Recovery of Memory B-cell Subsets and Persistence of Antibodies in Convalescent COVID-19 Patients

Abstract

It is essential to examine the longevity of the defensive immune response engendered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examined the SARS-CoV-2-specific antibody responses and ex vivo memory B-cell subsets in seven groups of individuals with COVID-19 classified based on days since reverse-transcription polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data showed that the levels of IgG and neutralizing antibodies started increasing from days 15 to 30 to days 61 to 90, and plateaued thereafter. The frequencies of naive B cells and atypical memory B cells decreased from days 15 to 30 to days 61 to 90, and plateaued thereafter. In contrast, the frequencies of immature B cells, classical memory B cells, activated memory B cells, and plasma cells increased from days 15 to 30 to days 61 to 90, and plateaued thereafter. Patients with severe COVID-19 exhibited increased frequencies of naive cells, atypical memory B cells, and activated memory B cells, and lower frequencies of immature B cells, central memory B cells, and plasma cells when compared with patients with mild COVID-19. Therefore, our data suggest modifications in memory B-cell subset frequencies and persistence of humoral immunity in convalescent individuals with COVID-19.

Figure 1.

Expansion of IgG and the neutralizing capacity and decrease of the IgA frequencies in convalescent COVID-19 individuals over time. The plasma levels of SARS-CoV2 spike protein-specific IgM and IgG, N protein-specific IgA, and neutralizing antibodies were measured in individuals with acute COVID-19 and convalescent individuals with COVID-19 classified as groups based on the number of days since reverse-transcription polymerase chain reaction confirmation of disease. The levels of antibodies are shown with the preferred model for the best fit curve, and each dot represents single individuals. The thick black line represents the best fit curve.

Figure 2.

Alterations in the frequencies of B-cell subsets in convalescent individuals with COVID-19 over time. Analysis of B-cell subsets from individuals with acute COVID-19 and convalescent individuals with COVID-19 classified as groups based on the number of days since reverse-transcription polymerase chain reaction confirmation of disease. The frequencies of B-cell subsets are shown with the preferred model for the best fit curve, and each dot represents single individuals. The thick black line represents the best fit curve.

Figure 3.

Severe COVID-19 disease is associated with altered frequencies of B-cell subsets. The frequencies of B-cell subsets in individuals with mild (N = 30) COVID-19 and severe (N = 15) COVID-19 sampled between days 15 and 60 after reverse-transcription polymerase chain reaction confirmation of disease. The data are denoted as scatter plots with each circle denoting a single individual. The Mann-Whitney U test was used to calculate P values.