Neuropsychiatric disorders as risk factors and consequences of COVID-19: A Mendelian randomization study

Background More than 170 million cases of COVID-19 have been reported worldwide. It has been proposed that psychiatric disorders may be risk factors and/or consequences of COVID-19 infection. However, observational studies could be affected by confounding bias. Methods We performed bi-directional two-sample Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of neuropsychiatric disorders or traits. We employed the latest GWAS summary statistics from the COVID-19 Host Genetics Initiative. A variety of MR methods including those accounting for horizontal pleiotropy were used. Results Overall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of post-traumatic stress disorder (PTSD), bipolar disorder (BD) (especially BD II), schizophrenia (SCZ), attention deficit hyperactivity disorder (ADHD) and suicidal thought (ST) when compared to the general population. On the other hand, liability to a few psychiatric traits/disorders, for example ADHD, alcohol and opioid use disorders may be causally associated with higher risks of COVID-19 infection or severe disease. In genetic correlation analysis, cannabis use disorder, ADHD, and anxiety showed significant and positive genetic correlation with critical or hospitalized infection. All the above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. For pneumonia, in general we observed a different pattern of associations, with bi-directional positive associations with depression- and anxiety-related phenotypes. Conclusions In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 (and severe infection) and a number of neuropsychiatric disorders. Further replications and prospective studies are required to verify the findings.

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Exploring causal relationships between COVID-19 and cardiometabolic disorders: A bi-directional Mendelian randomization study

10.1101/2021.03.20.21254008 ◽

2021 ◽

Author(s):

Yong XIANG ◽

Carlos Kwan-Long CHAU ◽

Jinghong QIU ◽

Shitao RAO ◽

Hon-Cheong So

Keyword(s):

Risk Factors ◽

Kidney Disease ◽

General Population ◽

Genetic Correlation ◽

Mendelian Randomization ◽

Severe Disease ◽

Severe Infection ◽

Large Artery ◽

Causal Relationships ◽

Cardiometabolic Disorders

Background: More than 100 million cases of COVID-19 have been reported worldwide. A number of risk factors for infection or severe infection have been identified, however observational studies were subject to confounding bias. In addition, there is still limited knowledge about the complications or medical consequences of the disease. Methods: Here we performed bi-directional Mendelian randomization (MR) analysis to evaluate causal relationships between liability to COVID-19 (and severe/critical infection) and a wide range of around 30 cardiometabolic disorders (CMD) or traits. Genetic correlation (rg) was assessed by LD score regression(LDSC). The latest GWAS summary statistics from the COVID-19 Host Genetics Initiative was used, which comprised comparisons of general population controls with critically ill, hospitalized and any infected cases. Results: Overall we observed evidence that liability to COVID-19 or severe infection may be causally associated with higher risks of type 2 diabetes mellitus(T2DM), chronic kidney disease(CKD), ischemic stroke (especially large artery stroke[LAS]) and heart failure(HF) when compared to the general population. On the other hand, our findings suggested that liability to atrial fibrillation (AF), stroke (especially LAS), obesity, diabetes (T1DM and T2DM), low insulin sensitivity and impaired renal function (low eGFR and diabetic kidney disease) may be causal risk factors for COVID-19 or severe disease. In genetic correlation analysis, T2DM, CAD, obesity, fasting insulin, CKD, gout, stroke and urate showed positive rg with critical or hospitalized infection. All above findings passed multiple testing correction at a false discovery rate (FDR)<0.05. Conclusions: In summary, this study provides evidence for tentative bi-directional causal associations between liability to COVID-19 and severe disease and a number of CM disorders. Further replications and prospective studies are required to verify the findings.

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Informing the public health response to COVID-19: a systematic review of risk factors for disease, severity, and mortality

BMC Infectious Diseases ◽

10.1186/s12879-021-05992-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

M. Flook ◽

C. Jackson ◽

E. Vasileiou ◽

C. R. Simpson ◽

M. D. Muckian ◽

...

