Non-severe COVID-19 may elicit more durable memory B cell response than severe COVID-19

Although highly effective vaccines have minimized the 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 global population still has limited access to these vaccines and remain at elevated risk of SARS-CoV-2 infection.

Immunity against SARS-CoV-2 (re)infection 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 in unvaccinated individuals recovered from COVID-19 suggest that natural immunity acquired from infection is maintained for nearly one year after infection. Furthermore, these natural immune responses also protect the individuals from subsequent re-infection, as SARS-CoV-2 infection elicits a powerful B cell response, which results in the generation of long-lasting plasma cells and memory B cells.

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

Determining the impact of COVID-19 severity on memory B cell response

A recent study conducted by researchers from the US aimed to measure the impact of severity of COVID-19 on memory B cell response and characterize changes in the memory B cell compartment during the period between recovery and five months after symptom onset. 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 spike protein of SARS-CoV-2 or the spike receptor-binding domain in COVID-19 recovered individuals. As a result, eight individuals were hospitalized with non-severe COVID-19, and five were hospitalized with severe disease.

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

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

“The increased percentage of B cells associated with long-lived immunity in non-severe COVID-19 patients may have consequences for long-term immunity against SARS-CoV-2 re-infection or severity of the resulting disease.”

Findings 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 in a relatively small number of individuals, it reiterated many of the findings reported earlier from larger cohorts. It confirmed the loss of IgM+ and IgA+ spike-specific memory B cells, anti-spike and anti-RBD plasma IgM, and the maintenance of IgG+ spike-specific memory B cells and anti-spike plasma IgG five months after symptom onset. They also stated that the most remarkable finding from their study is the higher proportion of spike-specific IgG+ B cells that express the transcription factor T-bet in individuals who had non-severe COVID-19 compared to those who had severe disease.

Distribution of major B cell subsets in recovered COVID-19 patients. A) Gating strategy to obtain non-antibody-secreting B cells (CD38lo) that are further divided into naïve, unswitched memory (uswM), switched memory (swM), and double negative (DN). SwM B cells were divided into activated and resting populations based on the expression of CD21. DN cells were divided into DN1 – 3 based on the expression of FcRL5 and CXCR5. B) Median percentage of each B cell subset in samples from individuals who recovered from non-severe COVID-19 and severe COVID-19. C) Percentage of unswitched memory B cells, which was increased in individuals who recovered from severe disease as compared to those who had non-severe COVID-19. D) Median proportions of the three different DN populations 1 month after non-severe or severe disease. In panel B – D, results are shown for individuals who 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
Distribution of major B cell subsets in recovered COVID-19 patients. A) Gating strategy to obtain non-antibody-secreting B cells (CD38lo) that are further divided into naïve, unswitched memory (uswM), switched memory (swM), and double-negative (DN). SwM B cells were divided into activated and resting populations based on the expression of CD21. DN cells were divided into DN1 – 3 based on the expression of FcRL5 and CXCR5. B) Median percentage of each B cell subset in samples from individuals who recovered from non-severe COVID-19 and severe COVID-19. C) Percentage of unswitched memory B cells, which was increased in individuals who recovered from severe disease as compared to those who had non-severe COVID-19. D) Median proportions of the three different DN populations 1 month after non-severe or severe disease. In panel B – D, results are shown for individuals who 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 observed that a higher percentage of total CD19+ T-bet+ IgG1+ B cells was linked to shorter symptom duration, this study showed that this association predominantly involves SARS-CoV-2 antigen-specific B cells which indicate the development of B cell memory.

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

“These data aid in the understanding of naturally acquired B cell responses against SARS-CoV-2 and help characterize the B cell populations that may be responsible for durable, long-lived immunity.”

*Important Notice

bioRxiv 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.

Journal reference:
Susha Cheriyedath

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.

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