Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months

Serwanga, J. et al. (2023) Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months. Frontiers in Immunology, 14, 1152522. (doi: 10.3389/fimmu.2023.1152522) (PMID:37006272) (PMCID:PMC10060567)

Abstract

Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman’s rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.

• Item Type: Articles
• Additional Information: The work was funded by the Government of Uganda under the Science, Technology, and Innovation Secretariat-Office of the President (STI-OP), grant number: MOSTI-PRESIDE-COVID-19-2020/15. This publication is based on research funded in part by the Bill & Melinda Gates Foundation through the GIISER Uganda Grant Agreement Investment ID; INV-036306. This project is part of the EDCTP2 program supported by the European Union (grant number RIA2020EF- 3008-COVAB). The work was conducted at the MRC/UVRI and LSHTM Uganda Research Unit which is jointly funded by the UK Medical Research Council (MRC), part of the UK Research and Innovation (UKRI) and the UK Foreign, Commonwealth, and Development office (FDCO) under the MRC/FDCO Concordat agreement, and is also part of the EDCTP2 programme supported by the European Union. Initial specimen collections were supported by the University of Glasgow GCRF COVID-19 Rapid Response Fund (Uganda COVID-19 Serological Responses UGANCOSER).
• Keywords: SARS-CoV-2 antibody persistence, spike and RBD, nucleoprotein, mild and asymptomatic COVID-19, IgG, IgM, IgA, Uganda.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cotten, Professor Matthew
• Authors: Serwanga, J., Ankunda, V., Sembera, J., Kato, L., Oluka, G. K., Baine, C., Odoch, G., Kayiwa, J., Auma, B. O., Jjuuko, M., Nsereko, C., Cotten, M., Onyachi, N., Muwanga, M., Lutalo, T., Fox, J., Musenero, M., and Kaleebu, P.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Frontiers in Immunology
• Publisher: Frontiers Media
• ISSN: 1664-3224
• ISSN (Online): 1664-3224
• Copyright Holders: Copyright © 2023 Serwanga, Ankunda, Sembera, Kato, Oluka, Baine, Odoch, Kayiwa, Auma, Jjuuko, Nsereko, Cotten, Onyachi, Muwanga, Lutalo, Fox, Musenero, Kaleebu and The COVID-19 Immunoprofiling Team
• First Published: First published in Frontiers in Immunology 14: 1152522
• Publisher Policy: Reproduced under a Creative Commons License