TY - JOUR
T1 - Risk Factors for Being Seronegative following SARS-CoV-2 Infection in a Large Cohort of Health Care Workers in Denmark
AU - Johannesen, Caroline Klint
AU - Rezahosseini, Omid
AU - Gybel-Brask, Mikkel
AU - Kristensen, Jonas Henrik
AU - Hasselbalch, Rasmus Bo
AU - Pries-Heje, Mia Marie
AU - Nielsen, Pernille Brok
AU - Knudsen, Andreas Dehlbæk
AU - Fogh, Kamille
AU - Norsk, Jakob Boesgaard
AU - Andersen, Ove
AU - Jensen, Claus Antonio Juul
AU - Torp-Pedersen, Christian
AU - Rungby, Jørgen
AU - Ditlev, Sisse Bolm
AU - Hageman, Ida
AU - Møgelvang, Rasmus
AU - Dessau, Ram B
AU - Sørensen, Erik
AU - Harritshøj, Lene Holm
AU - Folke, Fredrik
AU - Sten, Curt
AU - Møller, Maria Elizabeth Engel
AU - Engsig, Frederik Neess
AU - Ullum, Henrik
AU - Jørgensen, Charlotte Sværke
AU - Ostrowski, Sisse R
AU - Bundgaard, Henning
AU - Iversen, Kasper Karmark
AU - Fischer, Thea Kølsen
AU - Nielsen, Susanne Dam
PY - 2021/10/31
Y1 - 2021/10/31
N2 - 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 SARSCoV-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 SARSCoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.
AB - 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 SARSCoV-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 SARSCoV-2 reduces the risk of reinfection, efforts to protect HCW with risk factors for being seronegative may be needed in future COVID-19 surges.
KW - Asymptomatic infections
KW - Body mass index
KW - Health care workers
KW - Risk factor
KW - SARS-CoV-2
KW - Seroconversion
U2 - 10.1128/Spectrum.00904-21
DO - 10.1128/Spectrum.00904-21
M3 - Journal article
C2 - 34668738
SN - 2165-0497
VL - 9
JO - Microbiology Spectrum
JF - Microbiology Spectrum
IS - 2
M1 - e0090421
ER -