstract
Background: The 2019 novel coronavirus (SARS-CoV-2) is a new human coronavirus which is spreading with epidemic features in China and other Asian countries; cases have also been reported worldwide. This novel coronavirus disease (COVID-19) is associated with a respiratory illness that may lead to severe pneumonia and acute respiratory distress syndrome (ARDS). Although related to the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), COVID-19 shows some peculiar pathogenetic, epidemiological and clinical features which to date are not completely understood.

Aims: To provide a review of the differences in pathogenesis, epidemiology and clinical features of COVID-19, SARS and MERS.

Sources: The most recent literature in the English language regarding COVID-19 has been reviewed, and extracted data have been compared with the current scientific evidence about SARS and MERS epidemics.

Content: COVID-19 seems not to be very different from SARS regarding its clinical features. However, it has a fatality rate of 2.3%, lower than that of SARS (9.5%) and much lower than that of MERS (34.4%). The possibility cannot be excluded that because of the less severe clinical picture of COVID-19 it can spread in the community more easily than MERS and SARS. The actual basic reproductive number (R0) of COVID-19 (2.0-2.5) is still controversial. It is probably slightly higher than the R0 of SARS (1.7-1.9) and higher than that of MERS (<1). A gastrointestinal route of transmission for SARS-CoV-2, which has been assumed for SARS-CoV and MERS-CoV, cannot be ruled out and needs further investigation.

Implications: There is still much more to know about COVID-19, especially as concerns mortality and its capacity to spread on a pandemic level. Nonetheless, all of the lessons we learned in the past from the SARS and MERS epidemics are the best cultural weapons with which to face this new global threat.

Keywords: COVID-19; Coronavirus; Emerging infections; MERS; SARS.

Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Cited by 4 articles50 references
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4
Review Sci Total Environ
. 2020 Jul 10;725:138277. doi: 10.1016/j.scitotenv.2020.138277. Epub 2020 Apr 4.
COVID-19: A Promising Cure for the Global Panic
Balachandar Vellingiri 1, Kaavya Jayaramayya 2, Mahalaxmi Iyer 2, Arul Narayanasamy 3, Vivekanandhan Govindasamy 4, Bupesh Giridharan 5, Singaravelu Ganesan 6, Anila Venugopal 7, Dhivya Venkatesan 7, Harsha Ganesan 7, Kamarajan Rajagopalan 7, Pattanathu K S M Rahman 8, Ssang-Goo Cho 9, Nachimuthu Senthil Kumar 10, Mohana Devi Subramaniam 11
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PMID: 32278175 PMCID: PMC7128376 DOI: 10.1016/j.scitotenv.2020.138277
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Abstract
The novel Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2, which is the causative agent of a potentially fatal disease that is of great global public health concern. The outbreak of COVID-19 is wreaking havoc worldwide due to inadequate risk assessment regarding the urgency of the situation. The COVID-19 pandemic has entered a dangerous new phase. When compared with SARS and MERS, COVID-19 has spread more rapidly, due to increased globalization and adaptation of the virus in every environment. Slowing the spread of the COVID-19 cases will significantly reduce the strain on the healthcare system of the country by limiting the number of people who are severely sick by COVID-19 and need hospital care. Hence, the recent outburst of COVID-19 highlights an urgent need for therapeutics targeting SARS-CoV-2. Here, we have discussed the structure of virus; varying symptoms among COVID-19, SARS, MERS and common flu; the probable mechanism behind the infection and its immune response. Further, the current treatment options, drugs available, ongoing trials and recent diagnostics for COVID-19 have been discussed. We suggest traditional Indian medicinal plants as possible novel therapeutic approaches, exclusively targeting SARS-CoV-2 and its pathways.

Keywords: Coronavirus disease 2019 (COVID-19); Indian traditional medicine; Mechanism of action; SARS-CoV-2; Therapeutic approach.

Copyright © 2020 Elsevier B.V. All rights reserved.

Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Cited by 5 articles1 figure
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5
Review Front Immunol
. 2019 May 10;10:1071. doi: 10.3389/fimmu.2019.01071. eCollection 2019.
Impact of Obesity on Influenza A Virus Pathogenesis, Immune Response, and Evolution
Rebekah Honce 1 2, Stacey Schultz-Cherry 1
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PMID: 31134099 PMCID: PMC6523028 DOI: 10.3389/fimmu.2019.01071
Free PMC article
Abstract
With the rising prevalence of obesity has come an increasing awareness of its impact on communicable disease. As a consequence of the 2009 H1N1 influenza A virus pandemic, obesity was identified for the first time as a risk factor for increased disease severity and mortality in infected individuals. Over-nutrition that results in obesity causes a chronic state of meta-inflammation with systemic implications for immunity. Obese hosts exhibit delayed and blunted antiviral responses to influenza virus infection, and they experience poor recovery from the disease. Furthermore, the efficacy of antivirals and vaccines is reduced in this population and obesity may also play a role in altering the viral life cycle, thus complementing the already weakened immune response and leading to severe pathogenesis. Case studies and basic research in human cohorts and animal models have highlighted the prolonged viral shed in the obese host, as well as a microenvironment that permits the emergence of virulent minor variants. This review focuses on influenza A virus pathogenesis in the obese host, and on the impact of obesity on the antiviral response, viral shed, and viral evolution. We comprehensively analyze the recent literature on how and why viral pathogenesis is altered in the obese host along with the impact of the altered host and pathogenic state on viral evolutionary dynamics in multiple models. Finally, we summarized the effectiveness of current vaccines and antivirals in this populations and the questions that remain to be answered. If current trends continue, nearly 50% of the worldwide population is projected to be obese by 2050. This population will have a growing impact on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus.

Keywords: evolution; immunity; influenza; obesity; pathogenesis.

Cited by 11 articles146 references3 figures
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6
J Clin Microbiol
. 2020 May 26;58(6):e00461-20. doi: 10.1128/JCM.00461-20. Print 2020 May 26.
Evaluation of Nucleocapsid and Spike Protein-Based Enzyme-Linked Immunosorbent Assays for Detecting Antibodies Against SARS-CoV-2
Wanbing Liu # 1, Lei Liu # 1, Guomei Kou 1, Yaqiong Zheng 1, Yinjuan Ding 1, Wenxu Ni 1, Qiongshu Wang 2, Li Tan 2, Wanlei Wu 1, Shi Tang 1, Zhou Xiong 1, Shangen Zheng 3
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PMID: 32229605 DOI: 10.1128/JCM.00461-20
Abstract
At present, PCR-based nucleic acid detection cannot meet the demands for coronavirus infectious disease (COVID-19) diagnosis. Two hundred fourteen confirmed COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command of the People's Liberation Army between 18 January and 26 February 2020 were recruited. Two enzyme-linked immunosorbent assay (ELISA) kits based on recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, and their diagnostic feasibility was evaluated. Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, respectively. The positive rates of the rN-based and rS-based ELISAs for antibody (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of the rS-based ELISA for IgM detection was significantly higher than that of the rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG ELISAs was less than 60% during the early stage of the illness, 0 to 10 d.p.o., and that of IgM and IgG was obviously increased after 10 d.p.o. ELISA has a high sensitivity, especially for the detection of serum samples from patients after 10 d.p.o., so it could be an important supplementary method for COVID-19 diagnosis.

Keywords: COVID-19 diagnosis; ELISA; IgG; IgM; antibody; nucleocapsid protein; spike protein.

Copyright © 2020 American Society for Microbiology.

Cited by 2 articles
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7
JCI Insight
. 2019 Mar 7;4(5):e126556. doi: 10.1172/jci.insight.126556.
Single Cell RNA Sequencing Identifies Unique Inflammatory Airspace Macrophage Subsets
Kara J Mould 1 2, Nathan D Jackson 3, Peter M Henson 2 4, Max Seibold 2 3 4, William J Janssen 1 2
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PMID: 30721157 PMCID: PMC6483508 DOI: 10.1172/jci.insight.126556
Free PMC article
Abstract
Macrophages are well recognized for their dual roles in orchestrating inflammatory responses and regulating tissue repair. In almost all acutely inflamed tissues, 2 main subclasses of macrophages coexist. These include embryonically derived resident tissue macrophages and BM-derived recruited macrophages. While it is clear that macrophage subsets categorized in this fashion display distinct transcriptional and functional profiles, whether all cells within these categories and in the same inflammatory microenvironment share similar functions or whether further specialization exists has not been determined. To investigate inflammatory macrophage heterogeneity on a more granular level, we induced acute lung inflammation in mice and performed single cell RNA sequencing of macrophages isolated from the airspaces during health, peak inflammation, and resolution of inflammation. In doing so, we confirm that cell origin is the major determinant of alveolar macrophage (AM) programing, and, to our knowledge, we describe 2 previously uncharacterized, transcriptionally distinct subdivisions of AMs based on proliferative capacity and inflammatory programing.

Keywords: Immunology; Macrophages; Pulmonology.

Conflict of interest statement
Conflict of interest: The authors have declared that no conflict of interest exists.

Cited by 8 articles7 figures
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8
Review F1000Res
. 2019 May 2;8:F1000 Faculty Rev-610. doi: 10.12688/f1000research.18749.1. eCollection 2019.
The Long Road to Protect Infants Against Severe RSV Lower Respiratory Tract Illness
Sofia Jares Baglivo 1, Fernando P Polack 1
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PMID: 31105933 PMCID: PMC6498742 DOI: 10.12688/f1000research.18749.1
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Abstract
Severe respiratory syncytial virus (RSV) lower respiratory tract illness (LRTI) in infants has proven challenging to prevent. In the last 50 years, conceptually different approaches failed to evolve into viable preventive alternatives for routine use. Inactivated RSV vaccine (that is, formalin-inactivated RSV) elicited severe LRTI in RSV-infected toddlers pre-immunized as infants; early purified F protein approaches in pregnant women failed to elicit sufficient immunity more than a decade ago; a second-generation monoclonal antibody (mAb) of high potency against the virus (that is, motavizumab) caused severe adverse reactions in the skin, and owing to lack of efficacy against RSV subgroup B, an extended half-life mAb targeting site V in the RSV fusion protein (that is, REG2222) did not meet its primary endpoint. In the meantime, two protein F vaccines failed to prevent medically attended LRTI in the elderly. However, palivizumab and the recent results of the Novavax maternal immunization trial with ResVax demonstrate that severe RSV LRTI can be prevented by mAb and by maternal immunization (at least to a certain extent). In fact, disease prevention may also decrease the rates of recurrent wheezing and all-cause pneumonia for at least 180 days. In this review, we discuss the history of RSV vaccine development, previous and current vaccine strategies undergoing evaluation, and recent information about disease burden and its implications for the effects of successful preventive strategies.

Keywords: asthma; infants; monoclonal antibodies; pneumonia; respiratory syncytial virus; vaccines.

Conflict of interest statement
Competing interests: FPP reports grants and personal fees from Novavax, personal fees from Medimmune, grants and personal fees from Janssen, personal fees from Sanofi, personal fees from Bavarian Nordic, personal fees from Pfizer, personal fees from Merck, personal fees from ArkBio, personal fees from VirBio, personal fees from Regeneron and personal fees from Daiichi Sankyo. SJB reports no conflicts of interest.No competing interests were disclosed.No competing interests were disclosed.

Cited by 4 articles68 references
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9
AJR Am J Roentgenol
. 2020 Jun;214(6):1287-1294. doi: 10.2214/AJR.20.22975. Epub 2020 Mar 5.
CT Features of Coronavirus Disease 2019 (COVID-19) Pneumonia in 62 Patients in Wuhan, China
Shuchang Zhou 1, Yujin Wang 1, Tingting Zhu 1, Liming Xia 1
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PMID: 32134681 DOI: 10.2214/AJR.20.22975
Abstract
OBJECTIVE. The purpose of this study was to investigate 62 subjects in Wuhan, China, with laboratory-confirmed coronavirus disease (COVID-19) pneumonia and describe the CT features of this epidemic disease. MATERIALS AND METHODS. A retrospective study of 62 consecutive patients with laboratory-confirmed COVID-19 pneumonia was performed. CT images and clinical data were reviewed. Two thoracic radiologists evaluated the distribution and CT signs of the lesions and also scored the extent of involvement of the CT signs. The Mann-Whitney U test was used to compare lesion distribution and CT scores. The chi-square test was used to compare the CT signs of early-phase versus advanced-phase COVID-19 pneumonia. RESULTS. A total of 62 patients (39 men and 23 women; mean [± SD] age, 52.8 ± 12.2 years; range, 30-77 years) with COVID-19 pneumonia were evaluated. Twenty-four of 30 patients who underwent routine blood tests (80.0%) had a decreased lymphocyte count. Of 27 patients who had their erythrocyte sedimentation rate and high-sensitivity C-reactive protein level assessed, 18 (66.7%) had an increased erythrocyte sedimentation rate, and all 27 (100.0%) had an elevated high-sensitivity C-reactive protein level. Multiple lesions were seen on the initial CT scan of 52 of 62 patients (83.9%). Forty-eight of 62 patients (77.4%) had predominantly peripheral distribution of lesions. The mean CT score for the upper zone (3.0 ± 3.4) was significantly lower than that for the middle (4.5 ± 3.8) and lower (4.5 ± 3.7) zones (p = 0.022 and p = 0.020, respectively), and there was no significant difference in the mean CT score of the middle and lower zones (p = 1.00). The mean CT score for the anterior area (4.4 ± 4.1) was significantly lower than that for the posterior area (7.7 ± 6.3) (p = 0.003). CT findings for the patients were as follows: 25 patients (40.3%) had ground-glass opacities (GGO), 21 (33.9%), consolidation; 39 (62.9%), GGO plus a reticular pattern; 34 (54.8%), vacuolar sign; 28 (45.2%), microvascular dilation sign; 35 (56.5%), fibrotic streaks; 21 (33.9%), a subpleural line; and 33 (53.2%), a subpleural transparent line. With regard to bronchial changes seen on CT, 45 patients (72.6%) had air bronchogram, and 11 (17.7%) had bronchus distortion. In terms of pleural changes, CT showed that 30 patients (48.4%) had pleural thickening, 35 (56.5%) had pleural retraction sign, and six (9.7%) had pleural effusion. Compared with early-phase disease (≤ 7 days after the onset of symptoms), advanced-phase disease (8-14 days after the onset of symptoms) was characterized by significantly increased frequencies of GGO plus a reticular pattern, vacuolar sign, fibrotic streaks, a subpleural line, a subpleural transparent line, air bronchogram, bronchus distortion, and pleural effusion; however, GGO significantly decreased in advanced-phase disease. CONCLUSION. CT examination of patients with COVID-19 pneumonia showed a mixed and diverse pattern with both lung parenchyma and the interstitium involved. Identification of GGO and a single lesion on the initial CT scan suggested early-phase disease. CT signs of aggravation and repair coexisted in advanced-phase disease. Lesions presented with a characteristic multifocal distribution in the middle and lower lung regions and in the posterior lung area. A decreased lymphocyte count and an increased high-sensitivity C-reactive protein level were the most common laboratory findings.

Keywords: COVID-19; CT; coronavirus disease 2019; pneumonia.

Cited by 12 articles
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10
Comparative Study Respir Res
. 2019 Dec 18;20(1):267. doi: 10.1186/s12931-019-1206-8.
Electronic Cigarette Vapour Increases Virulence and Inflammatory Potential of Respiratory Pathogens
Deirdre F Gilpin 1, Katie-Ann McGown 2, Kevin Gallagher 2, Jose Bengoechea 3, Amy Dumigan 3, Gisli Einarsson 2, J Stuart Elborn 3, Michael M Tunney 2
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PMID: 31847850 PMCID: PMC6918581 DOI: 10.1186/s12931-019-1206-8
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Abstract
Introduction: Bacteria have been extensively implicated in the development of smoking related diseases, such as COPD, by either direct infection or bacteria-mediated inflammation. In response to the health risks associated with tobacco exposure, the use of electronic cigarettes (e-cigs) has increased. This study compared the effect of e-cig vapour (ECV) and cigarette smoke (CSE) on the virulence and inflammatory potential of key lung pathogens (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and Pseudomonas aeruginosa).

Methods: Biofilm formation, virulence in the Galleria mellonella infection model, antibiotic susceptibility and IL-8/TNF-α production in A549 cells, were compared between bacteria exposed to ECV, CSE and non-exposed bacteria.

Results: Statistically significant increases in biofilm and cytokine secretion were observed following bacterial exposure to either ECV or CSE, compared to non-exposed bacteria; the effect of exposure to ECV on bacterial phenotype and virulence was comparable, and in some cases greater, than that observed following CSE exposure. Treatment of A549 cells with cell signaling pathway inhibitors prior to infection, did not suggest that alternative signaling pathways were being activated following exposure of bacteria to either ECV or CSE.

Conclusions: These findings therefore suggest that ECV and CSE can induce changes in phenotype and virulence of key lung pathogens, which may increase bacterial persistence and inflammatory potential.

Keywords: Cigarette; Cytokine; E-cigarette; Inflammation; Lung; Pathogen; Persistence; Virulence.

Conflict of interest statement
The authors declare that they have no competing interests.

55 references4 figures
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11
BMC Pulm Med
. 2019 Dec 19;19(1):252. doi: 10.1186/s12890-019-1022-4.
Metagenomic Next-Generation Sequencing for Mixed Pulmonary Infection Diagnosis
Jiahui Wang 1, Yelei Han 1, Jing Feng 2
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PMID: 31856779 PMCID: PMC6921575 DOI: 10.1186/s12890-019-1022-4
Free PMC article
Abstract
Background: Metagenomic next-generation sequencing (mNGS) is emerging as a promising technique for pathogens detection. However, reports on the application of mNGS in mixed pulmonary infection remain scarce.

Methods: From July 2018 to March 2019, 55 cases were enrolled in this retrospective analysis. Cases were classified into mixed pulmonary infection (36 [65.5%]) and non-mixed pulmonary infection (19 [34.5%]) according to primary diagnoses. The performances of mNGS and conventional test on mixed pulmonary infection diagnosis and pathogen identification were compared.

Results: The sensitivity of mNGS in mixed pulmonary infection diagnosis was much higher than that of conventional test (97.2% vs 13.9%; P < 0.01), but the specificity was the opposite (63.2% vs 94.7%; P = 0.07). The positive predictive value of mNGS was 83.3% (95% CI, 68.0-92.5%), and the negative predictive value was 92.3% (95% CI, 62.1-99.6%). A total of 5 (9.1%) cases were identified as mixed pulmonary infection by both conventional tests and mNGS, however, the pathogens identification results were consistent between these two methods in only 1 (1.8%) case. In summary, the pathogens detected by mNGS in 3 (5.5%) cases were consistent with those by conventional test, and only 1 (1.8%) case was mixed pulmonary infection. According to our data, mNGS had a broader spectrum for pathogen detection than conventional tests. In particular, application of mNGS improved the diagnosis of pulmonary fungal infections. Within the 55 cases, mNGS detected and identified fungi in 31 (56.4%) cases, of which only 10 (18.2%) cases were positive for the same fungi by conventional test. The most common pathogen detected by mNGS was Human cytomegalovirus in our study, which was identified in 19 (34.5%) cases of mixed pulmonary infection. Human cytomegalovirus and Pneumocystis jirovecii, which were detected in 7 (12.7%) cases, were the most common co-pathogens in the group of mixed pulmonary infection.

Conclusions: mNGS is a promising technique to detect co-pathogens in mixed pulmonary infection, with potential benefits in speed and sensitivity.

Trial registration: (retrospectively registered): ChiCTR1900023727. Registrated 9 JUNE 2019.

Keywords: Diagnosis; Mixed pulmonary infection; mNGS.

Conflict of interest statement
The authors declare that they have no competing interests.

24 references1 figure
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12
Sci Immunol
. 2019 Jul 26;4(37):eaaw6693. doi: 10.1126/sciimmunol.aaw6693.
Alveolar Macrophages Generate a Noncanonical NRF2-driven Transcriptional Response to Mycobacterium tuberculosis in Vivo
Alissa C Rothchild 1, Gregory S Olson 1 2, Johannes Nemeth 1, Lynn M Amon 1, Dat Mai 1, Elizabeth S Gold 1, Alan H Diercks 3, Alan Aderem 3
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PMID: 31350281 PMCID: PMC6910245 DOI: 10.1126/sciimmunol.aaw6693
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Abstract
Alveolar macrophages (AMs) are the first cells to be infected during Mycobacterium tuberculosis (M.tb.) infection. Thus, the AM response to infection is the first of many steps leading to initiation of the adaptive immune response required for efficient control of infection. A hallmark of M.tb. infection is the slow initiation of the adaptive response, yet the mechanisms responsible for this are largely unknown. To study the initial AM response to infection, we developed a system to identify, sort, and analyze M.tb.-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described using in vitro systems, M.tb.-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment but not bacterial virulence. Computational approaches including pathway analysis and transcription factor motif enrichment analysis identify NRF2 as a master regulator of the response. Using knockout mouse models, we demonstrate that NRF2 drives expression of the cell-protective signature in AMs and impairs the control of early bacterial growth. AMs up-regulate a substantial pro-inflammatory response to M.tb. infection only 10 days after infection, yet comparisons with bystander AMs from the same infected animals demonstrate that M.tb.-infected AMs generate a less robust inflammatory response than the uninfected cells around them. Our findings demonstrate that the initial macrophage response to M.tb. in the lung is far less inflammatory than has previously been described by in vitro systems and may impede the overall host response to infection.

Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Conflict of interest statement
Competing interests: The authors declare that they have no competing interests.

Cited by 1 article7 figures
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13
Comparative Study Respir Res
. 2019 Dec 18;20(1):287. doi: 10.1186/s12931-019-1247-z.
Prognostic Differences Among Patients With Idiopathic Interstitial Pneumonias With Acute Exacerbation of Varying Pathogenesis: A Retrospective Study
Motoyasu Kato 1, Tomoko Yamada 2, Shunichi Kataoka 2, Yuta Arai 2, Keita Miura 2, Yusuke Ochi 2, Hiroaki Ihara 2, Ryo Koyama 2, Shinichi Sasaki 2, Kazuhisa Takahashi 2
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PMID: 31852459 PMCID: PMC6921398 DOI: 10.1186/s12931-019-1247-z
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Abstract
Background: Acute exacerbation of chronic fibrosing idiopathic interstitial pneumonias (AE-IIPs) is associated with a high mortality rate. In 2016, an international working group proposed a revised diagnostic criteria for AE-IIPs, suggesting that it be classified as idiopathic or triggered. Many factors are known to trigger AE-IIPs, including surgery, infection, and drugs. However, it is unknown which AE-IIPs triggers have a worse prognosis. We aimed to investigate the prognosis of patients with various clinical types of AE-IIPs, particularly infection-triggered, non-infection triggered, and idiopathic AE-IIPs.

Methods: We retrospectively collected data from 128 chronic fibrosing IIPs (CF-IIPs) patients who were hospitalized by respiratory failure between April 2009 and March 2019 at Juntendo University Hospital. Among these patients, we evaluated 79 patients who developed AE-IIPs and 21 who developed pneumonia superimposed on CF-IIPs. Patients with AE-IIPs were classified into three types: idiopathic, infection-triggered, and non-infection-triggered AE-IIPs. We analyzed differences in patient characteristics, examination findings; level of serum markers, results of pulmonary function, and radiological findings, prior treatment for baseline CF-IIPs, and prognosis. We then evaluated the risk factor for early death (death within 30 days from the onset of AE-IIPs) associated with AE-IIPs.

Results: Among the patients who developed AE-IIPs, 34 were characterized as having idiopathic, 25 were characterized as having infection-triggered, and 20 were categorized as having non-infection-triggered AE-IIPs. Survival time for pneumonia superimposed on IIPs was significantly longer than that for any AE-IIPs. Survival time for bacterial pneumonia superimposed on CF-IIPs was significantly longer than that for AE-IIPs (for each idiopathic and all triggered IIPs). Thereafter, survival time for infection-triggered was significantly longer than for idiopathic or non-infection-triggered AE-IIPs. The mortality rate was significantly lower in infection-triggered AE-IIPs than in other types of AE-IIPs. Furthermore, the incidence of infection-triggered AE-IIPs in winter was significantly higher than that in other seasons. Moreover, the clinical AE-IIPs types and radiological findings at AE-IIP onset were significant risk factors for AE-IIPs-induced early death.

Conclusions: Our findings suggest that patients with infection-triggered AE-IIPs can expect a better prognosis than can patients with other clinical types of AE-IIPs.

Keywords: Acute exacerbation; Idiopathic interstitial pneumonias; Idiopathic pulmonary fibrosis; Infection; Trigger.

Conflict of interest statement
The authors declare that they have no competing interests.

26 references3 figures
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14
N Engl J Med
. 2020 May 28;382(22):2081-2090. doi: 10.1056/NEJMoa2008457. Epub 2020 Apr 24.
Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility
Melissa M Arons 1, Kelly M Hatfield 1, Sujan C Reddy 1, Anne Kimball 1, Allison James 1, Jesica R Jacobs 1, Joanne Taylor 1, Kevin Spicer 1, Ana C Bardossy 1, Lisa P Oakley 1, Sukarma Tanwar 1, Jonathan W Dyal 1, Josh Harney 1, Zeshan Chisty 1, Jeneita M Bell 1, Mark Methner 1, Prabasaj Paul 1, Christina M Carlson 1, Heather P McLaughlin 1, Natalie Thornburg 1, Suxiang Tong 1, Azaibi Tamin 1, Ying Tao 1, Anna Uehara 1, Jennifer Harcourt 1, Shauna Clark 1, Claire Brostrom-Smith 1, Libby C Page 1, Meagan Kay 1, James Lewis 1, Patty Montgomery 1, Nimalie D Stone 1, Thomas A Clark 1, Margaret A Honein 1, Jeffrey S Duchin 1, John A Jernigan 1, Public Health–Seattle and King County and CDC COVID-19 Investigation Team
Collaborators, Affiliations expand
PMID: 32329971 PMCID: PMC7200056 DOI: 10.1056/NEJMoa2008457
Free PMC article
Abstract
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents.

Methods: We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic.

Results: Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide.

Conclusions: Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.

Copyright © 2020 Massachusetts Medical Society.

