Longitudinal Analysis of Human Memory T-Cell Response According to the Severity of Illness up to 8 Months After Severe Acute Respiratory Syndrome Coronavirus 2 Infection

Background. Understanding the memory T-cell response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for assessing the longevity of protective immunity after SARS-CoV-2 infection or coronavirus disease 2019 (COVID-19) vaccination. However, the longitudinal memory T-cell response up to 8 months post-symptom onset (PSO) according to the severity of illness is unknown. Methods. We analyzed peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with COVID-19 who experienced asymptomatic, mild, or severe illness at 2, 5, and 8 months PSO. SARS-CoV-2 spike, nucleocapsid, and membrane protein-stimulated PBMCs were subjected to flow cytometry analysis. Results. A total of 24 patients (7 asymptomatic, 9 with mild disease, and 8 with severe disease) and 6 healthy volunteers were analyzed. SARS-CoV-2-specific OX40(+)CD137(+)CD4(+) T cells and CD69(+)CD137(+)CD8(+) T cells persisted at 8 months PSO. Also, antigen-specific cytokine- producing or polyfunctional CD4(+) T cells were maintained for up to 8 months PSO. Memory CD4(+) T-cell responses tended to be greater in patients who had severe illness than in those with mild or asymptomatic disease. Conclusions. Memory response to SARS-CoV-2, based on the frequency and functionality, persists for 8 months PSO. Further investigations involving its longevity and protective effect from reinfection are warranted.

Automated summary

The memory T-cell response to SARS-CoV-2 persists for up to 8 months post-symptom onset, with potentially stronger responses in patients with severe illness compared to those with mild or asymptomatic disease. Further investigations are necessary to assess the longevity and protective effect of this immune response against reinfection.