Publications by authors named "Mark Loeb"

274 Publications

Joint testing of IgM and IgG has high value for ruling in SARS-CoV-2 infection.

Authors:
Mark Loeb

Ann Intern Med 2021 Apr 6. Epub 2021 Apr 6.

McMaster University, Hamilton, Ontario, Canada (M.L.).

Source Citation: Guo CC, Mi JQ, Nie H. Eur Rev Med Pharmacol Sci. 2020;24:10208-18. 33090430.
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http://dx.doi.org/10.7326/ACPJ202104200-047DOI Listing
April 2021

Aging and Interferons: Impacts on Inflammation and Viral Disease Outcomes.

Cells 2021 03 23;10(3). Epub 2021 Mar 23.

Department of Medicine, McMaster University, Hamilton, ON L8S 4L8, Canada.

As highlighted by the COVID-19 global pandemic, elderly individuals comprise the majority of cases of severe viral infection outcomes and death. A combined inability to control viral replication and exacerbated inflammatory immune activation in elderly patients causes irreparable immune-mediated tissue pathology in response to infection. Key to these responses are type I, II, and III interferons (IFNs), which are involved in inducing an antiviral response, as well as controlling and suppressing inflammation and immunopathology. IFNs support monocyte/macrophage-stimulated immune responses that clear infection and promote their immunosuppressive functions that prevent excess inflammation and immune-mediated pathology. The timing and magnitude of IFN responses to infection are critical towards their immunoregulatory functions and ability to prevent immunopathology. Aging is associated with multiple defects in the ability of macrophages and dendritic cells to produce IFNs in response to viral infection, leading to a dysregulation of inflammatory immune responses. Understanding the implications of aging on IFN-regulated inflammation will give critical insights on how to treat and prevent severe infection in vulnerable individuals. In this review, we describe the causes of impaired IFN production in aging, and the evidence to suggest that these impairments impact the regulation of the innate and adaptive immune response to infection, thereby causing disease pathology.
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http://dx.doi.org/10.3390/cells10030708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004738PMC
March 2021

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

Lancet Diabetes Endocrinol 2021 Mar 30. Epub 2021 Mar 30.

Barts and The London School of Medicine and Dentistry, and Asthma UK Centre for Applied Research, Queen Mary University of London, London, UK. Electronic address:

Background: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis.

Methods: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D, vitamin D, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633.

Findings: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I=35·6%, p=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I=53·5%, p=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I=31·2%, p=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I=38·1%, p=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I=46·0%, p=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I=0·0%, p=0·99). Risk of bias within individual studies was assessed as being low for all but three trials.

Interpretation: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation.

Funding: None.
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http://dx.doi.org/10.1016/S2213-8587(21)00051-6DOI Listing
March 2021

Recommendation mapping of the World Health Organization's guidelines on tuberculosis: A new approach to digitizing and presenting recommendations.

J Clin Epidemiol 2021 Mar 22. Epub 2021 Mar 22.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton (ON), Canada; World Health Organization Collaborating Center for Infectious Diseases, Research Methods and Recommendations, Michael G. DeGroote Cochrane Canada and GRADE Centres, McMaster University, Hamilton (ON), Canada; Department of Medicine, McMaster University, Hamilton (ON), Canada. Electronic address:

Objective: Having up-to-date health policy recommendations accessible in one location is in high demand by guideline users. We developed an easy to navigate interactive approach to organize recommendations and applied it to tuberculosis (TB) guidelines of the World Health Organization (WHO).

Study Design: We used a mixed-methods study design to develop a framework for recommendation mapping with seven key methodological considerations. We define a recommendation map as an online repository of recommendations from several guidelines on a condition, providing links to the underlying evidence and expert judgments that inform them, allowing users to filter and cross-tabulate the search results. We engaged guideline developers, users, and health software engineers in an iterative process to elaborate the WHO eTB recommendation map.

Results: Applying the seven-step framework, we included 228 recommendations, linked to 103 guideline questions and organized the recommendation map according to key components of the health question, including the original recommendations and rationale (https://who.tuberculosis.recmap.org/).

Conclusion: The recommendation mapping framework provides the entire continuum of evidence mapping by framing recommendations within a guideline questions' population, interventions, and comparators domains. Recommendation maps should allow guideline developers to organize their work meaningfully, standardize the automated publication of guidelines through links to the GRADEpro guideline development tool, and increase their accessibility and usability.
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http://dx.doi.org/10.1016/j.jclinepi.2021.02.009DOI Listing
March 2021

Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial.

JAMA Pediatr 2021 Mar 8. Epub 2021 Mar 8.

Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada.

Importance: Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required.

Objective: To determine whether 5 days of high-dose amoxicillin for CAP was associated with noninferior rates of clinical cure compared with 10 days of high-dose amoxicillin.

Design, Setting, And Participants: The SAFER (Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections) study was a 2-center, parallel-group, noninferiority randomized clinical trial consisting of a single-center pilot study from December 1, 2012, to March 31, 2014, and the follow-up main study from August 1, 2016, to December 31, 2019 at the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. Research staff, participants, and outcome assessors were blinded to treatment allocation. Eligible children were aged 6 months to 10 years and had fever within 48 hours, respiratory symptoms, chest radiography findings consistent with pneumonia as per the emergency department physician, and a primary diagnosis of pneumonia. Children were excluded if they required hospitalization, had comorbidities that would predispose them to severe disease and/or pneumonia of unusual origin, or had previous β-lactam antibiotic therapy. Data were analyzed from March 1 to July 8, 2020.

Interventions: Five days of high-dose amoxicillin therapy followed by 5 days of placebo (intervention group) vs 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin (control group).

Main Outcomes And Measures: Clinical cure at 14 to 21 days.

