Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark.

Johannesen, Caroline Klint; Rezahosseini, Omid; Gybel-Brask, Mikkel; Kristensen, Jonas Henrik; Hasselbalch, Rasmus Bo; Pries-Heje, Mia Marie; Nielsen, Pernille Brok; Knudsen, Andreas Dehlbæk; Fogh, Kamille; Norsk, Jakob Boesgaard; Andersen, Ove; Jensen, Claus Antonio Juul; Torp-Pedersen, Christian; Rungby, Jørgen; Ditlev, Sisse Bolm; Hageman, Ida; Møgelvang, Rasmus; Dessau, Ram B; Sørensen, Erik; Harritshøj, Lene Holm; Folke, Fredrik; Sten, Curt; Møller, Maria Elizabeth Engel; Engsig, Frederik Neess; Ullum, Henrik; Jørgensen, Charlotte Sværke; Ostrowski, Sisse R; Bundgaard, Henning; Iversen, Kasper Karmark; Fischer, Thea Kølsen; Nielsen, Susanne Dam

Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but being seronegative is observed in 1 to 9%. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. In a prospective cohort study, we screened health care workers (HCW) in the Capital Region of Denmark for SARS-CoV-2 antibodies. We performed three rounds of screening from April to October 2020 using an enzyme-linked immunosorbent assay (ELISA) method targeting SARS-CoV-2 total antibodies. Data on all participants' PCR for SARS-CoV-2 RNA were captured from national registries. The Kaplan-Meier method and Cox proportional hazards models were applied to investigate the probability of being seronegative and the related risk factors, respectively. Of 36,583 HCW, 866 (2.4%) had a positive PCR before or during the study period. The median (interquartile range [IQR]) age of 866 HCW was 42 (31 to 53) years, and 666 (77%) were female. After a median of 132 (range, 35 to 180) days, 21 (2.4%) of 866 were seronegative. In a multivariable model, independent risk factors for being seronegative were self-reported asymptomatic or mild infection hazard ratio (HR) of 6.6 (95% confidence interval [CI], 2.6 to 17; P < 0.001) and body mass index (BMI) of ≥30, HR 3.1 (95% CI, 1.1 to 8.8; P = 0.039). Only a few (2.4%) HCW were not seropositive. Asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges. IMPORTANCE Most individuals seroconvert after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but negative serology is observed in 1 to 9%. We found that asymptomatic or mild infection as well as a BMI above 30 were associated with being seronegative. Since the presence of antibodies against SARS-CoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.