Seroprevalence and infection fatality rate of the SARS-CoV-2 Omicron variant in Denmark: A nationwide serosurveillance study

Abstract

Background: Introduction of the Omicron variant caused a steep rise in SARS-CoV-2 infections despite high vaccination coverage in the Danish population. We used blood donor serosurveillance to estimate the percentage of recently infected residents in the similarly aged background population with no known comorbidity.

Methods: To detect SARS-CoV-2 antibodies induced due to recent infection, and not vaccination, we assessed anti-nucleocapsid (anti-N) immunoglobulin G (IgG) in blood donor samples. Individual level data on SARS-CoV-2 RT-PCR results and vaccination status were available. Anti-N IgG was measured fortnightly from January 18 to April 3, 2022. Samples from November 2021 were analysed to assess seroprevalence before introduction of the Omicron variant in Denmark.

Findings: A total of 43 088 donations from 35 309 Danish blood donors aged 17-72 years were screened. In November 2021, 1·2% (103/8 701) of donors had detectable anti-N IgG antibodies. Adjusting for test sensitivity (estimates ranging from 74%-81%) and November seroprevalence, we estimate that 66% (95% confidence intervals (CI): 63%-70%) of the healthy, similarly aged Danish population had been infected between November 1, 2021, and March 15, 2022. One third of infections were not captured by SARS-CoV-2 RT-PCR testing. The infection fatality rate (IFR) was 6·2 (CI: 5·1-7·5) per 100 000 infections.

Interpretation: Screening for anti-N IgG and linkage to national registers allowed us to detect recent infections and accurately assess assay sensitivity in vaccinated or previously infected individuals during the Omicron outbreak. The IFR was lower than during previous waves.

Funding: The Danish Ministry of Health.

Keywords: Infection fatality rate; SARS-CoV-2; Seroprevalence.

Figure 1

Anti-nucleocapsid IgG antibody response after recent infection. The level of the anti-N IgG antibody response is displayed as signal to cut-off (S/CO) ratio with an interpretation cut-off of 1·4 S/CO as recommended by the manufacturer (green line). The dotted vertical lines at 14 and 86 days indicate the end of the self-deferral period for blood donors after first positive SARS-CoV-2 test result and when the estimated mean IgG response was equal to the interpretation cut-off, respectively.

Figure 2

Cumulative percentage of SARS-CoV-2 RT-PCR positive test results and the estimated cumulative SARS-CoV-2 infections during the study period. November 1, 2021 was set to zero percent. Due to the 14 days delay between the PCR reference period and the median date of the test week, the calculated cumulative proportion of infected individuals for each test week is indicated as the percentage infected on the last date of the corresponding PCR reference period.