Results: Among the 281 participants, the median age was 2.6 (interquartile range, 1.6-4.9) years (160 boys [57.7%] of 279 with sex listed). Clinical cure was observed in 101 of 114 children (88.6%) in the intervention group and in 99 of 109 (90.8%) in the control group in per-protocol analysis (risk difference, -0.016; 97.5% confidence limit, -0.087). Clinical cure at 14 to 21 days was observed in 108 of 126 (85.7%) in the intervention group and in 106 of 126 (84.1%) in the control group in the intention-to-treat analysis (risk difference, 0.023; 97.5% confidence limit, -0.061).

Conclusions And Relevance: Short-course antibiotic therapy appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should consider recommending 5 days of amoxicillin for pediatric pneumonia management in accordance with antimicrobial stewardship principles.

Trial Registration: ClinicalTrials.gov Identifier: NCT02380352.
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http://dx.doi.org/10.1001/jamapediatrics.2020.6735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941245PMC
March 2021

Surviving Sepsis Campaign Guidelines on the Management of Adults With Coronavirus Disease 2019 (COVID-19) in the ICU: First Update.

Crit Care Med 2021 03;49(3):e219-e234

Adult Critical Care, St George's University Hospitals NHS Foundation Trust & St George's University of London, London, United Kingdom.

Background: The coronavirus disease 2019 pandemic continues to affect millions worldwide. Given the rapidly growing evidence base, we implemented a living guideline model to provide guidance on the management of patients with severe or critical coronavirus disease 2019 in the ICU.

Methods: The Surviving Sepsis Campaign Coronavirus Disease 2019 panel has expanded to include 43 experts from 14 countries; all panel members completed an electronic conflict-of-interest disclosure form. In this update, the panel addressed nine questions relevant to managing severe or critical coronavirus disease 2019 in the ICU. We used the World Health Organization's definition of severe and critical coronavirus disease 2019. The systematic reviews team searched the literature for relevant evidence, aiming to identify systematic reviews and clinical trials. When appropriate, we performed a random-effects meta-analysis to summarize treatment effects. We assessed the quality of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach, then used the evidence-to-decision framework to generate recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility.

Results: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued nine statements (three new and six updated) related to ICU patients with severe or critical coronavirus disease 2019. For severe or critical coronavirus disease 2019, the panel strongly recommends using systemic corticosteroids and venous thromboprophylaxis but strongly recommends against using hydroxychloroquine. In addition, the panel suggests using dexamethasone (compared with other corticosteroids) and suggests against using convalescent plasma and therapeutic anticoagulation outside clinical trials. The Surviving Sepsis Campaign Coronavirus Diease 2019 panel suggests using remdesivir in nonventilated patients with severe coronavirus disease 2019 and suggests against starting remdesivir in patients with critical coronavirus disease 2019 outside clinical trials. Because of insufficient evidence, the panel did not issue a recommendation on the use of awake prone positioning.

Conclusion: The Surviving Sepsis Campaign Coronavirus Diease 2019 panel issued several recommendations to guide healthcare professionals caring for adults with critical or severe coronavirus disease 2019 in the ICU. Based on a living guideline model the recommendations will be updated as new evidence becomes available.
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http://dx.doi.org/10.1097/CCM.0000000000004899DOI Listing
March 2021

The Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19: Molecular Diagnostic Testing.

Clin Infect Dis 2021 Jan 22. Epub 2021 Jan 22.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Background: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance.

Objective: The IDSA's goal was to develop an evidence-based diagnostic guideline to assist clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings and highlight important unmet research needs in the COVID-19 diagnostic testing space.

Methods: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations.

Results: The panel agreed on 17 diagnostic recommendations.

Conclusions: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered moderate to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform solid organ or hematopoietic stem cell transplantation timing. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.
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http://dx.doi.org/10.1093/cid/ciab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929045PMC
January 2021

Antibody and Cell-Mediated Immune Responses Are Correlates of Protection against Influenza Infection in Vaccinated Older Adults.

Vaccines (Basel) 2021 Jan 7;9(1). Epub 2021 Jan 7.

Health Sciences North Research Institute, Sudbury, ON P3E 5J1, Canada.

Despite efforts to design better vaccines for older adults, the risk for serious complications of influenza remains disproportionately high. Identifying correlates of vaccine effectiveness and understanding the heterogeneity of health outcomes in older adults are key to the vaccine development pipeline. We sought correlates of protection against laboratory-confirmed influenza illness (LCII) in a 4-year randomized trial of standard versus high-dose influenza vaccination of adults 65 years and older. To this end, we quantified serum hemagglutination-inhibition (HAI) titers and interferon-gamma (IFNγ) and interleukin-10 (IL-10) secretion by virus-challenged peripheral blood mononuclear cells. Of the 608 participants included, 26 developed either A/H3N2-( = 17) or B-LCII ( = 9) at 10-20 weeks post-vaccination. Antibody titres for A/H3N2 at 4-weeks post-vaccination were significantly associated with protection against LCII, where every 1-standard deviation increase reduced the odds of A/H3N2-LCII by 53%. Although B-titres did not correlate with protection against B-LCII, the fold-increase in IFNγ:IL-10 ratios from pre- to 4-weeks post-vaccination was significantly associated with protection against B-LCII, where every 1-standard deviation increase reduced the odds by 71%. Our results suggest that both antibody and cell-mediated immune measures are valuable and potentially complementary correlates of protection against LCII in vaccinated older adults, although this may depend on the viral type causing infection.
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http://dx.doi.org/10.3390/vaccines9010025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825602PMC
January 2021

In-Depth Analysis of Genetic Variation Associated with Severe West Nile Viral Disease.

Vaccines (Basel) 2020 Dec 8;8(4). Epub 2020 Dec 8.

Department of Internal Medicine, Yale School of Medicine, 300 Cedar Street, New Haven, CT 06520, USA.