Comment in
Asymptomatic Transmission, the Achilles' Heel of Current Strategies to Control Covid-19.
Gandhi M, Yokoe DS, Havlir DV.
N Engl J Med. 2020 May 28;382(22):2158-2160. doi: 10.1056/NEJMe2009758. Epub 2020 Apr 24.
PMID: 32329972 Free PMC article. No abstract available.
Screening for Covid-19 in Skilled Nursing Facilities.
Krsak M, Henao-Martínez AF, Franco-Paredes C.
N Engl J Med. 2020 May 29;382:10.1056/NEJMc2017362#sa1. doi: 10.1056/NEJMc2017362. Online ahead of print.
PMID: 32469480 No abstract available.
Screening for Covid-19 in Skilled Nursing Facilities.
Calbo E, Masats Ú, Garau J.
N Engl J Med. 2020 May 29;382:10.1056/NEJMc2017362#sa2. doi: 10.1056/NEJMc2017362. Online ahead of print.
PMID: 32469481 No abstract available.
Screening for Covid-19 in Skilled Nursing Facilities.
Huber DH.
N Engl J Med. 2020 May 29;382:10.1056/NEJMc2017362#sa3. doi: 10.1056/NEJMc2017362. Online ahead of print.
PMID: 32469482 No abstract available.
Screening for Covid-19 in Skilled Nursing Facilities. Reply.
Hatfield KM, Reddy SC, Jernigan JA.
N Engl J Med. 2020 May 29;382:10.1056/NEJMc2017362#sa4. doi: 10.1056/NEJMc2017362. Online ahead of print.
PMID: 32469483 No abstract available.
Screening for Covid-19 in Skilled Nursing Facilities. Reply.
Gandhi M, Yokoe DS, Havlir DV.
N Engl J Med. 2020 May 29;382:10.1056/NEJMc2017362#sa5. doi: 10.1056/NEJMc2017362. Online ahead of print.
PMID: 32469484 No abstract available.
Cited by 4 articles22 references4 figures
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15
Review Indian J Med Microbiol
. Oct-Dec 2019;37(4):459-477. doi: 10.4103/ijmm.IJMM_20_54.
Novel 2019-coronavirus on New Year's Eve
Parakriti Gupta 1, Kapil Goyal 1, Poonam Kanta 1, Arnab Ghosh 1, Mini P Singh 1
Affiliations expand
PMID: 32436867 DOI: 10.4103/ijmm.IJMM_20_54
Free article
Abstract
An ongoing apocalyptic outbreak of a new virus causing pneumonia-like clusters in Wuhan city, China, has gleamed the world. The outbreak, confirmed on the New Year's Eve 2020, has known no boundaries since then. The number has surpassed that of Severe Acute Respiratory Syndrome (SARS) and Middle East respiratory syndrome (MERS), and is uninterruptedly escalating. Being an RNA virus, it has a propensity to mutate due to the low proofreading capacity of RNA-dependent RNA polymerase. Step-wise mutations have led to the gradual spillover of virus and after crossing the inter-species interface, the virus has adapted itself for a stable human-to-human transmission. The disease caused by severe acute respiratory syndrome coronavirus (CoV)-2 (SARS-CoV-2) can prove deadlier if the so-called 'super-spreading events' emerge with time. Recent research has shown the maximum homology of 99% of SARS-CoV-2 to pangolins associated coronavirus, owing to which these can serve as potential intermediate host. India is responding swiftly to the emergency situation, and the whole of the country is under lockdown since 25 March 2020, to ensure social distancing. All the international flights are padlocked and the travellers are being screened at airports and seaports via thermal sensors, and quarantine for a period of 14 days is recommended. Three hundred and forty-five patients across the country tested positive with six fatalities as of 22 March 2020. No specific anti-CoV drugs are currently available. Patients are being treated with protease drugs are inhibitors, remdesivir, chloroquine, angiotensin-converting enzyme 2 inhibitors, ivermectin, sarilumab and tocilizumab, though none of these is Food and Drug Administration approved and are undergoing trials. Preventive measures such as social distancing, quarantine, cough etiquettes, proper hand washing, cleaning and decontaminating the surfaces are the mainstay for curbing the transmission of this virus. The present review highlights the update of novel SARS-CoV-2 in context to the Indian scenario.

Keywords: Angiotensin-converting enzyme-2; RNA-dependent RNA polymerase; SARS-CoV-2; Wuhan; bats; hand hygiene; quarantine; social distancing.

Conflict of interest statement
None

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16
Arch Med Res
. 2020 Apr;51(3):282-286. doi: 10.1016/j.arcmed.2020.03.004. Epub 2020 Mar 27.
Can Bioactive Lipids Inactivate Coronavirus (COVID-19)?
Undurti N Das 1
Affiliations expand
PMID: 32229155 DOI: 10.1016/j.arcmed.2020.03.004
Abstract
SARS-CoV-2, SARS and MERS are all enveloped viruses that can cause acute respiratory syndrome. Arachidonic acid (AA) and other unsaturated fatty acids (especially eicosapentaenoic acd, EPA and docosahexaenoic acid DHA) are known to inactivate enveloped viruses and inhibit proliferation of various microbial organisms. The pro-inflammatory metabolites of AA and EPA such as prostaglandins, leukotrienes and thromboxanes induce inflammation whereas lipoxins, resolvins, protectins and maresins derived from AA, EPA and DHA not only suppress inflammation but also enhance would healing and augment phagocytosis of macrophages and other immunocytes and decrease microbial load. In view of these actions, it is suggested that AA and other unsaturated fatty acids and their metabolites may serve as endogenous anti-viral compounds and their deficiency may render humans susceptible to SARS-CoV-2, SARS and MERS and other similar viruses' infections. Hence, oral or intravenous administration of AA and other unsaturated fatty acids may aid in enhancing resistance and recovery from SARS-CoV-2, SARS and MERS infections.

Keywords: Arachidonic acid; Inflammation; Lipoxin A4; MERS; Polyunsaturated fatty acids; Prostaglandins; Protectins and maresins; Resolvins; SARS; SARS-CoV-2.

Copyright © 2020 IMSS. Published by Elsevier Inc. All rights reserved.

Cited by 4 articles
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17
J Fr Ophtalmol
. 2019 Dec;42(10):1056-1061. doi: 10.1016/j.jfo.2019.06.008. Epub 2019 Nov 10.
[Orbital Cellulitis in Children: Report of 60 Cases]
[Article in French]
D Saadouli 1, S Yahyaoui 2, K Ben Mansour 3, M Masmoudi 3, M A El Afrit 3, A Sammoud 2
Affiliations expand
PMID: 31722808 DOI: 10.1016/j.jfo.2019.06.008
Abstract
The goal of this study was to describe the epidemiological, etiological, clinical and therapeutic features and clinical course of orbital cellulitis in children, and to assess the risk factors for retroseptal involvement.

Methods: This was a retrospective study including 60 children (67 eyes) diagnosed with orbital cellulitis. Two groups were defined according to the clinical form: pre- or retroseptal.

Results: We studied 29 cases (34 eyes) of preseptal cellulitis and 31 cases (33 eyes) of retroseptal cellulitis. The mean age was 4 years. The male: female ratio was 1.3. The prescription of anti-inflammatory drugs and antibiotics prior to hospitalization was noted in respectively four and 10 patients. Eyelid edema was the principal sign (100% of cases); exophthalmia was noted in 19 eyes, ptosis in 27 eyes and chemosis in 10 eyes. Oculomotor disorders were present in 4 eyes. The mean C-reactive protein level was 53.15±27mg/l in preseptal cellulitis and 92.09±21mg/l in the retro-septal cases. Orbital computed tomography was performed in 31 patients and MRI in 5 patients. The pathway of entry of the orbital infection was primarily from the sinuses (23 cases). All of our patients had received broad spectrum intravenous antibiotic therapy. Three children had a cavernous sinus thrombosis and had been treated with anticoagulant therapy. Surgical drainage was performed in five patients. The course was favorable and without sequelae for all the patients. Two independent risk factors for retroseptal involvement were identified: the prescription of anti-inflammatory drugs prior to hospitalization, and sinus involvement.

Conclusion: Orbital cellulitis in children is a serious infection and requires close collaboration between the ophthalmologist, otolaryngologist, and pediatrician in order to be diagnosed and treated early so as to improve the prognosis for vision and life.

Keywords: Antibiothérapie; Antibiotic; Cellulite; Cellulitis; Children; Enfant; Orbit; Orbite; Sinusite; Sinusitis.

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

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18
Science
. 2020 May 29;368(6494):1016-1020. doi: 10.1126/science.abb7015. Epub 2020 Apr 8.
Susceptibility of Ferrets, Cats, Dogs, and Other Domesticated Animals to SARS-coronavirus 2
Jianzhong Shi # 1, Zhiyuan Wen # 1, Gongxun Zhong # 1, Huanliang Yang # 1, Chong Wang # 1, Baoying Huang # 2, Renqiang Liu 1, Xijun He 3, Lei Shuai 1, Ziruo Sun 1, Yubo Zhao 1, Peipei Liu 2, Libin Liang 1, Pengfei Cui 1, Jinliang Wang 1, Xianfeng Zhang 3, Yuntao Guan 3, Wenjie Tan 2, Guizhen Wu 4, Hualan Chen 5, Zhigao Bu 5 3
Affiliations expand
PMID: 32269068 PMCID: PMC7164390 DOI: 10.1126/science.abb7015
Free PMC article
Abstract
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) causes the infectious disease COVID-19 (coronavirus disease 2019), which was first reported in Wuhan, China, in December 2019. Despite extensive efforts to control the disease, COVID-19 has now spread to more than 100 countries and caused a global pandemic. SARS-CoV-2 is thought to have originated in bats; however, the intermediate animal sources of the virus are unknown. In this study, we investigated the susceptibility of ferrets and animals in close contact with humans to SARS-CoV-2. We found that SARS-CoV-2 replicates poorly in dogs, pigs, chickens, and ducks, but ferrets and cats are permissive to infection. Additionally, cats are susceptible to airborne transmission. Our study provides insights into the animal models for SARS-CoV-2 and animal management for COVID-19 control.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Comment in
Coronavirus: a veterinary perspective.
da Hora AS.
Nature. 2020 Apr;580(7803):321. doi: 10.1038/d41586-020-01077-2.
PMID: 32286554 No abstract available.
The search for a COVID-19 animal model.
Lakdawala SS, Menachery VD.
Science. 2020 May 29;368(6494):942-943. doi: 10.1126/science.abc6141.
PMID: 32467379 No abstract available.
Cited by 5 articles35 references3 figures
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19
Review Stem Cell Rev Rep
. 2020 Jun;16(3):427-433. doi: 10.1007/s12015-020-09973-w.
Mesenchymal Stem Cell Therapy for COVID-19: Present or Future
Ali Golchin 1, Ehsan Seyedjafari 2, Abdolreza Ardeshirylajimi 3 4
Affiliations expand
PMID: 32281052 PMCID: PMC7152513 DOI: 10.1007/s12015-020-09973-w
Free PMC article
Abstract
"COVID-19" is the word that certainly isn't forgotten by everybody who lives in the first half of the twenty-first century. COVID-19, as a pandemic, has led many researchers from different biomedical fields to find solutions or treatments to manage the pandemic. However, no standard treatment for this disease has been discovered to date. Probably, preventing the severe acute respiratory infection form of COVID-19 as the most dangerous phase of this disease can be helpful for the treatment and reduction of the death rate. In this regard, mesenchymal stem cells (MSCs)-based immunomodulation treatment has been proposed as a suitable therapeutic approach and several clinical trials have begun. Recently, MSCs according to their immunomodulatory and regenerative properties attract attention in clinical trials. After the intravenous transplantation of MSCs, a significant population of cells accumulates in the lung, which they alongside immunomodulatory effect could protect alveolar epithelial cells, reclaim the pulmonary microenvironment, prevent pulmonary fibrosis, and cure lung dysfunction. Given the uncertainties in this area, we reviewed reported clinical trials and hypotheses to provide useful information to researchers and those interested in stem cell therapy. In this study, we considered this new approach to improve patient's immunological responses to COVID-19 using MSCs and discussed the aspects of this proposed treatment. However, currently, there are no approved MSC-based approaches for the prevention and/or treatment of COVID-19 patients but clinical trials ongoing.

Keywords: COVID-19; Clinical trials; Coronavirus; Immunomodulatory; Mesenchymal stem cell; Stem cell therapy.

Conflict of interest statement
We have no conflicts of interest.

34 references2 figures
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20
J Virol
. 2019 Jul 17;93(15):e00569-19. doi: 10.1128/JVI.00569-19. Print 2019 Aug 1.
Age-Dependent Effects of Immunoproteasome Deficiency on Mouse Adenovirus Type 1 Pathogenesis
Adithya Chandrasekaran 1, Laura J Adkins 1, Harrison M Seltzer 1, Krittika Pant 1 2, Stephen T Tryban 1 2, Caitlyn T Molloy 1, Jason B Weinberg 3 4
Affiliations expand
PMID: 31092582 PMCID: PMC6639286 DOI: 10.1128/JVI.00569-19
Free PMC article
Abstract
Acute respiratory infection with mouse adenovirus type 1 (MAV-1) induces activity of the immunoproteasome, an inducible form of the proteasome that shapes CD8 T cell responses by enhancing peptide presentation by major histocompatibility complex (MHC) class I. We used mice deficient in all three immunoproteasome subunits (triple-knockout [TKO] mice) to determine whether immunoproteasome activity is essential for control of MAV-1 replication or inflammatory responses to acute infection. Complete immunoproteasome deficiency in adult TKO mice had no effect on MAV-1 replication, virus-induced lung inflammation, or adaptive immunity compared to C57BL/6 (B6) controls. In contrast, immunoproteasome deficiency in neonatal TKO mice was associated with decreased survival and decreased lung gamma interferon (IFN-γ) expression compared to B6 controls, although without substantial effects on viral replication, histological evidence of inflammation, or expression of the proinflammatory cytokines tumor necrosis factor alpha and interleukin-1β in lungs or other organs. T cell recruitment and IFN-γ production was similar in lungs of infected B6 and TKO mice. In lungs of uninfected B6 mice, we detected low levels of immunoproteasome subunit mRNA and protein that increased with age. Immunoproteasome subunit expression was lower in lungs of adult IFN-γ-deficient mice compared to B6 controls. Together, these results demonstrate developmental regulation of the immunoproteasome that is associated with age-dependent differences in MAV-1 pathogenesis.IMPORTANCE MAV-1 infection is a useful model to study the pathogenesis of an adenovirus in its natural host. Host factors that control MAV-1 replication and contribute to inflammation and disease are not fully understood. The immunoproteasome is an inducible component of the ubiquitin proteasome system that shapes the repertoire of peptides presented by MHC class I to CD8 T cells, influences other aspects of T cell survival and activation, and promotes production of proinflammatory cytokines. We found that immunoproteasome activity is dispensable in adult mice. However, immunoproteasome deficiency in neonatal mice increased mortality and impaired IFN-γ responses in the lungs. Baseline immunoproteasome subunit expression in lungs of uninfected mice increased with age. Our findings suggest the existence of developmental regulation of the immunoproteasome, like other aspects of host immune function, and indicate that immunoproteasome activity is a critical protective factor early in life.

Keywords: adenovirus; immunoproteasome; interferon gamma; neonatal immunology; respiratory viruses.

Copyright © 2019 American Society for Microbiology.

Cited by 1 article8 figures
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21
J Med Virol
. 2019 Aug;91(8):1408-1414. doi: 10.1002/jmv.25479. Epub 2019 Apr 14.
Impact of Molecular Point-Of-Care Testing on Clinical Management and In-Hospital Costs of Patients Suspected of Influenza or RSV Infection: A Modeling Study
Janette Rahamat-Langendoen 1, Hans Groenewoud 2, Judith Kuijpers 1, Willem J G Melchers 1, Gert Jan van der Wilt 2
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PMID: 30950066 PMCID: PMC7166495 DOI: 10.1002/jmv.25479
Free PMC article
Abstract
Background: At hospital admission, patients suspected of infection with influenza or respiratory syncytial virus (RSV) are placed in isolation, pending the outcome of diagnostics. In a significant number, isolated care proves unnecessary. We investigated the potential impact of molecular point-of-care (POC) diagnostics on patient management and in-hospital costs.

Method: Prospective collection of data on resource utilization within the hospital from consecutive patients 18 years or older presenting at our university medical center with symptoms of respiratory tract infection from December 2016 to April 2017. A cost analysis was conducted using Markov modeling comparing the actual course of events (on the basis of routine diagnostic tests) with two hypothetical scenarios: when POC would impact time to diagnosis only (scenario 1) or on discharge from the hospital, too (scenario 2).

Results: A total of 283 patients were included, of whom 217 (76.7%) were admitted. Influenza and RSV were detected in 31% and 7% of the patients, respectively. Fifty-four percent of patients tested negative, of which 79% were kept in isolated care waiting for test results, with a median duration of 24 hours. Median length of stay was 6.0 days. Mean total in-hospital costs per patient were € 5243. Introducing POC would lower mean costs per patient to € 4904 (scenario 1) and € 4206 (scenario 2). At the hospital level, this would result in a total cost reduction of € 95 937 to € 293 471 in a single influenza season.

Conclusions: Introducing POC testing for patients presenting with symptoms of viral respiratory tract infection can reduce time-to-diagnosis, hospital stay and, thereby, in-hospital costs.

Keywords: cost benefit; influenza virus; rapid detection; respiratory syncytial virus (RSV).

© 2019 Wiley Periodicals, Inc.

Conflict of interest statement
The authors declare that there are no conflict of interests.

Cited by 1 article24 references2 figures
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22
Clinical Trial Int Forum Allergy Rhinol
. 2019 Dec;9(12):1470-1477. doi: 10.1002/alr.22423. Epub 2019 Aug 28.
Manuka Honey Sinus Irrigations in Recalcitrant Chronic Rhinosinusitis: Phase 1 Randomized, Single-Blinded, Placebo-Controlled Trial
Mian Li Ooi 1, Arvind Jothin 1, Catherine Bennett 1, Eng H Ooi 2, Sarah Vreugde 1, Alkis J Psaltis 1, Peter-John Wormald 1
Affiliations expand
PMID: 31461581 DOI: 10.1002/alr.22423
Abstract
Background: Manuka honey (MH) has significant antibiofilm activity in vitro and in vivo against Staphylococcus aureus, methicillin-resistant S aureus (MRSA), and Pseudomonas aeruginosa. This is the first randomized, single-blinded, placebo-controlled phase 1 clinical trial investigating the safety and preliminary efficacy of MH with augmented methylglyoxal (MGO) rinses in recalcitrant chronic rhinosinusitis (CRS).

Methods: Patients were included after previously undergoing endoscopic sinus surgery and presenting with signs and symptoms of sinus infection with positive bacterial cultures on sinus swabs. Patients were randomized to receive 14 days of twice-daily 16.5% MH + 1.3 mg/mL MGO sinonasal rinses and concurrent 10 days of placebo tablets (MH), or 14 days of twice-daily saline sinonasal rinses and concurrent 10 days of culture-directed antibiotic therapy (CON). Safety observations included the University of Pennsylvania Smell Identification Test (UPSIT) and adverse-event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund-Kennedy scores (LKSs), and symptom scores using the visual analog scale (VAS) and 22-item Sino-Nasal Outcome Test (SNOT-22).

Results: Twenty-five patients completed the study. MH demonstrated a good safety profile with no major AEs and no changes in UPSIT. Six of 10 (60%) MH patients had a reduction in bacterial culture rate with 1 of 10 of those having negative cultures, compared with 12 of 15 (80%) in the control group with 7 of 15 having negative cultures upon completion of the study.

Conclusion: This study concludes that twice-daily 16.5% MH augmented with 1.3 mg/mL MGO sinonasal rinses alone for 14 days is safe but not superior to culture-directed oral antibiotics and twice-daily saline rinses.

Keywords: antimicrobial; chronic rhinosinusitis; efficacy; infection; recalcitrant; safety; topical agent.

© 2019 ARS-AAOA, LLC.

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23
Comparative Study Science
. 2020 May 29;368(6494):1012-1015. doi: 10.1126/science.abb7314. Epub 2020 Apr 17.
Comparative Pathogenesis of COVID-19, MERS, and SARS in a Nonhuman Primate Model
Barry Rockx 1, Thijs Kuiken 2, Sander Herfst 2, Theo Bestebroer 2, Mart M Lamers 2, Bas B Oude Munnink 2, Dennis de Meulder 2, Geert van Amerongen 3, Judith van den Brand 2, Nisreen M A Okba 2, Debby Schipper 2, Peter van Run 2, Lonneke Leijten 2, Reina Sikkema 2, Ernst Verschoor 4, Babs Verstrepen 4, Willy Bogers 4, Jan Langermans 5 6, Christian Drosten 7, Martje Fentener van Vlissingen 8, Ron Fouchier 2, Rik de Swart 2, Marion Koopmans 2, Bart L Haagmans 1
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PMID: 32303590 PMCID: PMC7164679 DOI: 10.1126/science.abb7314
Free PMC article
Abstract
The current pandemic coronavirus, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), was recently identified in patients with an acute respiratory syndrome, coronavirus disease 2019 (COVID-19). To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or Middle East respiratory syndrome (MERS)-CoV and compared the pathology and virology with historical reports of SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in the absence of clinical signs and detected in type I and II pneumocytes in foci of diffuse alveolar damage and in ciliated epithelial cells of nasal, bronchial, and bronchiolar mucosae. In SARS-CoV infection, lung lesions were typically more severe, whereas they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 causes COVID-19-like disease in macaques and provides a new model to test preventive and therapeutic strategies.

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Cited by 6 articles30 references3 figures
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24
BMC Pulm Med
. 2019 Dec 23;19(1):260. doi: 10.1186/s12890-019-1021-5.
Dynamics of Microbiota During Mechanical Ventilation in Aspiration Pneumonia
Ken Otsuji 1 2, Kazumasa Fukuda 3, Midori Ogawa 3, Yoshihisa Fujino 4, Masayuki Kamochi 5, Mitsumasa Saito 3
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PMID: 31870355 PMCID: PMC6929358 DOI: 10.1186/s12890-019-1021-5
Free PMC article
Abstract
Background: The emergence of multi-drug resistant pathogens is an urgent health-related problem, and the appropriate use of antibiotics is imperative. It is often difficult to identify the causative bacteria in patients with aspiration pneumonia because tracheal aspirate contains contaminants of oral bacteria. We investigated the dynamics of microbiota in mechanically ventilated patients with aspiration pneumonia to develop a treatment strategy.

Methods: Twenty-two intubated patients with aspiration pneumonia were recruited. Saliva and tracheal aspirate of the subjects were collected at three time points: (A) within 2 h after intubation, (B) just before administration of antibiotics, and (C) 48-72 h after administration of antibiotics. The microbiota in each specimen was analyzed by using the 16S rRNA gene clone library sequencing method. Bacterial floras of the samples were analyzed by principal component analysis.

Results: Principal component analysis based on the composition of genus revealed that although the changes of microbiota in the saliva from (A) to (B) were not clear, the composition of anaerobes in the tracheal aspirate (B) was lower than (A). In fact, the reduction of anaerobes, not in the saliva but in the tracheal aspirate from (A) to (B), was confirmed by incident rate ratios estimated by a multilevel Poisson regression model (p < 0.001). The extent of decrease in anaerobes was fully dependent on the time difference between the sampling of tracheal aspirate (A) and (B)-in particular, over 3 h of mechanical ventilation. This indicates that the alterations of microbiota (involving the reduction of anaerobes in the lower respiratory tract) occurred during mechanical ventilation prior to the administration of antibiotics. After the administration of antibiotics, Enterobacter spp., Corynebacterium spp., Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, and Granulicatera adiacens were predominantly detected in the tracheal aspirate (C).

Conclusion: The microbiota of the lower respiratory tract changes dynamically during mechanical ventilation and during the administration of antibiotics in intubated patients with aspiration pneumonia. Antibiotics should be selected on the premise that dynamic changes in microbiota (involved in the reduction of anaerobes) may occur during the mechanical ventilation in these patients.

Keywords: Anaerobes; Aspiration pneumonia; Dynamics; Mechanical ventilation; Microbiota.

Conflict of interest statement
The authors declare that they have no competing interests.

39 references3 figures
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25
Chest
. 2019 Nov;156(5):843-851. doi: 10.1016/j.chest.2019.04.093. Epub 2019 May 8.
Antibiotic Use and Outcomes After Implementation of the Drug Resistance in Pneumonia Score in ED Patients With Community-Onset Pneumonia
Brandon J Webb 1, Jeffrey Sorensen 2, Ian Mecham 3, Whitney Buckel 4, Lilian Ooi 5, Al Jephson 2, Nathan C Dean 6
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PMID: 31077649 DOI: 10.1016/j.chest.2019.04.093
Abstract
Background: To guide rational antibiotic selection in community-onset pneumonia, we previously derived and validated a novel prediction tool, the Drug-Resistance in Pneumonia (DRIP) score. In 2015, the DRIP score was integrated into an existing electronic pneumonia clinical decision support tool (ePNa).

Methods: We conducted a quasi-experimental, pre-post implementation study of ePNa with DRIP score (2015) vs ePNa with health-care-associated pneumonia (HCAP) logic (2012) in ED patients admitted with community-onset pneumonia to four US hospitals. Using generalized linear models, we used the difference-in-differences method to estimate the average treatment effect on the treated with respect to ePNa with DRIP score on broad-spectrum antibiotic use, mortality, hospital stay, and cost, adjusting for available patient-level confounders.

Results: We analyzed 2,169 adult admissions: 1,122 in 2012 and 1,047 in 2015. A drug-resistant pathogen was recovered in 3.2% of patients in 2012 and 2.8% in 2015; inadequate initial empirical antibiotics were prescribed in 1.1% and 0.5%, respectively (P = .12). A broad-spectrum antibiotic was administered in 40.1% of admissions in 2012 and 33.0% in 2015 (P < .001). Vancomycin days of therapy per 1,000 patient days in 2012 were 287.3 compared with 238.8 in 2015 (P < .001). In the primary analysis, the average treatment effect among patients using the DRIP score was a reduction in broad-spectrum antibiotic use (OR, 0.62; 95% CI, 0.39-0.98; P = .039). However, the average effects for ePNa with DRIP on mortality, length of stay, and cost were not statistically significant.

Conclusions: Electronic calculation of the DRIP score was more effective than HCAP criteria for guiding appropriate broad-spectrum antibiotic use in community-onset pneumonia.

Keywords: antibiotic; antibiotic resistance; antimicrobial stewardship; health-care associated pneumonia.

Copyright © 2019 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

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26
Review Cell Immunol
. 2019 Nov;345:103992. doi: 10.1016/j.cellimm.2019.103992. Epub 2019 Oct 10.
Diminished Immune Responses With Aging Predispose Older Adults to Common and Uncommon Influenza Complications
Spencer R Keilich 1, Jenna M Bartley 2, Laura Haynes 3
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PMID: 31627841 PMCID: PMC6939636 (available on 2020-11-01) DOI: 10.1016/j.cellimm.2019.103992
Free PMC article
Abstract
Influenza (flu) is a serious disease for older adults, with increased severity of infection and greater risk for hospitalization and death. Flu infection is limited to pulmonary epithelial cells, yet there are many systemic symptoms and older adults are more susceptible to flu-related complications. In older adults, flu rarely comes without additional complications and there is a perfect storm for enhanced disease due to multiple factors including existing co-morbidities, plus impaired lung function and dysregulated immune responses that occur with even healthy aging. Commonly, opportunistic secondary bacterial infections prosper in damaged lungs. Intensified systemic inflammation with aging can cause dysfunction in extra-pulmonary organs and tissues such as cardiovascular, musculoskeletal, neuropathologic, hepatic, and renal complications. Often overlooked is the underappreciated connections between many of these conditions, which exacerbate one another when in parallel. This review focuses on flu infection and the numerous complications in older adults associated with diminished immune responses.

Keywords: Aging; Cardiovascular; Hepatic; Immunology; Influenza; Musculoskeletal; Neuropathologic; Renal; Secondary bacteria infection.

Copyright © 2019 Elsevier Inc. All rights reserved.

