Assessment of protection against reinfection with SARS-CoV-2 among 4 million people tested for PCR in Denmark in 2020.
Background
The extent to which SARS-CoV-2 infection confers protection against subsequent reinfection is not well described.
In 2020, as part of Denmark's comprehensive free and extensive PCR testing strategy, approximately 4 million people (69% of the population) underwent 106 million tests. Using these national 2020 PCR testing data, we estimated protection against 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 analyzed infection rates during the second surge of the COVID-19 epidemic, from September 1 to December 31, 2020, by comparing infection rates among persons with positive and negative PCR tests during the first surge (March to May 2020).
For the main analysis, we excluded persons 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, regardless of date.
We also investigated whether differences by age group, sex, and time since infection were found in the alternative cohort analysis. We calculated rate ratios (RR) adjusted for potential confounders and estimated protection against repeat infection as 1 - RR.
Results
During the first surge (i.e., before June 2020), 533,381 individuals were tested, of whom 11,727 (22%) tested positive for PCR and 525,339 were eligible for follow-up in the second surge, of whom 11,068 (211%) had tested positive during the first surge.
Among eligible PCR-positive individuals from the first surge, 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 provided 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 older than 65 years, the 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 (men 78.4% [72.1-83.2] vs. women 79.1% [73.9-83.3]) or evidence of declining protection over time (3-6 months follow-up 79 - 3% [74 - 4-83 - 3] vs. ≥7 months follow-up 77 - 7% [70 - 9-82 - 9]).
Covid reinfection is "rare" but more common in those over 65 years of age.
Interpretation
Some 80%, of the population has protection for 7 months, but in those over >65 years of age this is reduced to 47%.
Our findings could inform decisions about which groups should be vaccinated >and advocate vaccination of previously infected persons because natural protection cannot be relied upon, especially among the elderly.
Research in Context
Evidence prior to this study.
We searched PubMed and the bioRxiv and medRxiv preprint servers for publications between September 1, 2019 and February 14, 2021, with no language restrictions, using the terms ("SARS-CoV-2" OR "COVID-19" OR "COVID" OR "Coronavirus") AND "reinfection" AND "immunity".
For preprint articles, we included the search term "human" and found 695 articles, of which 192 were published on the bioRxiv server and 503 on the medRxiv server. In PubMed, we found 112 peer-reviewed publications and, after filtering for human studies, we identified 48 articles. Most of these peer-reviewed articles report that reinfection with SARS-CoV-2 is a rare event occurring in less than 1% of COVID-19 cases.
We then repeated our PubMed search and changed the search term "reinfection" to "seroprevalence" to assess SARS-CoV-2 immunity in the population at a given time point. We identified 47 studies that reported a seroprevalence of SARS-CoV-2 based on serum antibody responses of 0 - 37-22 - 1%, highlighting the absence or low level of immunity in the general population.
Looking at natural immunity, we identified three cohort studies: a peer-reviewed article on reinfections in residents of two nursing homes and two preprint articles, one that followed 43,000 people in Qatar and found an estimated 95% protection against reinfection, and one of over 20,000 healthcare workers in the UK that found an 83% lower risk of reinfection for at least 5 months after first infection.
Added value of this study
By analyzing Danish population-level surveillance data with more than 10 million person-identifiable PCR test results in 2020, we estimate protective immunity to be approximately 80% to 83% in persons younger than 65 years. We found no differences in immunity during the study period. Among persons aged 65 years and older, immunity was estimated to be approximately 47%.
Implications of all available evidence
Natural infection with SARS-CoV-2 led to an observed protection against
reinfection estimated at approximately 80% after 6 months.However, the low natural immunity observed in persons aged 65 years and older underscores the need to vaccinate previously infected persons, particularly in this age group.