West Nile virus (WNV) is a mosquito-borne virus which causes symptomatic disease in a minority of infected humans. To identify novel genetic variants associated with severe disease, we utilized data from an existing case-control study of WNV and included population controls for an expanded analysis. We conducted imputation and gene-gene interaction analysis in the largest and most comprehensive genetic study conducted to date for West Nile neuroinvasive disease (WNND). Within the imputed West Nile virus dataset (severe cases n = 381 and asymptomatic/mild controls = 441), we found novel loci within the MCF.2 Cell Line Derived Transforming Sequence Like () gene (rs9549655 and rs2297192) through the individual loci analyses, although none reached statistical significance. Incorporating population controls from the Wisconsin Longitudinal Study on Aging (n = 9012) did not identify additional novel variants, a possible reflection of the cohort's inclusion of individuals who could develop mild or severe WNV disease upon infection. Many of the top gene-gene interaction results were intergenic, with currently undefined biological roles, highlighting the need for further investigation into these regions and other identified gene targets in severe WNND. Further studies including larger sample sizes and more diverse populations reflective of those at risk are needed to fully understand the genetic architecture of severe WNDD and provide guidance on viable targets for therapeutic and vaccine development.
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http://dx.doi.org/10.3390/vaccines8040744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768385PMC
December 2020

Reliability of nonlocalizing signs and symptoms as indicators of the presence of infection in nursing-home residents.

Infect Control Hosp Epidemiol 2020 Dec 9:1-10. Epub 2020 Dec 9.

Division of Infectious Diseases, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.

Antibiotics are among the most common medications prescribed in nursing homes. The annual prevalence of antibiotic use in residents of nursing homes ranges from 47% to 79%, and more than half of antibiotic courses initiated in nursing-home settings are unnecessary or prescribed inappropriately (wrong drug, dose, or duration). Inappropriate antibiotic use is associated with a variety of negative consequences including Clostridioides difficile infection (CDI), adverse drug effects, drug-drug interactions, and antimicrobial resistance. In response to this problem, public health authorities have called for efforts to improve the quality of antibiotic prescribing in nursing homes.
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http://dx.doi.org/10.1017/ice.2020.1282DOI Listing
December 2020

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

medRxiv 2020 Nov 25. Epub 2020 Nov 25.

Institute for Population Health Sciences, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Background: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed.

Methods: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633).

Findings: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test).

Interpretation: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation.

Funding: None.
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http://dx.doi.org/10.1101/2020.07.14.20152728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709175PMC
November 2020

Efficacité et innocuité du plasma de convalescent en cas de forme grave de COVID-19, extrapolée de données relatives à d’autres formes graves d’infections respiratoires virales : revue systématique et méta-analyse.

CMAJ 2020 Nov;192(47):E1559-E1570

Instituts indiens de santé publique de Delhi (N. Devasenapathy), Fondation de santé publique de l'Inde, Gurgaon, Haryana, Inde; Département des méthodes, des données et de l'incidence de la recherche en santé (Z. Ye, M. Loeb, F. Fang, B. Tadayon Najafabadi, Y. Xiao, R. Couban, G. Guyatt), Université McMaster, Hamilton, Ont.; Université de médecine chinoise de Guangzhou (F. Fang), Guangzhou, Guangdong, Chine; École de soins infirmiers de Chine occidentale et Hôpital de Chine occidentale (Y. Xiao), Université du Sichuan, Chengdu, Sichuan, Chine; Département de médecine (p. Bégin), Université de Montréal, Montréal, Qué.

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http://dx.doi.org/10.1503/cmaj.200642-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721266PMC
November 2020

Traitement des patients atteints d’une forme modérée ou grave de maladie à coronavirus 2019: Ligne directrice fondée sur des données probantes.

CMAJ 2020 10;192(43):E1323-E1333

Départements de méthodes, données et impacts de la recherche en santé (Ye, Rochwerg, Guyatt, Colunga-Lozano) et de médecine (Rochwerg), Université McMaster, Hamilton, Ont.; Service de pharmacie (Wang), Hôpital Chaoyang de Beijing, Faculté de médecine de l'Université de Pékin, Beijing, Chine; Département de médecine, Division interdépartementale des soins intensifs (Adhikari, Fowler), Université de Toronto, Toronto, Ont.; Département de médecine de soins intensifs et Institut de recherche Sunnybrook (Adhikari, Fowler), Centre des sciences de la santé Sunnybrook, Toronto, Ont.; Département de pédiatrie (Murthy), Université de la Colombie-Britannique, Vancouver, C-B.; Département de médecine (Lamontagne), Université de Sherbrooke; Centre de recherche du CHU de Sherbrooke (Lamontagne), Sherbrooke, Qué; Département de médecine de soins intensifs (Qiu), Hôpital de Zhongda, Faculté de médecine, Université du Sud-Est, Nanjing, Chine; Service de pharmacie (Wei), Premier hôpital affilié au Centre hospitalier universitaire de Guangzhou; Service de médecine de soins intensifs (Sang), Premier hôpital affilié au Centre hospitalier universitaire de Guangzhou, Institut de pneumologie de Guangzhou, Guangzhou, Chine; Département de pathologie, de médecine moléculaire et de méthodes, données et impacts de la recherche en santé (Loeb), Université McMaster, Hamilton, Ont.; Service de pneumologie et de médecine de soins intensifs (Shen), Troisième hôpital universitaire de Pékin, Beijing, Chine; Guangdong Kuaiwen Technology Co. Ltd. (Huang), Guanzhong, Chine; Kunshan Guanghui Precise Metal Co. Ltd. (Jiang), Kunshan, Chine; Département de soins intensifs (Arabi), Centre hospitalier universitaire du Roi Saud bin Abdulaziz, Arabie saoudite; Département de médecine clinique (Colunga-Lozano), Centre des sciences de la santé, Université de Guadalajara, Guadalajara, Mexique; Département de médecine de soins intensifs (Jiang), Hôpital de Xuanwu, Faculté de médecine de l'Université de Pékin, Beijing, Chine; Département de pneumologie et de médecine de soins intensifs (Koh), Faculté de médecine de l'Université d'Ulsan, Séoul, Corée du Sud; Service de pharmacie (Liu), Hôpital de Tongji, Collège médical de Tongji, Université des sciences et de la technologie de Huazhong, Wuhan, Hubei, Chine; Service de pharmacie (Liu, Zhai), Troisième hôpital universitaire de Pékin, Beijing, Chine; Programmes de soins aigus et chroniques (Phua), Hôpital Alexandra, Centre hospitalier universitaire national, Singapour; Service de pharmacie, Premier hôpital affilié USTC, Division des sciences de la vie et de médecine, Université des sciences et de la technologie de Chine, Hefei (Shen), Anhui, Chine; Service de chirurgie générale (Huo), Troisième hôpital universitaire affilié à l'Université de Pékin, Beijing, Chine; Unité de soins intensifs médicaux (Du), Collège médical Union de Pékin, Beijing

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http://dx.doi.org/10.1503/cmaj.200648-fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577570PMC
October 2020

Consensus (CORE) versus Systematic (GRADE) Approach to Development of Guidelines for Community-Acquired Pneumonia.