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27
Comparative Study J Med Virol
. 2019 Aug;91(8):1562-1565. doi: 10.1002/jmv.25495. Epub 2019 May 14.
Evaluation of Rapid Influenza Diagnostic Tests for Influenza A and B in the Tropics
Yoong Min Chong 1, Xiu Hui Tan 1, Poh Sim Hooi 2, Lu Mei Lee 2, I-Ching Sam 1 2, Yoke Fun Chan 1
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PMID: 31032971 DOI: 10.1002/jmv.25495
Abstract
Rapid diagnosis of influenza is important for early treatment and institution of control measures. In developing tropical countries such as Malaysia, influenza occurs all year round, but molecular assays and conventional techniques (such as immunofluorescence and culture) for diagnosis are not widely available. Rapid influenza diagnostic tests (RIDTs) may be useful in this setting. A total of 552 fresh respiratory specimens were assessed from patients with respiratory symptoms at a teaching hospital in Kuala Lumpur, Malaysia from November 2017 to March 2018. Two digital immunoassays (DIAs), STANDARD F Influenza A/B Fluorescence Immunoassay (STANDARD F) and Sofia Influenza A + B Fluorescence Immunoassay (Sofia) and one conventional RIDT (immunochromatographic assay), SD Bioline Influenza Ag A/B/A(H1N1) Pandemic rapid test kit (SD Bioline) were evaluated in comparison with a WHO-recommended reverse transcription quantitative PCR (RT-qPCR). Of the 552 samples, influenza A virus was detected in 47 (8.5%) and influenza B virus in 7 (1.3%). The digital immunoassays STANDARD F and Sofia had significantly higher overall sensitivity rates (71.7% and 70.6%, respectively) than the conventional RIDT SD Bioline and immunofluorescence/viral culture (55.8% and 52.8%, respectively). Sensitivity rates were higher for influenza A than influenza B, and specificity rates were uniformly high, ranging from 98% to 100%. Digital readout RIDTs can be used in tropical settings with year-round influenza if PCR is unavailable.

Keywords: immunologic techniques; influenza virus; pathogenesis; research and analysis methods; respiratory tract; virus classification.

© 2019 Wiley Periodicals, Inc.

Cited by 1 article
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28
Int Forum Allergy Rhinol
. 2019 Dec;9(12):1462-1469. doi: 10.1002/alr.22425. Epub 2019 Sep 4.
Detection and Quantification of Staphylococcus in Chronic Rhinosinusitis
Brett Wagner Mackenzie 1, Jesse Baker 1 2, Richard G Douglas 1, Michael W Taylor 2, Kristi Biswas 2
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PMID: 31483577 DOI: 10.1002/alr.22425
Abstract
Background: The sinonasal microbiota has been implicated in chronic rhinosinusitis (CRS) pathogenesis, particularly related to the presence of Staphylococcus aureus. Staphylococcus epidermidis is also prevalent within the sinonasal microbiota and may inhibit S. aureus colonization. We investigated polymerase chain reaction (PCR) primer pairs for measuring absolute abundances of S. aureus and S. epidermidis, then compared bacterial community composition and absolute abundances of these species between CRS patients and controls.

Methods: Six candidate Staphylococcus species-specific primer pairs were tested in silico and in vitro against pure bacterial isolates. Quantitative PCR (qPCR) for absolute quantification of S. aureus, S. epidermidis, and overall bacterial load were assessed in 40 CRS (CRS without nasal polyposis [CRSsNP] = 22, CRS with nasal polyposis [CRSwNP] = 18) patients and 14 controls. Amplicon sequencing of the V3-V4 hypervariable regions of the 16S ribosomal RNA (rRNA) bacterial gene were conducted to investigate community composition.

Results: Primer pairs targeting the gmk gene of S. aureus and nrd gene from S. epidermidis were the most specific and sensitive primers. S. aureus (CRSsNP = 81.8% occurrence, CRSwNP = 83%, control = 92.9%) and S. epidermidis (CRSsNP = 95.5%, CRSwNP = 100%, control = 92.9%) were very prevalent, as indicated by qPCR results. Both CRSsNP and CRSwNP had significantly (p < 0.05) higher bacterial load when compared with controls (p < 0.05 for both). No significant correlation was observed between S. aureus and S. epidermidis abundances (p > 0.05).

Conclusion: Bacterial community sequencing detected Staphylococcus-assigned sequences in nearly all patients; however, it could not differentiate between S. aureus and S. epidermidis. Here, we present primer pairs that can distinguish between these species. We report a very high prevalence of S. aureus in both CRS patients and controls.

Keywords: Staphylococcus spp; bacteriology; chronic rhinosinusitis; paranasal sinuses; qPCR; statistics.

© 2019 ARS-AAOA, LLC.

47 references
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29
J Virol
. 2019 Aug 13;93(17):e00058-19. doi: 10.1128/JVI.00058-19. Print 2019 Sep 1.
Influenza Virus With Increased pH of Hemagglutinin Activation Has Improved Replication in Cell Culture but at the Cost of Infectivity in Human Airway Epithelium
Anika Singanayagam 1, Maria Zambon 2, Wendy S Barclay 3
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PMID: 31189708 PMCID: PMC6694820 DOI: 10.1128/JVI.00058-19
Free PMC article
Abstract
Pandemic H1N1 (pH1N1) influenza virus emerged from swine in 2009 with an adequate capability to infect and transmit between people. In subsequent years, it has circulated as a seasonal virus and evolved further human-adapting mutations. Mutations in the hemagglutinin (HA) stalk that increase pH stability have been associated with human adaptation and airborne transmission of pH1N1 virus. Yet, our understanding of how pH stability impacts virus-host interactions is incomplete. Here, using recombinant viruses with point mutations that alter the pH stability of pH1N1 HA, we found distinct effects on virus phenotypes in different experimental models. Increased pH sensitivity enabled viruses to uncoat in endosomes more efficiently, manifesting as increased replication rate in typical continuous cell cultures under single-cycle conditions. A more acid-labile HA also conferred a small reduction in sensitivity to antiviral therapeutics that act at the pH-sensitive HA fusion step. Conversely, in primary human airway epithelium cultured at the air-liquid interface, increased pH sensitivity attenuated multicycle viral replication by compromising virus survival in the extracellular microenvironment. In a mouse model of influenza pathogenicity, there was an optimum HA activation pH, and viruses with either more- or less-pH-stable HA were less virulent. Opposing pressures inside and outside the host cell that determine pH stability may influence zoonotic potential. The distinct effects that changes in pH stability exert on viral phenotypes underscore the importance of using the most appropriate systems for assessing virus titer and fitness, which has implications for vaccine manufacture, antiviral drug development, and pandemic risk assessment.IMPORTANCE The pH stability of the hemagglutinin surface protein varies between different influenza strains and subtypes and can affect the virus' ability to replicate and transmit. Here, we demonstrate a delicate balance that the virus strikes within and without the target cell. We show that a pH-stable hemagglutinin enables a human influenza virus to replicate more effectively in human airway cells and mouse lungs by facilitating virus survival in the extracellular environment of the upper respiratory tract. Conversely, after entering target cells, being more pH stable confers a relative disadvantage, resulting in less efficient delivery of the viral genome to the host cell nucleus. Since the balance we describe will be affected differently in different host environments, it may restrict a virus' ability to cross species. In addition, our findings imply that different influenza viruses may show variation in how well they are controlled by antiviral strategies targeting pH-dependent steps in the virus replication cycle.

Keywords: hemagglutinin; influenza; viral replication; virology.

Copyright © 2019 Singanayagam et al.

Cited by 4 articles65 references6 figures
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30
Editorial Clin Obes
. 2020 Jun;10(3):e12365. doi: 10.1111/cob.12365. Epub 2020 Apr 27.
COVID-19 and Obesity
Nick Finer 1, Sarah P Garnett 2, Jens M Bruun 3
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PMID: 32342637 DOI: 10.1111/cob.12365
9 references
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31
Editorial Int Forum Allergy Rhinol
. 2019 Dec;9(12):1399-1400. doi: 10.1002/alr.22496.
Aspirin Exacerbated Respiratory Disease (AERD) Treatment Revisited
David W Kennedy
PMID: 31816200 DOI: 10.1002/alr.22496
10 references
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32
Editorial Acta Physiol (Oxf)
. 2020 Jun;229(2):e13470. doi: 10.1111/apha.13470. Epub 2020 Apr 11.
SARS-CoV-2: What Do We Know So Far?
Pratik H Khedkar 1, Andreas Patzak 1
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PMID: 32220035 PMCID: PMC7228362 DOI: 10.1111/apha.13470
Free PMC article
Conflict of interest statement
We declare that we have no conflicts of interest to disclose.

44 references1 figure
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33
Observational Study Int Forum Allergy Rhinol
. 2019 Dec;9(12):1436-1442. doi: 10.1002/alr.22431. Epub 2019 Oct 14.
Predictors of Efficacy for Combination Oral and Topical Corticosteroids to Treat Patients With Chronic Rhinosinusitis With Nasal Polyps
Madison V Epperson 1, Katie M Phillips 2, David S Caradonna 3 4, Stacey T Gray 3 5, Ahmad R Sedaghat 1
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PMID: 31609091 DOI: 10.1002/alr.22431
Abstract
Background: A short-course oral corticosteroid taper and topical intranasal corticosteroids may be used to maximize the success of medical management for chronic rhinosinusitis with nasal polyps (CRSwNP). In this study, we sought to identify characteristics that would be predictive of efficacy for this combination regimen.

Methods: Sixty-four patients with CRS, bilateral polyps, a polyp score of at least 3, and a 22-item Sino-Nasal Outcome Test (SNOT-22) score ≥20 were prospectively enrolled and uniformly treated with a 15-day prednisone taper and twice daily dilute budesonide irrigations. Participants were assessed at enrollment and at follow up, 2 to 5 months later. Clinical and demographic characteristics were assessed at enrollment. At both time points, CRS symptoms were assessed with SNOT-22, and polyp score (range, 0 to 6) was assessed endoscopically. Associations were determined with regression.

Results: Pretreatment SNOT-22 score (adjusted β = -0.83; 95% CI, -1.08 to -0.58; p < 0.001) and comorbid asthma (adjusted β = 15.75; 95% CI, 4.74 to 26.75; p = 0.007) were associated with a change in SNOT-22 experienced over the study period. Achieving a greater-than-1 minimal clinically important difference (MCID) improvement in SNOT-22 score was also associated with pretreatment SNOT-22 score (adjusted OR = 1.09; 95% CI, 1.04 to 1.14; p < 0.001) and comorbid asthma (adjusted OR = 0.13; 95% CI, 0.03 to 0.72; p = 0.019). SNOT-22 score ≥47 had 81.5% sensitivity and 78.4% specificity to detect patients experiencing 1 MCID improvement. Pretreatment polyp score was not associated with any outcome metric.

Conclusion: In treatment of CRSwNP with prednisone and budesonide irrigations, pretreatment endoscopy was not informative of treatment response. Pretreatment SNOT-22 and comorbid asthma may be more predictive.

Keywords: CRSwNP; budesonide; chronic rhinosinusitis; corticosteroids; irrigation; polyps; treatment response.

© 2019 ARS-AAOA, LLC.

47 references
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34
Observational Study BMC Pregnancy Childbirth
. 2019 Dec 19;19(1):510. doi: 10.1186/s12884-019-2628-5.
Determinants of Influenza Vaccination Uptake in Pregnancy: A Large single-Centre Cohort Study
Stéphanie Bartolo 1 2, Emilie Deliege 3, Ophélie Mancel 3, Philippe Dufour 3, Sophie Vanderstichele 3, Marielle Roumilhac 3, Yamina Hammou 3, Sophie Carpentier 3, Rodrigue Dessein 4, Damien Subtil 5 3, Karine Faure 4 6
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PMID: 31856752 PMCID: PMC6924067 DOI: 10.1186/s12884-019-2628-5
Free PMC article
Abstract
Background: Although vaccination of pregnant women against influenza is recommended, the vaccination rate remains low. We conducted a study to identify determinants of influenza vaccination uptake in pregnancy in order to identify strategies to improve seasonal influenza vaccination rates.

Methods: Prospective observational hospital-based study in the French hospital performing the highest number of deliveries, located in the city of Lille, among all women who had given birth during the 2014-2015 influenza season. Data were collected through a self-completed questionnaire and from medical files. The vaccination uptake was self-reported. Determinants of vaccination uptake were identified using logistic regression analysis.

Results: Of the 2045 women included in the study, 35.5% reported that they had been vaccinated against influenza during their pregnancy. The principal factors significantly associated with greater vaccination uptake were previous influenza vaccination (50.9% vs 20.2%, OR 4.1, 95% CI 3.1-5.5), nulliparity (41.0% vs 31.3%, OR 2.5, 95% CI 1.7-3.7), history of preterm delivery < 34 weeks (43.4% vs 30.3%, OR 2.3, 95% CI 1.1-4.9), the mother's perception that the frequency of vaccine complications for babies is very low (54.6% vs 20.6%, OR 1.1, 95% CI 0.5-2.2), the mother's good knowledge of influenza and its vaccine (61.7% vs 24.4%, OR 3.1, 95% CI 2.2-4.4), hospital-based prenatal care in their first trimester of pregnancy (55.0% vs 30.2%, OR 2.1, 95% CI 1.2-3.7), vaccination recommendations during pregnancy by a healthcare worker (47.0% vs 2.7%, OR 18.8, 95% CI 10.0-35.8), receipt of a vaccine reimbursement form (52.4% vs 18.6%, OR 2.0, 95% CI 1.5-2.7), and information from at least one healthcare worker about the vaccine (43.8% vs 19.1%, OR 1.8, 95% CI 1.3-2.6).

Conclusions: Our findings suggest that in order to increase flu vaccination compliance among pregnant women, future public health programmes must ensure cost-free access to vaccination, and incorporate education about the risks of influenza and the efficacy/safety of vaccination and clear recommendations from healthcare professionals into routine antenatal care.

Keywords: Behaviours; Health knowledge; Influenza vaccine; Pregnancy.

Conflict of interest statement
The authors declare that they have no competing interests.

28 references1 figure
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35
Observational Study BMC Pulm Med
. 2019 Dec 9;19(1):238. doi: 10.1186/s12890-019-1013-5.
PedCAPNETZ - Prospective Observational Study on Community Acquired Pneumonia in Children and Adolescents
Martin Wetzke 1 2 3, Matthias Volkmar Kopp 3 4, Jürgen Seidenberg 5, Christian Vogelberg 6, Tobias Ankermann 7, Christine Happle 1 3, Gesche Voigt 3 4, Holger Köster 5, Thomas Illig 3 8, Christiane Lex 9, Antje Schuster 10, Marcus Panning 11, Grit Barten 3 12, Gernot Rohde 12 13, Tobias Welte 3 12 14, Gesine Hansen 15 16 17, pedCAPNETZ Study Group
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PMID: 31818288 PMCID: PMC6902429 DOI: 10.1186/s12890-019-1013-5
Free PMC article
Abstract
Background: Pediatric community acquired pneumonia (pedCAP) is one of the leading causes for childhood morbidity accounting for up to 20% of pediatric hospital admissions in high income countries. In spite of its high morbidity, updated epidemiological and pathogen data after introduction of preventive vaccination and novel pathogen screening strategies are limited. Moreover, there is a need for validated recommendations on diagnostic and treatment regimens in pedCAP. Through collection of patient data and analysis of pathogen and host factors in a large sample of unselected pedCAP patients in Germany, we aim to address and substantially improve this situation.

Methods: pedCAPNETZ is an observational, multi-center study on pedCAP. Thus far, nine study centers in hospitals, outpatient clinics and practices have been initiated and more than 400 patients with radiologically confirmed pneumonia have been enrolled, aiming at a total of 1000 study participants. Employing an online data base, information on disease course, treatment as well as demographical and socioeconomical data is recorded. Patients are followed up until day 90 after enrollment; Comprehensive biosample collection and a central pedCAPNETZ biobank allow for in-depth analyses of pathogen and host factors. Standardized workflows to assure sample logistics and data management in more than fifteen future study centers have been established.

Discussion: Through comprehensive epidemiological, clinical and biological analyses, pedCAPNETZ fills an important gap in pediatric and infection research. To secure dissemination of the registry, we will raise clinical and scientific awareness at all levels. We aim at participating in decision making processes for guidelines and prevention strategies. Ultimately, we hope the results of the pedCAPNETZ registry will help to improve care and quality of life in pedCAP patients in the future.

Conflict of interest statement
The authors have no competing interests to specify.

27 references2 figures
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36
J Am Coll Surg
. 2020 Jun;230(6):1098-1101. doi: 10.1016/j.jamcollsurg.2020.03.030. Epub 2020 Apr 2.
Precautions for Operating Room Team Members During the COVID-19 Pandemic
Joseph D Forrester 1, Aussama K Nassar 2, Paul M Maggio 2, Mary T Hawn 2
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PMID: 32247836 DOI: 10.1016/j.jamcollsurg.2020.03.030
Abstract
Background: The novel coronavirus SARS-CoV-2 (COVID-19) can infect healthcare workers. We developed an institutional algorithm to protect operating room team members during the COVID-19 pandemic and rationally conserve personal protective equipment (PPE).

Study design: An interventional platform (operating room, interventional suite, and endoscopy) PPE taskforce was convened by the hospital and medical school leadership and tasked with developing a common algorithm for PPE use, to be used throughout the interventional platform. In conjunction with our infectious disease experts, we developed our guidelines based on potential patterns of spread, risk of exposure, and conservation of PPE.

Results: A decision tree algorithm describing our institutional guidelines for precautions for operating room team members was created. This algorithm is based on urgency of operation, anticipated viral burden at the surgical site, opportunity for a procedure to aerosolize virus, and likelihood a patient could be infected based on symptoms and testing.

Conclusions: Despite COVID-19 being a new threat, we have shown that by developing an easy-to-follow decision tree algorithm for the interventional platform teams, we can ensure optimal health care worker safety.

Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Cited by 6 articles
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Review United European Gastroenterol J
. 2020 Jun;8(5):520-527. doi: 10.1177/2050640620920157. Epub 2020 Apr 11.
The Daily Impact of COVID-19 in Gastroenterology
Fernando Magro 1 2 3, Candida Abreu 4 5, Jean-François Rahier 6
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PMID: 32281517 DOI: 10.1177/2050640620920157
Abstract
A new strain of coronavirus, called SARS-CoV-2, emerged in Wuhan, China, in December 2019, probably originating from a wild-animal contamination. Since then, the situation rapidly evolved from a cluster of patients with pneumonia, to a regional epidemic and now to a pandemic called COrona VIrus Disease 2019 (COVID-19). This evolution is related to the peculiar modes of transmission of the disease and to the globalization and lifestyle of the 21st century that created the perfect scenario for virus spread. Even though research has not evidenced particular susceptibility of inflammatory bowel disease (IBD) patients to SARS-CoV-2 infection, immunosuppressive and immunomodulatory treatments were considered potential risk factors. In this context, initiating treatments with these agents should be cautiously weighted and regular ongoing treatments shall be continued, while the dose of corticosteroids should be reduced whenever possible. Due to the increased risk of contamination, elective endoscopic procedures and surgeries should be postponed and IBD online appointments shall be considered. IBD patients shall also follow the recommendations provided to the general population, such as minimization of contact with infected or suspected patients and to wash hands frequently. In the absence of effective treatments and vaccines, this pandemic can only be controlled through prevention of SARS-CoV-2 transmission with the main objectives of providing patients the best healthcare possible and reduce mortality.

Keywords: Gastroenterology; endoscopy; epidemiology; immunology; inflammatory bowel disease.

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38
J Virol
. 2019 Sep 12;93(19):e00644-19. doi: 10.1128/JVI.00644-19. Print 2019 Oct 1.
Serial Section Array Scanning Electron Microscopy Analysis of Cells From Lung Autopsy Specimens Following Fatal A/H1N1 2009 Pandemic Influenza Virus Infection
Michiyo Kataoka # 1, Kinji Ishida # 2, Katsutoshi Ogasawara 2, Takayuki Nozaki 2, Yoh-Ichi Satoh 3, Tetsutaro Sata 1, Yuko Sato 1, Hideki Hasegawa 1 4, Noriko Nakajima 5
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PMID: 31292247 PMCID: PMC6744253 DOI: 10.1128/JVI.00644-19
Free PMC article
Abstract
A/H1N1 2009 pandemic influenza virus (A/H1N1/pdm09) was first identified as a novel pandemic influenza A virus (IAV) in 2009. Previously, we reported that many viral antigens were detected in type II alveolar epithelial cells (AEC-IIs) within autopsied lung tissue from a patient with A/H1N1/pdm09 pneumonia. It is important to identify the association between the virus and host cells to elucidate the pathogenesis of IAV pneumonia. To investigate the distribution of virus particles and morphological changes in host cells, the autopsied lung specimens from this patient were examined using transmission electron microscopy (TEM) and a novel scanning electron microscopy (SEM) method. We focused on AEC-IIs as viral antigen-positive cells and on monocytes/macrophages (Ms/Mϕs) and neutrophils (Neus) as innate immune cells. We identified virus particles and intranuclear dense tubules, which are associated with matrix 1 (M1) proteins from IAV. Large-scale two-dimensional observation was enabled by digitally "stitching" together contiguous SEM images. A single whole-cell analysis using a serial section array (SSA)-SEM identified virus particles in vesicles within the cytoplasm and/or around the surfaces of AEC-IIs, Ms/Mϕs, and Neus; however, intranuclear dense tubules were found only in AEC-IIs. Computer-assisted processing of SSA-SEM images from each cell type enabled three-dimensional (3D) modeling of the distribution of virus particles within an ACE-II, a M/Mϕ, and a Neu.IMPORTANCE Generally, it is difficult to observe IAV particles in postmortem samples from patients with seasonal influenza. In fact, only a few viral antigens are detected in bronchial epithelial cells from autopsied lung sections. Previously, we detected many viral antigens in AEC-IIs from the lung. This was because the majority of A/H1N1/pdm09 in the lung tissue harbored an aspartic acid-to-glycine substitution at position 222 (D222G) of the hemagglutinin protein. A/H1N1/pdm09 harboring the D222G substitution has a receptor-binding preference for α-2,3-linked sialic acids expressed on human AECs and infects them in the same way as H5N1 and H7N9 avian IAVs. Here, we report the first successful observation of virus particles, not only in AEC-IIs, but also in Ms/Mϕs and Neus, using electron microscopy. The finding of a M/Mϕ harboring numerous virus particles within vesicles and at the cell surface suggests that Ms/Mϕs are involved in the pathogenesis of IAV primary pneumonia.

Keywords: autopsy; electron microscopy; influenza virus.

Copyright © 2019 Kataoka et al.

Cited by 1 article42 references8 figures
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39
Meta-Analysis BMC Pulm Med
. 2019 Dec 18;19(1):251. doi: 10.1186/s12890-019-0990-8.
Efficacy of Glucocorticoids for the Treatment of Macrolide Refractory Mycoplasma Pneumonia in Children: Meta-Analysis of Randomized Controlled Trials
Hwan Soo Kim 1, In Suk Sol 2 3, Donghe Li 4, Miyoung Choi 5, Yun Jung Choi 6, Kyung Suk Lee 7, Ju Hee Seo 8, Yong Ju Lee 9, Hyeon-Jong Yang 10, Hyun Hee Kim 1
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PMID: 31852460 PMCID: PMC6921474 DOI: 10.1186/s12890-019-0990-8
Free PMC article
Abstract
Background: Mycoplasma pneumoniae is one of the most common pathogens causing community acquired pneumonia in children. Although the rate of macrolide-refractory Mycoplasma pneumoniae (MRMP) has increased, systemic glucocorticoids as a treatment option has not been validated yet. The purpose of this study was to assess the efficacy of glucocorticoids add-on in the treatment of MRMP in children through systematic review and meta-analysis.

Methods: Data sources A systematic literature search was conducted using ten electronic bibliographic databases including English, Korean, Chinese and Japanese languages, up to March 8, 2018. Study selection The study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and selected randomized control trials which compared the efficacy of glucocorticoids add-on to macrolide in the treatment of MRMP in children. Data extraction Two independent reviewers extracted: primary outcomes as hospital days, fever duration, and change in C-reactive protein (CRP) and main analysis was performed through meta-analysis with random effects model.

Results: Twenty-four unique randomized controlled trials met the inclusion criteria. The mean length of hospital stay in glucocorticoids treatment group was significantly shorter than that in conventional macrolide-treatment group (Weighted mean difference (WMD) = - 4.03 days). The mean length of fever duration was significantly shorter in the glucocorticoid treatment group in comparison with the conventional treatment group (WMD = -3.32 days). Level of CRP after treatment was significantly lower in the glucocorticoid treatment group than that in the conventional treatment group (WMD = -16.03). Sensitivity analysis and subgroup analysis showed no significant improvement in heterogeneity. As limitations of the study, most of the studies included were from a single country and we were unable to control for heterogeneity across interventions, lack of standardized measures, and different time points of assessments across studies.

Conclusions: Glucocorticoid add-on treatment for MRMP can significantly shorten the duration of fever and hospital stay and decrease the level of CRP. These results should be confirmed by adequately powered studies in the future.

Keywords: Glucocorticoids; Macrolides; Mycoplasma; Pneumonia.

Conflict of interest statement
The authors declare that they have no competing interests.

46 references8 figures
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40
Int Forum Allergy Rhinol
. 2019 Dec;9(12):1424-1429. doi: 10.1002/alr.22436. Epub 2019 Oct 7.
Prevalence and Characterization of Chronic Rhinosinusitis in Patients With Non-Cystic Fibrosis Bronchiectasis at a Tertiary Care Center in the United States
Shaan N Somani 1, Jason H Kwah 1, Chen Yeh 2, David B Conley 3, Leslie C Grammer 3rd 1, Robert C Kern 1 3, Michelle Prickett 4, Robert P Schleimer 1 3, Stephanie S Smith 3, Whitney W Stevens 1 3, Bruce K Tan 1 3, Kevin C Welch 3, Anju T Peters 1 3
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PMID: 31589811 PMCID: PMC6913921 (available on 2020-12-01) DOI: 10.1002/alr.22436
Free PMC article
Abstract
Background: Chronic rhinosinusitis (CRS) is associated with bronchiectasis; however, this relationship has not been well studied in the United States (US) population. In this work we aimed to determine the prevalence of CRS among patients with bronchiectasis affiliated with a US tertiary medical center and identify which comorbid diseases are associated with the presence of CRS in patients with bronchiectasis.

Methods: This was a retrospective cohort study in which data were obtained from a large database warehouse at a tertiary care center. Patients with bronchiectasis were identified from 2007 to 2017 using diagnosis codes from the the ninth and tenth revisions of the International Classification of Diseases (ICD-9/10) and confirmed by radiographic evidence of bronchiectasis on chest computed tomography (CT) scans. Patients were divided into cohorts based on presence or absence of concomitant CRS. Characteristics analyzed included demographics, comorbidities, peripheral eosinophil counts, and pulmonary function testing.

Results: CRS was present in 45% (408 of 900) of patients with bronchiectasis. Females represented a majority of bronchiectasis patients, both with and without CRS (69% and 64%, respectively, p = 0.09). After controlling for demographic factors, asthma (p < 0.01), allergic rhinitis (p < 0.01), gastroesophageal reflux disease (p < 0.01), and antibody deficiency (p < 0.01) were associated with the presence of CRS in patients with bronchiectasis.

Conclusion: CRS had a high prevalence and was associated with numerous comorbid conditions in patients with bronchiectasis. These findings have clinical implications for the treatment of patients with bronchiectasis and future research.

Keywords: asthma; chronic disease; chronic rhinosinusitis.

© 2019 ARS-AAOA, LLC.

Conflict of interest statement
Potential conflict of interest: None provided.

