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Abstract
Objective To determine clinical and ethnodemographic correlates of serological responses against the SARS-CoV-2 spike glycoprotein following mild-to-moderate COVID-19.
Design A retrospective cohort study of healthcare workers who had self-isolated due to COVID-19.
Setting University Hospitals Birmingham NHS Foundation Trust, UK (UHBFT).
Participants 956 healthcare workers were recruited by open invitation via UHBFT trust email and social media between 27 April 2020 and the 8 June 2020.
Intervention Participants volunteered a venous blood sample that was tested for the presence of anti-SARS-CoV-2 spike glycoprotein antibodies. Results were interpreted in the context of the symptoms of their original illness and ethnodemographic variables.
Results Using an assay that simultaneously measures the combined IgG, IgA and IgM response against the spike glycoprotein (IgGAM), the overall seroprevalence within this cohort was 46.2% (n=442/956). The seroprevalence of immunoglobulin isotypes was 36.3%, 18.7% and 8.1% for IgG, IgA and IgM, respectively. IgGAM identified serological responses in 40.6% (n=52/128) of symptomatic individuals who reported a negative SARS-CoV-2 PCR test. Increasing age, non-white ethnicity and obesity were independently associated with greater IgG antibody response against the spike glycoprotein. Self-reported fever and fatigue were associated with greater IgG and IgA responses against the spike glycoprotein. The combination of fever and/or cough and/or anosmia had a positive predictive value of 92.3% for seropositivity in self-isolating individuals a time when Wuhan strain SARS-CoV-2 was predominant.
Conclusions and relevance Assays employing combined antibody detection demonstrate enhanced seroepidemiological sensitivity and can detect prior viral exposure even when PCR swabs have been negative. We demonstrate an association between known ethnodemographic risk factors associated with mortality from COVID-19 and the magnitude of serological responses in mild-to-moderate disease.
- respiratory infection
- clinical epidemiology
- COVID-19
Data availability statement
Data are available on reasonable request. The anonymised dataset will be made available on reasonable request. Proposals should be directed to the corresponding author.
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
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Data availability statement
Data are available on reasonable request. The anonymised dataset will be made available on reasonable request. Proposals should be directed to the corresponding author.
Supplementary materials
Supplementary Data
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Footnotes
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AMS and SEF contributed equally.
Contributors AS and SEF helped conceive the study, performed experiments, collated and analysed the data, produced the figures, wrote and revised the manuscript and should be considered joint first authors. MP-T and SJ performed experiments, collated and analysed the data. JDA, YW and MC produced the original trimeric spike-glycoprotein on which the serological assays are based and advised on methodology. AG, GM and JO'N recruited participants to the study, facilitated the acquisition of clinical samples and collated study results. MIG collated and interpreted trust-level data on infections within UHBFT inpatients. SAT, CB, LD, DE, BE and AF processed samples, undertook experiments and collated results for serological studies. MG provided trust inpatient data. DCW, AFC and MTD helped conceive the study and supervised analysis of data from the study. AGR is the senior and corresponding author for this manuscript and provided overall leadership for all aspects of the study. All authors helped revise the manuscript for publication.
Funding This paper presents independent research supported by the National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre at the University Hospitals Birmingham National Health Service (NHS) Foundation Trust and the University of Birmingham (Grant Reference Number BRC-1215-20009). The authors are grateful for funding from the UK Department of Health and Social Care, UKRI and UK CIC, as part of the PITCH Consortium, the Global Challenges Research Fund and The Institute for Global Innovation of the University of Birmingham, and the UK Medical Research Council (Grant Reference Number MC_PC_17183). The work in Professor Max Crispin’s laboratory was funded by the International AIDS Vaccine Initiative (IAVI) through grant INV-008352/OPP1153692 and the IAVI Neutralizing Antibody Center through the Collaboration for AIDS Vaccine Discovery grant OPP1196345/INV-008813, both funded by the Bill and Melinda Gates Foundation; the National Institute for Allergy and Infectious Diseases through the Scripps Consortium for HIV Vaccine Development (CHAVD) (AI144462); and the University of Southampton Coronavirus Response Fund.
Competing interests MTD reports personal fees from Abingdon Health, outside the submitted work.
Provenance and peer review Not commissioned; externally peer reviewed.
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