key: cord-0823534-5hhbdzam
authors: Langford, Bradley J.; So, Miranda; Raybardhan, Sumit; Leung, Valerie; Soucy, Jean-Paul R.; Westwood, Duncan; Daneman, Nick; MacFadden, Derek R.
title: Antibiotic prescribing in patients with COVID-19: rapid review and meta-analysis
date: 2021-01-05
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2020.12.018
sha: 800687b7e351570507bc528d243203e30fe06a6a
doc_id: 823534
cord_uid: 5hhbdzam

OBJECTIVE: The proportion of patients infected with SARS-CoV-2 that are prescribed antibiotics is uncertain, and may contribute to patient harm and global antibiotic resistance. Our objective was to estimate the prevalence and associated factors of antibiotic use in patients with confirmed COVID-19. METHODS: We searched MEDLINE, OVID Epub and EMBASE for published literature on human subjects in English up to June 9, 2020. Inclusion criteria were any healthcare settings and age groups; randomized controlled trials; cohort studies; case series with >10 patients; experimental or observational design that evaluated antibiotic prescribing. The main outcome of interest was proportion of COVID-19 patients prescribed an antibiotic, stratified by geographical region, severity of illness, and age. We pooled proportion data using random effects meta-analysis. RESULTS: We screened 7469 studies, from which 154 were included in the final analysis. Antibiotic data were available from 30,623 patients. The prevalence of antibiotic prescribing was 74.6% (95% CI 68.3 to 80.0%). On univariable meta-regression, antibiotic prescribing was lower in children (prescribing prevalence odds ratio (OR) 0.10, 95%CI 0.03 to 0.33) compared to adults. Antibiotic prescribing was higher with increasing patient age (OR 1.45 per 10 year increase, 95%CI 1.18 to 1.77) and higher with increasing proportion of patients requiring mechanical ventilation (OR 1.33 per 10% increase, 95%CI 1.15 to 1.54). Estimated bacterial co-infection was 8.6% (95% CI 4.7-15.2%) from 31 studies. CONCLUSIONS: Three-quarters of patients with COVID-19 receive antibiotics, prescribing is significantly higher than the estimated prevalence of bacterial co-infection. Unnecessary antibiotic use is likely high in patients with COVID-19. REGISTRATION: PROSPERO (ID CRD42020192286).

With millions of cases globally, the COVID-19 pandemic has had an immediate and devastating impact on the healthcare system and society as a whole. The long-term repercussions of COVID-19 on antimicrobial resistance have been raised as a grave concern due to elevated antibiotic use in patients infected with SARS-CoV-2 (1, 2) . Despite the viral nature of this syndrome, initial studies indicate that antibiotics are prescribed frequently to patients with COVID-19, largely due to suspected bacterial co-infections (3) (4) (5) .

Despite frequent antibiotic prescribing to patients with COVID-19, the prevalence of bacterial co-infection and secondary infection in patients hospitalized with COVID-19 is relatively low at 3.5% and 14.3%, respectively (5) . The gap between the prevalence of bacterial infection and frequency of antibiotic prescribing highlights the potential for significant antibiotic overuse in these patients. Over-prescribing of antibiotics in patients infected with SARS-CoV-2 can result in increased selective pressure for antimicrobial resistance. Antibiotic misuse, coupled with a strained healthcare workforce, and a reduced surveillance capacity for antibiotic-resistant organisms may lead to antimicrobial resistance as a lasting consequence of the COVID-19 pandemic (6, 7) .

Antibiotic stewardship interventions aimed at improving the appropriateness of antibiotic use are associated with reduced antibiotic utilization, and decreased incidence of drug-resistant infections (8) . Understanding patterns and predictors of antibiotic prescribing in COVID-19 can help to identify opportunities for interventions, and target antibiotic stewardship strategies to improve the quality and safety of antibiotic use. Our objective was to determine the prevalence of antibiotic use and identify the predictors of antibiotic use in patients with COVID-19.