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41
Int Forum Allergy Rhinol
. 2019 Dec;9(12):1456-1461. doi: 10.1002/alr.22444. Epub 2019 Sep 26.
Impact of Age on Outcomes Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis
Dana L Crosby 1 2, Jeb Jones 3, James N Palmer 4, Noam A Cohen 4, Michael A Kohanski 4, Nithin D Adappa 4
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PMID: 31557428 DOI: 10.1002/alr.22444
Abstract
Background: Chronic rhinosinusitis (CRS) is a common condition that affects people of all ages and negatively impacts quality of life. The goal of this study was to identify differences in outcomes by age following endoscopic sinus surgery (ESS) for CRS utilizing 22-item Sino-Nasal Outcome Test (SNOT-22) scores.

Methods: Data from 1252 adult CRS patients electing to undergo ESS (2007-2018) were collected retrospectively. The median age of 50 years was used to divide the data into 2 groups for comparison of the impact of age on SNOT-22 scores at 0, 3, and 6 months after surgery. Changes in SNOT-22 scores were analyzed using a mixed models analysis.

Results: After adjusting for gender, race, polyp status, and number of prior ESSs, patients younger than 50 years had a higher mean pre-ESS SNOT-22 score (44.0) compared to those of at least 50 years of age (38.9). Among patients younger than 50 years, SNOT-22 scores declined by 20.7 points at 3 months post-ESS and 16.1 points at 6 months post-ESS. The rate of change between the dichotomized age groups was not significantly different at 3 and 6 months post-ESS (p = 0.7952 and p = 0.1057, respectively).

Conclusion: Both age groups showed significant and durable improvement in SNOT-22 scores after ESS. Patients younger than 50 years of age have higher pre-ESS SNOT-22 scores, but converge to the same SNOT-22 scores by 3 months post-ESS. The rate of change of SNOT-22 scores is not different between those younger than 50 years and those of at least 50 years.

Keywords: SNOT-22; age; chronic sinusitis; endoscopic sinus surgery; outcomes.

© 2019 ARS-AAOA, LLC.

20 references
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42
Respir Res
. 2019 Dec 18;20(1):285. doi: 10.1186/s12931-019-1260-2.
Exchange Protein Directly Activated by cAMP (Epac) Protects Against Airway Inflammation and Airway Remodeling in Asthmatic Mice
Yi-Fei Chen 1, Ge Huang 1, Yi-Min Wang 1, Ming Cheng 1, Fang-Fang Zhu 2, Jin-Nan Zhong 1, Ya-Dong Gao 3
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PMID: 31852500 PMCID: PMC6921488 DOI: 10.1186/s12931-019-1260-2
Free PMC article
Abstract
Background: β2 receptor agonists induce airway smooth muscle relaxation by increasing intracellular cAMP production. PKA is the traditional downstream signaling pathway of cAMP. Exchange protein directly activated by cAMP (Epac) was identified as another important signaling molecule of cAMP recently. The role of Epac in asthmatic airway inflammation and airway remodeling is unclear.

Methods: We established OVA-sensitized and -challenged acute and chronic asthma mice models to explore the expression of Epac at first. Then, airway inflammation and airway hyperresponsiveness in acute asthma mice model and airway remodeling in chronic asthma mice model were observed respectively after treatment with Epac-selective cAMP analogue 8-pCPT-2'-O-Me-cAMP (8pCPT) and Epac inhibitor ESI-09. Next, the effects of 8pCPT and ESI-09 on the proliferation and apoptosis of in vitro cultured mouse airway smooth muscle cells (ASMCs) were detected with CCK-8 assays and Annexin-V staining. Lastly, the effects of 8pCPT and ESI-09 on store-operated Ca2+ entry (SOCE) of ASMCs were examined by confocal Ca2+ fluorescence measurement.

Results: We found that in lung tissues of acute and chronic asthma mice models, both mRNA and protein expression of Epac1 and Epac2, two isoforms of Epac, were lower than that of control mice. In acute asthma mice model, the airway inflammatory cell infiltration, Th2 cytokines secretion and airway hyperresponsiveness were significantly attenuated by 8pCPT and aggravated by ESI-09. In chronic asthma mice model, 8pCPT decreased airway inflammatory cell infiltration and airway remodeling indexes such as collagen deposition and airway smooth muscle cell proliferation, while ESI-09 increased airway inflammation and airway remodeling. In vitro cultured mice ASMCs, 8pCPT dose-dependently inhibited, whereas ESI-09 promoted ASMCs proliferation. Interestingly, 8pCPT promoted the apoptosis of ASMCs, whereas ESI-09 had no effect on ASMCs apoptosis. Lastly, confocal Ca2+ fluorescence examination found that 8pCPT could inhibit SOCE in ASMCs at 100 μM, and ESI-09 promoted SOCE of ASMCs at 10 μM and 100 μM. In addition, the promoting effect of ESI-09 on ASMCs proliferation was inhibited by store-operated Ca2+ channel blocker, SKF-96365.

Conclusions: Our results suggest that Epac has a protecting effect on asthmatic airway inflammation and airway remodeling, and Epac reduces ASMCs proliferation by inhibiting SOCE in part.

Keywords: Airway inflammation; Airway remodeling; Airway smooth muscle cells; Exchange protein directly activated by cAMP; Store-operated Ca2+ entry.

Conflict of interest statement
The authors declare that they have no competing interests.

42 references5 figures
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43
Clin Gastroenterol Hepatol
. 2020 Jun;18(7):1561-1566. doi: 10.1016/j.cgh.2020.04.002. Epub 2020 Apr 10.
Clinical Features of COVID-19-Related Liver Functional Abnormality
Zhenyu Fan 1, Liping Chen 1, Jun Li 1, Xin Cheng 1, Jingmao Yang 1, Cheng Tian 1, Yajun Zhang 1, Shaoping Huang 1, Zhanju Liu 2, Jilin Cheng 3
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PMID: 32283325 PMCID: PMC7194865 DOI: 10.1016/j.cgh.2020.04.002
Free PMC article
Abstract
Background & aims: Some patients with SARS-CoV-2 infection have abnormal liver function. We aimed to clarify the features of COVID-19-related liver damage to provide references for clinical treatment.

Methods: We performed a retrospective, single-center study of 148 consecutive patients with confirmed COVID-19 (73 female, 75 male; mean age, 50 years) at the Shanghai Public Health Clinical Center from January 20 through January 31, 2020. Patient outcomes were followed until February 19, 2020. Patients were analyzed for clinical features, laboratory parameters (including liver function tests), medications, and length of hospital stay. Abnormal liver function was defined as increased levels of alanine and aspartate aminotransferase, gamma glutamyltransferase, alkaline phosphatase, and total bilirubin.

Results: Fifty-five patients (37.2%) had abnormal liver function at hospital admission; 14.5% of these patients had high fever (14.5%), compared with 4.3% of patients with normal liver function (P = .027). Patients with abnormal liver function were more likely to be male, and had higher levels of procalcitonin and C-reactive protein. There was no statistical difference between groups in medications taken before hospitalization; a significantly higher proportion of patients with abnormal liver function (57.8%) had received lopinavir/ritonavir after admission compared to patients with normal liver function (31.3%). Patients with abnormal liver function had longer mean hospital stays (15.09 ± 4.79 days) than patients with normal liver function (12.76 ± 4.14 days) (P = .021).

Conclusions: More than one third of patients admitted to the hospital with SARS-CoV-2 infection have abnormal liver function, and this is associated with longer hospital stay. A significantly higher proportion of patients with abnormal liver function had received lopinavir/ritonavir after admission; these drugs should be given with caution.

Keywords: ALP; Antiviral Drug; Liver Injury; Prognosis.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

Cited by 3 articles
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44
Meta-Analysis Respir Res
. 2019 Dec 18;20(1):286. doi: 10.1186/s12931-019-1258-9.
Clinical Characteristics and Treatment Outcomes of Patients With Macrolide-Resistant Mycobacterium Avium Complex Pulmonary Disease: A Systematic Review and Meta-Analysis
Youngmok Park 1, Eun Hye Lee 1, Inkyung Jung 2, Goeun Park 2, Young Ae Kang 3
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PMID: 31852452 PMCID: PMC6921583 DOI: 10.1186/s12931-019-1258-9
Free PMC article
Abstract
Background: Macrolide is a key drug in the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Macrolide-resistant MAC is gaining importance, but there are little data in clinical characteristics and treatment outcomes of macrolide-resistant MAC-PD (MR-MAC-PD).

Methods: We performed a systematic review and meta-analysis of published studies reporting clinical characteristics and treatment outcomes of patients with MR-MAC-PD. Risk of bias was assessed using the modified Newcastle-Ottawa Scale.

Results: Nine studies (seven retrospective and two prospective) comprising 319 patients were identified through a database search. Around 73% were women, and 52% had the fibrocavitary form. Pooled sputum culture conversion rate after combined multiple antibiotics or surgical resection was 21% (95% confidence interval [CI], 14-30%), and the one-year all-cause mortality was 10% (95% CI, 5-20%). There was no significant difference in treatment outcomes between nodular bronchiectatic and fibrocavitary types.

Conclusions: Even combination therapy with fluoroquinolone, aminoglycoside, and surgical resection, the treatment outcomes of MR-MAC-PD were poor. The investigation of new treatment modalities is urgent.

Keywords: Clarithromycin; Drug resistance; Macrolides; Mycobacterium avium complex; Mycobacterium avium-intracellulare infection.

Conflict of interest statement
The authors declare that they have no competing interests.

30 references3 figures
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45
N Engl J Med
. 2020 May 28;382(22):2163-2164. doi: 10.1056/NEJMc2009316. Epub 2020 Apr 13.
Universal Screening for SARS-CoV-2 in Women Admitted for Delivery
Desmond Sutton 1, Karin Fuchs 1, Mary D'Alton 1, Dena Goffman 1
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PMID: 32283004 PMCID: PMC7175422 DOI: 10.1056/NEJMc2009316
Free PMC article
Cited by 4 articles3 references1 figure
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46
Respir Res
. 2019 Dec 16;20(1):283. doi: 10.1186/s12931-019-1256-y.
The Clinical Impact of Drug-Induced Hepatotoxicity on Anti-Tuberculosis Therapy: A Case Control Study
Jin Hwa Song 1, Seo-Young Yoon 2, Tae Yun Park 2, Eun Young Heo 2, Deog Kyeom Kim 2, Hee Soon Chung 2, Jung-Kyu Lee 3
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PMID: 31842883 PMCID: PMC6915938 DOI: 10.1186/s12931-019-1256-y
Free PMC article
Abstract
Background: There are limited data available on whether drug-induced hepatotoxicity (DIH) affects the clinical outcomes of tuberculosis (TB) treatment. We explored the effects of DIH on the clinical course and outcomes of pulmonary TB.

Methods: In this retrospective cohort study, we included patients with culture-proven pulmonary TB treated in a tertiary hospital from 2013 to 2016. DIH was defined as proposed by the official American Thoracic Society statement. We compared the clinical outcomes of DIH and non-DIH patients.

Results: Between January 1, 2013 and December 31, 2016, a total of 168 TB patients were included, and 20 (11.9%) were diagnosed with DIH. These patients were significantly older, had a higher Charlson Comorbidity Index score, exhibited more chronic liver disease, included more chronic alcoholics, and had a lower body mass index than non-DIH patients. We found no significant differences between DIH and non-DIH patients in the 2-month sputum culture conversion rate, the time to sputum culture conversion, treatment outcomes, or total treatment duration. However, the ratio of treatment interruption time to total treatment duration and the proportion of hepatotonic users were significantly higher among DIH patients.

Conclusion: DIH development during TB treatment does not significantly affect the clinical outcomes of pulmonary TB. However, treatment interruption caused by DIH may increase the risks of future relapse and acquired resistance. Further study is needed.

Keywords: Chemical- and drug-induced liver injury; Drug-related side-effects and adverse reactions; Tuberculosis, pulmonary.

Conflict of interest statement
No author has any competing interest. The abstract of this paper was presented at the American Thoracic Society Conference 2018 as a poster presentation with interim findings. The poster’s abstract was published in “Poster Abstracts” in American Journal of Respiratory and Critical Care Medicine (Am J Respir Crit Med 2018;197:A5559; https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2018.197.1_MeetingAbstracts.A5559).

29 references2 figures
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47
Stroke
. 2020 Jun;51(6):1891-1895. doi: 10.1161/STROKEAHA.120.029838. Epub 2020 Apr 1.
Protected Code Stroke: Hyperacute Stroke Management During the Coronavirus Disease 2019 (COVID-19) Pandemic
Houman Khosravani 1, Phavalan Rajendram 1, Lowyl Notario 2, Martin G Chapman 3, Bijoy K Menon 4
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PMID: 32233980 PMCID: PMC7258750 DOI: 10.1161/STROKEAHA.120.029838
Free PMC article
Abstract
Background and Purpose- Hyperacute assessment and management of patients with stroke, termed code stroke, is a time-sensitive and high-stakes clinical scenario. In the context of the current coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus, the ability to deliver timely and efficacious care must be balanced with the risk of infectious exposure to the clinical team. Furthermore, rapid and effective stroke care remains paramount to achieve maximal functional recovery for those needing admission and to triage care appropriately for those who may be presenting with neurological symptoms but have an alternative diagnosis. Methods- Available resources, COVID-19-specific infection prevention and control recommendations, and expert consensus were used to identify clinical screening criteria for patients and provide the required nuanced considerations for the healthcare team, thereby modifying the conventional code stroke processes to achieve a protected designation. Results- A protected code stroke algorithm was developed. Features specific to prenotification and clinical status of the patient were used to define precode screening. These include primary infectious symptoms, clinical, and examination features. A focused framework was then developed with regard to a protected code stroke. We outline the specifics of personal protective equipment use and considerations thereof including aspects of crisis resource management impacting team role designation and human performance factors during a protected code stroke. Conclusions- We introduce the concept of a protected code stroke during a pandemic, as in the case of COVID-19, and provide a framework for key considerations including screening, personal protective equipment, and crisis resource management. These considerations and suggested algorithms can be utilized and adapted for local practice.

Keywords: COVID-19; algorithms; consensus; pandemics; stroke.

Cited by 6 articles9 references2 figures
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48
Review J Am Acad Orthop Surg
. 2020 Jun 1;28(11):464-470. doi: 10.5435/JAAOS-D-20-00379.
Practice Management During the COVID-19 Pandemic
Alexander R Vaccaro 1, Charles L Getz, Bruce E Cohen, Brian J Cole, Chester J Donnally 3rd
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PMID: 32287086 PMCID: PMC7197337 DOI: 10.5435/JAAOS-D-20-00379
Free PMC article
Abstract
On March 14, 2020, the Surgeon General of the United States urged a widespread cessation of all elective surgery across the country. The suddenness of this mandate and the concomitant spread of the COVID-19 virus left many hospital systems, orthopaedic practices, and patients with notable anxiety and confusion as to the near, intermediate, and long-term future of our healthcare system. As with most businesses in the United States during this time, many orthopaedic practices have been emotionally and fiscally devastated because of this crisis. Furthermore, this pandemic is occurring at a time where small and midsized orthopaedic groups are already struggling to cover practice overhead and to maintain autonomy from larger health systems. It is anticipated that many groups will experience financial demise, leading to substantial global consolidation. Because the authors represent some of the larger musculoskeletal multispecialty groups in the country, we are uniquely positioned to provide a framework with recommendations to best weather the ensuing months. We think these recommendations will allow providers and their staff to return to an infrastructure that can adjust immediately to the pent-up healthcare demand that may occur after the COVID-19 pandemic. In this editorial, we address practice finances, staffing, telehealth, operational plans after the crisis, and ethical considerations.

Conflict of interest statement
None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Vaccaro, Dr. Getz, Dr. Cohen, Dr. Cole, and Dr. Donnally.

11 references3 figures
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49
Review Virus Res
. 2020 Jul 15;284:197989. doi: 10.1016/j.virusres.2020.197989. Epub 2020 Apr 30.
Natural Product-Derived Phytochemicals as Potential Agents Against Coronaviruses: A Review
Janice S Mani 1, Joel B Johnson 1, Jason C Steel 1, Daniel A Broszczak 2, Paul M Neilsen 1, Kerry B Walsh 1, Mani Naiker 3
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PMID: 32360300 PMCID: PMC7190535 DOI: 10.1016/j.virusres.2020.197989
Free PMC article
Abstract
Coronaviruses are responsible for a growing economic, social and mortality burden, as the causative agent of diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), avian infectious bronchitis virus (IBV) and COVID-19. However, there is a lack of effective antiviral agents for many coronavirus strains. Naturally existing compounds provide a wealth of chemical diversity, including antiviral activity, and thus may have utility as therapeutic agents against coronaviral infections. The PubMed database was searched for papers including the keywords coronavirus, SARS or MERS, as well as traditional medicine, herbal, remedy or plants, with 55 primary research articles identified. The overwhelming majority of publications focussed on polar compounds. Compounds that show promise for the inhibition of coronavirus in humans include scutellarein, silvestrol, tryptanthrin, saikosaponin B2, quercetin, myricetin, caffeic acid, psoralidin, isobavachalcone, and lectins such as griffithsin. Other compounds such as lycorine may be suitable if a therapeutic level of antiviral activity can be achieved without exceeding toxic plasma concentrations. It was noted that the most promising small molecules identified as coronavirus inhibitors contained a conjugated fused ring structure with the majority being classified as being polyphenols.

Keywords: COVID-19; Coronaviridae; Middle East respiratory syndrome (MERS); SARS-CoV-2; Severe acute respiratory syndrome (SARS); Traditional medicine.

Copyright © 2020 Elsevier B.V. All rights reserved.

Conflict of interest statement
Declaration of Competing Interest The authors declare that no conflict of interest exists.

122 references4 figures
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50
Editorial Ann Neurol
. 2020 Jun;87(6):794-797. doi: 10.1002/ana.25770.
SARS-CoV-2 and Multiple Sclerosis: Not All Immune Depleting DMTs Are Equal or Bad
Sandra Amor 1 2, David Baker 2, Samia J Khoury 3 4, Klaus Schmierer 2 5, Gavin Giovanonni 2 5
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PMID: 32383812 DOI: 10.1002/ana.25770
18 references
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51
Int Forum Allergy Rhinol
. 2019 Dec;9(12):1430-1435. doi: 10.1002/alr.22414. Epub 2019 Aug 20.
Prevalence of Chronic Rhinosinusitis in Bronchiectasis Patients Suspected of Ciliary Dyskinesia
Justin P McCormick 1, Christopher G Weeks 1, Nicholas J Rivers 1, Jacob D Owen 1, David R Kelly 2, Steven M Rowe 3 4 5 6, George M Solomon 3 4, Bradford A Woodworth 1 3, Do-Yeon Cho 1 3
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PMID: 31430425 PMCID: PMC6901752 (available on 2020-12-01) DOI: 10.1002/alr.22414
Free PMC article
Abstract
Background: Mucociliary clearance is a main defense mechanism of the airway and is impaired in ciliary dyskinesia. The objective of this study was to evaluate the prevalence of chronic rhinosinusitis (CRS) and its characteristics in bronchiectasis patients suspected of harboring ciliary dyskinesia.

Methods: Bronchiectasis patients referred to a rhinology clinic for nasal brush biopsy (NBB) were included in this study. NBB was performed using a curettage technique whereby ciliated epithelial cells were obtained from the surface of the inferior nasal turbinate. Results of transmission electron microscopy findings, primary ciliary dyskinesia (PCD) gene (35 genes) analyses (Invitae), and sinus computed tomography (CT) scans were reviewed.

Results: Twenty-three patients (age, 54 ± 2.9 years) were referred for NBB between 2015 and 2018. Thirteen patients (56.5%) met the criteria for diagnosis of CRS. Nineteen patients had ciliary ultrastructural defects. The most common finding was compound cilia (n = 11, 47.8%). Five patients (21.7%) had central microtubule defects (CMD) with higher forced expiratory volume in 1 second (FEV1 ) at the time of referral than those without CMD (CMD+ , 91 ± 3.7%; CMD- , 73.5 ± 5.7%; p = 0.023). Of 15 subjects with a PCD gene panel, 67% (9 of 15) carried at least 1 gene associated with PCD. Only 1 patient reached diagnosis of PCD. Approximately 50% of non-PCD carriers had a smoking history (p < 0.05). Lund-Mackay scores did not significantly differ between PCD and non-PCD carriers (p = 0.72).

Conclusion: Nearly half of bronchiectasis patients referred for NBB had concurrent CRS. The presence of ciliary abnormalities was not amplified in bronchiectasis patients with CRS compared to those without CRS. Extrinsic factors may be related to ciliary structural abnormalities in non-PCD gene carriers.

Keywords: acquired ciliary dyskinesia; bronchiectasis; chronic rhinosinusitis; electron microscopy; mucociliary clearance; primary ciliary dyskinesia; sinusitis; ultrastructure.

© 2019 ARS-AAOA, LLC.

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52
Review Stem Cell Rev Rep
. 2020 Jun;16(3):434-440. doi: 10.1007/s12015-020-09976-7.
CD147 as a Target for COVID-19 Treatment: Suggested Effects of Azithromycin and Stem Cell Engagement
Henning Ulrich 1, Micheli M Pillat 2
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PMID: 32307653 PMCID: PMC7167302 DOI: 10.1007/s12015-020-09976-7
Free PMC article
Abstract
The expressive number of deaths and confirmed cases of SARS-CoV-2 call for an urgent demand of effective and available drugs for COVID-19 treatment. CD147, a receptor on host cells, is a novel route for SARS-CoV-2 invasion. Thus, drugs that interfere in the spike protein/CD147 interaction or CD147 expression may inhibit viral invasion and dissemination among other cells, including in progenitor/stem cells. Studies suggest beneficial effects of azithromycin in reducing viral load of hospitalized patients, possibly interfering with ligand/CD147 receptor interactions; however, its possible effects on SARS-CoV-2 invasion has not yet been evaluated. In addition to the possible effect in invasion, azithromycin decreases the expression of some metalloproteinases (downstream to CD147), induces anti-viral responses in primary human bronchial epithelial infected with rhinovirus, decreasing viral replication and release. Moreover, resident lung progenitor/stem are extensively differentiated into myofibroblasts during pulmonary fibrosis, a complication observed in COVID-19 patients. This process, and the possible direct viral invasion of progenitor/stem cells via CD147 or ACE2, could result in the decline of these cellular stocks and failing lung repair. Clinical tests with allogeneic MSCs from healthy individuals are underway to enhance endogenous lung repair and suppress inflammation.

Keywords: Anti-viral responses; Asthma; Basigin; Cellular therapy; Coronavirus; Diabetes mellitus; EMMPRIN; Invasion; Lung stem cells; SARS-CoV-2.

Conflict of interest statement
The authors declare that there are no conflicts of interest regarding the publication of this paper.

46 references2 figures
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53
Review J Clin Virol
. 2020 Jun;127:104357. doi: 10.1016/j.jcv.2020.104357. Epub 2020 Apr 10.
Epidemiology and Clinical Features of COVID-19: A Review of Current Literature
Juan A Siordia Jr 1
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PMID: 32305884 PMCID: PMC7195311 DOI: 10.1016/j.jcv.2020.104357
Free PMC article
Abstract
Coronavirus disease 2019 is a pandemic influencing the first half of the year 2020. The virus has rapidly spread to many countries. Studies are rapidly published to share information regarding epidemiology, clinical and diagnostic patterns, and prognosis. The following review condenses the surge of information into an organized format.

Keywords: Coronavirus disease 2019; Diagnosis; Epidemiology; Pandemic; Severe acute respiratory disease.

Copyright © 2020 Elsevier B.V. All rights reserved.

Conflict of interest statement
Declaration of Competing Interest No conflict of interest to report.

87 references3 figures
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54
Meta-Analysis Int Forum Allergy Rhinol
. 2019 Dec;9(12):1443-1450. doi: 10.1002/alr.22443. Epub 2019 Sep 20.
Efficacy of Steroid-Eluting Stents in Management of Chronic Rhinosinusitis After Endoscopic Sinus Surgery: Updated Meta-Analysis
Khodayar Goshtasbi 1, Mehdi Abouzari 1, Arash Abiri 1, Tyler Yasaka 1, Ronald Sahyouni 1, Benjamin Bitner 1, Bobby A Tajudeen 2, Edward C Kuan 1
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PMID: 31539461 PMCID: PMC6901756 (available on 2020-12-01) DOI: 10.1002/alr.22443
Free PMC article
Abstract
Background: Recently, there has been mounting evidence suggesting the efficacy of steroid-eluting stents (SES) for management of chronic rhinosinusitis after endoscopic sinus surgery (ESS). This meta-analysis serves to evaluate the efficacy of SES in improving postoperative outcomes after ESS.

Methods: A systematic literature search was performed of PubMed for articles published between 1985 and 2018. The outcome variables were reported at, on average, 30 days postintervention.

Results: Seven of the 76 published studies, all of which were industry-sponsored, were included for a collective cohort of 444 SES and 444 control sinuses. In patients who received SES vs controls, collective odds ratios (ORs) for postoperative need for intervention, surgery, and oral steroid were 0.45 (95% confidence interval [CI], 0.33-0.62; p < 0.001), 0.30 (95% CI, 0.18-0.52; p < 0.001), and 0.58 (95% CI, 0.40-0.84; p = 0.004), respectively. In addition, collective ORs for frontal sinus ostia (FSO) patency, moderate-to-severe adhesion/scarring, and increase in polyp score were 2.53 (95% CI, 1.61-3.97; p < 0.001), 0.28 (95% CI, 0.13-0.59; p < 0.001), and 0.42 (95% CI, 0.25-0.74; p = 0.002), respectively. Collective mean differences for FSO/ethmoid inflammation and FSO diameter were -10.86 mm (p < 0.001) and +1.34 mm (p < 0.001), respectively.

Conclusion: Aggregate evidence suggests that SES can improve ESS outcomes by reducing rates of postoperative intervention and recurrent polyposis and inflammation, while promoting FSO patency. All included and analyzed studies were industry-sponsored and ruling-out publication bias was not possible. Future independent and nonsponsored studies to further evaluate SES's long-term efficacy are warranted.

Keywords: chronic rhinosinusitis; endoscopic sinus surgery; meta-analysis; steroid-eluting stent.

© 2019 ARS-AAOA, LLC.

Conflict of interest statement
Conflict of Interest: Edward C. Kuan is a consultant for Intersect ENT, Menlo Park, CA.

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55
Observational Study J Comp Eff Res
. 2019 Nov;8(15):1275-1284. doi: 10.2217/cer-2019-0041. Epub 2019 Nov 18.
Ceftriaxone Versus Ampicillin/Sulbactam for the Treatment of Aspiration-Associated Pneumonia in Adults
Shinya Hasegawa 1, Atsushi Shiraishi 2, Makito Yaegashi 3, Naoto Hosokawa 4, Konosuke Morimoto 5, Takahiro Mori 6 7 8
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PMID: 31736321 DOI: 10.2217/cer-2019-0041
Free article
Abstract
Aim: To compare hospital mortality in patients with aspiration-associated pneumonia treated with ceftriaxone (CTRX) and in those treated with ampicillin/sulbactam (ABPC/SBT). Methods: From a Japanese multicentre observational study cohort of patients with pneumonia, those diagnosed with pneumonia and having at least one aspiration-related risk factor were selected. Propensity score-matching analysis was used to balance baseline characteristics of the participants and compare hospital mortality of patients treated with CTRX and those treated with ABPC/SBT. Results: Hospital mortality did not significantly differ between patients treated with CTRX and those treated with ABPC/SBT (6.6 vs 10.7%, risk difference -4.0, 95% CI [-9.4, 1.3]; p = 0.143). Conclusion: Further studies are needed to compare CTRX and ABPC/SBT treatments in patients with aspiration-associated pneumonia.

