Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study

Abstract

Background The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10•6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. Methods In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1-RR. Findings During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2•20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2•11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0•65% [95% CI 0•51-0•82]) tested positive again during the second surge compared with 16 819 (3•27% [3•22-3•32]) of 514 271 who tested negative during the first surge (adjusted RR 0•195 [95% CI 0•155-0•246]). Protection against repeat infection was 80•5% (95% CI 75•4-84•5). The alternative cohort analysis gave similar estimates (adjusted RR 0•212 [0•179-0•251], estimated protection 78•8% [74•9-82•1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47•1% (95% CI 24•7-62•8). We found no difference in estimated protection against repeat infection by sex (male 78•4% [72•1-83•2] vs female 79•1% [73•9-83•3]) or evidence of waning protection over time (3-6 months of follow-up 79•3% [74•4-83•3] vs ≥7 months of follow-up 77•7% [70•9-82•9]). Interpretation Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.

The risk of symptomatic reinfection during the second COVID-19 wave in individuals previously exposed to SARS-CoV-2

“…The conducted analysis confirms the hypothesis that the likelihood of experiencing SARS-CoV-2 symptomatic infection is greatly reduced in individuals already infected in the previous 8-10 months 11 . In line with what observed elsewhere [7][8][9]13,14 , our findings suggest that the relative risk of symptomatic infection for individuals who previously tested positive to IgG antibodies compared to seronegative subjects is less than 6%.…”

“…Recent estimates suggest 80-85% protection from reinfection 8,9 and 99% against symptomatic disease 10 up to six months from the first infection. However, follow-up studies comparing infections in recovered individuals with well-matched naive individuals are still lacking 2 .…”

SARS-CoV-2 reinfection caused by the P.1 lineage in Araraquara city, Sao Paulo State, Brazil

“…The absence of pre-existent immunity against SARS-CoV-2 could be one of the factors associated with its rapid global spread. Previous studies suggest that immunoglobulin G (IgG) antibodies against SARS-CoV-2 generated post-infection are associated with around 80% protection from reinfection for at least six months 2 – 4 . Since the beginning of the pandemic, concerns on the possibility of reinfection have been raised.…”

Immunity after SARS-CoV-2 infections

“…While the T cell response was assessed in this study six months after the infection, it is unclear whether any participants had been reinfected during that time. This is unlikely, given the low rate of reinfections within six months of a primary SARS-CoV-2 infection, but this could have influenced measurements in some participants 8 . In addition, although the authors assessed the T cell response in relation to the earlier antibody response, it will be important for future studies to assess whether the early CD4 + T cell response predicts the quality and/or durability of the antibody response over time.…”