Clin Infect Dis 2020 Oct 16. Epub 2020 Oct 16.

Professor of Medicine, McMaster University, Hamilton, Canada.

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http://dx.doi.org/10.1093/cid/ciaa1567DOI Listing
October 2020

Influenza Vaccination to Reduce Cardiovascular Morbidity and Mortality in Patients With COVID-19: JACC State-of-the-Art Review.

J Am Coll Cardiol 2020 10;76(15):1777-1794

Cardiovascular Division, Department of Medicine, Women's College Hospital, Toronto, Ontario, Canada; Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Ontario, Canada. Electronic address:

Viral respiratory infections are risk factors for cardiovascular disease (CVD). Underlying CVD is also associated with an increased risk of complications following viral respiratory infections, including increased morbidity, mortality, and health care utilization. Globally, these phenomena are observed with seasonal influenza and with the current coronavirus disease 2019 (COVID-19) pandemic. Persons with CVD represent an important target population for respiratory virus vaccines, with capacity developed within 3 large ongoing influenza vaccine cardiovascular outcomes trials to determine the potential cardioprotective effects of influenza vaccines. In the context of COVID-19, these international trial networks may be uniquely positioned to redeploy infrastructure to study therapies for primary and secondary prevention of COVID-19. Here, we describe mechanistic links between influenza and COVID-19 infection and the risk of acute cardiovascular events, summarize the data to date on the potential cardioprotective effects of influenza vaccines, and describe the ongoing influenza vaccine cardiovascular outcomes trials, highlighting important lessons learned that are applicable to COVID-19.
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http://dx.doi.org/10.1016/j.jacc.2020.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7535809PMC
October 2020

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19:Serologic Testing.

Clin Infect Dis 2020 Sep 12. Epub 2020 Sep 12.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Background: The availability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic testing has rapidly increased. Current assays use a variety of technologies, measure different classes of immunoglobulin or immunoglobulin combinations and detect antibodies directed against different portions of the virus. The overall accuracy of these tests, however, has not been well-defined. The Infectious Diseases Society of America (IDSA) convened an expert panel to perform a systematic review of the coronavirus disease 2019 (COVID-19) serology literature and construct best practice guidance related to SARS-CoV-2 serologic testing. This guideline is the fourth in a series of rapid, frequently updated COVID-19 guidelines developed by IDSA.

Objective: IDSA's goal was to develop evidence-based recommendations that assist clinicians, clinical laboratories, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 serologic tests in a variety of settings. We also highlight important unmet research needs pertaining to the use of anti-SARS-CoV-2 antibody tests for diagnosis, public health surveillance, vaccine development and the selection of convalescent plasma donors.

Methods: A multidisciplinary panel of infectious diseases clinicians, clinical microbiologists and experts in systematic literature review identified and prioritized clinical questions related to the use of SARS-CoV-2 serologic tests. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations.

Results: The panel agreed on eight diagnostic recommendations.

Conclusions: Information on the clinical performance and utility of SARS-CoV-2 serologic tests are rapidly emerging. Based on available evidence, detection of anti-SARS-CoV-2 antibodies may be useful for confirming the presence of current or past infection in selected situations. The panel identified three potential indications for serologic testing including: 1) evaluation of patients with a high clinical suspicion for COVID-19 when molecular diagnostic testing is negative and at least two weeks have passed since symptom onset; 2) assessment of multisystem inflammatory syndrome in children; and 3) for conducting serosurveillance studies. The certainty of available evidence supporting the use of serology for either diagnosis or epidemiology was, however, graded as very low to moderate.
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http://dx.doi.org/10.1093/cid/ciaa1343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543294PMC
September 2020

Methodological and reporting quality of non-inferiority randomized controlled trials comparing antibiotic therapies: a systematic review.

Clin Infect Dis 2020 Sep 9. Epub 2020 Sep 9.

Division of Infectious Diseases, Department of Medicine, McMaster University, Hamilton, ON, Canada.

Background: Antibiotic non-inferiority randomized controlled trials (RCTs) are used for approval of new antibiotics and making changes to antibiotic prescribing in clinical practice. We conducted a systematic review to assess the methodological and reporting quality of antibiotic non-inferiority RCTs.

Methods: We searched MEDLINE, Embase, the Cochrane Database of Systematic Reviews and the FDA drug database from inception until Nov 22, 2019 for non-inferiority RCTs comparing different systemic antibiotic therapies. Comparisons between antibiotic types, doses, administration routes or durations were included. Methodological and reporting quality indicators were based on the CONSORT reporting guidelines. Two independent reviewers extracted the data.

Results: The systematic review included 227 studies. Of these, 135 (59.5%) studies were supported by pharmaceutical industry. Only 83 (36.6%) studies provided a justification for the non-inferiority margin. Reporting of both intention-to-treat (ITT) and per-protocol (PP) analyses were done in 165 (72.7%) studies. The conclusion was misleading in 34 (15.0%) studies. The studies funded by pharmaceutical industry were less likely to be stopped early due to logistical reasons (3.0% vs. 19.1%, OR=0.13 95% CI 0.04-0.37) and to show inconclusive results (11.1% vs. 42.9%, OR=0.17 95% CI 0.08-0.33). The quality of studies decreased over time with respect to blinding, early stopping, reporting of ITT with PP analysis and having misleading conclusions.

