Risk of SARS-CoV-2 infection and hospitalization in individuals with natural, vaccine-induced and hybrid immunity: a retrospective population-based cohort study from Estonia (preprint)

A large proportion of the worlds population has some form of immunity against SARS-CoV-2, through either infection (natural), vaccination or both (hybrid). This retrospective cohort study used data on SARS-CoV-2, vaccination, and hospitalization from national health system from February 2020 to June 2022 and Cox regression modelling to compare those with natural immunity to those with no (Cohort1, n=92917), hybrid (Cohort2, n=46813), and vaccine (Cohort3, n=252414) immunity. In Cohort 1, those with natural immunity were at lower risk for infection during the Delta (aHR 0.17, 95%CI 0.15-0.18) and higher risk (aHR 1.24, 95%CI 1.18-1.32) during the Omicron period than those with no immunity. Natural immunity conferred substantial protection against COVID-19-hospitalization. Cohort 2 - in comparison to natural immunity hybrid immunity offered strong protection during the Delta (aHR 0.61, 95%CI 0.46-0.80) but not the Omicron (aHR 1.05, 95%CI 0.93-1.1) period. COVID-19-hospitalization was extremely rare among individuals with hybrid immunity. In Cohort 3, individuals with vaccine-induced immunity were at higher risk than those with natural immunity for infection (Delta aHR 4.90, 95%CI 4.48-5.36; Omicron 1.13, 95%CI 1.06-1.21) and hospitalization (Delta aHR 7.19, 95%CI 4.02-12.84). These results show that risk of infection and severe COVID-19 are driven by personal immunity history and the variant of SARS-CoV-2 causing infection.

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

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 1:4) 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.

The 1st year of the COVID-19 epidemic in Estonia: an interrupted time series of population based nationwide cross-sectional studies. (preprint)

BackgroundDecisions about the continued need for control measures and the effect of introducing COVID-19 vaccinations rely on accurate and population-based data on SARS-CoV-2 positivity and risk factors for testing positive. MethodsIn this interrupted time series of population-based nationwide cross-sectional studies, data from nasopharyngeal testing and questionnaires were used to estimate the SARS-CoV-2 RNA prevalence and factors associated with test positivity over the 1st year of the COVID-19 epidemic. The study is registered with the ISRCTN Registry, ISRCTN10182320. ResultsBetween April 23, 2020 and February 2, 2021, results were available from 34,915 individuals and 27,870 samples from 11 consecutive studies. The percentage of people testing positive for SARS-CoV-2 decreased from 0.27% (95% CI 0.10% - 0.59%) in April to 0.04% (95% CI 0.00% - 0.22%) by the end of May and remained very low (0.01%, 95% CI 0.00% - 0.17%) until the end of August, followed by an increase since November (0.37%, 95% CI 0.18% - 0.68%) that escalated to 2.69% (95% CI 2.08% - 2.69%) in January 2021. In addition to substantial change in time, an increasing number of household members (for one additional OR 1.15, 95% CI 1.02-1.29), reporting current symptoms of COVID-19 (OR 2.21, 95% CI 1.59-3.09), and completing questionnaire in the Russian language (OR 1.85, 95% CI 1.15-2.99) were associated with increased odds for SARS-CoV-2 RNA positivity. ConclusionsSARS-CoV-2 population prevalence needs to be carefully monitored as vaccine programmes are rolled out in order to inform containment decisions. Strengths and limitations of this studyO_LIOur study relies upon nation-wide and population-based data on SARS-CoV-2 prevalence, and presents changes in prevalence over the whole 1st year of the Covid-19 epidemic. C_LIO_LIOur analysis of SARS-CoV-2 infection risk factors is not limited to notification or health care-based case data. C_LIO_LISelection bias may have been introduced as a result of low response rate. The direction of bias is unclear, but most likely operates rather uniformly over the period of observation, though this presents less of a threat to the SARS-CoV-2 prevalence trend analysis. C_LIO_LIOur data could be used to adequately project the future course of the SARS-CoV-2 epidemic and the effect of control measures. C_LI