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

journal contribution
submitted on 2024-05-09, 09:17 and posted on 2024-05-09, 09:22 authored by 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

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.

Other Information

Published in: Viruses
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  • English



Publication Year

  • 2021

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute - HBKU
  • Neurological Disorders Research Center - QBRI
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC
  • Anti-Doping Laboratory Qatar - QA-DC

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