Infection by novel coronavirus SARS-CoV-2 causes different presentations of COVID-19 and some patients may progress to a critical, fatal form of the disease that requires their admission to ICU and invasive mechanical ventilation. In order to predict in advance which patients could be more susceptible to develop a critical form of COVID-19, it is essential to define the most adequate biomarkers. In this study, we analyzed several parameters related to the cellular immune response in blood samples from 109 patients with different presentations of COVID-19 who were recruited in Hospitals and Primary Healthcare Centers in Madrid, Spain, during the first pandemic peak between April and June 2020. Hospitalized patients with the most severe forms of COVID-19 showed a potent inflammatory response that was not translated into an efficient immune response. Despite the high levels of effector cytotoxic cell populations such as NK, NKT and CD8+ T cells, they displayed immune exhaustion markers and poor cytotoxic functionality against target cells infected with pseudotyped SARS-CoV-2 or cells lacking MHC class I molecules. Moreover, patients with critical COVID-19 showed low levels of the highly cytotoxic TCRγδ+ CD8+ T cell subpopulation. Conversely, CD4 count was greatly reduced in association to high levels of Tregs, low plasma IL-2 and impaired Th1 differentiation. The relative importance of these immunological parameters to predict COVID-19 severity was analyzed by Random Forest algorithm and we concluded that the most important features were related to an efficient cytotoxic response. Therefore, efforts to fight against SARS-CoV-2 infection should be focused not only to decrease the disproportionate inflammatory response, but also to elicit an efficient cytotoxic response against the infected cells and to reduce viral replication.
【저자키워드】 COVID-19, SARS-CoV-2, cytotoxic response, NK and NKT cells, CD8 lymphocytes +, 【초록키워드】 immune response, pandemic, Biomarkers, Cellular immune response, T cells, SARS-COV-2 infection, Th1, COVID-19 severity, CD8+ T cells, hospitalized patients, CD4, immune, ICU, Novel coronavirus, T cell, Viral, viral replication, Algorithm, Patient, Spain, Random forest, plasma, MHC class I, Admission, Critical, predict, CD8+ T cell, IL-2, association, marker, Invasive mechanical ventilation, Inflammatory response, Tregs, target cells, target cell, cytotoxic cell, Blood samples, infected cells, novel coronavirus SARS-CoV-2, blood sample, effort, center, advance, infected cell, subpopulation, forest, parameter, pseudotyped SARS-CoV-2, cell population, MHC class I molecules, susceptible, feature, Cell, decrease, NKT, analyzed, develop, recruited, the disease, form, reduced, elicit, to define, cause, translated, immunological parameter, reduce viral replication, 【제목키워드】 response, PBMC, cytotoxic, Impaired,