Microbiology Spectrum (Oct 2021)

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

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

DOI
https://doi.org/10.1128/Spectrum.00904-21
Journal volume & issue
Vol. 9, no. 2

Abstract

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ABSTRACT 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.

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