Conclusions: There is room for improvement in the methodology and reporting of antibiotic non-inferiority trials. Quality can be improved across the entire spectrum from investigators, funding agencies, as well as during the peer-review process.
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http://dx.doi.org/10.1093/cid/ciaa1353DOI Listing
September 2020

Novel Antibiotics May Be Noninferior but Are They Becoming Less Effective?: a Systematic Review.

Antimicrob Agents Chemother 2020 10 20;64(11). Epub 2020 Oct 20.

Division of Infectious Diseases, McMaster University, Hamilton, Ontario, Canada.

Novel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Our systematic review of 175 noninferiority antibiotic trials found these scenarios to be rare.
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http://dx.doi.org/10.1128/AAC.01597-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577162PMC
October 2020

Clinical Course and Molecular Viral Shedding Among Asymptomatic and Symptomatic Patients With SARS-CoV-2 Infection in a Community Treatment Center in the Republic of Korea.

JAMA Intern Med 2020 Aug 6. Epub 2020 Aug 6.

Department of Internal Medicine, Soonchunhyang University Seoul Hospital, Soonchunhyang University College of Medicine, Seoul, Republic of Korea.

Importance: There is limited information about the clinical course and viral load in asymptomatic patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Objective: To quantitatively describe SARS-CoV-2 molecular viral shedding in asymptomatic and symptomatic patients.

Design, Setting, And Participants: A retrospective evaluation was conducted for a cohort of 303 symptomatic and asymptomatic patients with SARS-CoV-2 infection between March 6 and March 26, 2020. Participants were isolated in a community treatment center in Cheonan, Republic of Korea.

Main Outcomes And Measures: Epidemiologic, demographic, and laboratory data were collected and analyzed. Attending health care personnel carefully identified patients' symptoms during isolation. The decision to release an individual from isolation was based on the results of reverse transcription-polymerase chain reaction (RT-PCR) assay from upper respiratory tract specimens (nasopharynx and oropharynx swab) and lower respiratory tract specimens (sputum) for SARS-CoV-2. This testing was performed on days 8, 9, 15, and 16 of isolation. On days 10, 17, 18, and 19, RT-PCR assays from the upper or lower respiratory tract were performed at physician discretion. Cycle threshold (Ct) values in RT-PCR for SARS-CoV-2 detection were determined in both asymptomatic and symptomatic patients.

Results: Of the 303 patients with SARS-CoV-2 infection, the median (interquartile range) age was 25 (22-36) years, and 201 (66.3%) were women. Only 12 (3.9%) patients had comorbidities (10 had hypertension, 1 had cancer, and 1 had asthma). Among the 303 patients with SARS-CoV-2 infection, 193 (63.7%) were symptomatic at the time of isolation. Of the 110 (36.3%) asymptomatic patients, 21 (19.1%) developed symptoms during isolation. The median (interquartile range) interval of time from detection of SARS-CoV-2 to symptom onset in presymptomatic patients was 15 (13-20) days. The proportions of participants with a negative conversion at day 14 and day 21 from diagnosis were 33.7% and 75.2%, respectively, in asymptomatic patients and 29.6% and 69.9%, respectively, in symptomatic patients (including presymptomatic patients). The median (SE) time from diagnosis to the first negative conversion was 17 (1.07) days for asymptomatic patients and 19.5 (0.63) days for symptomatic (including presymptomatic) patients (P = .07). The Ct values for the envelope (env) gene from lower respiratory tract specimens showed that viral loads in asymptomatic patients from diagnosis to discharge tended to decrease more slowly in the time interaction trend than those in symptomatic (including presymptomatic) patients (β = -0.065 [SE, 0.023]; P = .005).

Conclusions And Relevance: In this cohort study of symptomatic and asymptomatic patients with SARS-CoV-2 infection who were isolated in a community treatment center in Cheonan, Republic of Korea, the Ct values in asymptomatic patients were similar to those in symptomatic patients. Isolation of asymptomatic patients may be necessary to control the spread of SARS-CoV-2.
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http://dx.doi.org/10.1001/jamainternmed.2020.3862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411944PMC
August 2020

Use of facemasks during the COVID-19 pandemic.

Lancet Respir Med 2020 10 3;8(10):954-955. Epub 2020 Aug 3.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON L8N 3Z5, Canada; Department of Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.

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http://dx.doi.org/10.1016/S2213-2600(20)30352-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398656PMC
October 2020

Review of high dose vancomycin in the treatment of infection.

Infect Dis (Lond) 2020 Nov - Dec;52(12):847-857. Epub 2020 Aug 3.

Department of Medicine, Division of Infectious Diseases, Memorial University, St John's, Canada.

Background: Guidelines recommend oral vancomycin as first-line therapy for infection. Guideline recommendations vary regarding dosing of vancomycin. Our aim was to summarize the current evidence on the efficacy and adverse effects of high dose oral and vancomycin retention enema (>500 mg/day) for the treatment of infection.

Methods: We searched clinical studies and major guidelines in the English language using MEDLINE, the Cochrane Library and Embase from 1985 until 15 April 2020.

Results: No evidence supports the use of high dose oral vancomycin in the treatment of severe infection. Weak evidence from observational studies supports the use of high dose oral vancomycin in addition to intravenous metronidazole and high dose vancomycin retention enema in fulminant infection. Vancomycin retention enema can be used in severe infection when oral administration is not possible, or in conditions when the oral formulation cannot reach the colon such as Hartman's pouch, ileostomies, or colon diversions.

Conclusions: The dosing schedules for oral vancomycin and vancomycin enemas are not clearly defined due to widely varying results in clinical studies. Large, comparative multicenter trials are urgently needed to define the role of high dose vancomycin in infection.
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http://dx.doi.org/10.1080/23744235.2020.1800080DOI Listing
August 2020

Drug treatments for covid-19: living systematic review and network meta-analysis.

BMJ 2020 07 30;370:m2980. Epub 2020 Jul 30.

