Seroprevalence of SARS-CoV-2 antibodies and reduced risk of reinfection through 6 months: a Danish observational cohort study of 44 000 healthcare workers
Kasper Iversen, Jonas Henrik Kristensen, Rasmus Bo Hasselbalch, Mia Pries-Heje, Pernille Brok Nielsen, Andreas Dehlbæk Knudsen, Kamille Fogh, Jakob Boesgaard Norsk, Ove Andersen, Thea Køhler Fischer, Claus Antonio Juul Jensen, Christian Torp-Pedersen, Jørgen Rungby, Sisse Bolm Ditlev, Ida Hageman, Rasmus Møgelvang, Mikkel Gybel-Brask, Ram B Dessau, Erik Sørensen, Lene Harritshøj, Fredrik Folke, Curt Sten, Maria Elizabeth Engel Møller, Thomas Benfield, Henrik Ullum, Charlotte Sværke Jørgensen, Christian Erikstrup, Sisse R Ostrowski, Susanne Dam Nielsen, Henning Bundgaard, Kasper Iversen, Jonas Henrik Kristensen, Rasmus Bo Hasselbalch, Mia Pries-Heje, Pernille Brok Nielsen, Andreas Dehlbæk Knudsen, Kamille Fogh, Jakob Boesgaard Norsk, Ove Andersen, Thea Køhler Fischer, Claus Antonio Juul Jensen, Christian Torp-Pedersen, Jørgen Rungby, Sisse Bolm Ditlev, Ida Hageman, Rasmus Møgelvang, Mikkel Gybel-Brask, Ram B Dessau, Erik Sørensen, Lene Harritshøj, Fredrik Folke, Curt Sten, Maria Elizabeth Engel Møller, Thomas Benfield, Henrik Ullum, Charlotte Sværke Jørgensen, Christian Erikstrup, Sisse R Ostrowski, Susanne Dam Nielsen, Henning Bundgaard
Abstract
Objectives: Antibodies to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are a key factor in protecting against coronavirus disease 2019 (COVID-19). We examined longitudinal changes in seroprevalence in healthcare workers (HCWs) in Copenhagen and the protective effect of antibodies against SARS-CoV-2.
Methods: In this prospective study, screening for antibodies against SARS-CoV-2 (ELISA) was offered to HCWs three times over 6 months. HCW characteristics were obtained by questionnaires. The study was registered at ClinicalTrials.gov, NCT04346186.
Results: From April to October 2020 we screened 44 698 HCWs, of whom 2811 were seropositive at least once. The seroprevalence increased from 4.0% (1501/37 452) to 7.4% (2022/27 457) during the period (p < 0.001) and was significantly higher than in non-HCWs. Frontline HCWs had a significantly increased risk of seropositivity compared to non-frontline HCWs, with risk ratios (RRs) at the three rounds of 1.49 (95%CI 1.34-1.65, p < 0.001), 1.52 (1.39-1.68, p < 0.001) and 1.50 (1.38-1.64, p < 0.001). The seroprevalence was 1.42- to 2.25-fold higher (p < 0.001) in HCWs from dedicated COVID-19 wards than in other frontline HCWs. Seropositive HCWs had an RR of 0.35 (0.15-0.85, p 0.012) of reinfection during the following 6 months, and 2115 out of 2248 (95%) of those who were seropositive during rounds one or two remained seropositive after 4-6 months. The 133 of 2248 participants (5.0%) who seroreverted were slightly older and reported fewer symptoms than other seropositive participants.
Conclusions: HCWs remained at increased risk of infection with SARS-CoV-2 during the 6-month period. Seropositivity against SARS-CoV-2 persisted for at least 6 months in the vast majority of HCWs and was associated with a significantly lower risk of reinfection.
Keywords: COVID; Healthcare workers; Immune response; SARS-CoV-2; Seroprevalence.
Copyright © 2021. Published by Elsevier Ltd.
Figures
References
- WHO Coronavirus (COVID-19) Dashboard . 2021. WHO Coronavirus Disease (COVID-19) Dashboard [Internet] [cited 24th Mar] Available from:
- Jeyanathan M., Afkhami S., Smaill F., Miller M.S., Lichty B.D., Xing Z. Immunological considerations for COVID-19 vaccine strategies. Nat Rev Immunol. 2020;20:615–632.
- Lumley S.F., O’Donnell D., Stoesser N.E., Matthews P.C., Howarth A., Hatch S.B., et al. Antibody status and incidence of SARS-CoV-2 infection in health care workers. N Engl J Med. 2021;384:533–540.
- Long Q.-X., Liu B.-Z., Deng H.-J., Wu G.-C., Deng K., Chen Y.-K., et al. Antibody responses to SARS-CoV-2 in patients with COVID-19. Nat Med. 2020;26:845–848.
- Wajnberg A., Mansour M., Leven E., Bouvier N.M., Patel G., Firpo-Betancourt A., et al. Humoral response and PCR positivity in patients with COVID-19 in the New York City region, USA: an observational study. Lancet Microbe. 2020;1:e283–e289.