Keywords: ampicillin/sulbactam; aspiration pneumonia; aspiration-associated pneumonia; ceftriaxone; propensity-score analysis.

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56
J Cell Physiol
. 2019 Aug;234(10):18879-18886. doi: 10.1002/jcp.28526. Epub 2019 Apr 10.
One Functional Variant in the 3'-untranslated Region of TLR4 Is Associated With the Elevated Risk of Ventilator-Associated Pneumonia in the Patients With Chronic Obstructive Pulmonary Disease
Xiaoyun Zhao 1 2, Jihong Feng 3, Li Zhang 1, Fang Zhao 1, Meifeng Li 3, Ying Du 3, Yuechuan Li 1, Qi Wu 2 4, Guanhua Li 1
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PMID: 30972742 DOI: 10.1002/jcp.28526
Abstract
The aim of this study was to identify the association polymorphism (rs11536889) in the 3'-untranslated region (3'-UTR) of Toll-like receptors 4 (TLR4) and the risk for ventilator-associated pneumonia (VAP). miRNA database online and luciferase assays were used to validate TLR4 as the target gene of miR-1236. Enzyme-linked immunosorbent assay analysis and western blot were used to analyze the level of TLR4 in different genotype groups. In the present study, miR-1236 was predicted to bind to the rs11536889 G allele rather than the rs11536889 C allele, which was further confirmed by the luciferase activity suppressed by a fragment of 3'-UTR containing the rs11536889 G allele induced by lipopolysaccharide (LPS) and interleukin-6 (IL-6). Bronchial epithelial cells isolated from participants genotyped as GG, GC, and CC, with no remarkable difference in TLR4 messenger RNA (mRNA) levels were observed among these genotype groups. After stimulating by LPS, a TLR4 ligand, the CC-genotyped cells expressed higher levels of IL-8, IL-6, and tumor necrosis factor alpha (TNF-α) on their surfaces than cells with the other genotypes. Finally, the western blot analysis results showed that the expression level of IL-8, IL-6, and TNF-α protein was much higher in the CC group than the GC and GG groups subsequent to stimulation by LPS, and the IL-8, IL-6, and TNF-α protein levels in the GC were grouped much lower compared with the GG group. These findings indicated the regulatory association of miR-1236 with TLR4 and the abnormal expression of TLR4 caused by the presence of rs11536889 in the 3'-UTR of mRNA, which interfere with its interaction with the miR-1236, contributing to the risk of VAP.

Keywords: 3′-untranslated region; COPD; TLR4; polymorphism; rs11536889; ventilator-associated pneumonia.

© 2019 Wiley Periodicals, Inc.

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57
Blood Cells Mol Dis
. 2020 Jul;83:102437. doi: 10.1016/j.bcmd.2020.102437. Epub 2020 Apr 13.
Increased Expression of CD8 Marker on T-cells in COVID-19 Patients
Ali Ganji 1, Iman Farahani 1, Behzad Khansarinejad 1, Ali Ghazavi 2, Ghasem Mosayebi 3
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PMID: 32325421 PMCID: PMC7194879 DOI: 10.1016/j.bcmd.2020.102437
Free PMC article
Abstract
Background: Cell-mediated immunity including T-cells (T helper and cytotoxic) plays an essential role in efficient antiviral responses against coronavirus disease-2019 (COVID-19). Therefore, in this study, we evaluated the ratio and expression of CD4 and CD8 markers in COVID-19 patients to clarify the immune characterizations of CD4 and CD8 T-cells in COVID-19 patients.

Methods: Peripheral blood samples of 25 COVID-19 patients and 25 normal individuals with similar age and sex as the control group were collected. White blood cells, platelets, and lymphocytes were counted and CD4 and CD8 T lymphocytes were evaluated by flow cytometry.

Results: The number of white blood cells, lymphocytes, and platelets were reduced significantly in COVID-19 patients (P < 0.05). The difference in CD4:CD8 ratio, CD4 T-cell frequency, CD8 T-cell frequency, and CD4 mean fluorescence intensity (MFI) was not significant between COVID-19 patients and healthy individuals (P > 0.05); however, the CD8 MFI increased significantly in COVID-19 infected patients (P < 0.05).

Conclusion: Although, there is no significant difference in the ratio of CD4 to CD8 between two groups, the expression level of CD8 in COVID-19 patients was significantly higher than the normal individuals. This result suggested that the cellular immune responses triggered by COVID-19 infection were developed through overexpression of CD8 and hyperactivation of cytotoxic T lymphocytes.

Keywords: 2019-nCov; CD4 lymphocyte; CD8 lymphocyte; COVID-19; Coronavirus.

Copyright © 2020. Published by Elsevier Inc.

Conflict of interest statement
Declaration of competing interest The authors report no conflicts of interest.

Cited by 1 article23 references3 figures
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58
BMC Pulm Med
. 2019 Dec 19;19(1):254. doi: 10.1186/s12890-019-1025-1.
Asthma and Treatment With Inhaled Corticosteroids: Associations With Hospitalisations With Pneumonia
Emil Ekbom 1, Jennifer Quint 2, Linus Schöler 3, Andrei Malinovschi 4, Karl Franklin 5, Mathias Holm 3, Kjell Torén 3, Eva Lindberg 1, Deborah Jarvis 2, Christer Janson 6 7
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PMID: 31856764 PMCID: PMC6923948 DOI: 10.1186/s12890-019-1025-1
Free PMC article
Abstract
Background: Pneumonia is an important cause of morbidity and mortality. COPD patients using inhaled corticosteroids (ICS) have an increased risk of pneumonia, but less is known about whether ICS treatment in asthma also increases the risk of pneumonia. The aim of this analysis was to examine risk factors for hospitalisations with pneumonia in a general population sample with special emphasis on asthma and the use of ICS in asthmatics.

Methods: In 1999 to 2000, 7340 subjects aged 28 to 54 years from three Swedish centres completed a brief health questionnaire. This was linked to information on hospitalisations with pneumonia from 2000 to 2010 and treatment with ICS from 2005 to 2010 held within the Swedish National Patient Register and the Swedish Prescribed Drug Register.

Results: Participants with asthma (n = 587) were more likely to be hospitalised with pneumonia than participants without asthma (Hazard Ratio (HR 3.35 (1.97-5.02)). Other risk factors for pneumonia were smoking (HR 1.93 (1.22-3.06)), BMI < 20 kg/m2 (HR 2.74 (1.41-5.36)) or BMI > 30 kg/m2 (HR 2.54 (1.39-4.67)). Asthmatics (n = 586) taking continuous treatment with fluticasone propionate were at an increased risk of being hospitalized with pneumonia (incidence risk ratio (IRR) 7.92 (2.32-27.0) compared to asthmatics that had not used fluticasone propionate, whereas no significant association was found with the use of budesonide (IRR 1.23 (0.36-4.20)).

Conclusion: Having asthma is associated with a three times higher risk of being hospitalised for pneumonia. This analysis also indicates that there are intraclass differences between ICS compounds with respect to pneumonia risk, with an increased risk of pneumonia related to fluticasone propionate.

Conflict of interest statement
CJ has received payments for educational activities from AstraZeneca, Boehringer Ingelheim, Chiesi, Novartis and Teva, and has served on advisory boards arranged by AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis and Teva. EL has received payments for educational activities from AstraZeneca. None of the other authors have any competing interests to declare.

38 references3 figures
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59
Science
. 2020 May 29;368(6494):945-946. doi: 10.1126/science.abb8923. Epub 2020 May 8.
Rapid COVID-19 Vaccine Development
Barney S Graham 1
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PMID: 32385100 DOI: 10.1126/science.abb8923
Cited by 1 article
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60
JCI Insight
. 2020 May 21;5(10):137799. doi: 10.1172/jci.insight.137799.
The Laboratory Tests and Host Immunity of COVID-19 Patients With Different Severity of Illness
Feng Wang 1, Hongyan Hou 1, Ying Luo 1, Guoxing Tang 1, Shiji Wu 1, Min Huang 1, Weiyong Liu 1, Yaowu Zhu 1, Qun Lin 1, Liyan Mao 1, Minghao Fang 2, Huilan Zhang 3, Ziyong Sun 1
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PMID: 32324595 DOI: 10.1172/jci.insight.137799
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Abstract
BACKGROUNDThe coronavirus disease 2019 (COVID-19), infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a severe outbreak throughout the world. The host immunity of COVID-19 patients is unknown.METHODSThe routine laboratory tests and host immunity in COVID-19 patients with different severity of illness were compared after patient admission.RESULTSA total of 65 SARS-CoV-2-positive patients were classified as having mild (n = 30), severe (n = 20), and extremely severe (n = 15) illness. Many routine laboratory tests, such as ferritin, lactate dehydrogenase, and D-dimer, were increased in severe and extremely severe patients. The absolute numbers of CD4+ T cells, CD8+ T cells, and B cells were gradually decreased with increased severity of illness. The activation markers such as HLA-DR and CD45RO expressed on CD4+ and CD8+ T cells were increased in severe and extremely severe patients compared with mild patients. The costimulatory molecule CD28 had opposite results. The percentage of natural Tregs was decreased in extremely severe patients. The percentage of IFN-γ-producing CD8+ T cells was increased in both severe and extremely severe patients compared with mild patients. The percentage of IFN-γ-producing CD4+ T cells was increased in extremely severe patients. IL-2R, IL-6, and IL-10 were all increased in extremely severe patients. The activation of DC and B cells was decreased in extremely severe patients.CONCLUSIONThe number and function of T cells are inconsistent in COVID-19 patients. The hyperfunction of CD4+ and CD8+ T cells is associated with the pathogenesis of extremely severe SARS-CoV-2 infection.FUNDINGThis work was funded by the National Mega Project on Major Infectious Disease Prevention (2017ZX10103005-007) and the Fundamental Research Funds for the Central Universities (2019kfyRCPY098).

Keywords: Adaptive immunity; Cellular immune response; Immunology; Infectious disease; Innate immunity.

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61
Euro Surveill
. 2019 Apr;24(15):1900104. doi: 10.2807/1560-7917.ES.2019.24.15.1900104.
Children Under 10 Years of Age Were More Affected by the 2018/19 Influenza A(H1N1)pdm09 Epidemic in Canada: ‎possible Cohort Effect Following the 2009 Influenza Pandemic
Danuta M Skowronski 1 2, Siobhan Leir 2, Gaston De Serres 3 4 5, Michelle Murti 6 7, James A Dickinson 8, Anne-Luise Winter 7, Romy Olsha 7, Matthew A Croxen 9 10, Steven J Drews 9 10, Hugues Charest 5, Christine Martineau 5, Suzana Sabaiduc 2, Nathalie Bastien 11, Yan Li 11, Martin Petric 1, Agatha Jassem 1 2, Mel Krajden 1 2, Jonathan B Gubbay 6 7
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PMID: 30994107 PMCID: PMC6470369 DOI: 10.2807/1560-7917.ES.2019.24.15.1900104
Free PMC article
Abstract
IntroductionFindings from the community-based Canadian Sentinel Practitioner Surveillance Network (SPSN) suggest children were more affected by the 2018/19 influenza A(H1N1)pdm09 epidemic.AimTo compare the age distribution of A(H1N1)pdm09 cases in 2018/19 to prior seasonal influenza epidemics in Canada.MethodsThe age distribution of unvaccinated influenza A(H1N1)pdm09 cases and test-negative controls were compared across A(H1N1)pdm09-dominant epidemics in 2018/19, 2015/16 and 2013/14 and with the general population of SPSN provinces. Similar comparisons were undertaken for influenza A(H3N2)-dominant epidemics.ResultsIn 2018/19, more influenza A(H1N1)pdm09 cases were under 10 years old than controls (29% vs 16%; p < 0.001). In particular, children aged 5-9 years comprised 14% of cases, greater than their contribution to controls (4%) or the general population (5%) and at least twice their contribution in 2015/16 (7%; p < 0.001) or 2013/14 (5%; p < 0.001). Conversely, children aged 10-19 years (11% of the population) were under-represented among A(H1N1)pdm09 cases versus controls in 2018/19 (7% vs 12%; p < 0.001), 2015/16 (7% vs 13%; p < 0.001) and 2013/14 (9% vs 12%; p = 0.12).ConclusionChildren under 10 years old contributed more to outpatient A(H1N1)pdm09 medical visits in 2018/19 than prior seasonal epidemics in Canada. In 2018/19, all children under 10 years old were born after the 2009 A(H1N1)pdm09 pandemic and therefore lacked pandemic-induced immunity. In addition, more than half those born after 2009 now attend school (i.e. 5-9-year-olds), a socio-behavioural context that may enhance transmission and did not apply during prior A(H1N1)pdm09 epidemics.

Keywords: A(H1N1)pdm09; A(H3N2); Canada; ILI; age; air-borne infections; epidemic; epidemiology; influenza; influenza virus; influenza-like illness; laboratory; laboratory surveillance; pandemic; sentinel surveillance; viral infections.

Conflict of interest statement
Conflict of interest: DMS is Principal Investigator on grants received from the Canadian Institutes of Health Research and the Public Health Agency of Canada in support of this work. GDS has received grants for investigator-initiated studies unrelated to influenza vaccine from Pfizer and provided paid expert testimony for the Ontario Nurses Association, the Quebec Ministry of Justice and GSK. JBG has received research grants from Pfizer Inc. to conduct microbiological surveillance of Streptococcus pneumoniae. MK has received research grants from Roche, Siemens and Hologic for unrelated studies. SJD is a content expert consultant to Johnson and Johnson (Janssen) Pharmaceuticals on a literature search for point-of-care testing for respiratory viruses. Other authors have no conflicts of interest to declare.

Cited by 2 articles38 references3 figures
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62
Review J Am Acad Orthop Surg
. 2020 Jun 1;28(11):436-450. doi: 10.5435/JAAOS-D-20-00360.
Orthopaedic Surgical Selection and Inpatient Paradigms During the Coronavirus (COVID-19) Pandemic
Patrick A Massey 1, Kaylan McClary, Andrew S Zhang, Felix H Savoie, R Shane Barton
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PMID: 32304401 PMCID: PMC7195848 DOI: 10.5435/JAAOS-D-20-00360
Free PMC article
Abstract
The novel coronavirus pandemic, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has placed an immense strain on healthcare systems across the entire world. Consequently, multiple federal and state governments have placed restrictions on hospitals such as limiting "elective surgery" and recommending social or physical distancing. We review the literature on several areas that have been affected including surgical selection, inpatient care, and physician well-being. These areas affecting inpatient paradigms include surgical priority, physical or social distancing, file sharing for online clinical communications, and physician wellness. During this crisis, it is important that orthopaedic departments place an emphasis on personnel safety and slowing the spread of the virus so that the department can still maintain vital functions. Physical distancing and emerging technologies such as inpatient telemedicine and online file sharing applications can enable orthopaedic programs to still function while attempting to protect medical staff and patients from the novel coronavirus spread. This literature review sought to provide evidence-based guidance to orthopaedic departments during an unprecedented time. Orthopaedic surgeons should follow the Centers for Disease Control and Prevention guidelines, wear personal protective equipment (PPE) when appropriate, have teams created using physical distancing, understand the department's policy on elective surgery, and engage in routines which enhance physician wellness.

Cited by 2 articles68 references3 figures
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63
J Am Coll Surg
. 2020 Jun;230(6):1102-1104. doi: 10.1016/j.jamcollsurg.2020.04.014. Epub 2020 Apr 10.
Novel Approach to Reduce Transmission of COVID-19 During Tracheostomy
Peter Foster 1, Tiffany Cheung 2, Patrick Craft 2, Kelsey Baran 2, Mark Kryskow 2, Ross Knowles 2, Alyssa Toia 2, Christian Galvez 2, Adam Bowling 2, Michael DiSiena 2
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PMID: 32283268 PMCID: PMC7146662 DOI: 10.1016/j.jamcollsurg.2020.04.014
Free PMC article
Abstract
Severe infection involving the novel coronavirus 2019 (COVID-19) has been associated with acute respiratory distress syndrome that subsequently requires patients to be intubated and dependent on mechanical ventilation. In the setting of the recent pandemic, there is a greater need to perform tracheostomy for these patients. With the high transmissibility of the virus, there has been an increasing concern for the development of techniques to perform surgical intervention while mitigating the risk for infecting hospital staff. As more data emerge pertaining to viral shedding in various bodily fluids, it has become more important to give special attention to precautions. In this article, we submit a novel approach for better protection and thus reduced transmission for tracheostomy in a COVID-19 positive patient. Importantly, this technique is functional, easy to set up, and can be used for additional operations that involve risk of aerosolization or droplet exposure to operating room staff.

Cited by 1 article2 references5 figures
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64
J Comp Eff Res
. 2019 Nov;8(15):1299-1316. doi: 10.2217/cer-2019-0101. Epub 2019 Sep 27.
Costs, Exacerbations and Pneumonia After Initiating Combination Tiotropium Olodaterol Versus Triple Therapy for Chronic Obstructive Pulmonary Disease
Swetha R Palli 1, Ami R Buikema 2, Mary DuCharme 2, Monica Frazer 2, Shuchita Kaila 1, Timothy Juday 1
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PMID: 31559852 DOI: 10.2217/cer-2019-0101
Free article
Abstract
Aim: To compare health plan-paid costs, exacerbations and pneumonia outcomes for patients with chronic obstructive pulmonary disease (COPD) initiating combination tiotropium olodaterol (TIO + OLO) versus triple therapy (TT: long-acting muscarinic antagonist + long-acting β2 agonists + inhaled corticosteroid). Patients & methods: COPD patients initiating TIO + OLO or TT between 1 January 2014 and 30 June 2016 were identified from a managed care Medicare database and balanced for baseline characteristics using inverse probability of treatment weighting before assessment of outcomes. Results: Annual COPD-related and all-cause costs were US$4118 (35%) and US$5384 (23%) lower for TIO + OLO versus TT (both p ≤ 0.001). TIO + OLO patients had nearly half the severe exacerbations (8.3 vs 15.5%; p = 0.014) and pneumonia was also less common (18.9 vs 30.9%; p < 0.001). Conclusion: TIO + OLO was associated with improved economic and COPD health outcomes versus TT.

Keywords: COPD exacerbation; healthcare costs; healthcare resource use; pneumonia; tiotropium olodaterol; triple therapy.

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65
Surg Technol Int
. 2020 May 28;36:18-21.
Emergency Colorectal Surgery in a COVID-19 Pandemic Epicenter
George Angelos 1, Andrew Grayson Dockter 2, Mahir Gachabayov 3, Rifat Latifi 4, Roberto Bergamaschi 5
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PMID: 32289868
Abstract
Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a considerable risk during emergency colorectal surgery in a pandemic epicenter. It is well known that the primary route of SARS-CoV-2 transmission is through respiratory droplets. However, little is known about shedding of the virus in bodily fluids and associated risks. Although the current moratorium on elective surgery addresses multiple ongoing concerns, including the management of precious resources as well as unknown exposure risks, surgeons undeniably must face and mitigate risks related to exposure to patient airway management-related aerosols, bodily fluids, surgical smoke, contaminated insufflation, and specimen handling in emergency colorectal surgery. Given the significant concern of airborne transmission, the authors recommend conventional, in lieu of laparoscopic, access in emergency colorectal surgery in a COVID-19 pandemic epicenter.

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66
Review Am J Dent
. 2020 Jun;33(3):135-137.
Taste and Smell as Chemosensory Dysfunctions in COVID-19 Infection
Pier Carmine Passarelli 1, Michele Antonio Lopez 2, Giuseppe Niccolò Mastandrea Bonaviri 3, Franklin Garcia-Godoy 4 5, Antonio D'Addona 6
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PMID: 32470238
Abstract
Purpose: To review the literature on the presence of two clinical manifestations in patients presenting COVID-19 (SARS-CoV-2) infection: loss of taste (ageusia) and loss of smell (anosmia).

Methods: PubMed and EMBASE were searched and studies were selected starting from November, 2019 until April 2020; also, the references of the selected articles were evaluated for methodological quality.

Results: Of the 19 studies analyzed, five were included to evaluate the presence of ageusia and/or anosmia as symptoms in patients who were tested and resulted positive for the SARS-CoV-2 virus. In a total of 10,818 patients, 8,823 presented ageusia (81.6%; range 5.6%-88%) and 8,088 presented anosmia (74.8%; range 5.1-85.6%). Only one study recorded both symptoms with a percentage of 18.6%.

Clinical significance: This systematic review demonstrated significant presence of ageusia and anosmia in the patients with COVID-19 infection. These symptoms may be considered as the first manifestation of the infection.

Copyright©American Journal of Dentistry.

Conflict of interest statement
The authors declared no conflict of interest.

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67
Infect Dis (Lond)
. 2020 Jul;52(7):511-512. doi: 10.1080/23744235.2020.1748705. Epub 2020 Apr 10.
Duration of SARS-CoV-2 Viral Shedding During COVID-19 Infection
Guo-Qing Qian 1, Xue-Qin Chen 1, Ding-Feng Lv 1, Ada Hoi Yan Ma 2, Li-Ping Wang 1, Nai-Bin Yang 1, Xiao-Min Chen 1
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PMID: 32275181 DOI: 10.1080/23744235.2020.1748705
Cited by 2 articles
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68
Comparative Study Clin Microbiol Infect
. 2020 Jun;26(6):773-779. doi: 10.1016/j.cmi.2020.04.001. Epub 2020 Apr 8.
Rapid and Visual Detection of 2019 Novel Coronavirus (SARS-CoV-2) by a Reverse Transcription Loop-Mediated Isothermal Amplification Assay
C Yan 1, J Cui 1, L Huang 2, B Du 1, L Chen 3, G Xue 1, S Li 1, W Zhang 1, L Zhao 1, Y Sun 1, H Yao 1, N Li 1, H Zhao 1, Y Feng 1, S Liu 1, Q Zhang 1, D Liu 4, J Yuan 5
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PMID: 32276116 PMCID: PMC7144850 DOI: 10.1016/j.cmi.2020.04.001
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Abstract
Objective: To evaluate a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and compare it with RT-PCR.

Methods: We designed primers specific to the orf1ab and S genes of SARS-CoV-2. Total viral RNA was extracted using the QIAamp Viral RNA Mini Kit. We optimized the RT-LAMP assay, and evaluated it for its sensitivity and specificity of detection using real-time turbidity monitoring and visual observation.

Results: The primer sets orf1ab-4 and S-123 amplified the genes in the shortest times, the mean (±SD) times were 18 ± 1.32 min and 20 ± 1.80 min, respectively, and 63°C was the optimum reaction temperature. The sensitivities were 2 × 101 copies and 2 × 102 copies per reaction with primer sets orf1ab-4 and S-123, respectively. This assay showed no cross-reactivity with 60 other respiratory pathogens. To describe the availability of this method in clinical diagnosis, we collected 130 specimens from patients with clinically suspected SARS-CoV-2 infection. Among them, 58 were confirmed to be positive and 72 were negative by RT-LAMP. The sensitivity was 100% (95% CI 92.3%-100%), specificity 100% (95% CI 93.7%-100%). This assay detected SARS-CoV-2 in a mean (±SD) time of 26.28 ± 4.48 min and the results can be identified with visual observation.

Conclusion: These results demonstrate that we developed a rapid, simple, specific and sensitive RT-LAMP assay for SARS-CoV-2 detection among clinical samples. It will be a powerful tool for SARS-CoV-2 identification, and for monitoring suspected patients, close contacts and high-risk groups.

Keywords: COVID-19; Detection; RT-LAMP; SARS-CoV-2; Visual.

Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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69
Clin Gastroenterol Hepatol
. 2020 Jun;18(7):1636-1637. doi: 10.1016/j.cgh.2020.03.043. Epub 2020 Mar 20.
Don't Overlook Digestive Symptoms in Patients With 2019 Novel Coronavirus Disease (COVID-19)
Shihua Luo 1, Xiaochun Zhang 2, Haibo Xu 1
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PMID: 32205220 PMCID: PMC7154217 DOI: 10.1016/j.cgh.2020.03.043
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Cited by 2 articles6 references
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70
Review J Med Microbiol
. 2020 May;69(5):653-656. doi: 10.1099/jmm.0.001191. Epub 2020 Apr 22.
Logic in the Time of Coronavirus
Timothy J J Inglis 1 2
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PMID: 32320375 DOI: 10.1099/jmm.0.001191
Abstract
Much has happened here since the local news media trumpeted the first Australian COVID-19 fatality, and stirred up a medieval fear of contagion. We now need to take a step back to examine the logic underlying the use of our limited COVID-19 countermeasures. Emerging infectious diseases by their nature, pose new challenges to the diagnostic-treatment-control nexus, and push our concepts of causality beyond the limits of the conventional Koch-Henle approach to aetiology. We need to use contemporary methods of assessing causality to ensure that clinical, laboratory and public health measures draw on a rational, evidence-based approach to argumentation. The purpose of any aetiological hypothesis is to derive actionable insights into this latest emerging infectious disease. This review is an introduction to a conversation with medical microbiologists, which will be supported by a moderated blog.

Keywords: COVID-19; SARS-CoV-2; coronavirus; countermeasures; principles of aetiology.

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71
Anat Sci Educ
. 2020 May;13(3):284-300. doi: 10.1002/ase.1968. Epub 2020 May 10.
Forced Disruption of Anatomy Education in Australia and New Zealand: An Acute Response to the Covid-19 Pandemic
Nalini Pather 1, Phil Blyth 2, Jamie A Chapman 3, Manisha R Dayal 4, Natasha A M S Flack 2, Quentin A Fogg 5, Rodney A Green 6, Anneliese K Hulme 1, Ian P Johnson 7, Amanda J Meyer 8, John W Morley 9, Peter J Shortland 4, Goran Štrkalj 1, Mirjana Štrkalj 7, Krisztina Valter 10, Alexandra L Webb 10, Stephanie J Woodley 2, Michelle D Lazarus 11 12
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PMID: 32306555 PMCID: PMC7264523 DOI: 10.1002/ase.1968
Free PMC article
Abstract
Australian and New Zealand universities commenced a new academic year in February/March 2020 largely with "business as usual." The subsequent Covid-19 pandemic imposed unexpected disruptions to anatomical educational practice. Rapid change occurred due to government-imposed physical distancing regulations from March 2020 that increasingly restricted anatomy laboratory teaching practices. Anatomy educators in both these countries were mobilized to adjust their teaching approaches. This study on anatomy education disruption at pandemic onset within Australia and New Zealand adopts a social constructivist lens. The research question was "What are the perceived disruptions and changes made to anatomy education in Australia and New Zealand during the initial period of the Covid-19 pandemic, as reflected on by anatomy educators?." Thematic analysis to elucidate "the what and why" of anatomy education was applied to these reflections. About 18 anatomy academics from ten institutions participated in this exercise. The analysis revealed loss of integrated "hands-on" experiences, and impacts on workload, traditional roles, students, pedagogy, and anatomists' personal educational philosophies. The key opportunities recognized for anatomy education included: enabling synchronous teaching across remote sites, expanding offerings into the remote learning space, and embracing new pedagogies. In managing anatomy education's transition in response to the pandemic, six critical elements were identified: community care, clear communications, clarified expectations, constructive alignment, community of practice, ability to compromise, and adapt and continuity planning. There is no doubt that anatomy education has stepped into a yet unknown future in the island countries of Australia and New Zealand.

Keywords: Australia; Covid-19 pandemic; New Zealand; active learning; gross anatomy education; medical education; online delivery; online practical anatomy; reflective practices; remote learning; student well-being; workload.

