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Article

Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort

1
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
2
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
3
Proteomics Core Facility, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar
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Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
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Hamad General Hospital, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar
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Anti-Doping Laboratory Qatar, Sports City Road, Aspire Zone, Doha P.O. Box 27775, Qatar
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Virology Lab, Level 2, Block C7, Infectious Disease Research Centre, Institute for Medical Research, Setia Alam, Selangor 40170, Malaysia
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Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa
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Wellcome Centre for Infectious Diseases Research in Africa, University of Cape Town, Cape Town 7925, South Africa
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Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
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Department of Immunology, National Health Laboratory Service (NHLS) and University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg 2196, South Africa
*
Authors to whom correspondence should be addressed.
These authors contributed equally to the work.
Academic Editors: Burtram C. Fielding and Georgia Schäfer
Viruses 2021, 13(5), 786; https://doi.org/10.3390/v13050786
Received: 25 March 2021 / Revised: 24 April 2021 / Accepted: 26 April 2021 / Published: 28 April 2021
(This article belongs to the Special Issue Coronaviruses Research in BRICS Countries)
The COVID-19 pandemic has affected all individuals across the globe in some way. Despite large numbers of reported seroprevalence studies, there remains a limited understanding of how the magnitude and epitope utilization of the humoral immune response to SARS-CoV-2 viral anti-gens varies within populations following natural infection. Here, we designed a quantitative, multi-epitope protein microarray comprising various nucleocapsid protein structural motifs, including two structural domains and three intrinsically disordered regions. Quantitative data from the microarray provided complete differentiation between cases and pre-pandemic controls (100% sensitivity and specificity) in a case-control cohort (n = 100). We then assessed the influence of disease severity, age, and ethnicity on the strength and breadth of the humoral response in a multi-ethnic cohort (n = 138). As expected, patients with severe disease showed significantly higher antibody titers and interestingly also had significantly broader epitope coverage. A significant increase in antibody titer and epitope coverage was observed with increasing age, in both mild and severe disease, which is promising for vaccine efficacy in older individuals. Additionally, we observed significant differences in the breadth and strength of the humoral immune response in relation to ethnicity, which may reflect differences in genetic and lifestyle factors. Furthermore, our data enabled localization of the immuno-dominant epitope to the C-terminal structural domain of the viral nucleocapsid protein in two independent cohorts. Overall, we have designed, validated, and tested an advanced serological assay that enables accurate quantitation of the humoral response post natural infection and that has revealed unexpected differences in the magnitude and epitope utilization within a population. View Full-Text
Keywords: immunoassay; SARS-CoV-2 nucleocapsid protein; epitope coverage; quantitative antibody binding; protein microarray; SARS-CoV-2 antibodies; humoral response immunoassay; SARS-CoV-2 nucleocapsid protein; epitope coverage; quantitative antibody binding; protein microarray; SARS-CoV-2 antibodies; humoral response
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MDPI and ACS Style

Smith, M.; Abdesselem, H.B.; Mullins, M.; Tan, T.-M.; Nel, A.J.M.; Al-Nesf, M.A.Y.; Bensmail, I.; Majbour, N.K.; Vaikath, N.N.; Naik, A.; Ouararhni, K.; Mohamed-Ali, V.; Al-Maadheed, M.; Schell, D.T.; Baros-Steyl, S.S.; Anuar, N.D.; Ismail, N.H.; Morris, P.E.; Mamat, R.N.R.; Rosli, N.S.M.; Anwar, A.; Ellan, K.; Zain, R.M.; Burgers, W.A.; Mayne, E.S.; El-Agnaf, O.M.A.; Blackburn, J.M. Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort. Viruses 2021, 13, 786. https://doi.org/10.3390/v13050786

AMA Style

Smith M, Abdesselem HB, Mullins M, Tan T-M, Nel AJM, Al-Nesf MAY, Bensmail I, Majbour NK, Vaikath NN, Naik A, Ouararhni K, Mohamed-Ali V, Al-Maadheed M, Schell DT, Baros-Steyl SS, Anuar ND, Ismail NH, Morris PE, Mamat RNR, Rosli NSM, Anwar A, Ellan K, Zain RM, Burgers WA, Mayne ES, El-Agnaf OMA, Blackburn JM. Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort. Viruses. 2021; 13(5):786. https://doi.org/10.3390/v13050786

Chicago/Turabian Style

Smith, Muneerah, Houari B. Abdesselem, Michelle Mullins, Ti-Myen Tan, Andrew J. M. Nel, Maryam A. Y. Al-Nesf, Ilham Bensmail, Nour K. Majbour, Nishant N. Vaikath, Adviti Naik, Khalid Ouararhni, Vidya Mohamed-Ali, Mohammed Al-Maadheed, Darien T. Schell, Seanantha S. Baros-Steyl, Nur D. Anuar, Nur H. Ismail, Priscilla E. Morris, Raja N. R. Mamat, Nurul S. M. Rosli, Arif Anwar, Kavithambigai Ellan, Rozainanee M. Zain, Wendy A. Burgers, Elizabeth S. Mayne, Omar M. A. El-Agnaf, and Jonathan M. Blackburn. 2021. "Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort" Viruses 13, no. 5: 786. https://doi.org/10.3390/v13050786

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