Department of Medicine, University of Calgary, Calgary, AB, Canada

Objective: To compare the effects of treatments for coronavirus disease 2019 (covid-19).

Design: Living systematic review and network meta-analysis.

Data Sources: WHO covid-19 database, a comprehensive multilingual source of global covid-19 literature, up to 3 December 2020 and six additional Chinese databases up to 12 November 2020.

Study Selection: Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles.

Methods: After duplicate data abstraction, a bayesian random effects network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance.

Results: 85 trials enrolling 41 669 patients met inclusion criteria as of 21 October 2020; 50 (58.8%) trials and 25 081 (60.2%) patients are new from the previous iteration; 43 (50.6%) trials evaluating treatments with at least 100 patients or 20 events met the threshold for inclusion in the analyses. Compared with standard care, corticosteroids probably reduce death (risk difference 17 fewer per 1000 patients, 95% credible interval 34 fewer to 1 more, moderate certainty), mechanical ventilation (29 fewer per 1000 patients, 54 fewer to 1 more, moderate certainty), and days free from mechanical ventilation (2.6 fewer, 0.2 fewer to 5.0 fewer, moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, length of hospital stay, and duration of symptoms is uncertain, but it probably does not substantially increase adverse effects leading to drug discontinuation (0 more per 1000, 9 fewer to 40 more, moderate certainty). Azithromycin, hydroxychloroquine, lopinavir/ritonavir, interferon-beta, and tocilizumab may not reduce risk of death or have an effect on any other patient-important outcome. The certainty in effects for all other interventions was low or very low.

Conclusion: Corticosteroids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas azithromycin, hydroxychloroquine, interferon-beta, and tocilizumab may not reduce either. Whether or not remdesivir confers any patient-important benefit remains uncertain.

Systematic Review Registration: This review was not registered. The protocol is included as a supplement.

Readers' Note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is the second update of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the version number and date of access for clarity.
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http://dx.doi.org/10.1136/bmj.m2980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7390912PMC
July 2020

Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19.

Clin Infect Dis 2020 Jun 16. Epub 2020 Jun 16.

Division of Nephrology and Hypertension, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas.

Background: Accurate molecular diagnostic tests are necessary for confirming a diagnosis of coronavirus disease 2019 (COVID-19). Direct detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acids in respiratory tract specimens informs patient, healthcare institution and public health level decision-making. The numbers of available SARS-CoV-2 nucleic acid detection tests are rapidly increasing, as is the COVID-19 diagnostic literature. Thus, the Infectious Diseases Society of America (IDSA) recognized a significant need for frequently updated systematic reviews of the literature to inform evidence-based best practice guidance.

Objective: The IDSA's goal was to develop an evidence-based diagnostic guideline to assists clinicians, clinical laboratorians, patients and policymakers in decisions related to the optimal use of SARS-CoV-2 nucleic acid amplification tests. In addition, we provide a conceptual framework for understanding molecular diagnostic test performance, discuss the nuance of test result interpretation in a variety of practice settings, and highlight important unmet research needs in the COVID-19 diagnostic testing space.

Methods: IDSA convened a multidisciplinary panel of infectious diseases clinicians, clinical microbiologists, and experts in systematic literature review to identify and prioritize clinical questions and outcomes related to the use of SARS-CoV-2 molecular diagnostics. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the certainty of evidence and make testing recommendations.

Results: The panel agreed on 15 diagnostic recommendations.

Conclusions: Universal access to accurate SARS-CoV-2 nucleic acid testing is critical for patient care, hospital infection prevention and the public response to the COVID-19 pandemic. Information on the clinical performance of available tests is rapidly emerging, but the quality of evidence of the current literature is considered low to very low. Recognizing these limitations, the IDSA panel weighed available diagnostic evidence and recommends nucleic acid testing for all symptomatic individuals suspected of having COVID-19. In addition, testing is recommended for asymptomatic individuals with known or suspected contact with a COVID-19 case. Testing asymptomatic individuals without known exposure is suggested when the results will impact isolation/quarantine/personal protective equipment (PPE) usage decisions, dictate eligibility for surgery, or inform administration of immunosuppressive therapy. Ultimately, prioritization of testing will depend on institutional-specific resources and the needs of different patient populations.
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http://dx.doi.org/10.1093/cid/ciaa760DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337674PMC
June 2020

Frailty Is Associated With Increased Hemagglutination-Inhibition Titers in a 4-Year Randomized Trial Comparing Standard- and High-Dose Influenza Vaccination.

Open Forum Infect Dis 2020 May 24;7(5):ofaa148. Epub 2020 Apr 24.

Health Sciences North Research Institute, Sudbury, Ontario, Canada.

Background: Although high-dose (HD) vaccines have been reported to stimulate higher antibody responses compared with standard-dose (SD) influenza vaccines, there have been limited studies on the impact of frailty on such responses.

Methods: We conducted a randomized, double-blind trial (2014/2015 to 2017/2018) of SD versus HD trivalent split-virus vaccine (Fluzone) in 612 study participants aged 65+ over 4 influenza seasons. Hemagglutination inhibition antibody titers for influenza H1N1, H3N2, and B vaccine subtypes were measured at baseline and at 4, 10, and 20 weeks postvaccination and frailty was measured using a validated frailty index.

Results: Geometric mean antibody titers were significantly higher in HD compared with SD vaccine recipients for all influenza subtypes at all time points postvaccination. However, frailty was positively correlated with 4-week titers and was associated with increased odds of being a vaccine responder. For influenza A subtypes, this was mostly limited to HD recipients.

Conclusions: Frailty was associated with higher titers and increased antibody responses at 4 weeks after influenza vaccination, which was partially dependent on vaccine dosage. Chronic inflammation or dysregulated immunity, both of which are commonly observed with frailty, may be responsible, but it requires further investigation.
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http://dx.doi.org/10.1093/ofid/ofaa148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255647PMC
May 2020

Efficacy and safety of convalescent plasma for severe COVID-19 based on evidence in other severe respiratory viral infections: a systematic review and meta-analysis.