We conducted a rapid review based on modified Cochrane Rapid Reviews Methods Group guidance (9) to determine the proportion of patients with COVID-19 that were prescribed an antibiotic during the course of their illness, herein referred to as prevalence of antibiotic use in patients with confirmed COVID-19 infection. We selected rapid review as the optimal J o u r n a l P r e -p r o o f 4 methodology to synthesize knowledge in a timely fashion for this emergent issue because we aimed to help clinicians apply the learnings to COVID-19 management strategies efficiently during the pandemic.

We included studies of humans with laboratory-confirmed SARS-CoV-2 infection, across all healthcare settings (i.e. hospital, community, long-term care) and age groups (pediatric and adult patients) as defined by study authors.

We included cohort studies, case series with 10 or more patients and randomized controlled trials (not evaluating antibiotic use as an intervention), but excluded reviews, editorials, letters and case studies. We considered studies to be eligible regardless of experimental or observational design, and irrespective of their primary objective. However, we excluded studies that did not report data on the number and percentage of patients receiving antibiotics.

This protocol was registered under PROSPERO, the international registry of systematic reviews (ID CRD42020192286).

We performed systematic searches of MEDLINE, OVID Epub, and EMBASE databases for published literature in the English language from January 1, 2019 to June 9, 2020 with assistance from a medical library information specialist. The limitation to English language articles was based on Cochrane Rapid Review Methods Group guidance (9) aimed at improving the timeliness while maintaining broad representation of the review. The search was structured to include COVID-19 terms and antibiotic, co-infection, bacterial infection, respiratory infection, epidemiology, or descriptive cohort study terms. The complete search strategy is described in the Online Supplement. The results of the search were imported into Covidence (Covidence, Melbourne, Australia), an online software tool for systematic reviews. Duplicate records were removed using Covidence.

J o u r n a l P r e -p r o o f 5 Initial screening of titles and abstracts from the search were shared by two authors (BL or VL), who independently identified studies that met all inclusion criteria and none of the exclusion criteria. For quality assurance, three other authors (MS, SR, or ND) then randomly selected 25% of the identified studies for duplicate screening. Disagreements that could not be resolved via consensus were reviewed independently by another author who had not participated in the screening. All full text studies meeting initial criteria were then reviewed by one of the authors (BL, MS, SR, or ND) for final inclusion in the rapid review. Studies potentially describing overlapping data were noted (e.g., same hospital and population during an overlapping time period).

One of five authors (BL, MS, SR, VL, or DM) independently extracted data from included studies using a standardized data collection form. For quality assurance, two authors (VL or DW) then randomly sampled 25% of data extraction forms to confirm accuracy and completeness. We collected data on the following variables for demographics and setting: author; country of study; start and end dates; name(s) of healthcare facility; study design (retrospective vs. prospective); healthcare setting (inpatient ICU vs. non ICU, outpatient); sample size; age group; patient population; mean or median age; and proportion of female patients. Regarding clinical characteristics, we collected information on COVID-19 severity; proportion of patients requiring mechanical ventilation; proportion of patients that were smokers; number of patients with comorbidities (chronic obstructive pulmonary disease, cardiovascular disease, or malignancy); and number of patients who were prescribed an antibiotic. We also collected information on the following parameters if reported: antibiotic classes prescribed; duration of therapy; timing of antibiotic initiation (on admission or empiric vs. after admission); antibiotic stewardship interventions; and prevalence of respiratory or bloodstream bacterial co-infections.

