T Cell Responses to SARS-CoV-2 Infection and Vaccination Are Elevated in B Cell Deficiency and Reduce Risk of Severe COVID-19

To explore the cellular immune responses following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination in patients who received rituximab therapy (RTX) and in patients with low B cell counts because of common variable immune deficiency (CVID) disease.Specimens from 89 individuals were analyzed. The control group consisted of 44 patients with intact B cell compartments (49%), whereas 33 patients had pharmacologic B cell deficiency secondary to RTX treatment (37%), and 12 patients had primary B cell deficiency secondary to CVID disease (14%). Of the RTX participants, 11 were previously infected, 15 had received an messenger (mRNA) vaccine series, and 7 were vaccinated after initial infection. All 12 CVID patients previously received the mRNA vaccine series and had no prior infection. Of the control group, 27 had been previously infected, 13 had received the mRNA vaccine series, and 4 had received the mRNA vaccine after initial infection.One hundred peripheral blood mononuclear cell samples were obtained. Effector and memory T cell responses were assessed in patients on active treatment with RTX or with CVID disease after SARS-CoV-2 infection and vaccination with the use of IFN-γ ELISpot and CFSE-based proliferation assays. T cell memory differentiation states were determined with the use of cell surface staining and flow cytometry. Clinical outcomes in regards to coronavirus disease 2019 severity were determined by chart review. In individuals with B cell deficiency, T cell response to common viral pathogens (CMV, EBV, and influenza) was also studied.In B cell-deficient individuals, increased effector and memory T cell responses (particularly CD8 + T cells) were noted after both SARS-CoV-2 infection and vaccination compared with healthy controls. A 4.8-fold reduction in odds of moderate or severe coronavirus disease 2019 infection was noted in RTX-treated patients who received vaccination despite the absence of vaccine-induced antibodies. RTX-treated individuals were found to have an increased frequency of naïve CD8 + T cells. However, this also led to a decrease in preexisting antiviral T cell immunity.Enhanced T cell immunity in B-cell deficient patients after both SARS-CoV-2 infection and vaccination may reduce hospitalization and account for reduced severity of disease from subsequent SARS-CoV-2 infection, even in patients with absent antibody responses.The findings presented in this study demonstrate increased T cell responses following SARS-CoV-2 infection or vaccination in patients with both primary and pharmacologic B cell deficiencies. The findings from this study support vaccination in immunocompromised patients to help reduce disease severity. Additional studies are needed to assess cellular and humoral immunity after infection and vaccination in immunocompromised individuals and its effects on clinical outcomes. Clinical and immune responses in the setting of subsequent infections in this vulnerable population need to be further explored to corroborate the results presented here.