© 2020 American Association for Anatomy.

56 references1 figure
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72
Review Biol Blood Marrow Transplant
. 2020 Jun;26(6):1043-1049. doi: 10.1016/j.bbmt.2020.04.005. Epub 2020 Apr 17.
American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Position Statement on Pharmacy Practice Management and Clinical Management for COVID-19 in Hematopoietic Cell Transplantation and Cellular Therapy Patients in the United States
Zahra Mahmoudjafari 1, Maurice Alexander 2, Julianna Roddy 3, Ryan Shaw 2, Terri Lynn Shigle 4, Colleen Timlin 5, Katie Culos 6
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PMID: 32305359 PMCID: PMC7162779 DOI: 10.1016/j.bbmt.2020.04.005
Free PMC article
Abstract
The coronavirus-19 (COVID-19) pandemic poses a significant risk to patients undergoing hematopoietic stem cell transplantation (HCT) or cellular therapy. The American Society for Transplantation and Cellular Therapy Pharmacy Special Interest Group Steering Committee aims to provide pharmacy practice management recommendations for how to transition clinical HCT or cellular therapy pharmacy services using telemedicine capabilities in the inpatient and outpatient settings to maintain an equivalent level of clinical practice while minimizing viral spread in a high-risk, immunocompromised population. In addition, the Steering Committee offers clinical management recommendations for COVID-19 in HCT and cellular therapy recipients based on the rapidly developing literature. As the therapeutic and supportive care interventions for COVID-19 expand, collaboration with clinical pharmacy providers is critical to ensure safe administration in HCT recipients. Attention to drug-drug interactions (DDIs) and toxicity, particularly QTc prolongation, warrants close cardiac monitoring and potential cessation of concomitant QTc-prolonging agents. Expanded indications for hydroxychloroquine and tocilizumab have already caused stress on the usual supply chain. Detailed prescribing algorithms, decision pathways, and specific patient population stock may be necessary. The COVID-19 pandemic has challenged all members of the healthcare team, and we must continue to remain vigilant in providing pharmacy clinical services to one of the most high-risk patient populations while also remaining committed to providing compassionate and safe care for patients undergoing HCT and cellular therapies.

Keywords: COVID-19; Cellular therapy; Coronavirus; HCT; Pharmacist; Pharmacy.

Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

46 references
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73
Clin Gastroenterol Hepatol
. 2020 Jun;18(7):1409-1411. doi: 10.1016/j.cgh.2020.03.020. Epub 2020 Mar 18.
What Should Gastroenterologists and Patients Know About COVID-19?
Ryan C Ungaro 1, Timothy Sullivan 2, Jean-Frederic Colombel 3, Gopi Patel 2
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PMID: 32197957 PMCID: PMC7156804 DOI: 10.1016/j.cgh.2020.03.020
Free PMC article
Abstract
No abstract available
Keywords: COVID-19; Coronavirus.

Cited by 2 articles17 references
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74
Indian Pediatr
. 2020 May 15;57(5):423-426. doi: 10.1007/s13312-020-1816-8. Epub 2020 Apr 7.
Radiographic and Clinical Features of Children With Coronavirus Disease (COVID-19) Pneumonia
Bo Li 1, Jie Shen 2, Liang Li 1, Chengxin Yu 1
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PMID: 32255437 PMCID: PMC7240239 DOI: 10.1007/s13312-020-1816-8
Free PMC article
Abstract
Objective: The purpose of this study was to investigate chest computed tomography (CT) findings in children with coronavirus disease-19 (COVID-19) pneumonia in our hospital.

Methods: This study included 22 pediatric patients with confirmed COVID-19 from January to March, 2020. The chest CT images and clinical data were reviewed.

Results: The most prevalent presenting symptoms were fever (64%) and cough (59%), and a mildly elevated mean (SD) C-reactive protein (CRP) level of 11.22(11.06) and erythrocyte sedimentation rateof 18.8(15.17) were detected. The major CT abnormalities observed were mixed ground-glass opacity and consolidation lesions (36%), consolidations (32%), and ground-glass opacities (14%). Peripheral distribution (45%) of lung lesions was predominant. Most of the lesions were multilobar(68%), with an average of three lung segments involved.

Conclusions: Children with COVID-19 had relatively milder symptoms and less severe lung inflammation than adults. Chest CT plays an important role in the management of children with COVID-19 pneumonia.

Cited by 1 article15 references
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75
Comparative Study J Clin Microbiol
. 2020 May 26;58(6):e00557-20. doi: 10.1128/JCM.00557-20. Print 2020 May 26.
Comparative Performance of SARS-CoV-2 Detection Assays Using Seven Different Primer-Probe Sets and One Assay Kit
Arun K Nalla 1, Amanda M Casto 2 3, Meei-Li W Huang 1, Garrett A Perchetti 1, Reigran Sampoleo 1, Lasata Shrestha 1, Yulun Wei 1, Haiying Zhu 1, Keith R Jerome 4 3, Alexander L Greninger 4
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PMID: 32269100 DOI: 10.1128/JCM.00557-20
Free article
Abstract
Nearly 400,000 people worldwide are known to have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beginning in December 2019. The virus has now spread to over 168 countries including the United States, where the first cluster of cases was observed in the Seattle metropolitan area in Washington. Given the rapid increase in the number of cases in many localities, the availability of accurate, high-throughput SARS-CoV-2 testing is vital to efforts to manage the current public health crisis. In the course of optimizing SARS-CoV-2 testing performed by the University of Washington Clinical Virology Lab (UW Virology Lab), we evaluated assays using seven different primer-probe sets and one assay kit. We found that the most sensitive assays were those that used the E-gene primer-probe set described by Corman et al. (V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25:2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045) and the N2 set developed by the CDC (Division of Viral Diseases, Centers for Disease Control and Prevention, 2020, https://www.cdc.gov/coronavirus/2019-ncov/downloads/rt-pcr-panel-primer-probes.pdf). All assays tested were found to be highly specific for SARS-CoV-2, with no cross-reactivity with other respiratory viruses observed in our analyses regardless of the primer-probe set or kit used. These results will provide valuable information to other clinical laboratories who are actively developing SARS-CoV-2 testing protocols at a time when increased testing capacity is urgently needed worldwide.

Keywords: E-gene; N2; SARS-CoV-2; primer; probe.

Copyright © 2020 Nalla et al.

Cited by 2 articles
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76
Editorial Neuroradiology
. 2020 Jun;62(6):647-648. doi: 10.1007/s00234-020-02437-5.
COVID-19: A Primer for Neuroradiologists
Kshitij Mankad 1, Michael D Perry 2, David M Mirsky 3, Andrea Rossi 4
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PMID: 32342126 PMCID: PMC7186113 DOI: 10.1007/s00234-020-02437-5
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Abstract
The potential for central nervous system (CNS) involvement in coronavirus disease 2019 (COVID-19) is a matter of grave concern and there is a relevant body of evidence in the basic sciences to support this possibility. A neuroradiologist should be aware of the potential mechanisms involved in the neuropathogenesis of this virus, as we begin to see cases with abnormal brain scans emerging from all parts of the world.

Keywords: ACE2; ANEC; CNS; COVID-19; Stroke.

Conflict of interest statement
The authors declare that they have no conflict of interest.

13 references
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77
Meta-Analysis BMJ Open Gastroenterol
. 2020 May;7(1):e000417. doi: 10.1136/bmjgast-2020-000417.
Novelty in the Gut: A Systematic Review and Meta-Analysis of the Gastrointestinal Manifestations of COVID-19
Vishnu Charan Suresh Kumar 1, Samiran Mukherjee 2, Prateek Suresh Harne 2, Abinash Subedi 2, Muthu Kuzhali Ganapathy 3, Venkata Suresh Patthipati 4, Bishnu Sapkota 5 6
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PMID: 32457035 DOI: 10.1136/bmjgast-2020-000417
Free article
Abstract
Background: The COVID-19 epidemic has affected over 2.6 million people across 210 countries. Recent studies have shown that patients with COVID-19 experience relevant gastrointestinal (GI) symptoms. We aimed to perform a systematic review and meta-analysis on the GI symptoms of COVID-19.

Methods: A literature search was conducted via electronic databases, including PubMed, Embase, Scopus, and Google Scholar, from inception until 20 March 2020. Data were extracted from relevant studies. A systematic review of GI symptoms and a meta-analysis comparing symptoms in severe and non-severe patients was performed using RevMan V.5.3.

Results: Pooled data from 2477 patients with a reverse transcription-PCR-positive COVID-19 infection across 17 studies were analysed. Our study revealed that diarrhoea (7.8%) followed by nausea and/or vomiting (5.5 %) were the most common GI symptoms. We performed a meta-analysis comparing the odds of having GI symptoms in severe versus non-severe COVID-19-positive patients. 4 studies for nausea and/or vomiting, 5 studies for diarrhoea and 3 studies for abdominal pain were used for the analyses. There was no significant difference in the incidence of diarrhoea (OR=1.32, 95% CI 0.8 to 2.18, Z=1.07, p=0.28, I2=17%) or nausea and/or vomiting (OR=0.96, 95% CI 0.42 to 2.19, Z=0.10, p=0.92, I2=55%) between either group. However, there was seven times higher odds of having abdominal pain in patients with severe illness when compared with non-severe patients (OR=7.17, 95% CI 1.95 to 26.34, Z=2.97, p=0.003, I2=0%).

Conclusion: Our study has reiterated that GI symptoms are an important clinical feature of COVID-19. Patients with severe disease are more likely to have abdominal pain as compared with patients with non-severe disease.

Keywords: abdominal pain; diarrhoea; epidemiology; gastrointestinal pathology; infectious diarrhoea.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Conflict of interest statement
Competing interests: None declared.

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78
Rev Neurol (Paris)
. 2019 Dec;175(10):614-618. doi: 10.1016/j.neurol.2019.03.002. Epub 2019 Apr 25.
Air Pollution and Humidity as Triggering Factors for Stroke. Results of a 12-year Analysis in the West Paris Area
C Hirel 1, L Berton 2, C Preda 3, O Richard 2, Y Lambert 2, F Pico 4
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PMID: 31030900 DOI: 10.1016/j.neurol.2019.03.002
Abstract
Background and purpose: Previous studies have suggested an association between stroke and meteorological factors, air pollution and acute respiratory infections as triggering factors. Often, these factors have been evaluated separately. We evaluated the association between all these environmental triggering factors and calls for suspected stroke in a suburb in west Paris from 2004 to 2015.

Methods: We used data from the emergency medical dispatching center of all calls for suspected stroke (SAMU 78), climatic parameters (MétéoFrance), pollution (AIRPARIF), and data from influenza epidemic surveillance networks (GROG and Sentinelles). The association between short-term exposure (1-day lag) to environmental triggering factors and stroke occurrence was analyzed using negative-binomial log linear regression model for counting time series.

Results: Between 2004 and 2015, a total of 11,037 calls for suspected stroke were recorded. In bivariate analysis, there were associations between calls for suspected stroke and temperature (mean, maximum and minimum), humidity and influenza epidemic. In multivariable analysis, only two variables were associated with calls for suspected stroke: humidity [3.93% excess relative risk (ERR) of stroke per 10% increase in humidity; 95% confidence interval (CI), 1.42 to 6.51; P<0.002] and pollution on the "Air Parif Atmo" scale (2.86% ERR of stroke per 1 unit increase; 95% CI, 1.01 to 4.75; P=0.002).

Conclusions: This study suggests that short-term exposure to air pollution and a high level of humidity are associated with a significant excess relative risk of calls for suspected stroke.

Keywords: Climate; Humidity; Influenza; Pollution; Stroke.

Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Cited by 1 article
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79
Review Monaldi Arch Chest Dis
. 2020 May 25;90(2). doi: 10.4081/monaldi.2020.1389.
Gender Differences in Patients With COVID-19: A Narrative Review
Immacolata Ambrosino 1, Elena Barbagelata 2, Elena Ortona 3, Anna Ruggieri 3, Grace Massiah 4, Orazio Valerio Giannico 5, Cecilia Politi 6, Anna Maria Moretti 7
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PMID: 32449614 DOI: 10.4081/monaldi.2020.1389
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Abstract
In December 2019 a novel coronavirus emerged in Wuhan, China causing many cases of severe pneumonia. World Health Organization (WHO) named this disease Coronavirus Disease 2019 (COVID-19). The infection has rapidly spread across China to many other countries, and on March 12, 2020 the WHO declared pandemic outbreak of COVID-19. As of May 16, 2020, COVID-19 has been diagnosed in more than 4,490,000 patients, associated to 305,976 deaths worldwide; in Italy 224,760 COVID-19 cases have been reported with 31,763 deaths. The main routes of transmission are respiratory droplets and direct contact with infected people, so numerous prevention strategies are employed to mitigate the spread of disease, including social distancing and isolation. The aim of this narrative review is to underline gender differences in epidemiology, etiopathogenesis, risk factors, clinical presentation, diagnosis, prognosis and mortality of patients infected with SARS-CoV-2. Currently data on the sex indicators for admitted or deceased patients are only available, but there is no analysis about other gender indicators. The data considered in our study are the only currently available in the literature, but it is appropriate to implement a specific analysis with all gender indicators to identify appropriate strategies. Moreover, the evaluation of a health service efficiency is a key element to define gender outcomes. Knowing the gender differences in COVID-19 outbreak would be a fundamental tool to understand the effects of a health emergency on individuals and communities as well as to carry out effective and equitable policies, public health measures and targeted solutions.

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80
J Clin Microbiol
. 2020 May 26;58(6):e00375-20. doi: 10.1128/JCM.00375-20. Print 2020 May 26.
A Method To Prevent SARS-CoV-2 IgM False Positives in Gold Immunochromatography and Enzyme-Linked Immunosorbent Assays
Qiang Wang # 1 2 3, Qin Du # 1 3, Bin Guo 1 2 3, Daiyong Mu 4, Xiaolan Lu 1 3, Qiang Ma 1 2 3, Yangliu Guo 1 2 3, Li Fang 1 2 3, Bing Zhang 4, Guoyuan Zhang 5 3, Xiaolan Guo 5 2 3
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PMID: 32277023 DOI: 10.1128/JCM.00375-20
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Abstract
We set out to investigate the interference factors that led to false-positive novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM detection results using gold immunochromatography assay (GICA) and enzyme-linked immunosorbent assay (ELISA) and the corresponding solutions. GICA and ELISA were used to detect SARS-CoV-2 IgM in 86 serum samples, including 5 influenza A virus (Flu A) IgM-positive sera, 5 influenza B virus (Flu B) IgM-positive sera, 5 Mycoplasma pneumoniae IgM-positive sera, 5 Legionella pneumophila IgM-positive sera, 6 sera of HIV infection patients, 36 rheumatoid factor IgM (RF-IgM)-positive sera, 5 sera from hypertensive patients, 5 sera from diabetes mellitus patients, and 14 sera from novel coronavirus infection disease 19 (COVID-19) patients. The interference factors causing false-positive reactivity with the two methods were analyzed, and the urea dissociation test was employed to dissociate the SARS-CoV-2 IgM-positive serum using the best dissociation concentration. The two methods detected positive SARS-CoV-2 IgM in 22 mid-to-high-level-RF-IgM-positive sera and 14 sera from COVID-19 patients; the other 50 sera were negative. At a urea dissociation concentration of 6 mol/liter, SARS-CoV-2 IgM results were positive in 1 mid-to-high-level-RF-IgM-positive serum and in 14 COVID-19 patient sera detected using GICA. At a urea dissociation concentration of 4 mol/liter and with affinity index (AI) levels lower than 0.371 set to negative, SARS-CoV-2 IgM results were positive in 3 mid-to-high-level-RF-IgM-positive sera and in 14 COVID-19 patient sera detected using ELISA. The presence of RF-IgM at mid-to-high levels could lead to false-positive reactivity of SARS-CoV-2 IgM detected using GICA and ELISA, and urea dissociation tests would be helpful in reducing SARS-CoV-2 IgM false-positive results.

Keywords: enzyme-linked immunosorbent assay; false-positive; gold immunochromatography assay; novel coronavirus; urea.

Copyright © 2020 Wang et al.

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81
J Vasc Surg
. 2020 Jun;71(6):2182-2183.e1. doi: 10.1016/j.jvs.2020.03.024. Epub 2020 Apr 1.
The Global Impact of COVID-19 on Vascular Surgical Services
Jun Jie Ng 1, Pei Ho 2, Rajesh Babu Dharmaraj 3, Julian C L Wong 3, Andrew M T L Choong 4
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PMID: 32247029 PMCID: PMC7194858 DOI: 10.1016/j.jvs.2020.03.024
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3 references1 figure
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82
Clin Microbiol Infect
. 2020 Jun;26(6):767-772. doi: 10.1016/j.cmi.2020.04.012. Epub 2020 Apr 15.
Risk Factors for Disease Severity, Unimprovement, and Mortality in COVID-19 Patients in Wuhan, China
J Zhang 1, X Wang 2, X Jia 1, J Li 1, K Hu 3, G Chen 3, J Wei 4, Z Gong 5, C Zhou 6, H Yu 1, M Yu 2, H Lei 7, F Cheng 8, B Zhang 9, Y Xu 10, G Wang 11, W Dong 12
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PMID: 32304745 PMCID: PMC7159868 DOI: 10.1016/j.cmi.2020.04.012
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Abstract
Objective: In December 2019, coronavirus disease (COVID-19) emerged in Wuhan. However, the characteristics and risk factors associated with disease severity, unimprovement and mortality are unclear and our objective is to throw some light on these.

Methods: All consecutive patients diagnosed with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 11 to February 6, 2020, were enrolled in this retrospective cohort study.

Results: A total of 663 COVID-19 patients were included in this study. Among these, 247 (37.3%) had at least one kind of chronic disease; 0.5% of the patients (n = 3) were diagnosed with mild COVID-19, while 37.8% (251/663), 47.5% (315/663), and 14.2% (94/663) were in moderate, severe, and critical conditions, respectively. In our hospital, during follow-up 251 of 663 patients (37.9%) improved and 25 patients died, a mortality rate of 3.77%. Older patients (>60 years old) and those with chronic diseases were prone to have a severe to critical COVID-19 condition, to show unimprovement, and to die (p <0.001, <0.001). Multivariate logistic regression analysis identified being male (OR = 0.486, 95%CI 0.311-0.758; p 0.001), having a severe COVID-19 condition (OR = 0.129, 95%CI 0.082-0.201; p <0.001), expectoration (OR = 1.796, 95%CI 1.062-3.036; p 0.029), muscle ache (OR = 0.309, 95%CI 0.153-0.626; p 0.001), and decreased albumin (OR = 1.929, 95%CI 1.199-3.104; p 0.007) as being associated with unimprovement in COVID-19 patients.

Conclusion: Male sex, a severe COVID-19 condition, expectoration, muscle ache, and decreased albumin were independent risk factors which influence the improvement of COVID-19 patients.

Keywords: COVID-19; disease severity; mortality; patients; unimprovement.

Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Conflict of interest statement
We declare no competing interests.

Cited by 2 articles15 references
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83
Nature
. 2020 Mar;579(7800):482-483. doi: 10.1038/d41586-020-00758-2.
The Coronavirus Pandemic in Five Powerful Charts
Ewen Callaway, David Cyranoski, Smriti Mallapaty, Emma Stoye, Jeff Tollefson
PMID: 32203366 DOI: 10.1038/d41586-020-00758-2
Abstract
No abstract available
Keywords: Diseases; Infection.

Cited by 8 articles
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84
Editorial CMAJ
. 2019 Dec 2;191(48):E1319-E1320. doi: 10.1503/cmaj.191503. Epub 2019 Nov 20.
Vaping-associated Lung Illnesses Highlight Risks to All Users of Electronic Cigarettes
Matthew B Stanbrook 1
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PMID: 31753840 PMCID: PMC6887566 DOI: 10.1503/cmaj.191503
Free PMC article
Conflict of interest statement
Competing interests: See www.cmaj.ca/site/misc/cmaj_staff.xhtml.

Comment on
Life-threatening bronchiolitis related to electronic cigarette use in a Canadian youth.
Landman ST, Dhaliwal I, Mackenzie CA, Martinu T, Steele A, Bosma KJ.
CMAJ. 2019 Dec 2;191(48):E1321-E1331. doi: 10.1503/cmaj.191402. Epub 2019 Nov 20.
PMID: 31753841 Free PMC article.
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85
Review J Transl Med
. 2020 May 18;18(1):203. doi: 10.1186/s12967-020-02380-2.
Rationale for the Clinical Use of Adipose-Derived Mesenchymal Stem Cells for COVID-19 Patients
Christopher J Rogers 1, Robert J Harman 2, Bruce A Bunnell 3, Martin A Schreiber 4, Charlie Xiang 5, Fu-Sheng Wang 6, Antonio F Santidrian 7, Boris R Minev 7 8
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PMID: 32423449 PMCID: PMC7232924 DOI: 10.1186/s12967-020-02380-2
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Abstract
In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan, capital city of Hubei province in China. Cases of SARS-CoV-2 infection quickly grew by several thousand per day. Less than 100 days later, the World Health Organization declared that the rapidly spreading viral outbreak had become a global pandemic. Coronavirus disease 2019 (COVID-19) is typically associated with fever and respiratory symptoms. It often progresses to severe respiratory distress and multi-organ failure which carry a high mortality rate. Older patients or those with medical comorbidities are at greater risk for severe disease. Inflammation, pulmonary edema and an over-reactive immune response can lead to hypoxia, respiratory distress and lung damage. Mesenchymal stromal/stem cells (MSCs) possess potent and broad-ranging immunomodulatory activities. Multiple in vivo studies in animal models and ex vivo human lung models have demonstrated the MSC's impressive capacity to inhibit lung damage, reduce inflammation, dampen immune responses and aid with alveolar fluid clearance. Additionally, MSCs produce molecules that are antimicrobial and reduce pain. Upon administration by the intravenous route, the cells travel directly to the lungs where the majority are sequestered, a great benefit for the treatment of pulmonary disease. The in vivo safety of local and intravenous administration of MSCs has been demonstrated in multiple human clinical trials, including studies of acute respiratory distress syndrome (ARDS). Recently, the application of MSCs in the context of ongoing COVID-19 disease and other viral respiratory illnesses has demonstrated reduced patient mortality and, in some cases, improved long-term pulmonary function. Adipose-derived stem cells (ASC), an abundant type of MSC, are proposed as a therapeutic option for the treatment of COVID-19 in order to reduce morbidity and mortality. Additionally, when proven to be safe and effective, ASC treatments may reduce the demand on critical hospital resources. The ongoing COVID-19 outbreak has resulted in significant healthcare and socioeconomic burdens across the globe. There is a desperate need for safe and effective treatments. Cellular based therapies hold great promise for the treatment of COVID-19. This literature summary reviews the scientific rationale and need for clinical studies of adipose-derived stem cells and other types of mesenchymal stem cells in the treatment of patients who suffer with COVID-19.

Keywords: ARDS; COVID-19; Mesenchymal stem cells; Pneumonia; SARS-CoV-2.

Conflict of interest statement
CR, RH declared equity in Personalized Stem Cells, Inc., but there is no conflict of interest. The other authors indicated no potential conflicts of interest.

243 references
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86
Editorial J Mycol Med
. 2020 Jun;30(2):100971. doi: 10.1016/j.mycmed.2020.100971. Epub 2020 Apr 6.
Invasive Fungal Diseases During COVID-19: We Should Be Prepared
J-P Gangneux 1, M-E Bougnoux 2, E Dannaoui 3, M Cornet 4, J R Zahar 5
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PMID: 32307254 PMCID: PMC7136887 DOI: 10.1016/j.mycmed.2020.100971
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Abstract
No abstract available
Keywords: Covid Aspergillus; Covid Pneumocystis; Covid aspergillosis; Covid fungal; Covid mucorales; Covid pneumocystosis.

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87
J Anxiety Disord
. 2020 May;72:102232. doi: 10.1016/j.janxdis.2020.102232. Epub 2020 May 4.
Development and Initial Validation of the COVID Stress Scales
Steven Taylor 1, Caeleigh A Landry 2, Michelle M Paluszek 2, Thomas A Fergus 3, Dean McKay 4, Gordon J G Asmundson 5
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PMID: 32408047 PMCID: PMC7198206 DOI: 10.1016/j.janxdis.2020.102232
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Abstract
Research and clinical observations suggest that during times of pandemic many people exhibit stress- or anxiety-related responses that include fear of becoming infected, fear of coming into contact with possibly contaminated objects or surfaces, fear of foreigners who might be carrying infection (i.e., disease-related xenophobia), fear of the socio-economic consequences of the pandemic, compulsive checking and reassurance-seeking regarding possible pandemic-related threats, and traumatic stress symptoms about the pandemic (e.g., nightmares, intrusive thoughts). We developed the 36-item COVID Stress Scales (CSS) to measure these features, as they pertain to COVID-19. The CSS were developed to better understand and assess COVID-19-related distress. The scales were intentionally designed so they could be readily adapted for future pandemics. The CSS were developed and initially validated in population-representative samples from Canada (N = 3479) and the United States (N = 3375). A stable 5-factor solution was identified, corresponding to scales assessing COVID-related stress and anxiety symptoms: (1) Danger and contamination fears, (2) fears about economic consequences, (3) xenophobia, (4) compulsive checking and reassurance seeking, and (5) traumatic stress symptoms about COVID-19. The scales performed well on various indices of reliability and validity. The scales were intercorrelated, providing evidence of a COVID Stress Syndrome. The scales offer promise as tools for better understanding the distress associated with COVID-19 and for identifying people in need of mental health services.

Keywords: Anxiety; COVID-19; Coronavirus; Fear; Pandemic; Stress; Xenophobia.

Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Cited by 1 article35 references
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88
J Med Virol
. 2019 Aug;91(8):1423-1431. doi: 10.1002/jmv.25459. Epub 2019 Mar 28.
A 28-year Study of Human Parainfluenza in Rio Grande Do Sul, Southern Brazil
Tatiana Schäffer Gregianini 1, Claudete Farina Seadi 1, Luiz Domingos Zavarize Neto 2 3, Letícia Garay Martins 4, Guilherme Cerutti Muller 3, Selir Maria Straliotto 1, Ana Beatriz Gorini da Veiga 2
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PMID: 30866089 PMCID: PMC7166594 DOI: 10.1002/jmv.25459
Free PMC article
Abstract
Problem: Human parainfluenza virus (hPIV) is an important pathogen in respiratory infections, however the health burden of hPIV is underestimated. This study describes the infections by hPIV1-3 in Rio Grande do Sul, Brazil, from 1990 to 2017, providing data of the frequency and seasonality of cases and associated clinical symptoms.

Method of study: Nasopharyngeal samples of patients with respiratory infection were collected, clinical data were analyzed, and immunofluorescence was used to detect hPIV.

Results: Respiratory viruses were detected in 33.63% of respiratory infections. In a total of 11 606 cases of viral respiratory infection, 781 were positive for hPIV; hPIV prevalence ranged from 2.14% to 27% of viral respiratory infections. hPIV1 circulates mainly during fall; hPIV3 circulation, in turn, starts in fall and peaks during spring; and cases of hPIV2 are reported along the year, with peaks in fall and early spring. The most affected age group was children, with hPIV prevalence of 74.23% in patients for less than 1 year. A higher proportion of girls were infected than boys, however, no difference by sex was observed considering all age groups. The most frequent type was hPIV3, especially in hospitalized patients. Both hPIV1 and 3 were associated with dyspnea, while hPIV2 caused mild symptoms mainly in nonhospitalized patients. Nineteen fatalities occurred, 89.5% of them associated with risk factors (prematurity; chronic diseases; age, <1 or >60 years).

