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

Autor: Nathalia Mantovani Pena, Luiz Claudio Santana, James R Hunter, Vinicius Fontanesi Blum, Tania Vergara, Celso Gouvea, Elcio Leal, Nancy Bellei, Mauro Schechter, Ricardo Sobhie Diaz
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMC Infectious Diseases, Vol 24, Iss 1, Pp 1-11 (2024)
Druh dokumentu: article
ISSN: 1471-2334
DOI: 10.1186/s12879-024-09490-y
Popis: 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 = 0·043). 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). Interpretation 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.
Databáze: Directory of Open Access Journals
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