Keyword(s):

Public Health ◽

Risk Factors ◽

Systematic Review ◽

At Risk ◽

Risk Factor ◽

Disease Severity ◽

Severe Disease ◽

Public Health Response ◽

Wide Range ◽

Multivariable Analyses

Abstract Background Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. Methods Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. Conclusions The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. Registration This review was registered on PROSPERO as CRD42020177714.

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Combating escalating harms associated with pharmaceutical opioid use in Australia: the POPPY II study protocol

BMJ Open ◽

10.1136/bmjopen-2018-025840 ◽

2018 ◽

Vol 8 (12) ◽

pp. e025840 ◽

Cited By ~ 5

Author(s):

Natasa Gisev ◽

Sallie-Anne Pearson ◽

Timothy Dobbins ◽

David C Currow ◽

Fiona Blyth ◽

...

Keyword(s):

Risk Factors ◽

Opioid Dependence ◽

Service Use ◽

Population Level ◽

Ethics Committee ◽

Adverse Outcomes ◽

Opioid Use ◽

Research Committee ◽

Services Research ◽

Wide Range

IntroductionOpioid prescribing has increased 15-fold in Australia in the past two decades, alongside increases in a range of opioid-related harms such as opioid dependence and overdose. However, despite concerns about increasing opioid use, extramedical use and harms, there is a lack of population-level evidence about the drivers of long-term prescribed opioid use, dependence, overdose and other harms.Methods and analysisWe will form a cohort of all adult residents in New South Wales (NSW), Australia, who initiated prescribed opioids from 2002 using Pharmaceutical Benefits Scheme dispensing records. This cohort will be linked to a wide range of other datasets containing information on sociodemographic and clinical characteristics, health service use and adverse outcomes (eg, opioid dependence and non-fatal and fatal overdose). Analyses will initially examine patterns and predictors of prescribed opioid use and then apply regression and survival analysis to quantify the risks and risk factors of adverse outcomes associated with prescribed opioid use.Ethics and disseminationThis study has received full ethical approval from the Australian Institute of Health and Welfare Ethics Committee, the NSW Population and Health Services Research Committee and the ACT Health Human Research Ethics Committee. This will be the largest postmarketing surveillance study of prescribed opioids undertaken in Australia, linking exposure and outcomes and examining risk factors for adverse outcomes of prescribed opioids. As such, this work has important translational promise, with direct relevance to regulatory authorities and agencies worldwide. Project findings will be disseminated at scientific conferences and in peer-reviewed journals. We will also conduct targeted dissemination with policy makers, professional bodies and peak bodies in the pain, medicine and addiction fields through stakeholder workshops and advisory groups. Results will be reported in accordance with the REporting of studies Conducted using Observational Routinely collected Data (RECORD) Statement.

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Neuropsychiatric Aspects of Congenital Heart Disease: A Review of Current Literatures

Biomedical Journal of Indonesia: Jurnal Biomedik Fakultas Kedokteran Universitas Sriwijaya ◽

10.32539/bji.v7i2.312 ◽

2021 ◽

Vol 7 (2) ◽

pp. 374-382

Author(s):

Herick Alvenus Willim ◽

Kartini Rita Sari ◽

Nurfadella ◽

Nurlia Desyanti

Keyword(s):

Risk Factors ◽

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart ◽

Neuropsychiatric Disorders ◽

Team Approach ◽

Structural Abnormality ◽

Post Traumatic Stress ◽

Post Traumatic ◽

Anxiety Depression

Congenital heart disease (CHD) is a structural abnormality in the heart or majorintrathoracic blood vessel that is present at birth. Advances in modern medicalscience and technology have contributed to an increase in life expectancy andpopulation of CHD patients. Survivors of CHD may not only experience complexmedical problems due to sequelae or complications of the underlying CHD but mayalso experience neuropsychiatric disorders. This review article aims to provide anunderstanding of the neuropsychiatric aspects of CHD, including clinicalmanifestations, risk factors and mechanisms, detection, and management ofneuropsychiatric disorders in CHD. This review showed that CHD patients areprone to behavioral disorders, neurodevelopmental disorders, and mental healthdisorders such as anxiety, depression, and post-traumatic stress disorder whichcan cause a decrease in quality of life. The risk factors and mechanisms ofneuropsychiatric disorders in CHD are complex and multifactorial. Early detectionand referral of neuropsychiatric disorders are important. Management requires amultidisciplinary team approach.