- Post N., Eddy D., Huntley C., van Schalkwyk M.C.I., Shrotri M., Leeman D., et al. Antibody response to SARS-CoV-2 infection in humans: a systematic review. PLoS One. 2020;15:e0244126.
- Tillett R.L., Sevinsky J.R., Hartley P.D., Kerwin H., Crawford N., Gorzalski A., et al. Genomic evidence for reinfection with SARS-CoV-2: a case study. Lancet Infect Dis. 2021;21:52–58.
- Van Elslande J., Vermeersch P., Vandervoort K., Wawina-Bokalanga T., Vanmechelen B., Wollants E., et al. Symptomatic SARS-CoV-2 reinfection by a phylogenetically distinct strain. Clin Infect Dis. 2021;73:354–356.
- Prado-Vivar B., Becerra-Wong M., Guadalupe J.J., Marquez S., Gutierrez B., Rojas-Silva P., et al. COVID-19 re-infection by a phylogenetically distinct SARS-CoV-2 variant, first confirmed event in South America. SSRN Electron J [Internet] 2020 [cited 2021 Feb 5]
- To K.K., Hung I.F., Ip J.D., Chu A.W., Chan W.M., Tam A.R., et al. Coronavirus Disease 2019 (COVID-19) re-infection by a phylogenetically distinct severe acute respiratory syndrome coronavirus 2 Strain confirmed by whole genome sequencing. Clin Infect Dis. 2021;73:e2946–e2951.
- Gupta V., Bhoyar R.C., Jain A., Srivastava S., Upadhayay R., Imran M., et al. Asymptomatic reinfection in 2 healthcare workers from India with genetically distinct severe acute respiratory syndrome coronavirus 2. Clin Infect Dis. 2021;73:e2823–e2825.
- Mumoli N., Vitale J., Mazzone A. Clinical immunity in discharged medical patients with COVID-19. Int J Infect Dis. 2020;99:229–230.
- Gousseff M., Penot P., Gallay L., Batisse D., Benech N., Bouiller K., et al. Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound? J Infect. 2020;81:816–846.
- Reinfection with SARS-CoV-2: considerations for public health response [Internet] 2020. Available from:
- Long Q.X., Tang X.J., Shi Q.L., Li Q., Deng H.J., Yuan J., et al. Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med. 2020;26:1200–1204.
- Iversen K., Bundgaard H., Hasselbalch R.B., Kristensen J.H., Nielsen P.B., Pries-Heje M., et al. Risk of COVID-19 in health-care workers in Denmark: an observational cohort study. Lancet Infect Dis. 2020;20:1401–1408.
- Harris P.A., Taylor R., Minor B.L., Elliott V., Fernandez M., O’Neal L., et al. The REDCap consortium: building an international community of software platform partners. J Biomed Inform. 2019;95:103208.
- Harris P.A., Taylor R., Thielke R., Payne J., Gonzalez N., Conde J.G. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42:377–381.
- Erikstrup C., Hother C.E., Pedersen O.B.V., Mølbak K., Skov R.L., Holm D.K., et al. Estimation of SARS-CoV-2 infection fatality rate by real-time antibody screening of blood donors. Clin Infect Dis. 2020;72:249–253.
- Hansen C.H., Michlmayr D., Gubbels S.M., Mølbak K., Ethelberg S. Assessment of protection against reinfection with SARS-CoV-2 among 4 million PCR-tested individuals in Denmark in 2020: a population-level observational study. Lancet. 2021;397:1204–1212.
- Harvey R.A., Rassen J.A., Kabelac C.A., Turenne W., Leonard S., Klesh R., et al. Association of SARS-CoV-2 seropositive antibody test with risk of future infection. JAMA Intern Med. 2021;181:672–679.
- Public Health England . 2020. Weekly national Influenza and COVID-19 surveillance report.
- Wajnberg A., Amanat F., Firpo A., Altman D.R., Bailey M.J., Mansour M., et al. Robust neutralizing antibodies to SARS-CoV-2 infection persist for months. Science. 2020;370:1227–1230.
- Harvey R.A., Rassen J.A., Kabelac C.A., Turenne W., Leonard S., Klesh R., et al. Real-world data suggest antibody positivity to SARS-CoV-2 is associated with a decreased risk of future infection. medRxiv. 2020 2020.12.18.2024833. Preprint.
- Choe P.G., Kang C.K., Suh H.J., Jung J., Song K.H., Bang J.H., et al. Waning antibody responses in asymptomatic and symptomatic SARS-CoV-2 infection. Emerg Infect Dis. 2021;27:327–329.
- Madsen J.R., Nielsen J.P.S., Fogh K., Hansen C.B., Nielsen P.B., Lange T., et al. Anti-SARS-CoV-2 seropositivity among medical students in Copenhagen. Open Forum Infect Dis. 2021;8:ofab273.
Source: PubMed