Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset.

Juan Francisco Gutiérrez-Bautista,Francisco Ruiz-Cabello,Antonio Rodriguez-Nicolas,Per Anderson,Miguel Ángel López-Ruz,Pilar Jiménez,Federico Garrido,Antonio Rosales-Castillo

doi:10.3389/fimmu.2020.596553

Abstract

The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.

Highlights

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic that emerged in Wuhan (China) in early December 2019 [1]
Most COVID-19 patients presented at the time of hospital admission a clinical inflammatory syndrome, characterized by the elevation of several biochemical inflammatory markers
Brain natriuretic peptide (BNP) was elevated in 53% of tested nonICU hospitalized patients and procalcitonin was raised in 32%

Summary

Introduction

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the coronavirus disease 2019 (COVID-19) pandemic that emerged in Wuhan (China) in early December 2019 [1]. On the 30th of January 2020, the world health organization declared the SARS-CoV-2 outbreak an international health emergency and 9 months later more than 41,000,000 infected have been reported worldwide, with more than 1,125,000 deaths [2]. SARS-CoV-2 belongs to the betacoronavirus (b-CoVs) genus, as do the SARS-CoV and MERS-CoV [3]. It is a zoonotic virus whose possible reservoirs are bats and/or pangolins [4]. Like SARS-CoV, SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) as a receptor for entry into the cells, infecting type II pneumocytes of the lung epithelium [6, 7]. ACE2 is expressed in the upper epithelium of the esophagus, ileum and colon enterocytes, myocardial cells, cells of the proximal kidney tubule, bladder urothelium, and the oral mucosa [8]

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