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Predictors for Severe COVID-19 Infection

Clinical Infectious Diseases ◽

10.1093/cid/ciaa674 ◽

2020 ◽

Vol 71 (8) ◽

pp. 1962-1968 ◽

Cited By ~ 26

Author(s):

Ashish Bhargava ◽

Elisa Akagi Fukushima ◽

Miriam Levine ◽

Wei Zhao ◽

Farah Tanveer ◽

...

Keyword(s):

Risk Factors ◽

Renal Disease ◽

Medical Center ◽

Severe Disease ◽

Academic Medical Center ◽

Severe Infection ◽

Supplemental Oxygen ◽

Multivariable Logistic Regression Analysis ◽

Cell Counts ◽

Novel Coronavirus

Abstract Background COVID-19 is a pandemic disease caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Predictors for severe COVID-19 infection have not been well defined. Determination of risk factors for severe infection would enable identifying patients who may benefit from aggressive supportive care and early intervention. Methods We conducted a retrospective observational study of 197 patients with confirmed COVID-19 admitted to a tertiary academic medical center. Results Of 197 hospitalized patients, the mean (SD) age of the cohort was 60.6 (16.2) years, 103 (52.3%) were male, and 156 (82.1%) were black. Severe COVID-19 infection was noted in 74 (37.6%) patients, requiring intubation. Patients aged above 60 were significantly more likely to have severe infection. Patients with severe infection were significantly more likely to have diabetes, renal disease, and chronic pulmonary disease and had significantly higher white blood cell counts, lower lymphocyte counts, and increased C-reactive protein (CRP) than patients with nonsevere infection. In multivariable logistic regression analysis, risk factors for severe infection included pre-existing renal disease (odds ratio [OR], 7.4; 95% CI, 2.5–22.0), oxygen requirement at hospitalization (OR, 2.9; 95% CI, 1.3–6.7), acute renal injury (OR, 2.7; 95% CI, 1.3–5.6), and CRP on admission (OR, 1.006; 95% CI, 1.001–1.01). Race, age, and socioeconomic status were not independent predictors. Conclusions Acute or pre-existing renal disease, supplemental oxygen upon hospitalization, and admission CRP were independent predictors for the development of severe COVID-19. Every 1-unit increase in CRP increased the risk of severe disease by 0.06%.

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Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study

PLoS Medicine ◽

10.1371/journal.pmed.1003410 ◽

2020 ◽

Vol 17 (12) ◽

pp. e1003410

Author(s):

Daniel B. Rosoff ◽

George Davey Smith ◽

Nehal Mehta ◽

Toni-Kim Clarke ◽

Falk W. Lohoff

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Alcohol Consumption ◽

Tobacco Use ◽

Mendelian Randomization ◽

European Ancestry ◽

Large Artery ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Wide Range

Background Alcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events. Methods and findings Using large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04–0.47, P value = 1.72 × 10−28), triglycerides (TRG) (beta −0.23, 95% CI, −0.30, −0.15, P value = 4.69 × 10−10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03–0.18, P value = 4.72 × 10−3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03–0.16, P value = 5.24 × 10−3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014–0.027, P value = 6.59 × 10−12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03–1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01–1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01–1.03, P value = 5.56 × 10−4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10−6), CHD (OR = 1.64, 95% CI, 1.28–2.09, P value = 8.07 × 10−5), heart failure (HF) (OR = 1.61, 95% CI, 1.32–1.95, P value = 1.9 × 10−6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41–4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10–2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14–2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38–4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations. Conclusions Evaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk.

