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.