The main outcome of interest was the overall prevalence of antibiotic prescribing among patients with COVID-19. We evaluated the number of patients prescribed an antibiotic at any J o u r n a l P r e -p r o o f 6 point during the course of their illness while under study observation as a proportion of all patients with laboratory-proven COVID-19. First, we stratified by region to identify differences in prescribing practices based on geography. Second, we stratified prescribing by severity of COVID-19 illness based on the study's quartile of the proportion of mechanically ventilated patients and by study population: 1) critically ill patients (admitted to intensive care unit); 2) all hospitalized patients; and 3) mixed hospitalized/outpatient population. Third, we stratified by the month in which the study completed follow up to determine if antibiotic prescribing decreased as the pandemic progressed, as more information became available regarding the low rates of co-infection in patients with COVID-19. Fourth, we stratified by study age group to evaluate differences in antibiotic prescribing between pediatric and adult patients. We pooled proportion data across studies via a random-effects meta-analysis using a generalized linear mixed model (GLMM) with logit link approach (10, 11) . Results were illustrated using forest plots. Heterogeneity was assessed by I 2 statistic, with < 40% considered low heterogeneity, 30-60% considered moderate heterogeneity, and 50-90% considered substantial heterogeneity, and 75-100% considered considerable heterogeneity (12) . All analyses were carried out using R version 3.6.0 with the packages metafor and meta. The statistical code for this analysis is made available online (13) .

To predict the effect of specific patient characteristics on antibiotic prescribing, we performed univariable meta-regression evaluating patient demographic characteristics (age, sex, comorbidities), markers of severity (mechanical ventilation, healthcare setting), geography (grouped by China, Middle East, East/Southeast Asia, Europe, North America, multiple countries), Healthcare Access and Quality Index (a novel measure of health system quality for 195 countries based on age-standardized mortality for 32 conditions with largely avoidable cause of death (14) ), and end-month of study. Prevalence differences in antibiotic prescribing for each variable were described in terms of the prevalence odds ratio (OR).

J o u r n a l P r e -p r o o f 7 We considered a formal assessment for risk of bias to be of limited utility, given the lack of appropriate assessment tool (e.g., most appraisal questions are not applicable). Although a risk of bias tool has been developed for meta-analyses of disease prevalence (15) , there are no tools that are directly relevant to our research question addressing the prevalence of antibiotic prescribing. Therefore, our modified rapid review approach incorporated study quality into our sensitivity analysis by estimating the quality of antibiotic prescribing data based on whether the study reported detail on antibiotic classes. In additional sensitivity analyses, we removed studies focusing exclusively on populations where antibiotic prescribing may differ from the general population (i.e., transplant, malignancy, obstetrics, older age (i.e., 60 years or older), chronic obstructive pulmonary disease (COPD), diabetes, fatal COVID infection, HIV, surgery, dialysis and acute kidney injury), and we removed studies with potentially overlapping patient cohorts (studies occurring in the same patient population in the same hospital during the same time frame).

University of Toronto, Department of Medicine, Network Seed Funding Grant supported the role of a research coordinator (DW) to provide research project management. The University was not involved in study concept, analysis or synthesis of evidence, nor the decision to publish.

Of 16,378 studies identified, after duplicate removal, we reviewed a total of 7469 studies via title and abstract screening, 523 of which were assessed via full-text screening. We included 154 studies in the final analysis (Figure 1 ). Study design was primarily retrospective in nature (n=135), followed by prospective cohort (n=11), randomized controlled (n=6) and mixed prospective and retrospective design (n=1 

The prevalence of antibiotic use across regions had considerable heterogeneity with I 2 = 99%. In order of increasing prevalence of use, antibiotic prescribing in Europe was 63 

As an estimate of antibiotic prescribing data quality, studies reporting information on antibiotic classes prescribed showed numerically higher prevalence of prescribing ( 

In the meta-regression, geographic region was not identified as a predictor of antibiotic prescribing prevalence differences. In terms of study date, prescribing was noted to be lower in April 2020 (OR 0.28, 95%CI 0.08 to 0.98) compared to January 2020. Antibiotic prescribing was also lower in studies evaluating children (prescribing prevalence OR 0.10, 95%CI 0.03 to 0.33) and combined children and adults (OR 0.33, 95%CI 0.17 to 0.65) compared to studies examining only adults. Antibiotic prescribing was higher with increasing median or mean patient age (OR Figure 5 .

The number of patients with COVID-19 and concomitant bacterial infection was reported in 31 studies. Pooled data from all studies reporting bacterial infection indicated that the prevalence was 8.6% (95%CI 4.7 to 15.2%). There was a considerable degree of heterogeneity between studies I 2 =96%.