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1156. Clinical and epidemiological features and outcomes of Blastomycosis in a tertiary hospital in Kentucky

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1342 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S604-S605

Author(s):

Evelyn Villacorta Cari ◽

Nicole Leedy ◽

Julie A Ribes ◽

Jaime Soria ◽

Thein Myint

Keyword(s):

Risk Factors ◽

Severe Disease ◽

Multivariable Analysis ◽

Severe Infection ◽

Tertiary Hospital ◽

Outpatient Setting ◽

University Of Kentucky ◽

Factors Associated ◽

Duration Of Illness ◽

Associated Risk Factors

Abstract Background Blastomycosis is an endemic dimorphic fungal infection caused by Blastomyces dermatitidis. The risk factors associated with severe presentation are not well defined. Methods Retrospective study of patients treated for blastomycosis at the University of Kentucky Hospital from 2004-2019. Statistical analyses were performed with STATA version 12.0 (College Station, Texas). Logistic regression was used to identify variables associated with severe infections. Results Among 82 patients, median age was 48 years old (range: 16 - 89); 66 (80.5%) were male and 71 (92.2%) were white, 25/77 (32.4%) were obese, 24 (29.2%) were diabetic, 21 (25.6%) had COPD, 26 (31.7%) had at least one immunosuppressive condition. The median duration of illness was 86 (3-365) days. 37 (45.1%) had cough and 35 (42.6%) had dyspnea 19 (23.1%) patients were treated in the ICU, 42 (51.3%) in non-ICU inpatient wards, and 21 (25.6%) in an outpatient setting. Cultures were obtained in 69 cases, 59 (85.5%) reported as positive, KOH stain positive in 30/61 (49.1%). Histopathology was positive in 48/66 (72.7%) samples. Urine Histoplasma or Blastomyces antigen was positive in 41/58 (70.6%), and Serum Histoplasma or Blastomyces antigen was positive in 22/34 (64.7%). Among 64 (78.0%) patients with pulmonary blastomycosis, acute and chronic pneumonia were 16 (25.0%) and 12 (18.7%) cases respectively, and nodular lung lesions were reported in 36 (56.2%). Initial antifungal treatment was amphotericin B liposomal in 38/80 (47.5%), overall mortality was 11 (13.4%). A multivariable analysis was performed to find predictors of severe blastomycosis infection, no association was seen with factors as male sex (IRR 1.96; 95%CI 0.84 – 4.55), and was confirmed that significant independent associated risk factors for severe infection were age older than 50 (IRR 3.5; 95%CI 1.42-8.83), obesity (IRR 3.1; 95% CI 1.41-6.87), diabetes (IRR 2.5; 95% CI 1.16-5.50), leukocytosis (IRR 1.03; 95%CI 1.00-1.07) and anemia (IRR 3.0; 95% CI 1.55-5.85). Conclusion Pulmonary Blastomycosis is the most common presentation. Culture and histopathology are more sensitive than antigen assay. Independent factors associated to severe disease were older age, obesity, diabetes, and anemia at admission. Disclosures All Authors: No reported disclosures

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Clinical Characteristics And Analysis Of Risk Factors For Disease Progression Of COVID-19 Among Patients Within Wad Medani Isolation Centers, Gezira State: A Prospective Cohort Study From Sudan

10.21203/rs.3.rs-967313/v1 ◽

2021 ◽

Author(s):

Mohammed Yousif Elnaeem Yousif ◽

Moh.Mah.Fadel Allah Eljack ◽

Osman Amir ◽

Mohammed Alfatih ◽

Akram Khalid Al Tigany Al Shiekh ◽

...

