SARS-CoV-2 Reinfections in Denmark Confirmed by Whole Genome Sequencing

Background: It is unclear how often reinfections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occur. The aim of this study is to identify reinfections in the Danish population by real-time reverse transcription polymerase chain reaction (RT-PCR) and whole genome sequencing (WGS).Methods: In this population-based retrospective study, we analyzed approximately 19 million real-time RT-PCR tests from 4·4 million individuals between March 202 and March 2021 as part of Denmark’s SARS-CoV-2 surveillance system. Suspected reinfection cases were defined as individuals with two or more SARS-CoV-2 PCR positive tests and > than 60 days between the two tests and confirmed by WGS analysis. Additionally, WGS confirmed reinfection cases with less than 60 days between first and second infection were also included in this study.Findings: Based on real-time RT- PCR positive results we identified 593 suspected reinfection cases, and 15 WGS confirmed reinfection cases within the Danish population. In nine persons, confirmed reinfections occurred within 60 days after the first SARS-CoV-2 positive test. A unique set of amino acid changes occurred within the S protein sequence of SARS-CoV-2 isolated from first and second infection samples from each confirmed reinfection case.Interpretation: Most reinfections occurred before the recommended 60-90 day threshold between the first and second episode of infection and we suggest to re-examine the case definition for reinfection cases for SARS-CoV-2. This may have important implications for intervention measures to control the ongoing pandemic and allows us gain a better understanding of natural immunity to SARS-CoV-2.Funding Information: Daniela Michlmayr was supported by the European Programme for Public Health Microbiology (EUPHEM), European Centre for Disease Prevention and Control, (ECDC). Declaration of Interests: The authors declare no conflict of interest.Ethics Approval Statement: Our analyses are based on existing Danish national Covid-19 surveillance data and did not require ethical approval.