Background 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. Methods 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. Results 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%. Conclusions 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.
【저자키워드】 COVID-19, disease severity, immunophenotype, T cell subtypes, regulatory T cells, 【초록키워드】 Stratification, severe COVID-19, Hospitalization, T cells, SARS-COV-2 infection, severity, disease severity, Th1, Ventilation, COVID-19 severity, Gender, risk, progression, outcome, CD4, flow cytometry, Peripheral blood, lymphopenia, Regulatory, Probability, Disease progression, lymphocyte, T cell, Regulatory T cell, Host immune response, severity of COVID-19, clinical, management, Patient, hyper-inflammation, WHO, Hospital admission, aggravation, Patient management, predict, regulatory T cells, inflammation markers, association, Clinical severity, Combination, Analysis, severe disease, ROC Curve, AUC, dysregulation, an area, respiratory capacity, Support, dysfunction, Regression analyses, FiO2, PaO2, worsening, PaO2/FiO2 ratio, circulating, clinical evolution, subpopulation, parameter, Phenotypic analysis, circulating cell, T cell dysregulation, peripheral, Result, shown, described, identify, performed, affected, significantly, reduced, correlated, significantly higher, presenting, T cell subset, baseline, worsened, 【제목키워드】 clinical, regulatory T cells,