SARS-CoV-2-Associated T-Cell Responses in the Presence of Humoral Immunodeficiency

Gupta, Sudhir; Su, Houfen; Narsai, Tejal; Agrawal, Sudhanshu

We report perhaps the most comprehensive study of subsets of CD4+ and CD8+ and subsets of B cells in a mild symptomatic SARS-CoV-2+ immunocompetent patient and a common variable immunodeficiency disease (CVID) patient who had normal absolute lymphocyte counts and remained negative for SARS-CoV-2 IgG antibodies. Naïve (TN), central memory (TCM), effector memory (TEM), and terminally differentiated effector memory (TEMRA) subsets of CD4+ and CD8+ T cells, subsets of T follicular helper cells (cTFH, TFH1, TFH2, TFH17, TFH1/TFH17, and TFR), CD4 Treg, CD8 Treg, mature B cells, transitional B cells, marginal zone B cells, germinal center (GC) B cells, CD21(low) B cells, antibody-secreting cells (plasmablasts), and Breg cells were examined in patients and age-matched controls with appropriate monoclonal antibodies and isotype controls using multicolor flow cytometry. Different patterns of abnormalities (often contrasting) were observed in the subsets of CD4+ T, CD8+ T, B-cell subsets, and regulatory lymphocytes among the immunocompetent patient and CVID patient as compared to corresponding healthy controls. Furthermore, when data were analyzed between the 2 patients, the immunocompetent patient demonstrated greater changes in various subsets as compared to the CVID patient. These data demonstrate different immunological responses to SARS-CoV-2 infection in an immunocompetent patient and the CVID patient. A marked decrease in GC B cells and plasmablasts may be responsible for failure to make SARS-CoV-2 antibodies. The lack of SARS-CoV-2 antibodies with mild clinical disease suggests an important role of T-cell response in defense against SARS-CoV-2 infection.