Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response
Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response
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.
COVID-19, clinical epidemiology, respiratory infection
Shields, Adrian M
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Faustini, Sian E
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Perez-Toledo, Marisol
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Jossi, Sian
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Allen, Joel D
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Al-Taei, Saly
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Backhouse, Claire
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Dunbar, Lynsey A
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Ebanks, Daniel
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Emmanuel, Beena
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Faniyi, Aduragbemi A
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Garvey, Mark
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Grinbergs, Annabel
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McGinnell, Golaleh
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O'Neill, Joanne
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Watanabe, Yasunori
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Crispin, Max
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Wraith, David C
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Cunningham, Adam F
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Drayson, Mark T
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Richter, Alex G
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24 September 2021
Shields, Adrian M
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Faustini, Sian E
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Perez-Toledo, Marisol
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Jossi, Sian
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Allen, Joel D
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Al-Taei, Saly
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Backhouse, Claire
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Dunbar, Lynsey A
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Ebanks, Daniel
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Emmanuel, Beena
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Faniyi, Aduragbemi A
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Garvey, Mark
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Grinbergs, Annabel
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McGinnell, Golaleh
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O'Neill, Joanne
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Watanabe, Yasunori
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Crispin, Max
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Wraith, David C
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Cunningham, Adam F
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Drayson, Mark T
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Richter, Alex G
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Shields, Adrian M, Faustini, Sian E, Perez-Toledo, Marisol, Jossi, Sian, Allen, Joel D, Al-Taei, Saly, Backhouse, Claire, Dunbar, Lynsey A, Ebanks, Daniel, Emmanuel, Beena, Faniyi, Aduragbemi A, Garvey, Mark, Grinbergs, Annabel, McGinnell, Golaleh, O'Neill, Joanne, Watanabe, Yasunori, Crispin, Max, Wraith, David C, Cunningham, Adam F, Drayson, Mark T and Richter, Alex G
(2021)
Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response.
BMJ Open Respiratory Research, 8 (1), [e000872].
(doi:10.1136/bmjresp-2020-000872).
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.
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More information
Accepted/In Press date: 30 August 2021
Published date: 24 September 2021
Additional Information:
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.
Keywords:
COVID-19, clinical epidemiology, respiratory infection
Identifiers
Local EPrints ID: 451826
URI: http://eprints.soton.ac.uk/id/eprint/451826
ISSN: 2052-4439
PURE UUID: 351b8299-a0a3-465f-8dc3-54adc738a75a
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Date deposited: 28 Oct 2021 16:36
Last modified: 17 Mar 2024 04:09
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Contributors
Author:
Adrian M Shields
Author:
Sian E Faustini
Author:
Marisol Perez-Toledo
Author:
Sian Jossi
Author:
Saly Al-Taei
Author:
Claire Backhouse
Author:
Lynsey A Dunbar
Author:
Daniel Ebanks
Author:
Beena Emmanuel
Author:
Aduragbemi A Faniyi
Author:
Mark Garvey
Author:
Annabel Grinbergs
Author:
Golaleh McGinnell
Author:
Joanne O'Neill
Author:
Yasunori Watanabe
Author:
David C Wraith
Author:
Adam F Cunningham
Author:
Mark T Drayson
Author:
Alex G Richter
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