T Cell Activation, Highly Armed Cytotoxic Cells and a Shift in Monocytes CD300 Receptors Expression Is Characteristic of Patients With Severe COVID-19

Abstract

COVID-19 manifests with a wide diversity of clinical phenotypes characterized by dysfunctional and exaggerated host immune responses. Many results have been described on the status of the immune system of patients infected with SARS-CoV-2, but there are still aspects that have not been fully characterized or understood. In this study, we have analyzed a cohort of patients with mild, moderate and severe disease. We performed flow cytometric studies and correlated the data with the clinical characteristics and clinical laboratory values of the patients. Both conventional and unsupervised data analyses concluded that patients with severe disease are characterized, among others, by a higher state of activation in all T cell subsets (CD4, CD8, double negative and T follicular helper cells), higher expression of perforin and granzyme B in cytotoxic cells, expansion of adaptive NK cells and the accumulation of activated and immature dysfunctional monocytes which are identified by a low expression of HLA-DR and an intriguing shift in the expression pattern of CD300 receptors. More importantly, correlation analysis showed a strong association between the alterations in the immune cells and the clinical signs of severity. These results indicate that patients with severe COVID-19 have a broad perturbation of their immune system, and they will help to understand the immunopathogenesis of COVID-19.

Transcriptional Changes in CD16+ Monocytes May Contribute to the Pathogenesis of COVID-19

“…Two studies showed by flow cytometry that the numbers of CD16+ monocytes were lower in the peripheral blood of individuals with severe COVID-19 compared to mild and control groups, and that within this population, there was decreased HLA-DR expression ( 21 , 41 ). Although we did not examine HLA-DR protein expression in this study, HLA-DR cell surface protein expression was reported to be decreased in CD14+ and CD16+ monocytes in people with COVID-19, with decreased expression correlating with disease severity ( 21 , 26 , 40 , 48 , 76 ). Additionally, a flow cytometry study showed that protein expression of HLA-DR and CD86 was found to be decreased, and CD163 increased on CD14+ and CD16+ monocytes in severe cases of COVID-19 ( 77 ).…”

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

“…Along this line, flow cytometric analysis of 19 COVID-19 patients revealed a higher state of T cell activation in all T cell compartments (CD4 + , CD8 + , Double negative (DN)) (Zenarruzabeitia et al, 2021).…”

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection

“…These data indicated that activated cTfh cell responses were associated with robust antibody responses elicited during SARS-CoV-2 infection, which may be valuable as potential biomarkers in vaccine clinical trials. Similarly, CD38 + HLA-DR + cTfh cells, activated CD4 + T cells and cytotoxic CD8 + T cells were expanded in COVID-19 patients, and increased CD38 + HLA-DR + cTfh cells indicated a recent antigen encounter and emigration from the GC of the patients ( 161 ). The frequencies of PD-1 + ICOS + cTfh, cytotoxic CD4 + T and exhausted T cells were strongly expanded in COVID-19 patients, particularly in severe patients compared to healthy individuals, which suggested that extensive T cell dysfunction was associated with COVID-19 severity ( 162 ).…”