Open AccessRisk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark
Author(s) -
Caroline Klint Johannesen,
Omid Rezahosseini,
Mikkel Gybel-Brask,
Jonas Henrik Kristensen,
Rasmus Bo Hasselbalch,
Mia Pries-Heje,
Pernille B Nielsen,
Andreas Dehlbæk Knudsen,
Kamille Fogh,
Jakob Norsk,
Ove Andersen,
Claus Antonio Juul Jensen,
Christian TorpPedersen,
Jørgen Rungby,
Sisse B. Ditlev,
Ida Hageman,
Rasmus Møgelvang,
Ram Benny Dessau,
Erik Sørensen,
Lene Holm Harritshøj,
Fredrik Folke,
Curt Sten,
Maria Elizabeth Engel Møller,
Frederik Neess Engsig,
Henrik Ullum,
Charlotte Sværke Jørgensen,
Sisse Rye Ostrowski,
Henning Bundgaard,
Kasper Iversen,
Thea Kølsen Fischer,
Susanne Dam Nielsen
Publication year - 2021
Publication title -
microbiology spectrum
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.502
H-Index - 51
ISSN - 2165-0497
DOI - 10.1128/spectrum.00904-21
Subject(s) - medicine , hazard ratio , interquartile range , asymptomatic , confidence interval , proportional hazards model , cohort study , body mass index , cohort , prospective cohort study , immunology
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.