Switched and unswitched memory B cells detected during SARS-CoV-2 convalescence correlate with limited symptom duration

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the pandemic human respiratory illness COVID-19, is a global health emergency. While severe acute disease has been linked to an expansion of antibody-secreting plasmablasts, we sought to identify B cell responses that correlated with positive clinical outcomes in convalescent patients. We characterized the peripheral blood B cell immunophenotype and plasma antibody responses in 40 recovered non-hospitalized COVID-19 subjects that were enrolled as donors in a convalescent plasma treatment study. We observed a significant negative correlation between the frequency of peripheral blood memory B cells and the duration of symptoms for convalescent subjects. Memory B cell subsets in convalescent subjects were composed of classical CD24+ class-switched memory B cells, but also activated CD24-negative and natural unswitched CD27+ IgD+ IgM+ subsets. Memory B cell frequency was significantly correlated with both IgG1 and IgM responses to the SARS-CoV-2 spike protein receptor binding domain (RBD) in most seropositive subjects. IgM+ memory, but not switched memory, directly correlated with virus-specific antibody responses, and remained stable over 3 months. Our findings suggest that the frequency of memory B cells is a critical indicator of disease resolution, and that IgM+ memory B cells may play an important role in SARS-CoV-2 immunity.

Early cross-coronavirus reactive signatures of humoral immunity against COVID-19

“…Importantly, given the remarkable avidity and functional potency of IgM, able to drive robust complement and opsonophagocytic activity (76)(77)(78), it is plausible that IgM responses may be sufficient in the context of acute infection to drive rapid control and clearance of the pathogen. Moreover, SARS-CoV-2 specific IgM monoclonal therapeutics are more potent than IgG therapeutics in the treatment of SARS-CoV-2 infection in animal models (79)(80)(81), potentially pointing to the possibility that individuals able to selectively expand their OC43-specific IgM or IgG will respond better to COVID-19.…”

Persistent COVID-19 Symptoms Minimally Impact the Development of SARS-CoV-2-Specific T Cell Immunity

“…Study design: Convalescent COVID-19 patients were recruited for this study at the SUNY Upstate Medical University Clinical Research Unit starting in March 2020 under the SUNY Upstate Convalescent Plasma Donor Program [ 19 ]. This study was reviewed by the SUNY Upstate Medical University IRB, reviewed and approved by the Western Institutional Review Board (IRB # 1587400), and performed under informed consent.…”

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

“…Only depletion of peripheral IgM+ memory B cells seems to be a hallmark of SARS-CoV-2 infection ( Carsetti et al, 2020 ; Lenti et al, 2020 ). Intriguingly, the percentage of IgM+ and switched memory B cells showed an inverse correlation with symptoms duration in convalescent patients, with no age or gender related influence ( Newell et al, 2021 ).…”

“…This lack of homogeneity mirrors the absence of an agreement about the stratification of COVID-19 cases according to severity. In addition, the selected statistical analysis strategy, especially in the presence of multiple comparisons, may “mask” some statistically significant results, requiring a larger sample size or a different statistical approach to reveal relevant differences among the compared categories ( Jurado et al, 2020 ; Sosa-Hernández et al, 2020 ; Woodruff et al, 2020 ; d’Alessandro et al, 2021 ; Newell et al, 2021 ; Shuwa et al, 2021 ). As a result, the abundance of confounding reports slows down the extrapolation of prognostic and predictive pieces of information from published reports.…”

“…DN B lymphocytes reached a statistically significant expansion in both COVID-19 patients and convalescent subjects vs. controls ( Table 7 ; Mathew et al, 2020 ; Shuwa et al, 2021 ). However, at an individual patient level, DN B cell fraction tends to decrease from acute disease to convalescent status ( Newell et al, 2021 ; Shuwa et al, 2021 ). A keen characterization of DN B cell subsets, revealed that the increase of DN B cells in severe and critical patients may be attributable to an augmented CD38–CD24–CD21–CD11c+ DN2 and CD38–/+CD24–CD21–CD11c– DN3 fraction ( Table 7 ; Sosa-Hernández et al, 2020 ).…”