CMAJ 2020 07 22;192(27):E745-E755. Epub 2020 May 22.

Indian Institute of Public Health-Delhi (Devasenapathy), Public Health Foundation of India, Gurgaon, Haryana, India; Department of Health Research Methods, Evidence and Impact (Ye, Loeb, Fang, Tadayon Najafabadi, Xiao, Couban, Guyatt), McMaster University, Hamilton, Ont.; Guangzhou University of Chinese Medicine (Fang), Guangzhou, Guangdong, China; West China School of Nursing and West China Hospital (Xiao), Sichuan University, Chengdu, Sichuan, China; Department of Medicine (Bégin), Université de Montréal, Que.

Background: The safety and efficacy of convalescent plasma in severe coronavirus disease 2019 (COVID-19) remain uncertain. To support a guideline on COVID-19 management, we conducted a systematic review and meta-analysis of convalescent plasma in COVID-19 and other severe respiratory viral infections.

Methods: In March 2020, we searched international and Chinese biomedical literature databases, clinical trial registries and prepublication sources for randomized controlled trials (RCTs) and nonrandomized studies comparing patients receiving and not receiving convalescent plasma. We included patients with acute coronavirus, influenza and Ebola virus infections. We conducted a meta-analysis using random-effects models and assessed the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.

Results: Of 1099 unique records, 6 studies were eligible, and none of these included patients with COVID-19. One nonrandomized study ( = 40) on convalescent plasma in severe acute respiratory syndrome coronavirus (SARS-CoV) provided uninformative results regarding mortality (relative risk [RR] 0.10, 95% confidence interval [CI] CI 0.01 to 1.70). Pooled estimates from 4 RCTs on influenza ( = 572) showed no convincing effects on deaths (4 RCTs, RR 0.94, 95% CI 0.49 to 1.81), complete recovery (2 RCTs, odds ratio 1.04, 95% CI 0.69 to 1.64) or length of stay (3 RCTs, mean difference -1.62, 95% CI -3.82 to 0.58, d). The quality of evidence was very low for all efficacy outcomes. Convalescent plasma caused few or no serious adverse events in influenza RCTs (RR 0.85, 95% CI 0.56 to 1.29, low-quality evidence).

Interpretation: Studies of non-COVID-19 severe respiratory viral infections provide indirect, very low-quality evidence that raises the possibility that convalescent plasma has minimal or no benefit in the treatment of COVID-19 and low-quality evidence that it does not cause serious adverse events.
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http://dx.doi.org/10.1503/cmaj.200642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7828893PMC
July 2020

Ventilation Techniques and Risk for Transmission of Coronavirus Disease, Including COVID-19: A Living Systematic Review of Multiple Streams of Evidence.

Ann Intern Med 2020 08 22;173(3):204-216. Epub 2020 May 22.

American University of Beirut Medical Center, Beirut, Lebanon (J.K., A.E., F.C., L.H., R.E., S.Y., Z.S., I.B.A., E.A.A.).

Background: Mechanical ventilation is used to treat respiratory failure in coronavirus disease 2019 (COVID-19).

Purpose: To review multiple streams of evidence regarding the benefits and harms of ventilation techniques for coronavirus infections, including that causing COVID-19.

Data Sources: 21 standard, World Health Organization-specific and COVID-19-specific databases, without language restrictions, until 1 May 2020.

Study Selection: Studies of any design and language comparing different oxygenation approaches in patients with coronavirus infections, including severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS), or with hypoxemic respiratory failure. Animal, mechanistic, laboratory, and preclinical evidence was gathered regarding aerosol dispersion of coronavirus. Studies evaluating risk for virus transmission to health care workers from aerosol-generating procedures (AGPs) were included.

Data Extraction: Independent and duplicate screening, data abstraction, and risk-of-bias assessment (GRADE for certainty of evidence and AMSTAR 2 for included systematic reviews).

Data Synthesis: 123 studies were eligible (45 on COVID-19, 70 on SARS, 8 on MERS), but only 5 studies (1 on COVID-19, 3 on SARS, 1 on MERS) adjusted for important confounders. A study in hospitalized patients with COVID-19 reported slightly higher mortality with noninvasive ventilation (NIV) than with invasive mechanical ventilation (IMV), but 2 opposing studies, 1 in patients with MERS and 1 in patients with SARS, suggest a reduction in mortality with NIV (very-low-certainty evidence). Two studies in patients with SARS report a reduction in mortality with NIV compared with no mechanical ventilation (low-certainty evidence). Two systematic reviews suggest a large reduction in mortality with NIV compared with conventional oxygen therapy. Other included studies suggest increased odds of transmission from AGPs.

Limitation: Direct studies in COVID-19 are limited and poorly reported.

Conclusion: Indirect and low-certainty evidence suggests that use of NIV, similar to IMV, probably reduces mortality but may increase the risk for transmission of COVID-19 to health care workers.

Primary Funding Source: World Health Organization. (PROSPERO: CRD42020178187).
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http://dx.doi.org/10.7326/M20-2306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7281716PMC
August 2020

Safe management of bodies of deceased persons with suspected or confirmed COVID-19: a rapid systematic review.

BMJ Glob Health 2020 05;5(5)

Clinical Research Institute, American University of Beirut, Beirut, Lebanon

Introduction: Proper strategies to minimise the risk of infection in individuals handling the bodies of deceased persons infected with 2019 novel coronavirus (2019-nCoV) are urgently needed. The objective of this study was to systematically review the literature to scope and assess the effects of specific strategies for the management of the bodies.

Methods: We searched five general, three Chinese and four coronavirus disease (COVID-19)-specific electronic databases. We searched registries of clinical trials, websites of governmental and other relevant organisations, reference lists of the included papers and relevant systematic reviews, and Epistemonikos for relevant systematic reviews. We included guidance documents providing practical advice on the handling of bodies of deceased persons with suspected or confirmed COVID-19. Then, we sought primary evidence of any study design reporting on the efficacy and safety of the identified strategies in coronaviruses. We included evidence relevant to contextual factors (ie, acceptability). A single reviewer extracted data using a pilot-tested form and graded the certainty of the evidence using the GRADE approach. A second reviewer verified the data and assessments.