Keyword(s):

Risk Factors ◽

Cohort Study ◽

Mortality Rate ◽

Clinical Characteristics ◽

Severe Disease ◽

Severe Infection ◽

Chi Square ◽

Factors Associated ◽

Glucose Levels ◽

Chi Square Test

Abstract Background : (COVID-19) had a great impact on the world’s health systems since December 2019. A little is known about the clinical characteristics and risk factors associated with COVID-19 severity in Sudanese Patients; therefor it is necessary to summarize the clinical characteristics of patients with COVID-19 and to explore the risk factors associated with COVID-19 severity. Methods : A one-year retrospective cohort study (May 2020- May2021) was done at three isolation centers in Wad Medani. Sample contained all COVID-19 patients who are over 18 years old and were confirmed to be COVID-19 by nucleic acid testing or features Suggestive of Covid19 on Chest CT scan. Results : This study included 418 patients confirmed COVID-19 cases with a median age of 66.3±13years. 179 (64.2%) patients were men. Hypertension (n=195; 46.7%) and diabetes (n=187; 44.7%) were the most common comorbidities. The most common symptoms at COVID-19 onset were fever (n=303; 72.5%), cough (n=278; 66.5%) and dyspnea (n= 256; 61.2%). the overall mortality rate was 35.4% (n=148). The morality rate was 42.3% (n=118) among patients with severe disease. The Chi-square test and ANOVA analysis revealed that older age, anemia, neutrophilia and lymphcytopenia, higher glucose levels, HbA1c levels and creatinine levels were variables associated with severe COVID-19. In inflammatory markers, the levels of CRP and d-dimer were elevated in severe infection more than moderate and mild infections. Conclusion : Patients with these factors are more likely to deteriorate into severe infection and have higher mortality rate than those without these factors.

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Severe SARS-CoV-2 infection in humans is defined by a shift in the serum lipidome resulting in dysregulation of eicosanoid immune mediators

10.1101/2020.07.09.20149849 ◽

2020 ◽

Cited By ~ 3

Author(s):

Benjamin Schwarz ◽

Lokesh Sharma ◽

Lydia Roberts ◽

Xiaohua Peng ◽

Santos Bermejo ◽

...

Keyword(s):

Risk Factors ◽

Severe Disease ◽

Severe Infection ◽

Factors Associated ◽

Immune Mediators ◽

Mechanistic Insight ◽

Immune Balance ◽

Diabetes And Obesity ◽

Insight Into

The COVID-19 pandemic has affected more than 10 million people worldwide with mortality exceeding half a million patients. Risk factors associated with severe disease and mortality include advanced age,hypertension, diabetes, and obesity. Clear mechanistic understanding of how these comorbidities converge to enable severe infection is lacking. Notably each of these risk factors pathologically disrupts the lipidome and this disruption may be a unifying feature of severe COVID-19. Here we provide the first in depth interrogation of lipidomic changes, including structural-lipids as well as the eicosanoids and docosanoids lipid mediators (LMs), that mark COVID-19 disease severity. Our data reveal that progression from moderate to severe disease is marked by a loss of specific immune regulatory LMs and increased pro-inflammatory species. Given the important immune regulatory role of LMs, these data provide mechanistic insight into the immune balance in COVID-19 and potential targets for therapy with currently approved pharmaceuticals.

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Informing the public health response to COVID-19 (and lessons learnt for future pandemics): a systematic review of risk factors for disease, severity, and mortality.

10.21203/rs.3.rs-36375/v1 ◽

2020 ◽

Author(s):

Mary Flook ◽

Charlotte Jackson ◽

Eleftheria Vasileiou ◽

Colin R. Simpson ◽

Marisa D. Muckian ◽

...

Keyword(s):

Public Health ◽

Risk Factors ◽

Systematic Review ◽

At Risk ◽

Risk Factor ◽

Disease Severity ◽

Severe Disease ◽

Lessons Learnt ◽

Wide Range ◽

Multivariable Analyses

Abstract BackgroundSevere Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature, to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics. MethodsMedline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised. Results1,238 papers were identified post-deduplication. 33 met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity. ConclusionsThe volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected. This review was registered on PROSPERO as CRD42020177714.

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