SARS-CoV-2 spike-specific memory B cells express higher levels of T-bet and FcRL5 after non-severe COVID-19 as compared to severe disease.

Robin E. Tragus,Gabriel Catano,Evelien M. Bunnik,S. Jake Gonzales,Thomas F. Patterson,Rolando Garza,Angelene M. Cantwell,Menno C van Zelm,Sebastiaan Bol,Raphael A. Reyes,Kathleen Clarke

doi:10.1371/journal.pone.0261656

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 and FcRL5, as compared to individuals who experienced severe disease. While the frequency of T-bet+ spike-specific IgG+ B cells differed between the two groups, these cells predominantly showed an activated switched memory B cell phenotype in both groups. 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 highlight subtle differences in the B cells response after non-severe and severe COVID-19 and suggest that the memory B cell response elicited during non-severe COVID-19 may be of higher quality than the response after severe disease.

Highlights

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global coronavirus disease 2019 (COVID-19) pandemic resulting in more than 5 million deaths reported worldwide as of December 2021 [1]
Assessments of B cell responses up to one year post-infection suggest that both neutralizing antibodies and memory B cells against the SARS-CoV-2 spike protein remain detectable in the circulation of most recovered COVID-19 patients and are stable or decay slowly at this time point
We aimed to better understand the memory B cell response and to determine whether the severity of COVID-19 disease course influences the development of B cell responses

Summary

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the global coronavirus disease 2019 (COVID-19) pandemic resulting in more than 5 million deaths reported worldwide as of December 2021 [1]. The majority of the world’s population lives in areas with low vaccination rates and remain at higher risk of SARS-CoV-2 infection and COVID19. Both vaccination and natural infection elicit immunological protection against SARSCoV-2 (re-)infection. MRNA vaccination elicits higher antibody titers and more diverse antibody responses against the SARS-CoV-2 spike protein than natural infection [2, 3], results from the first longitudinal studies in unvaccinated individuals with prior COVID-19 suggest that naturally acquired immune responses are maintained for at least a year after infection and that these responses protect from subsequent re-infection [4,5,6,7,8,9,10,11]. Because many people remain unvaccinated, it will be important to understand the immune response elicited by natural infection and whether the durability of naturally acquired immunity is influenced by the severity of disease

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