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

• Published in: BMC infectious diseases Vol. 24; no. 1; pp. 612 - 11
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 20.06.2024; BioMed Central; BMC
• Subjects: Adult; Aged; Antiviral agents; Antiviral response; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell activation; Cellular immune response; Clinical trials; Complications and side effects; Coronaviruses; Correlation; COVID-19; COVID-19 - immunology; COVID-19 severity; Development and progression; Disease; DNA polymerase; Enzyme-linked immunosorbent assay; Enzymes; Female; Health aspects; Histocompatibility antigen HLA; HIV; HIV (Viruses); HIV-1; Human immunodeficiency virus; Humans; Immune response; Immune response (cell-mediated); Immune system; Immunity, Cellular; Immunological research; Immunology; Infection; Infections; Inflammation; Inflammation - immunology; Interferon-gamma - genetics; Interferon-gamma - immunology; Leukocytes (mononuclear); Leukocytes, Mononuclear - immunology; Lymphocyte Activation; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Male; Middle Aged; Penicillin; Peptides; Peripheral blood mononuclear cells; Physiological aspects; Prognosis; Proteins; Respiratory diseases; Respiratory failure; SARS-CoV-2 - immunology; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; T cells; Tissue typing; Viral diseases; Viral Load; γ-Interferon; Germany; United States > US; HIV-1; Antiviral response; COVID-19 severity; Cellular immune response
• ISSN: 1471-2334; 1471-2334
• DOI: 10.1186/s12879-024-09490-y

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. 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. CD4 T cell activation was 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 the IFN-γ signal, was higher at baseline for patients who progressed to mild disease compared to patients who 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). Mounting specific cellular immune responses in the first days after symptom onset, as inferred by IFN-γ 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.