Assessment of Natural Immunity after Infection with SARS-CoV-2: An Analysis of Repeat Infections Among All 4 Million PCR Tested Individuals in Denmark in 2020

Abstract

Background: The degree to which infection with SARS-CoV-2 confers immunity towards subsequent infection is not yet known. In 2020, as part of Denmark’s extensive, free-of-charge PCR-testing strategy, 4 million individuals (69% of the population) underwent 10.6 million tests. Using these national PCR-test data from 2020, we estimated the natural immunity towards SARS-CoV-2 after infection and investigated differences by age, sex and time since infection. Methods: Analysing the second surge of the epidemic (September–December, 2020) we compared infection rates between those with and without a previous positive test from the first surge (March–May). In an alternative time-to-event analysis, we compared infection rates throughout the year between those with and without a previous confirmed infection three or more months earlier. Rate ratios were adjusted for potential cofounders and natural immunity was estimated as one minus the rate ratio. Findings: Among PCR positive individuals from the first surge, 0·65% tested positive again during the second surge compared with 3·3% without a previous infection. The natural immunity was 80·5% (95% CI 75·4–84·5). The time-to-event analysis gave a similar estimate, as did the use of two and four months’ separation between repeat positive tests, and limiting the cohort to frequently tested health staff only. Among those aged 65+ years, observed immunity was 47% (95% CI 24·7–62·8). There was no difference in immunity by sex or evidence of waning immunity over time. Interpretation: Person-identifiable test results from large scale national PCR-testing in Denmark suggest that the within-season immunity following symptomatic or non-symptomatic infection is around 80%, although significantly lower in the elderly. These findings may inform decisions of which groups to vaccinate and advocate for vaccination of previously infected individuals as natural protection among elderly citizens cannot be relied upon. Funding: No designated funding was received for this study. DM was funded by the European Centers for Disease Control and Prevention programme EUPHEM. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The present study was based on existing administrative data and did not require ethical approval.