Clinical Characteristics and Risk Factors for COVID-19 Infection and Disease Severity: A Nationwide Observational Study in Estonia (preprint)

ABSTRACT

Background: COVID-19 pandemic has required overloading of health systems all over the world. For reliable risk stratification, knowledge on factors predisposing to SARS-CoV-2 infection and to severe COVID-19 disease course is needed for decision-making at the individual, provider, and government levels. Data to identify these factors should be easily obtainable.Methods: Retrospective cohort study of nationwide e-health databases in Estonia. We used longitudinal health records from 66,295 people tested positive for SARS-CoV-2 RNA from 26 February 2020 to 28 February 2021 and 254,958 randomly selected controls from the reference population with no known history of SARS-CoV-2 infection or clinical COVID-19 diagnosis (case to control ratio 14) to predict risk factors of infection and severe course of COVID-19. We analysed sociodemographic and health characteristics of study participants.Findings: The SARS-CoV-2 infection risk was slightly higher among women, and was higher among those with comorbid conditions or obesity. Dementia (RRR 3.77, 95%CI 3.30⎼4.31), renal disease (RRR 1.88, 95%CI 1.56⎼2.26), and cerebrovascular disease (RRR 1.81, 95%CI 1.64⎼2.00) increased the risk of infection. Of all SARS-CoV-2 infected people, 92% had a non-severe disease course, 4.8% severe disease (requiring hospitalisation), 1.7% critical disease (needing intensive care), and 1.5% died. Male sex, increasing age and comorbid burden contributed significantly to more severe COVID-19, and the strength of association for male sex increased with the increasing severity of COVID-19 outcome. The strongest contributors to critical illness (expressed as RRR with 95% CI) were renal disease (7.71, 4.71⎼12.62), the history of previous myocardial infarction (3.54, 2.49⎼5.02) and obesity (3.56, 2.82⎼4.49). The strongest contributors to a lethal outcome were renal disease (6.48, 3.74⎼11.23), cancer (3.81, 3.06⎼4.75), liver disease (3.51, 1.36⎼9.02) and cerebrovascular disease (3.00, 2.31⎼3.89).Interpretation: We found divergent effect of age and gender on infection risk and severity of COVID-19 ⎼ age and gender did not contribute substantially to infection risk, but did so for the risk of severe disease. Co-morbid health conditions, especially those affecting renin-angiotensin system, had impact on both, the risk of infection and severe disease course. Age and male sex had the most significant impact on the risk of severe COVID-19.Funding Information Research was carried out with the support of Estonian Research Council, European Regional Development Fund and European Social Fund via IT Academy programme.Declaration of Interests The authors declared no potential conflicts of interest.Ethics Approval Statement The study was approved by the Research Ethics Committee of the University of Tartu.