In this large rapid review and meta-analysis evaluating patients with COVID-19 in the first six months of the global pandemic, we found that nearly three-quarters of patients received antibiotic therapy. Prescribing was very heterogeneous but overall consistently high across healthcare setting and geography. Prescribing was elevated in older age groups and those with higher severity of illness, as marked by proportion of patients requiring mechanical ventilation and fatal infections. Consistent with our data, bacterial co-infection rates for SARS-CoV-2 have been estimated between 6.1% and 8.0% (4, 5, 172, 173) . As such, antibiotic prescribing is 

The authors have no conflicts of interest to declare. 

Concept and design: All authors.

Acquisition, analysis, or interpretation of data: All authors.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: All authors.

We thank Ashley Farrell, BA, MLIS, AHIP, Information Specialist for her support with formulating and executing the search strategy for this systematic review.

We thank the Toronto Antimicrobial Resistance Research Network (TARRN), an interprofessional forum of clinicians and researchers that acted as a venue for bringing together this research team, and a repository for our rapid review. 

COVID-19 and Antimicrobial Resistance: Parallel and Interacting Health Emergencies

The impact of the COVID-19 pandemic on antimicrobial resistance: a debate

Bacterial and fungal co-infection in individuals with coronavirus: A rapid review to support COVID-19 antimicrobial prescribing

Co-infections in people with COVID-19: a systematic review and meta-analysis

Bacterial coinfection and secondary infection in patients with COVID-19: a living rapid review and metaanalysis

COVID-19 and the potential long-term impact on antimicrobial resistance

COVID-19: don't neglect antimicrobial stewardship principles!

Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: a systematic review and meta-analysis

Cochrane Rapid Reviews Interim Guidance from the Cochrane Rapid Reviews Methods Group

Arcsine-based transformations for meta-analysis of proportions: Pros, cons, and alternatives

Meta-analysis of Proportions Using Generalized Linear Mixed Models

Cochrane Handbook for Systematic Reviews of Interventions

Antibiotic Prescribing in COVID-19 Statistical Code

Measuring performance on the Healthcare Access and Quality Index for 195 countries and territories and selected subnational locations: a systematic analysis from the Global Burden of Disease Study

Assessing risk of bias in prevalence studies: modification of an existing tool and evidence of interrater agreement

Clinical Course, Imaging Features, and Outcomes of COVID-19 in Kidney Transplant Recipients

A single center observational study of the clinical characteristics and short-term outcome of 20 kidney transplant patients admitted for SARS-CoV2 pneumonia

A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection

Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series

SARS-Cov-2 in Spanish Intensive Care: Early Experience with 15-day Survival In Vitoria

Clinical Features and Outcomes of 105 Hospitalized patients with COVID-19 in

Early administered antibiotics do not impact mortality in critically ill patients with COVID-19

A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features

COVID-19 in a Designated Infectious Diseases Hospital Outside Hubei Province

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19

Clinical Characteristics of Re-hospitalized Patients with COVID-19 in China

Clinical characteristics of 54 medical staff with COVID-19: A retrospective study in a single center in Wuhan

Clinical characteristics of coronavirus disease (COVID-19) early findings from a teaching hospital in Pavia

A multinational report to characterise SARS-CoV-2 infection in people with cystic fibrosis

(Bell) The Prince Charles Hospital

course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study

High-resolution Chest CT Features and Clinical Characteristics of Patients Infected with COVID-19 in Jiangsu, China

Arbidol combined with LPV/r versus LPV/r alone against Corona Virus Disease 2019: A retrospective cohort study

Clinical characteristics of fatal and recovered cases of coronavirus disease 2019 (COVID-19) in Wuhan, China: a retrospective study

Eleven Faces of Coronavirus Disease

Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan

Effectiveness of convalescent plasma therapy in severe COVID-19 patients

Early Short Course Corticosteroids in Hospitalized Patients with COVID-19

Clinical Features of COVID-19-Related Liver Functional Abnormality

COVID-19 with Different Severities: A Multicenter Study of Clinical Features

Characteristics and Outcomes of Coronavirus Disease Patients under Nonsurge Conditions

