In a recent study posted to the medRxiv* preprint server, researchers investigated the breadth and longevity of immunity induced by natural severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure among the Kenyan population.
Study: Kinetics of naturally induced binding and neutralizing anti-SARS-CoV-2 antibody levels and potencies among Kenyan patients with diverse grades of COVID-19 severity. Image Credit: Corona Borealis Studio/Shutterstock
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
Background
The SARS-CoV-2 infection triggers neutralizing antibodies (nAbs), the most well-established correlate of protection against all infectious pathogens. These nAbs confer protection against viruses via several mechanisms - neutralization, opsonization, and antibody-dependent cellular cytotoxicity.
SARS-CoV-2-induced nAbs trigger robust immunoglobulin G (IgG), IgM, and IgA antibody responses. However, only a few have a neutralization function. Of nAbs with neutralization function, over 90% target the receptor binding domain (RBD) of SARS-CoV-2 spike (S) protein.
Previous studies surveying the general population of high-income countries (e.g., European countries) have shown that anti-SARS-CoV-2 nAbs could be short-lived. Some COVID-19 patients remain seronegative despite being SARS-CoV-2 positive. These observations raise the possibility of inter-population differences in people’s abilities to generate and maintain antiSARS-CoV-2 antibodies.
In sub-Saharan countries, for instance, Kenya, the COVID-19 vaccine coverage is poor. Nearly 70% of the Kenyan population was unvaccinated against SARS-CoV-2 as of September 2022, providing a unique setting to understand naturally acquired immunity to SARS-CoV-2.
Comparing anti-SARS-CoV-2 immune responses between patients from different geographical locations and clinical phenotypes could help find potential correlates of COVID-19 disease severity. Moreover, it could help determine the presence and longevity of antibody neutralization function in those who have acquired immunity through natural infection rather than vaccination.
About the study
In the present study, researchers determined the kinetics of naturally acquired anti-SARS-CoV-2 neutralizing antibodies in a cohort of Kenyan patients with varying degrees of COVID-19 severity. They followed up with these patients for six months following COVID-19 diagnosis to assess the titers of anti-SARS-CoV-2 binding and neutralizing antibodies and their subsequent waning.
The team sampled the recruited patients at baseline, referred to as day 0. Then, they collected blood samples on days 7, 14, 28, and 180 (6 months) of a positive COVID-19 test. Further, they graded COVID-19 presentations of all patients per the National institute of health (NIH) guidelines into asymptomatic, mild, moderate, and severely sick. The team used an in-house enzyme-linked immunosorbent assay (ELISA) targeting the full-length trimeric S to measure the level of IgG antibodies in patient-provided serum samples.
Study findings
From 309 patients, the researchers collected 585 blood samples across the five-time points of the study. The study cohort had 70% male patients, with most patients belonging to the mild and severe groups, 121/309 and 141/309, respectively.
The antibody neutralization potency increased until day 28 and then declined until day 180 in the participants recruited before April 2021. Conversely, for those recruited post-April 2021, the immune responses were more heterogenous, with nAb levels increasing until day 28 and then plateauing between day 28 and day 180. Infection-induced nAbs were more potent against the Wuhan-Hu1 strain than SARS-CoV-2 VOCs that became prevalent later. Also, the results pointed to a strong correlation between the antibody binding levels, neutralizing potencies, and an increase in disease severity.
Only a few studies have determined the kinetics of anti-SARS-CoV-2 antibody kinetics in the Sub-Saharan African population for a longer duration. For instance, a South African study quantified IgG antibodies weekly over three months among COVID-19 patients and demonstrated rapid waning of anti-SARS-CoV-2 RBD IgA and IgM nAbs.
However, the current study results showed the significance of longer durations of follow-ups in longitudinal studies ascertaining anti-SARS-CoV-2 antibody kinetics following infection.
Anti-SARS-CoV-2 antibodies with neutralizing function decayed three-fold by the sixth month of follow-up. It explains possible re-infections in the current study cohort, where a few patients had binding and neutralizing antibodies increasing after day 28 of COVID-19 diagnosis without vaccination. Similarly, other studies have shown occurrences of SARS-CoV-2 re-infections.
Conclusions
The study results showed that anti-SARS-CoV-2 nAbs are short-lived, while other antibodies may be long-lasting. During recovery, binding antibodies are not an accurate surrogate of neutralizing function. Antibodies work via cellular cytotoxicity and complement deposition mechanisms, and mediate viral clearance. However, such roles remain unexplored for SARS-CoV-2.
It is crucial to investigate these mechanisms because COVID-19 vaccines use them for viral clearance, which contributes more to sterile immunity. Understanding the magnitude and functional aspects of antibody kinetics would inform the development of next-generation COVID-19 vaccines that could offer much-needed long-term protection.
Finally, even in sub-Saharan African populations, vaccine boosters will help sustain the high levels of neutralizing antibodies that peak after acute infection. Thus, concerted efforts to vaccinate the sub-Saharan African population could help broaden and extend their current levels of naturally acquired anti-SARS-CoV-2 immunity.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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