Discussion
In this study, we investigated the formation of S- protein-specific BMEMORY cells in convalescent COVID-19 patients. We employed a control group to rule out significant cross-reactivity. Our findings indicated that there were minimal cross-reactive responses in healthy donors. Studying immunological memory and protection after SARS-CoV-2 infection is of particular importance for understanding the formation of B cell memory and, subsequently, the effectiveness of vaccination approaches as well as the need for further booster dosing. Thus, this study represents a step toward understanding COVID-19 long-term immunity.
Serological testing offers the potential for screening, contact tracing, evaluating the viral reservoir, and supporting epidemiologic assessments by detecting SARS-Cov-2 specific antibodies. Another challenge for a broad and robust application of antibody-based SARS-CoV-2 detection assays, especially in the long-term, is the currently questionable durability and high variability of the SARS-CoV-2 induced antibody responses, where neutralizing antibody titers decrease over time in SARS-CoV-2 infected individuals in some studies6–10. Furthermore, recent studies provided evidence that a proportion of SARS-CoV-2 infected individuals did not develop specific antibodies11,34,35. Thus, failed antibody formation or their rapid wane in circulation may limit our ability to verify COVID-19 immunity in the long-term, especially for mild or asymptomatic disease.
We, therefore, aimed at exploring immune responses to SARS-CoV-2 by studying and characterizing the B cell response. Such an approach enables us to understand long-term immunity more thoroughly. We were able to detect BMEMORY cells specific to SARS-CoV-2 S-Protein, which also persisted in patients for more than 200 days. B cells can provide serological memory for decades or potentially the entire lifespan of individuals25–27. Thus, although the antibodies that B cells produce during initial exposure may disappear within a few weeks, the generated BMEMORYcells can persist for much longer. For instance, previous studies were able to identify IgG memory B cells specific to the receptor-binding domain (RBD) in the blood of COVID-19 subjects22,24,29,36. Moreover, Zhang et al. demonstrated protective immunity formation with detectable levels of BMEMORY cells in a pediatric population37. Similarly, a recent study addressing SARS-CoV-2 infection in rhesus macaques showed that two recovered subjects were resistant to reinfection one month later38. Our analysis of the S-protein SARS-CoV-2 specific BMEMORY cells in samples collected at different time points revealed that these cells remain in peripheral blood at least up to 6 months after COVID-19 diagnosis. Thus, our study performed on a central European cohort of patients is in line with the data on the recently published US American and Australian cohorts and thus, confirms and extends the knowledge on the B cell response against SARS-CoV-229,30. Therefore, our results demonstrating the longevity of SARS-CoV-2-specific B cell response can improve the general acceptance towards immunization in the broad community.
We acknowledge the limitations of our studies. First, only convalescent patients were studied, hence studying the B cell in patients with acute SARS-CoV-2 infection should be considered in further studies. Subsequent studies should also enroll larger patient cohorts with greater demographic variability and longer follow-up periods to decipher potential intra- and inter variability and to validate the finding that COVID-19 BMEMORY cells reflect a long-term immunity. Furthermore, our control cohort was significantly younger than the COVID-19 cohort, with a median difference of 10 years. However, this difference does not negatively affect the differences observed in SARS-CoV-2-specific BMEMORY in the two cohorts, since younger patients are supposed to have a stronger immune response. Nevertheless, we did not observe specific staining in the healthy donor cohort as evidenced by the lack of significant blocking of the staining.
In conclusion, our study evaluated the long-term immunity through the characterization of SARS-COV-2 specific BMEMORY cells in a cohort of mild/moderate symptomatic COVID-19 patients versus healthy control subjects. We were able to detect S-specific B cells in the COVID-19 cohort even in mild cases. Overall, our study demonstrating the formation of SARS-CoV-2-specific long-term immunity may enable further opportunities for improving general vaccination acceptance thus supporting efforts to implement effective public health care measures during the COVID-19 pandemic.