Clinical Outcomes and Serologic Response in Solid Organ Transplant Recipients with COVID-19: A Case Series from the United States

Clinical features and outcomes of HIV patients with coronavirus disease 2019

30-day mortality in patients hospitalized with COVID-19 during the first wave of the Italian epidemic: A prospective cohort study

The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China(An) Intensive Care Unit, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University

Clinical Characteristics of Coronavirus Disease 2019 in China

Clinical Characteristics of Elderly Patients with COVID-19 in Hunan Province, China: A Multicenter, Retrospective Study

The clinical course and its correlated immune status in COVID-19 pneumonia

COVID-19 in persons with haematological cancers

Covid-19 in solid organ transplant recipients: A single center experience

Clinical Features and Outcomes of 98 Patients Hospitalized with SARS-CoV-2 Infection in Daegu, South Korea: A Brief Descriptive Study

Clinical characteristics of Coronavirus Disease 2019 and development of a prediction model for prolonged hospital length of stay

Efficacy and Safety of Lianhuaqingwen Capsules, a repurposed Chinese Herb, in Patients with Coronavirus disease 2019: A multicenter, prospective, randomized controlled trial

Clinical characteristics of 16 patients with COVID-19 infection outside of Wuhan, China: A retrospective, single-center study

Clinical characteristics of laboratory confirmed positive cases of SARS-CoV-2 infection in Wuhan, China: A retrospective single center analysis

Clinical features of patients infected with 2019 novel coronavirus in Wuhan

Clinical characteristics and drug therapies in patients with the common-type coronavirus disease 2019 in Hunan, China

Clinical findings of patients with coronavirus disease 2019 in Jiangsu province, China: A retrospective, multi-center study

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

Factors Associated With Intubation and Prolonged Intubation in Hospitalized Patients With COVID-19. Otolaryngol -Head Neck Surg U S [Internet

Determining Host Factors Contributing to Disease Severity in a Family Cluster of 29 Hospitalized SARS-CoV-2 Patients: Could Genetic Factors Be Relevant in the Clinical Course of COVID-19?

Characteristics of disease progress in patients with coronavirus disease 2019 in Wuhan

Clinical characteristics of 60 discharged cases of 2019 novel coronavirus-infected pneumonia in Taizhou

Epidemiological, clinical and virological characteristics of 74 cases of coronavirus-infected disease 2019 (COVID-19) with gastrointestinal symptoms

Association of renin-angiotensin-aldosterone system inhibitors with COVID-19-related outcomes in Korea: a nationwide population-based cohort study

Outcomes of COVID-19 among Patients on In-Center Hemodialysis: An Experience from the Epicenter in South Korea

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship

Clinical and virologic characteristics of the first 12 patients with coronavirus disease 2019 (COVID-19) in the United States

Early experience of an infectious and tropical diseases unit during the coronavirus disease (COVID-19) pandemic

Clinical and Epidemiological Characteristics of 1,420 European Patients with mild-to-moderate Coronavirus Disease

Clinical characteristics and outcomes of patients undergoing surgeries during the incubation period of COVID-19 infection

A cross-sectional comparison of epidemiological and clinical features of patients with coronavirus disease (COVID-19) in Wuhan and outside Wuhan, China

Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19: A Randomized Clinical Trial

Deng) Department of Pharmacy, Key Laboratory for Molecular Diagnosis of Hubei Province, The central Hospital of Wuhan, Tongji Medical College

Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19

Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID-19

Association of clinical and radiographic findings with the outcomes of 93 patients with COVID-19 in Wuhan

Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study

Characteristics of respiratory virus infection during the outbreak of 2019 novel coronavirus in Beijing

Clinical and pathological investigation of severe COVID-19 patients

Risk factors for severity and mortality in adult COVID-19 inpatients in Wuhan

Epidemiological, clinical, and virological characteristics of 465 hospitalized cases of coronavirus disease 2019 (COVID-19) from Zhejiang province in China

