Early Response of CD8+ T Cells in COVID-19 Patients.

Maja Barbaric,Deni Ramljak,Bejana Purisevic,Una Glamoclija,Marina Curlin,Katarina Vukojevic,Violeta Soljic,Olivera Peric,Martina Vukoja

doi:10.3390/jpm11121291

Maja Barbaric, Deni Ramljak + Show 7 more

Open Access

https://doi.org/10.3390/jpm11121291

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Abstract

Healthy and controlled immune response in COVID-19 is crucial for mild forms of the disease. Although CD8+ T cells play important role in this response, there is still a lack of studies showing the gene expression profiles in those cells at the beginning of the disease as potential predictors of more severe forms after the first week. We investigated a proportion of different subpopulations of CD8+ T cells and their gene expression patterns for cytotoxic proteins (perforin-1 (PRF1), granulysin (GNLY), granzyme B (GZMB), granzyme A (GZMA), granzyme K (GZMK)), cytokine interferon-γ (IFN-γ), and apoptotic protein Fas ligand (FASL) in CD8+ T cells from peripheral blood in first weeks of SARS-CoV-2 infection. Sixteen COVID-19 patients and nine healthy controls were included. The absolute counts of total lymphocytes (p = 0.007), CD3+ (p = 0.05), and CD8+ T cells (p = 0.01) in COVID-19 patients were significantly decreased compared to healthy controls. In COVID-19 patients in CD8+ T cell compartment, we observed lower frequency effector memory 1 (EM1) (p = 0.06) and effector memory 4 (EM4) (p < 0.001) CD8+ T cells. Higher mRNA expression of PRF1 (p = 0.05) and lower mRNA expression of FASL (p = 0.05) at the fifth day of the disease were found in COVID-19 patients compared to healthy controls. mRNA expression of PRF1 (p < 0.001) and IFN-γ (p < 0.001) was significantly downregulated in the first week of disease in COVID-19 patients who progressed to moderate and severe forms after the first week, compared to patients with mild symptoms during the entire disease course. GZMK (p < 0.01) and FASL (p < 0.01) mRNA expression was downregulated in all COVID-19 patients compared to healthy controls. Our results can lead to a better understanding of the inappropriate immune response of CD8+ T cells in SARS-CoV2 with the faster progression of the disease.

Highlights

IntroductionA new disease named Coronavirus Disease 2019 (COVID-19) was diagnosed for the first time in December 2019 in patients with acute respiratory syndrome in Wuhan
The results revealed differences between the fifth day of the disease compared to control and between patients with stabile mild disease and patients who had deterioration after the tenth day of the disease compared to control
PRF1, granzyme B (GZMB), and GNLY genes expressed at the fifth day of infection were upregulated

Summary

Introduction

A new disease named Coronavirus Disease 2019 (COVID-19) was diagnosed for the first time in December 2019 in patients with acute respiratory syndrome in Wuhan. Since it spread rapidly and became a world-wide problem [1]. Studies in Wuhan show that around 60% of COVID-19 patients suffered from lymphopenia, and patients who died of COVID-19 had a lower number of lymphocytes than patients who survived [3]. Other studies showed that lymphopenia is associated with the severity of the disease [4,5]. CD8+ T cell, but not CD4+ T cell, reduction by SARS-CoV-2 is associated with a worse prognosis in COVID-19 patients [6].

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