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

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dc.contributor.authorSmith, Muneerah
dc.contributor.authorAbdesselem, Houari B
dc.contributor.authorMullins, Michelle
dc.contributor.authorTan, Ti-Myen
dc.contributor.authorNel, Andrew J. M.
dc.contributor.authorAl-Nesf, Maryam A Y
dc.contributor.authorBensmail, Ilham
dc.contributor.authorMajbour, Nour K
dc.contributor.authorVaikath, Nishant N
dc.contributor.authorNaik, Adviti
dc.contributor.authorOuararhni, Khalid
dc.contributor.authorMohamed-Ali, Vidya
dc.contributor.authorAl-Maadheed, Mohammed
dc.contributor.authorSchell, Darien T.
dc.contributor.authorBaros-Steyl, Seanantha S
dc.contributor.authorAnuar, Nur D
dc.contributor.authorIsmail, Nur H
dc.contributor.authorMorris, Priscilla E
dc.contributor.authorMamat, Raja N R
dc.contributor.authorRosli, Nurul S M
dc.contributor.authorAnwar, Arif
dc.contributor.authorEllan, Kavithambigai
dc.contributor.authorZain, Rozainanee M
dc.contributor.authorBurgers, Wendy A
dc.contributor.authorMayne, Elizabeth S
dc.contributor.authorEl-Agnaf, Omar M A
dc.contributor.authorBlackburn, Jonathan M
dc.date.accessioned2021-10-13T08:23:52Z
dc.date.available2021-10-13T08:23:52Z
dc.date.issued2021-04-28
dc.date.updated2021-05-24T15:10:43Z
dc.description.abstractThe 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 (<i>n</i> = 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 (<i>n</i> = 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.en_US
dc.identifierdoi: 10.3390/v13050786
dc.identifier.apacitationSmith, M., Abdesselem, H. B., Mullins, M., Tan, T., Nel, Andrew J. M., Al-Nesf, M. A. Y., ... Blackburn, J. M. (2021). Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort. <i>Viruses</i>, 13(5), 786. http://hdl.handle.net/11427/35221en_ZA
dc.identifier.chicagocitationSmith, Muneerah, Houari B Abdesselem, Michelle Mullins, Ti-Myen Tan, Andrew J. M. Nel, Maryam A Y Al-Nesf, Ilham Bensmail, et al "Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort." <i>Viruses</i> 13, 5. (2021): 786. http://hdl.handle.net/11427/35221en_ZA
dc.identifier.citationSmith, M., Abdesselem, H.B., Mullins, M., Tan, T., Nel, Andrew J. M., Al-Nesf, M.A.Y., Bensmail, I. & Majbour, N.K. et al. 2021. Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort. <i>Viruses.</i> 13(5):786. http://hdl.handle.net/11427/35221en_ZA
dc.identifier.ris TY - Journal Article AU - Smith, Muneerah AU - Abdesselem, Houari B AU - Mullins, Michelle AU - Tan, Ti-Myen AU - Nel, Andrew J. M. AU - Al-Nesf, Maryam A Y AU - Bensmail, Ilham AU - Majbour, Nour K AU - Vaikath, Nishant N AU - Naik, Adviti AU - Ouararhni, Khalid AU - Mohamed-Ali, Vidya AU - Al-Maadheed, Mohammed AU - Schell, Darien T. AU - Baros-Steyl, Seanantha S AU - Anuar, Nur D AU - Ismail, Nur H AU - Morris, Priscilla E AU - Mamat, Raja N R AU - Rosli, Nurul S M AU - Anwar, Arif AU - Ellan, Kavithambigai AU - Zain, Rozainanee M AU - Burgers, Wendy A AU - Mayne, Elizabeth S AU - El-Agnaf, Omar M A AU - Blackburn, Jonathan M AB - 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 (<i>n</i> = 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 (<i>n</i> = 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. DA - 2021-04-28 DB - OpenUCT DP - University of Cape Town IS - 5 J1 - Viruses LK - https://open.uct.ac.za PY - 2021 T1 - Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort TI - Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort UR - http://hdl.handle.net/11427/35221 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35221
dc.identifier.vancouvercitationSmith M, Abdesselem HB, Mullins M, Tan T, Nel Andrew J M, Al-Nesf MAY, et al. Age, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohort. Viruses. 2021;13(5):786. http://hdl.handle.net/11427/35221.en_ZA
dc.language.isoenen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceVirusesen_US
dc.source.journalissue5en_US
dc.source.journalvolume13en_US
dc.source.pagination786en_US
dc.source.urihttps://www.mdpi.com/journal/viruses
dc.titleAge, Disease Severity and Ethnicity Influence Humoral Responses in a Multi-Ethnic COVID-19 Cohorten_US
dc.typeJournal Articleen_US
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