Umifenovir treatment is not associated with improved outcomes in patients with coronavirus disease 2019: a retrospective study

Fatal Outcomes of COVID-19 in Patients with Severe Acute Kidney Injury

Pregnancy and Perinatal Outcomes of Women With Coronavirus Disease (COVID-19) Pneumonia: A Preliminary Analysis

Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression

Clinical and radiological changes of hospitalised patients with COVID-19 pneumonia from disease onset to acute exacerbation: a multicentre paired cohort study

Analysis of factors associated with disease outcomes in hospitalized patients with 2019 novel coronavirus disease

Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients

Epidemiological and Clinical Characteristics of Patients With Coronavirus Disease-2019 in Shiyan City

Evaluation of SARS-CoV-2 RNA shedding in clinical specimens and clinical characteristics of 10 patients with COVID-19 in Macau

Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in

COVID-19 in kidney transplant recipients

Clinical characteristics and short-term outcomes of coronavirus disease 2019: retrospective, singlecenter experience of designated hospital in Poland

COVID-19 pneumonia in patients with HIV -A Case Series

Clinical Characteristics of Hospitalized Individuals Dying with COVID-19 by Age Group in Italy

Clinical Characteristics of COVID-19 Patients With Digestive Symptoms in Hubei, China: A Descriptive, Cross-Sectional, Multicenter Study

Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes

Clinical course of Coronavirus Disease-2019 (COVID-19) in pregnancy

Clinical course of severe and critical COVID-19 in hospitalized pregnancies: a US cohort study

Clinical presentation and initial management critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brescia, Italy

Clinical Characteristics of Patients Hospitalized with Coronavirus Disease

Higher levels of IL-6 early after tocilizumab distinguish survivors from non-survivors in COVID-19 pneumonia: a possible indication for deeper targeting IL-6

Analysis of clinical features and outcomes of 161 patients with severe and critical COVID-19: A multicenter descriptive study

Clinical Characteristics and Risk Factors for Mortality of COVID-19 Patients With Diabetes in Wuhan, China: A Two-Center

Association of Cardiac Injury with Mortality in Hospitalized Patients with COVID-19 in Wuhan, China

Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing

Clinical features of pediatric patients with coronavirus disease (COVID-19)

SARS-CoV-2 infection in infants under 1 year of age in Wuhan City

Incidence of Adverse Drug Reactions in COVID-19 patients in China: an active monitoring study by Hospital Pharmacovigilance System

Clinical Features of Patients with Coronavirus Disease 2019 (COVID-19) from a Designated Hospital in Beijing

Associations between Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blocker Use, Gastrointestinal Symptoms, and Mortality among Patients with COVID-19

COVID-19 Medical Team, West Campus of Wuhan Union Hospital

Epidemiologic and clinical characteristics of 10 children with coronavirus disease 2019 in Changsha

Clinical characteristics and risk factors associated with COVID-19 disease severity in patients with cancer in Wuhan, China: a multicentre, retrospective, cohort study

Clinical Characteristics and Reasons for Differences in Duration From Symptom Onset to Release From Quarantine Among Patients With COVID-19 in Liaocheng

First experience of SARS-CoV-2 infections in solid organ transplant recipients in the Swiss Transplant Cohort Study

Enteric involvement in hospitalised patients with COVID-19 outside Wuhan

Establishing a model for predicting the outcome of COVID-19 based on combination of laboratory tests

Clinical characteristics of 80 hospitalized frontline medical workers infected with COVID-19 in Wuhan

Clinical course and outcome of 107 patients infected with the novel coronavirus, SARS-CoV-2, discharged from two hospitals in Wuhan

Clinical characteristics of invasive pulmonary aspergillosis in patients with COVID-19 in Zhejiang, China: a retrospective case series

Epidemiologic and Clinical Characteristics of 26 Cases of COVID-19 Arising from Patient-to-Patient Transmission in Liaocheng, China

