Abstract

ABSTRACTMost 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.

Highlights

  • Citation Johannesen CK, Rezahosseini O, Gybel-Brask M, Kristensen JH, Hasselbalch RB, Pries-Heje MM, Nielsen PB, Knudsen AD, Fogh K, Norsk JB, Andersen O, Jensen CAJ, TorpPedersen C, Rungby J, Ditlev SB, Hageman I, Møgelvang R, Dessau RB, Sørensen E, Harritshøj LH, Folke F, Sten C, Møller MEE, Engsig FN, Ullum H, Jørgensen CS, Ostrowski SR, Bundgaard H, Iversen KK, Fischer TK, Nielsen SD. 2021

  • In this large cohort of health care workers (HCW) with PCR-confirmed SARS-CoV-2 infection, we found that only 2.4% were seronegative

  • Compared to symptomatic HCW, those who were asymptomatic or had mild symptoms were at almost seven times higher risk of being seronegative, corroborating previous reports [8,9,10,11]

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Summary

Introduction

Citation Johannesen CK, Rezahosseini O, Gybel-Brask M, Kristensen JH, Hasselbalch RB, Pries-Heje MM, Nielsen PB, Knudsen AD, Fogh K, Norsk JB, Andersen O, Jensen CAJ, TorpPedersen C, Rungby J, Ditlev SB, Hageman I, Møgelvang R, Dessau RB, Sørensen E, Harritshøj LH, Folke F, Sten C, Møller MEE, Engsig FN, Ullum H, Jørgensen CS, Ostrowski SR, Bundgaard H, Iversen KK, Fischer TK, Nielsen SD. 2021. Risk factors for being seronegative following SARS-CoV-2 infection in a large cohort of health care workers in Denmark. We aimed to investigate the risk factors associated with being seronegative following PCR-confirmed SARS-CoV-2 infection. 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. We aimed to investigate the risk factors for being seronegative following PCR-confirmed SARS-CoV-2 infection in a large prospective cohort of health care workers (HCW) in Denmark [7]

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