T cell immune memory and protective correlates in Ugandans with mild Covid-19 disease.

Abstract

Background: This study explores T cell immune memory and protective correlates in Ugandans with mild COVID-19 disease, focusing on those with low immunoglobulin G (IgG) antibody levels. Understanding the mechanisms that confer protection in the absence of strong humoral immunity is crucial for developing effective therapeutic and preventive strategies against SARS-CoV-2. Objective: To identify T cell correlates of protection in individuals with mild COVID-19 and low IgG antibody responses, aiming to elucidate the role of T cell-mediated immunity in the absence of robust humoral responses. Methods: A longitudinal prospective study was conducted using peripheral blood mononuclear cell (PBMC) samples from SARS-CoV-2 positive individuals at three time points: month zero (M0), month one (M1), and month six (M6). Participants were categorized into high IgG and neutralizers (HN) and low IgG and non-neutralizers (LNn). Flow cytometry evaluated T cell activation markers, cytokine profiles, and memory T cell subsets in response to SARS-CoV-2 predicted CD4 and CD8 T cell epitopes. Results: Significant differences were observed in T cell responses between the HN and LNn groups. LNn individuals exhibited higher net percentages of CD4+/OX40+ cells (P=0.01) and lower percentages of naïve T cells (P=0.04) upon CD4S peptide stimulation, indicating enhanced T cell activation and differentiation. CD4+/CD137+ cells were lower in the LNn group following CD4R stimulation (P=0.02), suggesting reliance on alternative activation pathways. CD8A stimulation revealed that LNn individuals had lower proliferative responses in CD8+ T cells, as indicated by lower Ki67 expression (P=0.02), but higher percentages of terminally differentiated effector memory T cells (TEMRA, P=0.02), highlighting the importance of robust cytotoxic memory T cell responses. Conclusion: The study underscores the crucial role of T cell-mediated immunity in SARS-CoV-2 protection, particularly in individuals with low antibody responses. These findings provide insights into immune mechanisms in mild COVID-19 and suggest potential targets for enhancing vaccine-induced protection in low seroconversion populations.