SARS-CoV-2-Specific and Functional Cytotoxic CD8 Cells in Primary Antibody Deficiency: Natural Infection and Response to Vaccine

Purpose CD8 cytotoxic T cells (CTLs) play a critical role in the clearance of virally infected cells. SARS-CoV-2-specific CD8 T cells and functional CTLs in natural infections and following COVID-19 vaccine in primary antibody deficiency (PAD) have not been reported. In this study, we evaluated T cell response following COVID-19 or COVID-19 mRNA vaccination in patients with PADs by assessing SARS-CoV-2 tetramer-positive CD8 T cells and functional CTLs. Methods SARS-CoV-2-specific CD8 and functional CTLs were examined in a patient with X-linked agammaglobulinemia (XLA) and a patient with common variable immunodeficiency (CVID) following COVID-19 infection, and in 5 patients with CVID and 5 healthy controls 1 month following 2nd dose of COVID-19 mRNA vaccine (Pfizer-BioNTech). Cells were stained with SARS-CoV-2 spike protein-specific tetramers, and for functional CTLs (CD8 (+) CD107a(+) granzyme B+ perforin(+)), with monoclonal antibodies and isotype controls and analyzed by flow cytometry. Results SARS-CoV-2-specific tetramer +CD8 T cells and functional CTLs in the patient with XLA following COVID-19 infection were higher, as compared to healthy control subject following COVID-19 infection. On the other hand, SARS-CoV2-tetramer +CD8 T cells and functional CTLs were lower in CVID patient following COVID19 infection as compared to healthy control following COVID-19 infection. SARS-CoV2-tetramer +CD8 T cells and functional CTLs were significantly lower in SARS-CoV2-naive CVID patients (n = 10) following vaccination when compared to SARS-CoV-2-naive healthy vaccinated controls (n = 10) . Conclusions CVID is associated with reduced SARS-CoV-2-specific CD8 T cells and functional CTLs in both natural SARS-CoV-2 infection and in response to SARS-CoV-2 mRNA vaccine, whereas natural infection in XLA is associated with a robust SARS-CoV-2-specific CD8 and functional CTL responses.

Automated summary

This study evaluated the T cell response to COVID-19 infection and vaccination in patients with primary antibody deficiencies. The results showed that COVID-19 infection led to higher levels of SARS-CoV-2-specific CD8 and functional CTLs in a patient with XLA, while in CVID patients, both natural infection and vaccination resulted in lower levels of these cells.