Results: We identified one study proposing an uncommon strategy for autopsies for patients with severe acute respiratory syndrome. The study provided very low-certainty evidence that it reduced the risk of transmission. We identified 23 guidance documents providing practical advice on the steps of handling the bodies: preparation, packing, and others and advice related to both the handling of the dead bodies and the use of personal protective equipment by individuals handling them. We did not identify COVID-19 evidence relevant to any of these steps.

Conclusion: While a substantive number of guidance documents propose specific strategies, we identified no study providing direct evidence for the effects of any of those strategies. While this review highlights major research gaps, it allows interested entities to build their own guidance.
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http://dx.doi.org/10.1136/bmjgh-2020-002650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7234869PMC
May 2020

Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline.

CMAJ 2020 05 29;192(20):E536-E545. Epub 2020 Apr 29.

Department of Health Research Methods, Evidence and Impact Canada (Ye, Rochwerg, Guyatt, Colunga-Lozano) and of Medicine (Rochwerg), McMaster University, Hamilton, Ont.; Department of Pharmacy (Wang), Beijing Chaoyang Hospital, Capital Medical University, Beijing, China; Department of Medicine, Interdepartmental Division of Critical Care Medicine (Adhikari, Fowler), University of Toronto, Toronto, Ont.; Department of Critical Care Medicine and Sunnybrook Research Institute (Adhikari, Fowler), Sunnybrook Health Sciences Centre, Toronto, Ont.; Department of Pediatrics (Murthy), University of British Columbia, Vancouver, BC; Department of Medicine (Lamontagne), Université de Sherbrooke; Centre de recherche du CHUS de Sherbrooke (Lamontagne), Sherbrooke, Que.; Department of Critical Care Medicine (Qiu), Zhongda hospital, School of Medicine, Southeast University, Nanjing, China; Department of Pharmacy (Wei), the First Affiliated Hospital of Guangzhou University of Medical; Department of Critical Care Medicine (Sang), the First Affiliated Hospital of Guangzhou Medical University, Guangzhou Institute of Respiratory Health, Guangzhou, China; Department of Pathology and Molecular Medicine and Health Research Methods, Evidence, and Impact (Loeb), McMaster University, Hamilton, Ont.; Department of Respiratory and Critical Care Medicine (Shen), Peking University Third Hospital, Beijing, China; Guangdong kuaiwen information technology co. LTD (Huang), Guanzhong, China; Kunshan Guanghui Precise Metal Co. Ltd. (Jiang), Kunshan, China; Intensive Care Department (Arabi), King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia; Department of Clinical Medicine (Colunga-Lozano), Health Science Center, Universidad de Guadalajara, Guadalajara, Mexico; Department of Critical Care Medicine (Jiang), Xuanwu Hospital, Capital Medical School, Beijing, China; Department of Pulmonary and Critical Care Medicine (Koh), University of Ulsan College of Medicine, Seoul, South Korea; Department of Pharmacy (Liu), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China; Department of Pharmacy (Liu, Zhai), Peking University Third Hospital, Beijing, China; Fast and Chronic Programmes (Phua), Alexandra Hospital, National University Health System, Singapore; Department of Pharmacy, the First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei (Shen), Anhui, China; General Surgery Department (Huo), Peking University Third Hospital, Beijing, China; Medical Intensive Care Unit (Du), Peking Union Medical College Hospital, Beijing.

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http://dx.doi.org/10.1503/cmaj.200648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241888PMC
May 2020

Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: A systematic review and meta-analysis of randomized trials.

Influenza Other Respir Viruses 2020 07 21;14(4):365-373. Epub 2020 Apr 21.

Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada.

Background: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID-19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID-19 are limited.

Purpose: To compare medical masks to N95 respirators in preventing laboratory-confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers.

Data Sources: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014.

Study Selection: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers.

Data Extraction: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence.

Data Synthesis: Four RCTs were meta-analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory-confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90-1.25; I  = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98-2.28; I  = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49).

Limitations: Indirectness and imprecision of available evidence.

Conclusions: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non-aerosol-generating care. Preservation of N95 respirators for high-risk, aerosol-generating procedures in this pandemic should be considered when in short supply.
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http://dx.doi.org/10.1111/irv.12745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298295PMC
July 2020

Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19).

Crit Care Med 2020 06;48(6):e440-e469

Adult Critical Care, St George's University Hospitals NHS Foundation Trust & St George's University of London, London, UK.

Background: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, Coronavirus Disease 2019 (COVID-19), affecting thousands of people around the world. Urgent guidance for clinicians caring for the sickest of these patients is needed.

Methods: We formed a panel of 36 experts from 12 countries. All panel members completed the World Health Organization conflict of interest disclosure form. The panel proposed 53 questions that are relevant to the management of COVID-19 in the ICU. We searched the literature for direct and indirect evidence on the management of COVID-19 in critically ill patients in the ICU. We identified relevant and recent systematic reviews on most questions relating to supportive care. We assessed the certainty in the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, then generated recommendations based on the balance between benefit and harm, resource and cost implications, equity, and feasibility. Recommendations were either strong or weak, or in the form of best practice recommendations.

Results: The Surviving Sepsis Campaign COVID-19 panel issued 54 statements, of which four are best practice statements, nine are strong recommendations, and 35 are weak recommendations. No recommendation was provided for six questions. The topics were: 1) infection control, 2) laboratory diagnosis and specimens, 3) hemodynamic support, 4) ventilatory support, and 5) COVID-19 therapy.

Conclusion: The Surviving Sepsis Campaign COVID-19 panel issued several recommendations to help support healthcare workers caring for critically ill ICU patients with COVID-19. When available, we will provide new evidence in further releases of these guidelines.
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http://dx.doi.org/10.1097/CCM.0000000000004363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7176264PMC
June 2020