Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort
Muneerah Smith,
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,
Jonathan M. Blackburn
Affiliations
Muneerah Smith
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
Houari B. Abdesselem
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Michelle Mullins
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
Ti-Myen Tan
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Andrew J. M. Nel
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
Maryam A. Y. Al-Nesf
Hamad General Hospital, Hamad Medical Corporation, Doha P.O. Box 3050, Qatar
Ilham Bensmail
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Nour K. Majbour
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Nishant N. Vaikath
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Adviti Naik
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Khalid Ouararhni
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
Seanantha S. Baros-Steyl
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
Nur D. Anuar
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Nur H. Ismail
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Priscilla E. Morris
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Raja N. R. Mamat
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Nurul S. M. Rosli
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Arif Anwar
Sengenics Corporation, Level M, Plaza Zurich, Damansara Heights, Kuala Lumpur 50490, Malaysia
Kavithambigai Ellan
Virology Lab, Level 2, Block C7, Infectious Disease Research Centre, Institute for Medical Research, Setia Alam, Selangor 40170, Malaysia
Rozainanee M. Zain
Virology Lab, Level 2, Block C7, Infectious Disease Research Centre, Institute for Medical Research, Setia Alam, Selangor 40170, Malaysia
Wendy A. Burgers
Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa
Elizabeth S. Mayne
Department of Immunology, National Health Laboratory Service (NHLS) and University of the Witwatersrand, Charlotte Maxeke Johannesburg Academic Hospital, Johannesburg 2196, South Africa
Omar M. A. El-Agnaf
Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University, Qatar. Foundation, Doha P.O. Box 34110, Qatar
Jonathan M. Blackburn
Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town 7925, South Africa
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.