Conclusion: hPIV causes a high number of respiratory infections, leading to hospitalization especially in children; epidemiological and surveillance studies are important for the control and management of respiratory infections.

Keywords: acute respiratory infection; hPIV infection; respiratory virus; severe acute respiratory infection.

© 2019 Wiley Periodicals, Inc.

Conflict of interest statement
The authors declare that there are no conflict of interests.

47 references3 figures
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89
Rev Esp Salud Publica
. 2020 May 27;94:e202005055.
[Coronavirus Covid-19 Infection and Breastfeeding: An Exploratory Review]
[Article in Spanish]
Francisco Javier Fernández-Carrasco 1, Juana María Vázquez-Lara 2, Urbano González-Mey 3, Juan Gómez-Salgado 4 5, Tesifón Parrón-Carreño 6 7, Luciano Rodríguez-Díaz 2
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PMID: 32458823
Free article
Abstract in English , Spanish
Background: The new coronavirus disease is an infectious disease caused by the SARS-Cov-2 virus, considered by the World Health Organization (WHO) an international public health emergency that may have negative consequences during breastfeeding. The objective of this work is to investigate the action plan on breastfeeding in postpartum women with SARS-CoV-2 and her newborn.

Methods: A literature search has been conducted through the Medline, Web of Science, Scopus, BVS, and Cuiden databases. The methodological quality of the articles has been assessed using the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE). This study has not been registered in PROSPERO.

Results: A total of 14 documents have been found, of which 9 are observational empirical studies. Most of the studies were conducted in China, Italy, the USA, and Australia. A total of 114 mothers infected with coronavirus with their respective newborns have been assessed. The analyzed investigations state that it is best for the newborn to be breastfed; given that mother's milk samples were analyzed, detecting the presence of antibodies of the coronavirus in them, being a protective factor against infection.

Conclusions: Breastfeeding in postpartum women with SARS-CoV-2 is highly recommended for the newborn, if the health of the mother and newborn allow it. When direct breastfeeding is favoured, the appropriate respiratory hygiene measures always have to be considered. Whether the mother's health does not permit direct breastfeeding, her breast milk should be previously extracted and kept unpasteurized. To secure the newborn feeding, milk banks are also an appropriate option.

Keywords: COVID-19; Maternal breastfeeding; Neonate; New-born; Pregnancy; Scoping review; Spain.

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90
Science
. 2020 May 29;368(6494):948-950. doi: 10.1126/science.abc5312. Epub 2020 May 11.
A Strategic Approach to COVID-19 Vaccine R&D
Lawrence Corey 1 2, John R Mascola 3, Anthony S Fauci 4, Francis S Collins 5
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PMID: 32393526 DOI: 10.1126/science.abc5312
Cited by 1 article
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91
Editorial N Engl J Med
. 2020 May 28;382(22):2158-2160. doi: 10.1056/NEJMe2009758. Epub 2020 Apr 24.
Asymptomatic Transmission, the Achilles' Heel of Current Strategies to Control Covid-19
Monica Gandhi 1, Deborah S Yokoe 1, Diane V Havlir 1
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PMID: 32329972 PMCID: PMC7200054 DOI: 10.1056/NEJMe2009758
Free PMC article
Comment on
Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility.
Arons MM, Hatfield KM, Reddy SC, Kimball A, James A, Jacobs JR, Taylor J, Spicer K, Bardossy AC, Oakley LP, Tanwar S, Dyal JW, Harney J, Chisty Z, Bell JM, Methner M, Paul P, Carlson CM, McLaughlin HP, Thornburg N, Tong S, Tamin A, Tao Y, Uehara A, Harcourt J, Clark S, Brostrom-Smith C, Page LC, Kay M, Lewis J, Montgomery P, Stone ND, Clark TA, Honein MA, Duchin JS, Jernigan JA; Public Health–Seattle and King County and CDC COVID-19 Investigation Team.
N Engl J Med. 2020 May 28;382(22):2081-2090. doi: 10.1056/NEJMoa2008457. Epub 2020 Apr 24.
PMID: 32329971 Free PMC article.
Cited by 2 articles10 references
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92
Clinical Trial Lancet
. 2020 May 30;395(10238):1695-1704. doi: 10.1016/S0140-6736(20)31042-4. Epub 2020 May 10.
Triple Combination of Interferon beta-1b, Lopinavir-Ritonavir, and Ribavirin in the Treatment of Patients Admitted to Hospital With COVID-19: An Open-Label, Randomised, Phase 2 Trial
Ivan Fan-Ngai Hung 1, Kwok-Cheung Lung 2, Eugene Yuk-Keung Tso 3, Raymond Liu 4, Tom Wai-Hin Chung 5, Man-Yee Chu 6, Yuk-Yung Ng 7, Jenny Lo 4, Jacky Chan 8, Anthony Raymond Tam 9, Hoi-Ping Shum 10, Veronica Chan 3, Alan Ka-Lun Wu 11, Kit-Man Sin 7, Wai-Shing Leung 8, Wai-Lam Law 6, David Christopher Lung 12, Simon Sin 13, Pauline Yeung 13, Cyril Chik-Yan Yip 5, Ricky Ruiqi Zhang 1, Agnes Yim-Fong Fung 14, Erica Yuen-Wing Yan 14, Kit-Hang Leung 14, Jonathan Daniel Ip 14, Allen Wing-Ho Chu 14, Wan-Mui Chan 14, Anthony Chin-Ki Ng 14, Rodney Lee 11, Kitty Fung 15, Alwin Yeung 4, Tak-Chiu Wu 6, Johnny Wai-Man Chan 6, Wing-Wah Yan 10, Wai-Ming Chan 13, Jasper Fuk-Woo Chan 14, Albert Kwok-Wai Lie 9, Owen Tak-Yin Tsang 8, Vincent Chi-Chung Cheng 5, Tak-Lun Que 16, Chak-Sing Lau 9, Kwok-Hung Chan 14, Kelvin Kai-Wang To 14, Kwok-Yung Yuen 17
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PMID: 32401715 PMCID: PMC7211500 DOI: 10.1016/S0140-6736(20)31042-4
Free PMC article
Abstract
Background: Effective antiviral therapy is important for tackling the coronavirus disease 2019 (COVID-19) pandemic. We assessed the efficacy and safety of combined interferon beta-1b, lopinavir-ritonavir, and ribavirin for treating patients with COVID-19.

Methods: This was a multicentre, prospective, open-label, randomised, phase 2 trial in adults with COVID-19 who were admitted to six hospitals in Hong Kong. Patients were randomly assigned (2:1) to a 14-day combination of lopinavir 400 mg and ritonavir 100 mg every 12 h, ribavirin 400 mg every 12 h, and three doses of 8 million international units of interferon beta-1b on alternate days (combination group) or to 14 days of lopinavir 400 mg and ritonavir 100 mg every 12 h (control group). The primary endpoint was the time to providing a nasopharyngeal swab negative for severe acute respiratory syndrome coronavirus 2 RT-PCR, and was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT04276688.

Findings: Between Feb 10 and March 20, 2020, 127 patients were recruited; 86 were randomly assigned to the combination group and 41 were assigned to the control group. The median number of days from symptom onset to start of study treatment was 5 days (IQR 3-7). The combination group had a significantly shorter median time from start of study treatment to negative nasopharyngeal swab (7 days [IQR 5-11]) than the control group (12 days [8-15]; hazard ratio 4·37 [95% CI 1·86-10·24], p=0·0010). Adverse events included self-limited nausea and diarrhoea with no difference between the two groups. One patient in the control group discontinued lopinavir-ritonavir because of biochemical hepatitis. No patients died during the study.

Interpretation: Early triple antiviral therapy was safe and superior to lopinavir-ritonavir alone in alleviating symptoms and shortening the duration of viral shedding and hospital stay in patients with mild to moderate COVID-19. Future clinical study of a double antiviral therapy with interferon beta-1b as a backbone is warranted.

Funding: The Shaw-Foundation, Richard and Carol Yu, May Tam Mak Mei Yin, and Sanming Project of Medicine.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Comment in
Interferon beta-1b for COVID-19.
Shalhoub S.
Lancet. 2020 May 30;395(10238):1670-1671. doi: 10.1016/S0140-6736(20)31101-6. Epub 2020 May 10.
PMID: 32401712 Free PMC article. No abstract available.
Cited by 3 articles30 references2 figures
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93
J Clin Microbiol
. 2020 May 26;58(6):e00599-20. doi: 10.1128/JCM.00599-20. Print 2020 May 26.
Clinical Evaluation of the Cobas SARS-CoV-2 Test and a Diagnostic Platform Switch During 48 Hours in the Midst of the COVID-19 Pandemic
Mario Poljak # 1, Miša Korva # 1, Nataša Knap Gašper 1, Kristina Fujs Komloš 1, Martin Sagadin 1, Tina Uršič 1, Tatjana Avšič Županc 1, Miroslav Petrovec 2
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PMID: 32277022 DOI: 10.1128/JCM.00599-20
Free article
Abstract
Laboratories are currently witnessing extraordinary demand globally for sampling devices, reagents, consumables, and diagnostic instruments needed for timely diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To meet diagnostic needs as the pandemic grows, the U.S. Food and Drug Administration (FDA) recently granted several commercial SARS-CoV-2 tests Emergency Use Authorization (EUA), but manufacturer-independent evaluation data are scarce. We performed the first manufacturer-independent evaluation of the fully automated sample-to-result two-target test cobas 6800 SARS-CoV-2 (cobas) (Roche Molecular Systems, Branchburg, NJ), which received U.S. FDA EUA on 12 March 2020. The comparator was a standardized 3-h SARS-CoV-2 protocol, consisting of RNA extraction using an automated portable instrument, followed by a two-target reverse transcription real-time PCR (RT-PCR), which our laboratory has routinely used since January 2020 [V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25(3):pii=2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045]. cobas and the comparator showed overall agreement of 98.1% and a kappa value of 0.95 on an in-house validation panel consisting of 217 well-characterized retrospective samples. Immediate prospective head-to-head comparative evaluation followed on 502 samples, and the diagnostic approaches showed overall agreement of 99.6% and a kappa value of 0.98. A good correlation (r 2 = 0.96) between cycle threshold values for SARS-CoV-2-specific targets obtained by cobas and the comparator was observed. Our results showed that cobas is a reliable assay for qualitative detection of SARS-CoV-2 in nasopharyngeal swab samples collected in the Universal Transport Medium System (UTM-RT) (Copan, Brescia, Italy). Under the extraordinary circumstances that laboratories are facing worldwide, a safe diagnostic platform switch is feasible in only 48 h and in the midst of the COVID-19 pandemic if carefully planned and executed.

Keywords: COVID-19; SARS-CoV-2; cobas; cobas 6800.

Copyright © 2020 Poljak et al.

Cited by 1 article
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94
Comment Eur Respir J
. 2019 Mar 14;53(3):1802184. doi: 10.1183/13993003.02184-2018. Print 2019 Mar.
Pulmonary Rehabilitation Is Effective in Patients With Tuberculosis Pulmonary Sequelae
Dina Visca 1 2 3, Elisabetta Zampogna 1 3, Giovanni Sotgiu 4 3, Rosella Centis 1 3, Laura Saderi 4, Lia D'Ambrosio 5, Valentina Pegoraro 2, Patrizia Pignatti 6, Marcela Muňoz-Torrico 7, Giovanni Battista Migliori 1, Antonio Spanevello 1 2
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PMID: 30872556 DOI: 10.1183/13993003.02184-2018
Conflict of interest statement
Conflict of interest: D. Visca has nothing to disclose. Conflict of interest: E. Zampogna has nothing to disclose. Conflict of interest: G. Sotgiu has nothing to disclose. Conflict of interest: R. Centis has nothing to disclose. Conflict of interest: L. Saderi has nothing to disclose. Conflict of interest: L. D'Ambrosio has nothing to disclose. Conflict of interest: V. Pegoraro has nothing to disclose. Conflict of interest: P. Pignatti has nothing to disclose. Conflict of interest: M. Muňoz-Torrico has nothing to disclose. Conflict of interest: G.B. Migliori has nothing to disclose. Conflict of interest: A. Spanevello has nothing to disclose.

Comment on
Tuberculosis in the European Union and European Economic Area: a survey of national tuberculosis programmes.
Collin SM, de Vries G, Lönnroth K, Migliori GB, Abubakar I, Anderson SR, Zenner D.
Eur Respir J. 2018 Dec 6;52(6):1801449. doi: 10.1183/13993003.01449-2018. Print 2018 Dec.
PMID: 30309977
Cited by 2 articles
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95
Review J Cardiovasc Pharmacol Ther
. 2020 Jul;25(4):299-306. doi: 10.1177/1074248420921720. Epub 2020 Apr 30.
Evidence for Use or Disuse of Renin-Angiotensin System Modulators in Patients Having COVID-19 With an Underlying Cardiorenal Disorder
Himanshu Sankrityayan 1, Ajinath Kale 1, Nisha Sharma 1, Hans-Joachim Anders 2, Anil Bhanudas Gaikwad 1
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PMID: 32351121 DOI: 10.1177/1074248420921720
Abstract
Coronavirus disease 19 (COVID-19) originated in Wuhan, China, in December 2019 has been declared pandemic by World Health Organization due to an exponential rise in the number of infected and deceased persons across the globe. Emerging reports suggest that susceptibility and mortality rates are higher in patients with certain comorbidities when compared to the average population. Cardiovascular diseases and diabetes are important risk factors for a lethal outcome of COVID-19. Extensive research ensuing the outbreak of coronavirus-related severe acute respiratory syndrome in the year 2003, and COVID-19 recently revealed a role of renin-angiotensin system (RAS) components in the entry of coronavirus wherein angiotensin-converting enzyme 2 (ACE2) had garnered the significant attention. This raises the question whether the use of RAS inhibitors, the backbone of treatment of cardiovascular, neurovascular, and kidney diseases could increase the susceptibility for coronavirus infection or unfortunate outcomes of COVID-19. Thus, currently, there is a lack of consensus regarding the effects of RAS inhibitors in such patients. Moreover, expert bodies like American Heart Association, American College of Cardiology, and so on have now released official statements that RAS inhibitors must be continued, unless suggested otherwise by a physician. In this brief review, we will elaborate on the role of RAS and ACE2 in pathogenesis of COVID-19. Moreover, we will discuss the potential effect of the use and disuse of RAS inhibitors in patients having COVID-19 with cardiometabolic comorbidities.

Keywords: ACE2; COVID-19; SARS; cardiovascular disease; hypertension; renin–angiotensin system.

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96
Review J Am Acad Orthop Surg
. 2020 Jun 1;28(11):451-463. doi: 10.5435/JAAOS-D-20-00227.
Perioperative Considerations in Urgent Surgical Care of Suspected and Confirmed COVID-19 Orthopaedic Patients: Operating Room Protocols and Recommendations in the Current COVID-19 Pandemic
Mohamed E Awad 1, Jacob C L Rumley, Jose A Vazquez, John G Devine
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PMID: 32282441 PMCID: PMC7197335 DOI: 10.5435/JAAOS-D-20-00227
Free PMC article
Abstract
By April 7, 2020, severe acute respiratory syndrome coronavirus 2 was responsible for 1,383,436 confirmed cases of Coronavirus disease 2019 (COVID-19), involving 209 countries around the world; 378,881 cases have been confirmed in the United States. During this pandemic, the urgent surgical requirements will not stop. As an example, the most recent Centers of Disease Control and Prevention reports estimate that there are 2.8 million trauma patients hospitalized in the United States. These data illustrate an increase in the likelihood of encountering urgent surgical patients with either clinically suspected or confirmed COVID-19 in the near future. Preparation for a pandemic involves considering the different levels in the hierarchy of controls and the different phases of the pandemic. Apart from the fact that this pandemic certainly involves many important health, economic, and community ramifications, it also requires several initiatives to mandate what measures are most appropriate to prepare for mitigating the occupational risks. This article provides evidence-based recommendations and measures for the appropriate personal protective equipment for different clinical and surgical activities in various settings. To reduce the occupational risk in treating suspected or confirmed COVID-19 urgent orthopaedic patients, recommended precautions and preventive actions (triage area, emergency department consultation room, induction room, operating room, and recovery room) are reviewed.

Conflict of interest statement
None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Awad, Dr. Rumley, Dr. Vazquez, and Dr. Devine.

Cited by 1 article59 references3 figures
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97
Nature
. 2020 Mar;579(7800):481. doi: 10.1038/d41586-020-00798-8.
Coronavirus Vaccines: Five Key Questions as Trials Begin
Ewen Callaway
PMID: 32203367 DOI: 10.1038/d41586-020-00798-8
Abstract
No abstract available
Keywords: Infection; Virology.

Cited by 1 article
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98
Comparative Study J Clin Virol
. 2020 Jun;127:104374. doi: 10.1016/j.jcv.2020.104374. Epub 2020 Apr 20.
Interpret With Caution: An Evaluation of the Commercial AusDiagnostics Versus In-House Developed Assays for the Detection of SARS-CoV-2 Virus
H Rahman 1, I Carter 1, K Basile 2, L Donovan 1, S Kumar 1, T Tran 1, D Ko 1, S Alderson 1, T Sivaruban 1, J-S Eden 3, R Rockett 4, M V O'Sullivan 5, V Sintchenko 5, S C-A Chen 5, S Maddocks 1, D E Dwyer 5, J Kok 4
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PMID: 32361322 PMCID: PMC7195305 DOI: 10.1016/j.jcv.2020.104374
Free PMC article
Abstract
Introduction: There is limited data on the analytical performance of commercial nucleic acid tests (NATs) for laboratory confirmation of COVID-19 infection.

Methods: Nasopharyngeal, combined nose and throat swabs, nasopharyngeal aspirates and sputum was collected from persons with suspected SARS-CoV-2 infection, serial dilutions of SARS-CoV-2 viral cultures and synthetic positive controls (gBlocks, Integrated DNA Technologies) were tested using i) AusDiagnostics assay (AusDiagnostics Pty Ltd); ii) in-house developed assays targeting the E and RdRp genes; iii) multiplex PCR assay targeting endemic respiratory viruses. Discrepant SARS-CoV-2 results were resolved by testing the N, ORF1b, ORF1ab and M genes.

Results: Of 52 clinical samples collected from 50 persons tested, respiratory viruses were detected in 22 samples (42 %), including SARS CoV-2 (n = 5), rhinovirus (n = 7), enterovirus (n = 5), influenza B (n = 4), hMPV (n = 5), influenza A (n = 2), PIV-2 (n = 1), RSV (n = 2), CoV-NL63 (n = 1) and CoV-229E (n = 1). SARS-CoV-2 was detected in four additional samples by the AusDiagnostics assay. Using the in-house assays as the "gold standard", the sensitivity, specificity, positive and negative predictive values of the AusDiagnostics assay was 100 %, 92.16 %, 55.56 % and 100 % respectively. The Ct values of the real-time in-house-developed PCR assay targeting the E gene was significantly lower than the corresponding RdRp gene assay when applied to clinical samples, viral culture and positive controls (mean 21.75 vs 28.1, p = 0.0031).

Conclusions: The AusDiagnostics assay is not specific for the detection SARS-CoV-2. Any positive results should be confirmed using another NAT or sequencing. The case definition used to investigate persons with suspected COVID-19 infection is not specific.

Keywords: Covid-19; NAT; SARS-CoV-2.

Copyright © 2020 Elsevier B.V. All rights reserved.

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99
Case Reports Int J STD AIDS
. 2018 Dec;29(14):1448-1450. doi: 10.1177/0956462418788129. Epub 2018 Aug 16.
Treatment of Disseminated Histoplasmosis in Advanced HIV Using Itraconazole With Increased Bioavailability
Rekha P Mangalore 1, Michael A Moso 1, Katie Cronin 1, Katrina Young 2, James H McMahon 1 3
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PMID: 30114999 DOI: 10.1177/0956462418788129
Abstract
Disseminated histoplasmosis (DH), an endemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, is a life-threatening infection in immunocompromised hosts. A patient with newly-diagnosed human immunodeficiency virus (HIV) infection presented with a violaceous, raised, indurated, pruritic rash over the face, arms and trunk on a background of significant weight loss, fevers with sweats, diarrhoea and worsening shortness of breath. His CD4+ T cell count was 14 cells/µl (12%). Histoplasmosis was diagnosed from histology, fungal stain and culture of skin biopsy. In addition to DH, he was found to have Pneumocystis jiroveci pneumonia and multi-resistant Salmonella choleraesuis bacteraemia. He improved with treatment with antibiotics and was commenced on conventional itraconazole, orally. Antiretroviral therapy was commenced soon after. He was unable to achieve therapeutic levels with the conventional formulation due to gastrointestinal side effects and had ongoing fevers. A newer formulation of oral itraconazole with improved bioavailability was commenced. He achieved therapeutic drug levels and had no further intolerance. His fevers settled and the rash improved. He has now completed one year of treatment and is well. To our knowledge this is the first case of moderate DH in an advanced HIV patient treated successfully with oral itraconazole with improved bioavailability.

Keywords: HIV; Histoplasmosis; bioavailability; itraconazole.

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100
Sci Total Environ
. 2020 Jul 10;725:138436. doi: 10.1016/j.scitotenv.2020.138436. Epub 2020 Apr 4.
Correlation Between Weather and Covid-19 Pandemic in Jakarta, Indonesia
Ramadhan Tosepu 1, Joko Gunawan 2, Devi Savitri Effendy 3, La Ode Ali Imran Ahmad 4, Hariati Lestari 5, Hartati Bahar 6, Pitrah Asfian 7
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PMID: 32298883 DOI: 10.1016/j.scitotenv.2020.138436
Abstract
This study aims to analyze the correlation between weather and covid-19 pandemic in Jakarta Indonesia. This study employed a secondary data analysis of surveillance data of covid-19 from the Ministry of Health of the Republic of Indonesia and weather from the Meteorological Department of the Republic of Indonesia. The components of weather include minimum temperature (°C), maximum temperature (°C), temperature average (°C), humidity (%), and amount of rainfall (mm). Spearman-rank correlation test was used for data analysis. Among the components of the weather, only temperature average (°C) was significantly correlated with covid-19 pandemic (r = 0.392; p < .01). The finding serves as an input to reduce the incidence rate of covid-19 in Indonesia.

Keywords: Coronavirus; Covid-19; Humidity; Indonesia; Rainfall; Temperature.

Copyright © 2020 Elsevier B.V. All rights reserved.

Cited by 5 articles
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101
Multicenter Study BMJ Open
. 2019 May 28;9(5):e027540. doi: 10.1136/bmjopen-2018-027540.
Relationship Between Physician Financial Incentives and Clinical Pathway Compliance: A Cross-Sectional Study of 18 Public Hospitals in China
Jie Bai 1 2, Kate Bundorf 3, Fei Bai 4, Huiqin Tang 5, Di Xue 1 2
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PMID: 31142531 PMCID: PMC6549614 DOI: 10.1136/bmjopen-2018-027540
Free PMC article
Abstract
Objectives: Many strategies have been either used or recommended to promote physician compliance with clinical practice guidelines and clinical pathways (CPs). This study examines the relationship between hospitals' use of financial incentives to encourage physician compliance with CPs and physician adherence to CPs.

Design: A retrospectively cross-sectional study of the relationship between the extent to which patient care was consistent with CPs and hospital's use of financial incentives to influence CP compliance.

Setting: Eighteen public hospitals in three provinces in China.

Participants: Stratified sample of 2521 patients discharged between 3 January 2013 and 31 December 2014.

Primary outcome measures: The proportion of key performance indicators (KPIs) met for patients with (1) community-acquired pneumonia (pneumonia), (2) acute myocardial infarction (AMI), (3) acute left ventricular failure (heart failure), (4) planned caesarean section (C-section) and (5) gallstones associated with acute cholecystitis and associated cholecystectomy (cholecystectomy).

Results: The average implementation rate of CPs for five conditions (pneumonia, AMI, heart failure, C-section and cholecystectomy) based on 2521 cases in 18 surveyed hospitals was 57% (ranging from 44% to 67%), and the overall average compliance rate for the KPIs for the five conditions was 69.48% (ranging from 65.07% to 77.36%). Implementation of CPs was associated with greater compliance within hospitals only when hospitals adopted financial incentives directed at physicians to promote compliance.

Conclusion: CPs are viewed as important strategies to improve medical care in China, but they have not been widely implemented or adhered to in Chinese public hospitals. In addition to supportive resources, education/training and better administration in general, hospitals should provide financial incentives to encourage physicians to adhere to CPs.

Keywords: clinical pathway; compliance; financial incentives; influencing factor.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Conflict of interest statement
Competing interests: JB is a PhD student at the School of Public Health, Fudan University and is a staff member of Pudong Institute for Health Development.

37 references
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102
Review J Am Acad Orthop Surg
. 2020 Jun 1;28(11):e456-e464. doi: 10.5435/JAAOS-D-20-00292.
Orthopaedic Education During the COVID-19 Pandemic
Monica Kogan 1, Sandra E Klein, Charles P Hannon, Michael T Nolte
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PMID: 32282439 PMCID: PMC7195844 DOI: 10.5435/JAAOS-D-20-00292
Free PMC article
Abstract
The COVID-19 global pandemic presents a challenge to orthopaedic education. Around the world, including in the United States, elective surgeries are being deferred and orthopaedic residents and fellows are being asked to make drastic changes to their daily routines. In the midst of these changes are unique opportunities for resident/fellow growth and development. Educational tools in the form of web-based learning, surgical simulators, and basic competency tests may serve an important role. Challenges are inevitable, but appropriate preparation may help programs ensure continued resident growth, development, and well-being while maintaining high-quality patient care.

Conflict of interest statement
None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Kogan, Dr. Klein, Dr. Hannon, and Dr. Nolte.

Cited by 1 article40 references2 figures
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103
Maturitas
. 2020 Mar;133:60-67. doi: 10.1016/j.maturitas.2020.01.004. Epub 2020 Jan 8.
Factors Associated With Sarcopenia: A Cross-Sectional Analysis Using UK Biobank
Fanny Petermann-Rocha 1, Minghao Chen 2, Stuart R Gray 2, Frederick K Ho 3, Jill P Pell 3, Carlos Celis-Morales 4
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PMID: 32005425 DOI: 10.1016/j.maturitas.2020.01.004
Abstract
Introduction: The critical sociodemographic, lifestyle and diseases factors influencing sarcopenia, defined by the current European Working Group on Sarcopenia 2 (EWGSOP2) classification and cut-off points, have not yet been fully elucidated. This study aimed, therefore, to determine sociodemographic, anthropometric, lifestyle and health-related factors associated with sarcopenia using the new EWGSOP2 definition.

Study design: 396,283 participants (52.8 % women, age 38-73 years) were included in this cross-sectional study. The potential factors associated with sarcopenia were allocated to four categories: sociodemographic (sex, age, education, income and professional qualification), anthropometric (nutritional status, abdominal obesity, body fat and birth weight), lifestyle (physical activity, smoking, sleeping, sitting time, TV viewing, alcohol, and dietary intakes) and health status (self-reported prevalent diseases). P-values were corrected for multiple testing using the Bonferroni method.

