COVID-19 Clinical Severity, T Cell-Mediated Immune Response, and Correlates of Inflammation: Not an Intuitive Guess

Background: Predictors of 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 or correlate to the clinical outcome of COVID-19.Methods: The magnitude and breadth of T cell-mediated responses were measured within 36 hours of symptom onset for individuals developing divergent clinical outcomes. 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 through Luminex technology.Findings: CD4+ T cell activation was found to be negatively correlated with SARS-CoV-2 basal viral load in patients with severe COVID-19 (p = 0·043). The overall cellular immune response, as inferred by IFN-γ signal, was higher at baseline for patients that progressed to mild disease compared to patients that progressed to severe disease (p = 0·0044). Subjects with milder disease developed higher T cell responses for MHC class I and II-restricted peptides (p = 0·033).Interpretation: Mounting specific cellular immune responses in the initial hours after symptom onset 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, as well as a higher number of in silico predicted high-affinity class I HLA alleles.Funding Information: This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) - Grant 2020/10396-2 and Conselho Nacional de Desenvolvimento Científico e Tecnológico - Grant 441817/2018-1.Declaration of Interests: The authors have declared that no competing interests exist.Ethics Approval Statement: This study was approved by the Research Ethics Committee of the Federal University of 88 São Paulo (#0566/2020).