Epidemiological and clinical features of 125 Hospitalized Patients with COVID-19 in

Clinical Course and Outcomes of 344 Intensive Care Patients with COVID-19

Clinical Features of 69 Cases with Coronavirus Disease

Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

A cluster of health care workers with COVID-19 pneumonia caused by SARS-CoV-2

Zhou) Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College

Clinical Features of Maintenance Hemodialysis Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China

Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease

Clinical characteristics of COVID-19 infection in chronic obstructive pulmonary disease: A multicenter, retrospective, observational study

Clinical and Immune Features of Hospitalized Pediatric Patients With Coronavirus Disease

Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19)

Clinical Characteristics of Imported Cases of COVID-19 in Jiangsu Province: A Multicenter Descriptive Study

Epidemiological and clinical characteristics of discharged patients infected with SARS-CoV-2 on the Qinghai plateau

Clinical Characteristics of and Medical Interventions for COVID-19 in Hemodialysis Patients in Wuhan

Clinical Characteristics and Outcomes of 421 Patients With COVID-19 Treated in a Mobile Cabin Hospital

Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: Retrospective case series

Coronavirus disease 2019 in pregnant women: a report based on 116 cases

Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study

Epidemiological and clinical features of 200 hospitalized patients with corona virus disease 2019 outside Wuhan, China: A descriptive study

Analysis of the clinical characteristics, drug treatments and prognoses of 136 patients with coronavirus disease 2019

Clinical features and outcomes of pregnant women suspected of coronavirus disease 2019

A retrospective study of risk factors for severe acute respiratory syndrome coronavirus 2 infections in hospitalized adult patients

Patients with COVID-19 in 19 ICUs in Wuhan, China: A cross-sectional study

He, Chen) Research Institute of Gynecology and Obstetrics, Key Laboratory for Major Obstetric Diseases of Guangdong Province

Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19)

Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China

Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. The Lancet

Deep Vein Thrombosis in Hospitalized Patients With COVID-19 in Wuhan, China: Prevalence, Risk Factors, and Outcome. Circulation

Clinical characteristics of 194 cases of COVID-19 in Huanggang and Taian

Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study

Comparison of clinical characteristics and outcomes of patients with coronavirus disease 2019 at different ages

Clinical characteristics of patients with 2019 coronavirus disease in a non-Wuhan area of Hubei Province, China: A retrospective study

Clinical characteristics and outcomes of COVID-19 patients with gastrointestinal symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan

Clinical Characteristics of Children with Coronavirus Disease

Clinical characteristics of 34 COVID-19 patients admitted to intensive care unit in Hangzhou

Epidemiological and clinical characteristics analysis of COVID-19 in the surrounding areas of Wuhan, Hubei Province in 2020

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet

Clinical and Autoimmune Characteristics of Severe and Critical Cases of COVID-19

Clinical characteristics of a case series of children with coronavirus disease 2019

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

2020;((Cao) Zhejiang Provincial Key Laboratory for Diagnosis and Treatment of Aging and Physic-chemical Injury Diseases

Bacterial and fungal coinfection among hospitalized patients with COVID-19: a retrospective cohort study in a UK secondary-care setting

Toronto Antimicrobial Resistance Research Network. Bacterial Co-Infection and Secondary Infection in Patients with COVID-19: A Rapid Systematic Review and Meta-Analysis

The frequency of influenza and bacterial coinfection: a systematic review and meta-analysis. Influenza Other Respir Viruses

Antibiotic Utilization and Opportunities for Stewardship Among Hospitalized Patients With Influenza Respiratory Tract Infection

COVID-19 will not result in increased antimicrobial resistance prevalence

PRO: The COVID-19 pandemic will result in increased antimicrobial resistance rates

Stockholm: European Centre for Disease Prevention and Control

Multidrug-Resistant Bacterial Infections in U.S. Hospitalized Patients

World Health Organization. Clinical Management of COVID-19 Interim Guidance

World Health Organization

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

COVID-19 rapid guideline: antibiotics for pneumonia in adults in hospital