Journal Article

Regulatory T Cells as Predictors of Clinical Course in Hospitalised COVID-19 Patients

Prato, Marco, Angheben, Andrea, Caldrer, Sara, Bernardi, Milena, Rodari, Paola, Mazzi, Cristina, Tiberti, Natalia, Ronzoni, Niccolò, Piubelli, Chiara

2021

Overview

The host immune response has a prominent role in the progression and outcome of SARS-CoV-2 infection. Lymphopenia has been described as an important feature of SARS-CoV-2 infection and has been associated with severe disease manifestation. Lymphocyte dysregulation and hyper-inflammation have been shown to be associated with a more severe clinical course; however, a T cell subpopulation whose dysfunction correlate with disease progression has yet to be identify. We performed an immuno-phenotypic analysis of T cell sub-populations in peripheral blood from patients affected by different severity of COVID-19 (n=60) and undergoing a different clinical evolution. Clinical severity was established based on a modified WHO score considering both ventilation support and respiratory capacity (PaO2/FiO2 ratio). The ability of circulating cells at baseline to predict the probability of clinical aggravation was explored through multivariate regression analyses. The immuno-phenotypic analysis performed by multi-colour flow cytometry confirmed that patients suffering from severe COVID-19 harboured significantly reduced circulating T cell subsets, especially for CD4 T, Th1, and regulatory T cells. Peripheral T cells also correlated with parameters associated with disease severity, i.e., PaO2/FiO2 ratio and inflammation markers. CD4 T cell subsets showed an important significant association with clinical evolution, with patients presenting markedly decreased regulatory T cells at baseline having a significantly higher risk of aggravation. Importantly, the combination of gender and regulatory T cells allowed distinguishing between improved and worsened patients with an area under the ROC curve (AUC) of 82%. The present study demonstrates the association between CD4 T cell dysregulation and COVID-19 severity and progression. Our results support the importance of analysing baseline regulatory T cell levels, since they were revealed able to predict the clinical worsening during hospitalization. Regulatory T cells assessment soon after hospital admission could thus allow a better clinical stratification and patient management.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Biomarkers / CD4 antigen / COVID-19 / COVID-19 - diagnosis / COVID-19 - epidemiology / COVID-19 - immunology / COVID-19 - virology / COVID-19 Serological Testing / Cytokines - blood / Cytokines - metabolism / Disease / Disease Progression / disease severity / Flow cytometry / Hospitalization / Humans / Immunity (Disease) / Immunology / immunophenotype / Immunophenotyping / Immunoregulation / Inflammation / Inflammation Mediators - blood / Inflammation Mediators - metabolism / Intubation / Kruskal-Wallis test / Lymphocyte Count / Lymphocytes / Lymphocytes T / Lymphopenia / Missing data / Neutrophils / Patients / Peripheral blood / Prognosis / Public Health Surveillance / regulatory T cells / ROC Curve / SARS-CoV-2 - immunology / Severe acute respiratory syndrome coronavirus 2 / Severity of Illness Index / Steroids / T cell subtypes / T-Lymphocyte Subsets - immunology / T-Lymphocyte Subsets - metabolism / T-Lymphocytes, Regulatory - immunology / T-Lymphocytes, Regulatory - metabolism