Results: Age, women, lower education, higher deprivation, underweight, lower birth weight, and chronic diseases such as rheumatoid arthritis, chronic bronchitis and osteoporosis were associated with a higher likelihood of sarcopenia. Conversely, overweight, obesity, as well as a self-reported higher intake of energy, protein, vitamins (B12 and B9) and minerals (potassium, calcium and magnesium) were associated with lower odds of sarcopenia.

Conclusion: Women, people aged over 65 years, underweight people and those with rheumatoid arthritis were most likely to have sarcopenia. Considering the increase in the ageing population, sarcopenia is likely to become more prevalent. Identifying factors associated with sarcopenia could inform future strategies for early identification of individuals at high risk of sarcopenia and therefore the implementation of preventive strategies against the disease.

Keywords: EWGSOP2; Lifestyle; Risk factors; Sarcopenia.

Copyright © 2020 Elsevier B.V. All rights reserved.

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104
Circulation
. 2020 May 26;141(21):e823-e831. doi: 10.1161/CIRCULATIONAHA.120.047063. Epub 2020 Mar 31.
Guidance for Cardiac Electrophysiology During the COVID-19 Pandemic From the Heart Rhythm Society COVID-19 Task Force; Electrophysiology Section of the American College of Cardiology; And the Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, American Heart Association
Dhanunjaya R Lakkireddy # 1, Mina K Chung # 2, Rakesh Gopinathannair 1, Kristen K Patton 3, Ty J Gluckman 4, Mohit Turagam 5, Jim Cheung 6, Parin Patel 7, Juan Sotomonte 8, Rachel Lampert 9, Janet K Han 10, Bharath Rajagopalan 11, Lee Eckhardt 12, Jose Joglar 13, Kristin Sandau 14, Brian Olshansky 15, Elaine Wan 16, Peter A Noseworthy 17, Miguel Leal 12, Elizabeth Kaufman 18, Alejandra Gutierrez 19, Joseph E Marine 20, Paul J Wang 21, Andrea M Russo # 22
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PMID: 32228309 PMCID: PMC7243667 DOI: 10.1161/CIRCULATIONAHA.120.047063
Free PMC article
Abstract
Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators. We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations. In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.

Keywords: COVID-19; electrophysiology; health planning guidelines; pandemics; pathology; practice guideline; virus.

Cited by 3 articles19 references3 figures
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105
Review Knee Surg Sports Traumatol Arthrosc
. 2020 Jun;28(6):1699-1704. doi: 10.1007/s00167-020-06031-3. Epub 2020 Apr 27.
Returning to Orthopaedic Business as Usual After COVID-19: Strategies and Options
Francesca de Caro 1, Thomas Michael Hirschmann 2 3, Peter Verdonk 4 5
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PMID: 32342140 PMCID: PMC7185264 DOI: 10.1007/s00167-020-06031-3
Free PMC article
Abstract
Purpose: The aim of this manuscript is to review the available strategies in the international literature to efficiently and safely return to both normal orthopaedic surgical activities and to normal outpatient clinical activities in the aftermath of a large epidemic or pandemic. This information would be beneficial to adequately reorganize outpatient clinics and hospitals to provide the highest possible level of orthopaedic care to our patients in a safe and efficient manner.

Methods: A literature search was performed for relevant research articles. In addition, the World Health Organisation (WHO), the US Centers for Disease Control (CDC), American Association of Orthopaedic Surgeons (AAOS), the EU CDC and other government health agency websites were searched for any relevant information. In particular, interest was paid to strategies and advise on managing the orthopaedic patient flow during outpatient clinics as well as surgical procedures including the necessary safety measures, while still providing a high-quality patient experience. The obtained information is provided as a narrative review.

Results: There was not any specific literature concerning the organization of an outpatient clinic and surgical activities and the particular challenges in dealing with a high-volume practice, in the afterwave of a pandemic.

Conclusion: As the COVID-19 crisis has abruptly halted most of the orthopaedic activities both in the outpatient clinic and the operating room, a progressive start-up scenario needs to be planned. The exact timing largely depends on factors outside of our control. After restrictions will be lifted, clinical and surgical volume will progressively increase. This paper offers key points and possible strategies to provide the highest level of safety to both the orthopaedic patient and the orthopaedic team including administrative staff and nurses, during the start-up phase.

Level of evidence: Review, Level V.

Keywords: COVID; Coronavirus; Orthopaedic surgery; Outpatient clinic.

Conflict of interest statement
Authors declare no conflict of interest.

Cited by 2 articles13 references
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106
J Am Coll Surg
. 2020 Jun;230(6):1080-1091.e3. doi: 10.1016/j.jamcollsurg.2020.03.019. Epub 2020 Mar 30.
Maximizing the Calm Before the Storm: Tiered Surgical Response Plan for Novel Coronavirus (COVID-19)
Samuel Wade Ross 1, Cynthia W Lauer 2, William S Miles 2, John M Green 2, A Britton Christmas 2, Addison K May 2, Brent D Matthews 2
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PMID: 32240770 PMCID: PMC7128345 DOI: 10.1016/j.jamcollsurg.2020.03.019
Free PMC article
Abstract
The novel coronavirus (COVID-19) was first diagnosed in Wuhan, China in December 2019 and has now spread throughout the world, being verified by the World Health Organization as a pandemic on March 11. This had led to the calling of a national emergency on March 13 in the US. Many hospitals, healthcare networks, and specifically, departments of surgery, are asking the same questions about how to cope and plan for surge capacity, personnel attrition, novel infrastructure utilization, and resource exhaustion. Herein, we present a tiered plan for surgical department planning based on incident command levels. This includes acute care surgeon deployment (given their critical care training and vertically integrated position in the hospital), recommended infrastructure and transfer utilization, triage principles, and faculty, resident, and advanced care practitioner deployment.

Copyright © 2020 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Cited by 3 articles21 references1 figure
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107
Sci Total Environ
. 2020 Jul 10;725:138532. doi: 10.1016/j.scitotenv.2020.138532. Epub 2020 Apr 6.
Challenges and Solutions for Addressing Critical Shortage of Supply Chain for Personal and Protective Equipment (PPE) Arising From Coronavirus Disease (COVID19) Pandemic - Case Study From the Republic of Ireland
Neil J Rowan 1, John G Laffey 2
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PMID: 32304970 PMCID: PMC7195029 DOI: 10.1016/j.scitotenv.2020.138532
Free PMC article
Abstract
Coronavirus (COVID-19) is highly infectious agent that causes fatal respiratory illnesses, which is of great global public health concern. Currently, there is no effective vaccine for tackling this COVID19 pandemic where disease countermeasures rely upon preventing or slowing person-to-person transmission. Specifically, there is increasing efforts to prevent or reduce transmission to front-line healthcare workers (HCW). However, there is growing international concern regarding the shortage in supply chain of critical one-time-use personal and protective equipment (PPE). PPE are heat sensitive and are not, by their manufacturer's design, intended for reprocessing. Most conventional sterilization technologies used in hospitals, or in terminal medical device sterilization providers, cannot effectively reprocess PPE due to the nature and severity of sterilization modalities. Contingency planning for PPE stock shortage is important. Solutions in the Republic of Ireland include use of smart communication channels to improve supply chain, bespoke production of PPE to meets gaps, along with least preferred option, use of sterilization or high-level disinfection for PPE reprocessing. Reprocessing PPE must consider material composition, functionality post treatment, along with appropriate disinfection. Following original manufacturer of PPE and regulatory guidance is important. Technologies deployed in the US, and for deployment in the Republic of Ireland, are eco-friendly, namely vaporised hydrogen peroxide (VH2O2), such as for filtering facepiece respirators and UV irradiation and High-level liquid disinfection (Actichlor+) is also been pursed in Ireland. Safeguarding supply chain of PPE will sustain vital healthcare provision and will help reduce mortality.

Keywords: COVID19; Healthcare workers; PPE; Resource utilization; Sterilization; Sustainability.

Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Conflict of interest statement
Declaration of competing interest The authors declare that they have no competing or conflict of interests.

Cited by 3 articles30 references6 figures
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108
Review J Am Acad Orthop Surg
. 2020 Jun 1;28(11):e469-e476. doi: 10.5435/JAAOS-D-20-00380.
Departmental Experience and Lessons Learned With Accelerated Introduction of Telemedicine During the COVID-19 Crisis
Alexander E Loeb 1, Sandesh S Rao, James R Ficke, Carol D Morris, Lee H Riley 3rd, Adam S Levin
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PMID: 32301818 PMCID: PMC7195846 DOI: 10.5435/JAAOS-D-20-00380
Free PMC article
Abstract
Despite the use of digital technology in healthcare, telemedicine has not been readily adopted. During the COVID-19 pandemic, healthcare systems have begun crisis management planning. To appropriately allocate resources and prevent virus exposure while maintaining effective patient care, our orthopaedic surgery department rapidly introduced a robust telemedicine program during a 5-day period. Implementation requires attention to patient triage, technological resources, credentialing, education of providers and patients, scheduling, and regulatory considerations. This article provides practical instruction based on our experience for physicians who wish to implement telemedicine during the COVID-19 pandemic. Between telemedicine encounters and necessary in-person visits, providers may be able to achieve 50% of their typical clinic volume within 2 weeks. When handling the massive disruption to the routine patient care workflow, it is critical to understand the key factors associated with an accelerated introduction of telemedicine for the safe and effective continuation of orthopaedic care during this pandemic. LEVEL OF EVIDENCE:: V.

Conflict of interest statement
None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Loeb, Dr. Rao, Dr. Ficke, Dr. Morris, Dr. Riley, Dr. Levin.

Cited by 1 article21 references1 figure
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109
J Epidemiol Community Health
. 2019 Feb;73(2):142-147. doi: 10.1136/jech-2018-211231. Epub 2018 Oct 30.
Tuberculosis and Diabetes: Bidirectional Association in a UK Primary Care Data Set
Fiona Pearson 1, Peijue Huangfu 1, Richard McNally 2, Mark Pearce 2, Nigel Unwin 3, Julia A Critchley 1
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PMID: 30377249 DOI: 10.1136/jech-2018-211231
Abstract
Background: Many studies have found an increased risk of pulmonary tuberculosis (PTB) among those with diabetes mellitus (DM). However, evidence on whether the association is bidirectional remains sparse. This study investigates DM rates among those with and without prior tuberculosis (TB) disease as well as the reverse.

Methods: Data on a UK general practice population, between 2003 and 2009, were obtained from The Health Improvement Network database. A series of retrospective cohort studies were completed. Individuals were successively classified as 'exposed' or 'unexposed' to TB, PTB, extrapulmonary TB (EPTB) or DM. Multivariate negative binomial regression was used to calculate incidence rate ratios (IRR) among each exposure group for outcomes of interest (TB, PTB, EPTB or DM in turn) adjusting for plausible confounding variables (age, sex, region, Townsend quintile and smoking status). Potential confounding due to ethnicity was adjusted for using McNamee's external method.

Results: DM risk was substantially raised among individuals with a history of TB disease (IRR 5.65 (95% CI 5.19 to 6.16)), PTB (IRR 5.74 (95% CI 5.08 to 6.50)) and EPTB (IRR 4.66 (95% CI 3.94 to 5.51)) compared with those without; results were attenuated after external adjustment for ethnicity (IRR 2.33 (95% CI 2.14 to 2.53)). TB risk was raised modestly among individuals with DM (IRR 1.50 (95% CI 1.27 to 1.76)) and was attenuated slightly after adjustment for ethnicity (IRR 1.26 (95% CI 1.07 to 1.48)).

Conclusion: DM risk was raised among those with previous TB disease; this finding has implications for follow-up and screening of patients with TB, who may be at high risk of developing DM or related complications.

Keywords: co-morbidity; diabetes; epidemiology; public health; tuberculosis.

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Conflict of interest statement
Competing interests: None declared.

Cited by 2 articles
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110
Blood
. 2020 May 21;135(21):1912-1915. doi: 10.1182/blood.2020006288.
The BTK Inhibitor Ibrutinib May Protect Against Pulmonary Injury in COVID-19-infected Patients
Steven P Treon 1 2, Jorge J Castillo 1 2, Alan P Skarbnik 3, Jacob D Soumerai 2 4, Irene M Ghobrial 1 2, Maria Luisa Guerrera 1 2, Kirsten Meid 1, Guang Yang 1 2
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PMID: 32302379 DOI: 10.1182/blood.2020006288
Cited by 1 article
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111
Pediatr Gastroenterol Hepatol Nutr
. 2020 May;23(3):251-258. doi: 10.5223/pghn.2020.23.3.251. Epub 2020 May 8.
Lactobacillus rhamnosus GG Usage in the Prevention of Gastrointestinal and Respiratory Tract Infections in Children With Gastroesophageal Reflux Disease Treated With Proton Pump Inhibitors: A Randomized Double-Blinded Placebo-Controlled Trial
Piotr Dziechciarz 1, Katarzyna Krenke 2, Hania Szajewska 1, Andrea Horvath 1
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PMID: 32483546 PMCID: PMC7231745 DOI: 10.5223/pghn.2020.23.3.251
Free PMC article
Abstract
Purpose: Proton-pump inhibitors (PPIs) are frequently used to treat gastroesophageal reflux disease (GERD) in children, but recent evidence suggests a potential association between PPI treatment and some types of infections. The aim of this study was to assess the effectiveness of Lactobacillus rhamnosus GG (LGG) for the prevention of gastrointestinal and respiratory tract infections in children with GERD treated with PPI (omeprazol).

Methods: Children younger than 5 years with GERD were assigned by a computer-generated list to receive LGG (109 colony-forming units) or placebo, twice daily, concomitantly with PPI treatment for 4-6 weeks; they were followed up for 12 weeks after therapy. The primary outcome measures were the percentage of children with a minimum of one episode of respiratory tract infection and the percentage of children with a minimum of one episode of gastrointestinal infection during the study.

Results: Of 61 randomized children, 59 patients (LGG n=30; placebo n=29, mean age 11.3 months) were analyzed. There was no significant difference found between the LGG and placebo groups, either for the proportion of children with at least one respiratory tract infection (22/30 vs. 25/29, respectively; relative risk [RR] 0.85, 95% confidence interval [CI] 0.66-1.10) or for the proportion of children with at least one gastrointestinal infection (9/30 vs. 9/29, respectively; RR 0.97, 95% CI 0.45-2.09).

Conclusion: LGG was not effective in the prevention of infectious complications in children with GERD receiving PPI. Caution is needed in interpreting these results, as the study was terminated early due to slow subject recruitment.

Keywords: GERD; Gastroesophageal reflux disease; Infant; Lactobacillus rhamnosus.

Copyright © 2020 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.

Conflict of interest statement
Conflicts of Interest: The authors have no financial conflicts of interest.

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112
Public Health
. 2020 May;182:170-172. doi: 10.1016/j.puhe.2020.04.009. Epub 2020 Apr 18.
Rapid Point-Of-Care Testing for SARS-CoV-2 in a Community Screening Setting Shows Low Sensitivity
M Döhla 1, C Boesecke 2, B Schulte 3, C Diegmann 4, E Sib 4, E Richter 3, M Eschbach-Bludau 3, S Aldabbagh 3, B Marx 3, A-M Eis-Hübinger 3, R M Schmithausen 4, H Streeck 3
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PMID: 32334183 PMCID: PMC7165286 DOI: 10.1016/j.puhe.2020.04.009
Free PMC article
Abstract
Objective: With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)-based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting.

Study design: Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed.

Methods: The evaluated rapid test is an IgG/IgM-based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance.

Results: Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%).

Conclusion: Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.

Keywords: COVID-19; Coronavirus; Outbreak; Rapid test; SARS-CoV-2.

Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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113
N Engl J Med
. 2020 May 28;382(22):2075-2077. doi: 10.1056/NEJMp2005687. Epub 2020 Apr 2.
Flattening the Curve for Incarcerated Populations - Covid-19 in Jails and Prisons
Matthew J Akiyama 1, Anne C Spaulding 1, Josiah D Rich 1
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PMID: 32240582 DOI: 10.1056/NEJMp2005687
Cited by 2 articles
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114
Editorial Knee Surg Sports Traumatol Arthrosc
. 2020 Jun;28(6):1683-1689. doi: 10.1007/s00167-020-06023-3. Epub 2020 Apr 25.
Management of Orthopaedic and Traumatology Patients During the Coronavirus Disease (COVID-19) Pandemic in Northern Italy
Pietro Simone Randelli 1 2 3, Riccardo Compagnoni 4 5 6
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PMID: 32335697 PMCID: PMC7183254 DOI: 10.1007/s00167-020-06023-3
Free PMC article
Abstract
Purpose: This article aims to share northern Italy's experience in hospital re-organization and management of clinical pathways for traumatic and orthopaedic patients in the early stages of the COVID-19 pandemic.

Methods: Authors collected regional recommendations to re-organize the healthcare system during the initial weeks of the COVID-19 pandemic in March, 2020. The specific protocols implemented in an orthopaedic hospital, selected as a regional hub for minor trauma, are analyzed and described in this article.

Results: Two referral centres were identified as the hubs for minor trauma to reduce the risk of overload in general hospitals. These two centres have specific features: an emergency room, specialized orthopaedic surgeons for joint diseases and trauma surgeons on-call 24/7. Patients with trauma without the need for a multi-disciplinary approach or needing non-deferrable elective orthopaedic surgery were moved to these hospitals. Authors report the internal protocols of one of these centres. All elective surgery was stopped, outpatient clinics limited to emergencies and specific pathways, ward and operating theatre dedicated to COVID-19-positive patients were implemented. An oropharyngeal swab was performed in the emergency room for all patients needing to be admitted, and patients were moved to a specific ward with single rooms to wait for the results. Specific courses were organized to demonstrate the correct use of personal protection equipment (PPE).

Conclusion: The structure of the orthopaedic hubs, and the internal protocols proposed, could help to improve the quality of assistance for patients with musculoskeletal disorders and reduce the risk of overload in general hospitals during the COVID-19 pandemic.

Keywords: Coronavirus; Orthopaedic; Pathways; SARS-CoV-2; Traumatology; Triage.

Conflict of interest statement
The authors declare that they have no conflict of interest

5 references2 figures
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115
JCI Insight
. 2020 May 21;5(10):137662. doi: 10.1172/jci.insight.137662.
Characteristics and Diagnosis Rate of 5630 Subjects Receiving SARS-CoV-2 Nucleic Acid Tests From Wuhan, China
Na Shen, Yaowu Zhu, Xiong Wang, Jing Peng, Weiyong Liu, Feng Wang, Yanjun Lu, Liming Cheng, Ziyong Sun
PMID: 32352933 DOI: 10.1172/jci.insight.137662
Free article
Abstract
BACKGROUNDThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a novel viral pneumonia (COVID-19), which is rapidly spreading throughout the world. The positive result of nucleic acid test is a golden criterion to confirm SARS-CoV-2 infection, but the detection features remain unclear.METHODSWe performed a retrospective analysis in 5630 high-risk individuals receiving SARS-CoV-2 nucleic acid tests in Wuhan, China, and investigated their characteristics and diagnosis rates.RESULTSThe overall diagnosis rate was 34.7% (1952/5630). Male (P = 0.025) and older populations (P = 2.525 × 10-39) were at significantly higher risk of SARS-CoV-2 infection. People were generally susceptible, and most cases concentrated in people of 30-79 years. Furthermore, we investigated the association between diagnosis rate and the amount of testing in 501 subjects. Results revealed a 1.27-fold improvement (from 27.9% to 35.5%) of diagnosis rate from testing once to twice (P = 5.847 × 10-9) and a 1.43-fold improvement (from 27.9% to 39.9%) from testing once to 3 times (P = 7.797 × 10-14). More than 3 testing administrations was not helpful for further improvement. However, this improvement was not observed in subjects with pneumonia (P = 0.097).CONCLUSIONAll populations are susceptible to SARS-CoV-2 infection, and male and older-aged populations are at significantly higher risk. Increasing the amount of testing could significantly improve diagnosis rates, except for subjects with pneumonia. It is recommended to test twice in those high-risk individuals whose results are negative the first time, and performing 3 tests is better, if possible.FUNDINGThis work was supported by National Mega Project on Major Infectious Disease Prevention (no. 2017ZX10103005-007) and National Key Research and Development Program of China (no. 2018YFE0204500).

Keywords: COVID-19; Infectious disease; Molecular diagnosis.

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116
Review Viruses
. 2020 May 26;12(6):E582. doi: 10.3390/v12060582.
Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2
Nadin Younes 1, Duaa W Al-Sadeq 1 2, Hadeel Al-Jighefee 1, Salma Younes 3, Ola Al-Jamal 1, Hanin I Daas 4, Hadi M Yassine 1 3, Gheyath K Nasrallah 1 3
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PMID: 32466458 DOI: 10.3390/v12060582
Free article
Abstract
The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.

Keywords: COVID-19; SARS-CoV-2; diagnostic challenges; molecular testing; serology; viruses.

Conflict of interest statement
The authors declare no conflict of interest.

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117
Editorial Haemophilia
. 2020 May;26(3):371-372. doi: 10.1111/hae.14001. Epub 2020 Apr 20.
The COVID-19 Pandemic: New Global Challenges for the Haemophilia Community
Cedric Hermans 1, Alain Weill 2, Glenn F Pierce 2
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PMID: 32246879 DOI: 10.1111/hae.14001
Comment on
A Novel Coronavirus from Patients with Pneumonia in China, 2019.
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, Zhao X, Huang B, Shi W, Lu R, Niu P, Zhan F, Ma X, Wang D, Xu W, Wu G, Gao GF, Tan W; China Novel Coronavirus Investigating and Research Team.
N Engl J Med. 2020 Feb 20;382(8):727-733. doi: 10.1056/NEJMoa2001017. Epub 2020 Jan 24.
PMID: 31978945 Free PMC article.
11 references
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118
Review Knee Surg Sports Traumatol Arthrosc
. 2020 Jun;28(6):1690-1698. doi: 10.1007/s00167-020-06022-4. Epub 2020 Apr 27.
COVID-19 Coronavirus: Recommended Personal Protective Equipment for the Orthopaedic and Trauma Surgeon
Michael T Hirschmann 1 2, Alister Hart 3, Johann Henckel 3, Patrick Sadoghi 4, Romain Seil 5 6, Caroline Mouton 5
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PMID: 32342138 PMCID: PMC7184806 DOI: 10.1007/s00167-020-06022-4
Free PMC article
Abstract
Purpose: With the COVID-19 crisis, recommendations for personal protective equipment (PPE) are necessary for protection in orthopaedics and traumatology. The primary purpose of this study is to review and present current evidence and recommendations for personal protective equipment and safety recommendations for orthopaedic surgeons and trauma surgeons.

Methods: A systematic review of the available literature was performed using the keyword terms "COVID-19", "Coronavirus", "surgeon", "health-care workers", "protection", "masks", "gloves", "gowns", "helmets", and "aerosol" in several combinations. The following databases were assessed: Pubmed, Cochrane Reviews, Google Scholar. Due to the paucity of available data, it was decided to present it in a narrative manner. In addition, participating doctors were asked to provide their guidelines for PPE in their countries (Austria, Luxembourg, Switzerland, Germany, UK) for consideration in the presented practice recommendations.

Results: World Health Organization guidance for respiratory aerosol-generating procedures (AGPs) such as intubation in a COVID19 environment was clear and included the use of an FFP3 (filtering face piece level 3) mask and face protection. However, the recommendation for surgical AGPs, such as the use of high-speed power tools in the operating theatre, was not clear until the UK Public Health England (PHE) guidance of 27 March 2020. This guidance included FFP3 masks and face protection, which UK surgeons quickly adopted. The recommended PPE for orthopaedic surgeons, working in a COVID19 environment, should consist of level 4 surgical gowns, face shields or goggles, double gloves, FFP2-3 or N95-99 respirator masks. An alternative to the mask, face shield and goggles is a powered air-purifying respirator, particularly if the surgeons fail the mask fit test or are required to undertake a long procedure. However, there is a high cost and limited availabilty of these devices at present. Currently available surgical helmets and toga systems may not be the solution due to a permeable top for air intake. During the current COVID-19 crisis, it appeared that telemedicine can be considered as an electronic personal protective equipment by reducing the number of physical contacts and risk contamination.

Conclusion: Orthopaedic and trauma surgery using power tools, pulsatile lavage and electrocautery are surgical aerosol-generating procedures and all body fluids contain virus particles. Raising awareness of these issues will help avoid occupational transmission of COVID-19 to the surgical team by aerosolization of blood or other body fluids and hence adequate PPE should be available and used during orthopaedic surgery. In addition, efforts have to be made to improve the current evidence in this regard.

Level of evidence: IV.

Keywords: Aerosols; COVID-19; Corona; Helmet; Masks; Personal protective equipment; Protection; Respirator masks; Suits; Surgeon.

Conflict of interest statement
The authors declare that they have no competing interests.

Cited by 1 article34 references4 figures
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119
J Med Virol
. 2019 Aug;91(8):1394-1399. doi: 10.1002/jmv.25469. Epub 2019 Apr 9.
Influenza Surveillance During the 2009-2010, 2010-2011, 2011-2012, and 2012-2013 Seasons in Algeria
Fawzi Derrar 1, Nicolas Voirin 2, Nagham Khanafer 3 4, Kahéna Izri 1, El-Aalia Gradi 1, Assia Aitaissa 1, Baya Hadjal 1, Zahida Mehdi 5, Salima Bouzeghoub 5
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PMID: 30908683 DOI: 10.1002/jmv.25469
Abstract
We report the activity and circulation of influenza viruses in Algeria during four influenza seasons, from a national surveillance study carried out from 2009-2010 to 2012-2013. A total of 2766 samples from in- and outpatients, with no age restriction, were collected. The overall proportion of specimens that tested influenza positive was 46.0%. Overall, 96.6% of influenza A viruses were subtyped, and A/H1 subtypes accounted for 57.3% of influenza A viruses. Influenza A/H1 and A/H3 virus subtypes cocirculated in 2009-2010. In 2010-2011, a high proportion of type B viruses (66.2%) was observed. The subtype H3N2 was identified in 99% of cases typed in 2011-2012. Influenza A/H3N2 and B virus cocirculated in 2012-2013. A remarkably low influenza vaccination rate of 2.4% was observed among all age groups. Antibiotics were prescribed for 926 (41.3%) patients, and no difference was observed between patients with confirmed influenza and patients with influenza-like illness not related to influenza. The burden of influenza is largely undocumented in Algeria and strategies to expand this surveillance across the country are needed. Strategies to increase vaccination coverage are warranted to control and prevent influenza in individuals at risk of complications as well as in the general population.

Keywords: Algeria; epidemiology; influenza; surveillance; viruses.

© 2019 Wiley Periodicals, Inc.

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120
Int J Risk Saf Med
. 2020;31(2):47-51. doi: 10.3233/JRS-201017.
Coronavirus Drugs: Using Plasma From Recovered Patients as a Treatment for COVID-19
Foad Alzoughool 1, Lo'ai Alanagreh 1
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PMID: 32310190 DOI: 10.3233/JRS-201017
Abstract
The ongoing COVID-19 pandemic has infected nearly 3,582,233 individuals with 248,558 deaths since it was first identified in human populations in December 2019 in Wuhan, China. No antiviral therapies or vaccines are available for their treatment or prevention. Passive immunization PI through broadly neutralizing antibodies that bind to the specific antigens of SARS-CoV 2 might be a potential solution to address the immediate health threat of COVID-19 pandemic while vaccines are being developed. The PI approach in treating COVID-19 is discussed herein, including a summary of its historical applications to confront epidemics.

Keywords: COVID-19; convalescent plasma; coronaviruses; passive immunization.

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