Seroprevalence of SARS-CoV-2 antibodies and reduced risk of reinfection through 6 months: a Danish observational cohort study of 44 000 healthcare workers

Abstract

Objectives: Antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor in protecting against coronavirus disease 2019 (COVID-19). We examined longitudinal changes in seroprevalence in healthcare workers (HCWs) in Copenhagen and the protective effect of antibodies against SARS-CoV-2.

Methods: In this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCWs three times over 6 months. HCW characteristics were obtained by questionnaires. The study was registered at ClinicalTrials.gov, NCT04346186.

Results: From April to October 2020 we screened 44 698 HCWs, of whom 2811 were seropositive at least once. The seroprevalence increased from 4.0% (1501/37 452) to 7.4% (2022/27 457) during the period (p < 0.001) and was significantly higher than in non-HCWs. Frontline HCWs had a significantly increased risk of seropositivity compared to non-frontline HCWs, with risk ratios (RRs) at the three rounds of 1.49 (95%CI 1.34-1.65, p < 0.001), 1.52 (1.39-1.68, p < 0.001) and 1.50 (1.38-1.64, p < 0.001). The seroprevalence was 1.42- to 2.25-fold higher (p < 0.001) in HCWs from dedicated COVID-19 wards than in other frontline HCWs. Seropositive HCWs had an RR of 0.35 (0.15-0.85, p 0.012) of reinfection during the following 6 months, and 2115 out of 2248 (95%) of those who were seropositive during rounds one or two remained seropositive after 4-6 months. The 133 of 2248 participants (5.0%) who seroreverted were slightly older and reported fewer symptoms than other seropositive participants.

Conclusions: HCWs remained at increased risk of infection with SARS-CoV-2 during the 6-month period. Seropositivity against SARS-CoV-2 persisted for at least 6 months in the vast majority of HCWs and was associated with a significantly lower risk of reinfection.

Keywords: COVID; Healthcare workers; Immune response; SARS-CoV-2; Seroprevalence.

Fig. 1

Flow of participants in the study: healthcare workers (HCWs) participating in the study during the period from April to October 2020.

Fig. 2

Risk of seropositivity according to occupational exposure: seroprevalence among healthcare workers (HCWs) at each round stratified by HCWs working in dedicated coronavirus disease 2019 (COVID-19) wards, HCWs not on COVID-19 wards but working frontline, and remaining HCWs.

Fig. 3

Seroprevalence stratified by medical specialty for doctors, nurses and assistant nurses. The figure shows seroprevalence among doctors, nurses and assistant nurses stratified by medical specialty. Some specialties are more involved in the treatment of patients with coronavirus disease 2019 (COVID-19) than others, for example a high seroprevalence is noted for respiratory medicine, infectious diseases and emergency medicine. Elderly and/or immunosuppressed patients may shed more virus, which may explain why geriatrics and haematology rank high. Also, in geriatrics, healthcare workers (HCWs) visit patients in their homes where transmission may be higher than in hospitals. Surprisingly, the seroprevalence in intensive care is low compared to other specialties.

Fig. 4

Signal/cutoff ratio (S/CO ratio) for participants who were seropositive in round one and participated in all three rounds (n = 817). (a) S/CO ratio in all three rounds (n = 745). (b) Seroreverters in round two (n = 26) (positive in round one and negative in rounds two and three). (c) Seroreverters in round three (n = 21) (positive in round one and negative in rounds two and three). (d) Possible reinfections (n = 25) (positive in round one, negative in round two and positive in round three). The dotted line signifies 1.1, above which was considered positive.