SARS-CoV-2 spike-specific memory B cells express markers of durable immunity after non-severe COVID-19 but not after severe disease

Abstract

SARS-CoV-2 infection elicits a robust B cell response, resulting in the generation of long-lived plasma cells and memory B cells. Here, we aimed to determine the effect of COVID-19 severity on the memory B cell response and characterize changes in the memory B cell compartment between recovery and five months post-symptom onset. Using high-parameter spectral flow cytometry, we analyzed the phenotype of memory B cells with reactivity against the SARS-CoV-2 spike protein or the spike receptor binding domain (RBD) in recovered individuals who had been hospitalized with non-severe (n=8) or severe (n=5) COVID-19. One month after symptom onset, a substantial proportion of spike-specific IgG+ B cells showed an activated phenotype. In individuals who experienced non-severe disease, spike-specific IgG+ B cells showed increased expression of markers associated with durable B cell memory, including T-bet, FcRL5, and CD11c, which was not observed after severe disease. Five months post-symptom onset, the majority of spike-specific memory B cells had a resting phenotype and the percentage of spike-specific T-bet+ IgG+ memory B cells decreased to baseline levels. Collectively, our results suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

Dynamics of humoral immune response in SARS-CoV-2 infected individuals with different clinical stages

“…Although we do not analyze the response of SARS-CoV-2specific B cells, several authors have reported an expansion of MBCs one-month post-symptom onset, and an increase of Sspecific IgG + switched MBC at fivemonths of follow-up. Moreover, the quality of response looks to be differential since individuals with non-severe COVID-19 have a phenotype associated with durable memory that is least frequently observed in severe COVID-19 (33). In agreement with those findings, severe COVID 19 induces an exhaustion phenotype on S1-specific IgG + MBCs compared with healthy and recovered individuals (34).…”

Autoantibodies elicited with SARS-CoV-2 infection are linked to alterations in double negative B cells

“…In support of this, a decreased frequency of RBD-specific DN2 cells was observed 10 weeks post-infection when compared to levels during acute infection (22), suggesting that expansion of virusspecific DN2 cells is transient and resolves with infection. However, it should be noted that even five months postrecovery from severe infection, RBD-specific Double Negative B cells are still detectable (40), indicating that expansion of virally-associated DN subsets likely contracts with infection but are not lost. Furthermore, expansion of atypical memory B cells (CD27 -CD21 lo/-), which would include both DN2 and DN3 subsets, is resolved in patients recovered from severe SARS-CoV-2 infection (41,42).…”

Identification of virus-specific B-cell epitopes by convalescent plasma from COVID-19 patients

“…The expression of T-bet - a reliable marker of memory B cell antiviral function - is increased during SARS-CoV-2 infection, especially in symptomatic patients ( Notarbartolo et al, 2021 , Reyes et al, 2021 , Rodda et al, 2021 ), and is maintained at high levels for a few months after disease onset ( Rodda et al, 2021 ). At this point, the frequency of virus-specific T-bet + IgG + memory B cells decreases to a baseline level ( Reyes et al, 2021 ). Our data further demonstrated that T-bet + memory B cells rapidly declined in COVID-19 patients after 3 months of recovery.…”