Identification of Immune Activation Markers in the Early Onset of COVID-19 Infection.

Johannes J Kovarik,Robert Strassl,Veronique Touzeau-Roemer,Christopher C Kaltenecker,Markus Wahrmann,Susanne Haindl,Marcus D Säemann,Manuel Kussmann,Klaus G Schmetterer,Ludwig Traby,Care Ay,Anna K Kämpf,Monika Breuer,Katharina Grabmeier-Pfistershammer,Oliver Robak,Harald Willschke,Anna N Herdina,Fabian Gasser,Florian Mayer

doi:10.3389/fcimb.2021.651484

Abstract

This study aimed to determine the specific cytokine profile in peripheral blood during the early onset of COVID-19 infection. This was a cross-sectional exploratory, single center study. A total of 55 plasma samples were studied. Serum samples of adults showing symptoms of COVID-19 infection who were tested positive for SARS-CoV-2 infection (CoV+, n=18) at the COVID-19 outpatient clinic of the Medical University of Vienna were screened for immune activation markers by Luminex technology. Additionally, age and gender-matched serum samples of patients displaying COVID-19 associated symptoms, but tested negative for SARS-CoV-2 (CoV-, n=16) as well as healthy controls (HC, n=21) were analyzed. COVID-19 positive (CoV+) patients showed a specific upregulation of BLC (141; 74-189 pg/mL), SCD30 (273; 207-576 pg/mL), MCP-2 (18; 12-30 pg/mL) and IP-10 (37; 23-96 pg/mL), compared to patients with COVID19-like symptoms but negative PCR test (CoV-), BLC (61; 22-100 pg/mL), sCD30L (161; 120-210 pg/mL), MCP-2 (8; 5-12 pg/mL) and IP-10 (9; 6-12 pg/mL) and healthy controls (HC) (BLC 22; 11-36 pg/mL, sCD30 74; 39-108 pg/mL, MCP-2 6; 3-9. pg/mL, IP-10 = 8; 5-13). The markers APRIL, sIL-2R, IL7, MIF, MIP-1b, SCF, SDF-1a, sTNF-RII were elevated in both CoV+ and CoV- patient groups compared to healthy controls. HGF, MDC and VEGF-A were elevated in CoV- but not CoV+ compared to healthy controls. BLC, sCD30, MCP-2 and IP-10 are specifically induced during early stages of COVID-19 infection and might constitute attractive targets for early diagnosis and treatment of this disease.

Highlights

According to World Health Organization (WHO), the outbreak of a novel coronavirus strain termed severe acute respiratory syndrome coronavirus type 2, SARS-Coronavirus Disease (COVID)-19 negative tested patients (CoV-)2 at the end of the year 2019 has led to an unprecedented global pandemic having infected an estimated more than 80 million people
A total of 34 patients who presented to the COVID-19 outpatient ward of the Medical University of Vienna between March 2020 and August 2020 with typical COVID-19 symptoms including cough, fever, sore throat, myalgia, loss of taste and/or smell, fatigue or dyspnoea were selected from the database for this cross-sectional analysis
All patients were tested for the presence of SARS-COVID-19 negative tested patients (CoV-)2 ribonucleic acid (RNA) by routine PCR testing from nasopharyngeal swabs at the time of presentation and stratified into a symptomatic COVID-19 negative (CoV-; n=16) and a symptomatic COVID-19 positive (CoV+; n=18) group

Summary

Introduction

According to World Health Organization (WHO), the outbreak of a novel coronavirus strain termed severe acute respiratory syndrome coronavirus type 2, SARS-CoV-2 at the end of the year 2019 has led to an unprecedented global pandemic having infected an estimated more than 80 million people. Inflammation is governed by the interaction of multiple different cell types such as granulocytes, macrophages, endothelial along with epithelial cells which interact with cells of the adaptive immune system Many of these interactions are regulated by the early secretion of cytokines, chemokines, and other messenger substances resulting in an exacerbation of the inflammatory reaction, that can culminate in a systemic cytokine storm activating inflammasomes affecting multiple compartments of the organism (Rodrigues et al, 2021). Recent trials using the broadly anti-inflammatory glucocorticoids showed promising results regarding mortality in critically ill patients (Horby et al, 2020) Though it has not been established yet whether the overall quality or quantity of the SARS-CoV-2 induced cytokine inflammatory response differs from that caused by other common respiratory infections. A deeper knowledge of disease specific cytokine patterns especially at the early onset of the disease is necessary to ameliorate clinical symptoms and to personalize treatment

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