Longitudinal Analysis of Human Memory T-Cell Response according to the Severity of Illness up to 8 Months after SARS-CoV-2 Infection

Abstract

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—seven asymptomatic and nine with mild and eight with severe disease—as well as six 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.