Non-severe COVID-19 may cause a longer lasting memory B cell response than severe COVID-19

Although highly effective vaccines have minimized transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and significantly reduced morbidity and mortality in countries with access to COVID-19 vaccines, most of the world’s population still has limited access to these vaccines. and remain at high risk of infection with SARS-CoV-2.

Immunity against (re) infection with SARS-CoV-2 can be acquired by both vaccination and natural infection. Although vaccines elicit higher antibody titers and a more diverse immune response against the SARS-CoV-2 spike protein compared to natural infection, longitudinal studies conducted on unvaccinated individuals recovered from COVID- 19 suggest that the natural immunity acquired from infection is maintained for almost a year after infection. In addition, these natural immune responses also protect individuals from subsequent reinfection, as infection with SARS-CoV-2 elicits a powerful B-cell response, resulting in the generation of long-lasting plasma cells and memory B cells.

Since many people around the world have limited access to vaccines, it is crucial to understand the immune response induced by natural infection and the impact of disease severity on the sustainability of natural immunity.

Determining the Impact of COVID-19 Severity on Memory B Cell Response

A recent study by researchers in the United States aimed to measure the impact of the severity of COVID-19 on the memory B cell response and characterize the changes in the memory B cell compartment during the period between recovery and five months after the onset of symptoms. This study is available on the bioRxiv* preprint server.

The researchers used high-parameter spectral flow cytometry to analyze the phenotype of memory B cells reactive against the SARS-CoV-2 spike protein or spike receptor binding domain in individuals recovered from COVID-19. As a result, eight people were hospitalized with non-serious COVID-19 and five were hospitalized with serious illness.

One month after the onset of symptoms, a significant proportion of spike-specific IgG + B cells exhibited an activated phenotype. Spike-specific IgG + B cells from individuals who had non-severe COVID-19 showed increased expression of enduring B-cell memory-related markers such as T-bet, CD11c, and FcRL5. This increased expression of the markers was not observed in individuals who had severe disease.

Five months after symptom onset, most spike-specific memory B cells exhibited a resting phenotype, and the proportion of spike-specific T-bet + IgG + memory B cells decreased to baseline. Overall, the results show that non-severe COVID-19 can cause a better memory B cell response than severe COVID-19.

“The increased percentage of B cells associated with long-lasting immunity in non-severe COVID-19 patients may have implications for long-term immunity to SARS-CoV-2 reinfection or the severity of the disease that result. “

Results show that patients with severe and non-severe COVID-19 develop different memory B cell response

According to the authors, although this study was conducted on a relatively small number of individuals, it repeated many of the results previously reported from larger cohorts. It confirmed the loss of memory B cells specific to peaks of IgM + and IgA +, anti-peak and anti-RBD plasma IgMs, and the maintenance of memory B cells specific to peaks of plasma IgG + and IgG anti-peaks five months after the onset of symptoms. They also said that the most notable finding from their study is the higher proportion of spike-specific IgG + B cells that express the T-bet transcription factor in people who did not have severe COVID-19 compared to those who had serious illness.

Distribution of major B cell subsets in recovered COVID-19 patients. A) Triggering strategy to obtain non-antibody secreting B cells (CD38lo) which are then divided into naive, unswitched (uswM), switched (swM) and double negative (DN) memory. SwM B cells were divided into activated and resting populations based on CD21 expression. DN cells were divided into DN1 – 3 based on the expression of FcRL5 and CXCR5. B) Median percentage of each subset of B cells in samples from individuals who have recovered from non-severe COVID-19 and severe COVID-19. C) Percentage of unswitched memory B cells, which increased in people who recovered from severe illness compared to those who did not have severe COVID-19. D) Median proportions of the three different populations of DN 1 month after a non-serious or serious illness. In panels B to D, results are shown for people who have recovered from non-severe COVID-19 (n = 8) and severe COVID-19 (n = 5). See Figure S1 for graphs with individual data points for the data shown in panels B and D. * P <0.05

While previous studies had observed that a higher percentage of total CD19 + T-bet + IgG1 + B cells was linked to a shorter duration of symptoms, this study showed that this association mainly involves B cells specific for the antigen of the SARS-CoV-2 which indicate the development of B cell memory.

To conclude, the observations of this study show that patients with severe and non-severe COVID-19 disease develop a memory B cell response differently against the SARS-CoV-2 spike protein. People who recovered from non-severe disease had more spike-specific B cells that express B cell markers associated with long-lasting immunity, characterized by expression of T-bet, CD11c, and FcRL5, and low expression of CD21.

“These data help understand the naturally acquired B cell responses to SARS-CoV-2 and help characterize the B cell populations that may be responsible for long-lasting and long-lasting immunity.”

*Important Notice

bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.