T cell-mediated Immune response and correlates of inflammation and their relationship with COVID-19 clinical severity: not an intuitive guess

Author(s)

Pena, Nathalia Mantovani ; Santana, Luiz Claudio ; Hunter, James R. ; Blum, Vinicius Fontanesi ; Vergara, Tania ; Gouvea, Celso ; Leal, Elcio ; Bellei, Nancy ; Schechter, Mauro ; Diaz, Ricardo Sobhie

• Document type: Journal article
• Source: BMC INFECTIOUS DISEASES; v. 24, n. 1, p. 11-pg., 2024-06-20.

Abstract

Background Predictors of the outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remain to be fully determined. We evaluated selected viral characteristics and immunological responses that might predict and/or correlate to the clinical outcome of COVID-19.Methods For individuals developing divergent clinical outcomes, the magnitude and breadth of T cell-mediated responses were measured within 36 h of symptom onset. Peripheral Blood Mononuclear Cells (PBMCs) were subjected to in vitro stimulation with SARS-CoV-2-based peptides. In addition, SARS-CoV-2 sequences were generated by metagenome, and HLA typing was performed using Luminex technology.Findings CD4+ T cell activation was negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0<middle dot>043). The overall cellular immune response, as inferred by the IFN-gamma signal, was higher at baseline for patients who progressed to mild disease compared to patients who progressed to severe disease (p = 0<middle dot>0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0<middle dot>033).Interpretation Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-gamma magnitude in the ELISPOT assay, may efficiently favor a positive outcome. In contrast, progression to severe COVID-19 was accompanied by stronger cellular immune responses, higher CD4 + T cell activation, and a higher number of in silico predicted high-affinity class I HLA alleles. (AU)

• FAPESP's process: 20/10396-2 - Multiple interventions to eliminate HIV reservoirs among antiretroviral treated individuals in order to obtain sustained HIV remission without antiretrovirals
• Grantee: Ricardo Sobhie Diaz
• Support Opportunities: Research Projects - Thematic Grants