Characteristics of lymphocyte subset alterations in COVID-19 patients with different levels of disease severity

Abstract

Background Coronavirus disease 2019 (COVID-19) is a respiratory disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which had rapidly spread all over the world and caused public health emergencies in the past two years. Although the diagnosis and treatment for COVID-19 have been well defined, the immune cell characteristics and the key lymphocytes subset alterations in COVID-19 patients have not been thoroughly investigated. Methods The levels of immune cells including T cells, B cells, and natural killer (NK) cells in 548 hospitalized COVID-19 patients, and 30 types of lymphocyte subsets in 125 hospitalized COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China were measured using flow cytometry. The relationship between lymphocytes subsets with the cytokine interleukin-6 (IL-6) and the characteristics of lymphocyte subsets in single-cell RNA sequencing (scRNA-seq) data obtained from peripheral blood mononuclear cells (PBMCs) were also analysed in COVID-19 patients. Results In this study, we found that patients with critical COVID-19 infection exhibited an overall decline in lymphocytes including CD4+ T cells, CD8+ T cells, total T cells, B cells, and NK cells compared to mild and severe patients. However, the number of lymphocyte subsets, such as CD21low CD38low B cells, effector T4 cells, and PD1+ depleted T8 cells, was moderately increased in critical COVID-19 patients compared to mild cases. Notably, except for effector memory T4 cells, plasma blasts and Tregs, the number of all lymphocyte subsets was markedly decreased in COVID-19 patients with IL-6 levels over 30-fold higher than those in healthy cases. Moreover, scRNA-seq data showed obvious differences in the distribution and numbers of lymphocyte subsets between COVID-19 patients and healthy persons, and subsets-specific marker genes of lymphocyte subsets including CD4, CD19, CCR7, and IL7R, were markedly decreased in COVID-19 patients compared with those in healthy cases. Conclusion A comprehensive decrease in immune cell and lymphocyte subsets in critical COVID-19 patients, and peripheral lymphocyte subset alterations showed a clear association with clinical characteristics.

Immune responses in mildly versus critically ill COVID-19 patients

“…Transient lymphopenia may be associated with a direct effect of SARS-CoV-2 infection on the production and/or differentiation of lymphocytes in primary lymphoid organs and their release into the circulation (115,128). High levels of IL-6, IL-10 or TNF-alpha directly promote thymic dysfunction and indirectly promote T cell apoptosis (127,(129)(130)(131)(132).…”

“…Subsequently, activated T cells migrate to the site of infection, producing antiviral cytokines, chemokines and cytotoxic molecules ( 124 ). Acute and severe SARS-CoV-2 infections are associated with lymphopenia and remarkable loss of CD4 + and CD8 + T cells, which is reversed by disease recovery ( 125 – 127 ). Transient lymphopenia may be associated with a direct effect of SARS-CoV-2 infection on the production and/or differentiation of lymphocytes in primary lymphoid organs and their release into the circulation ( 115 , 128 ).…”

“…Transient lymphopenia may be associated with a direct effect of SARS-CoV-2 infection on the production and/or differentiation of lymphocytes in primary lymphoid organs and their release into the circulation ( 115 , 128 ). High levels of IL-6, IL-10 or TNF-alpha directly promote thymic dysfunction and indirectly promote T cell apoptosis ( 127 , 129 – 132 ). In early studies on COVID-19, impairment in function and increased expression of markers, which are hallmarks for activation and/or exhaustion of CD4 + and CD8 + T cells, were observed in patients.…”

Changes in Cellular Immunity Indicators in Patients with COVID-19 Coronavirus Infection, Depending on the Severity of the Disease

“…Коронавирусная инфекция в течение почти трех лет стала широко распространенной и глобальной проблемой здравоохранения, приведшей к высоким уровням заболеваемости и смертности. Тесное взаимодействие между коронавирусом и иммунной системой человека стало причиной различных клинических проявлений данного заболевания [2].…”

In Response to Author: COVID-19 and T Cells: Do T Cells Really Matter?

“…Fifth, lymphopenia was seen in the elderly COVID-19 patients’ findings similar to what we have observed. 1 , 4 …”