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

tetano

Editor, Senior Moderator
Microbiol Spectr


. 2021 Oct 20;e0090421.
doi: 10.1128/Spectrum.00904-21. Online ahead of print.
Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark


Caroline Klint Johannesen[SUP] #[/SUP][SUP] 1 [/SUP], Omid Rezahosseini[SUP] 2 [/SUP], Mikkel Gybel-Brask[SUP] 3 [/SUP], Jonas Henrik Kristensen[SUP] 4 5 6 [/SUP], Rasmus Bo Hasselbalch[SUP] 4 5 6 [/SUP], Mia Marie Pries-Heje[SUP] 7 [/SUP], Pernille Brok Nielsen[SUP] 4 5 [/SUP], Andreas Dehlbæk Knudsen[SUP] 2 7 [/SUP], Kamille Fogh[SUP] 4 5 [/SUP], Jakob Boesgaard Norsk[SUP] 4 5 [/SUP], Ove Andersen[SUP] 6 8 9 [/SUP], Claus Antonio Juul Jensen[SUP] 10 [/SUP], Christian Torp-Pedersen[SUP] 11 12 13 [/SUP], Jørgen Rungby[SUP] 14 15 [/SUP], Sisse Bolm Ditlev[SUP] 15 16 [/SUP], Ida Hageman[SUP] 17 [/SUP], Rasmus Møgelvang[SUP] 7 [/SUP], Ram B Dessau[SUP] 18 19 [/SUP], Erik Sørensen[SUP] 3 [/SUP], Lene Holm Harritshøj[SUP] 3 [/SUP], Fredrik Folke[SUP] 4 6 20 [/SUP], Curt Sten[SUP] 21 [/SUP], Maria Elizabeth Engel Møller[SUP] 22 [/SUP], Frederik Neess Engsig[SUP] 22 [/SUP], Henrik Ullum[SUP] 23 [/SUP], Charlotte Sværke Jørgensen[SUP] 23 [/SUP], Sisse R Ostrowski[SUP] 3 6 [/SUP], Henning Bundgaard[SUP] 6 7 [/SUP], Kasper Karmark Iversen[SUP] 4 5 6 [/SUP], Thea Kølsen Fischer[SUP] #[/SUP][SUP] 1 24 [/SUP], Susanne Dam Nielsen[SUP] #[/SUP][SUP] 2 6 [/SUP]



Affiliations

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.

Keywords: SARS-CoV-2; asymptomatic infections; body mass index; health care workers; risk factor; seroconversion.
 
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