AUTHOR=Jacobs Lotte M. C. , Wintjens Marieke S. J. N. , Nagy Magdolna , Willems Loes , ten Cate Hugo , Spronk Henri M. H. , van Kuijk Sander M. J. , Ghossein-Doha Chahinda , Netea Mihai G. , Groh Laszlo A. , van Petersen André S. , Warlé Michiel C. 

TITLE=Biomarkers of sustained systemic inflammation and microvascular dysfunction associated with post-COVID-19 condition symptoms at 24 months after SARS-CoV-2-infection

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1182182

DOI=10.3389/fimmu.2023.1182182

ISSN=1664-3224

ABSTRACT=The aim of this single-centre cohort study was to investigate serum biomarkers of coagulation activation, microvascular dysfunction, and inflammation in relation to symptoms two years after acute COVID-19. Patients diagnosed with acute SARS-CoV-2 infection between February and June 2020 were recruited. Outcome measures included the CORona Follow-Up (CORFU) questionnaire which is based on an internationally developed and partially validated basic questionnaire on persistent symptoms after COVID-19post-COVID-19 condition (PCC) symptoms. Also, plasma biomarkers reflecting coagulation activation, endothelial dysfunction and systemic inflammation were measured. 167 individuals were approached of which 148 (89%) completed the CORFU questionnaire. At 24 months after acute infection, fatigue was the most prevalent post-COVIDPCC symptom (84.5%). Over 50% of patients experienced symptoms related to breathing, cognition, sleep or mobility; 30.3% still experienced at least one severe or extreme (4 or 5 on a 5-point scale) post-COVIDPCC symptom. Multiple correlations were found between several post-COVIDPCC symptoms and markers of endothelial dysfunction (endothelin-1 and von Willebrand factor) and systemic inflammation (Interleukin-1 Receptor antagonist). Additional proteomic analysis revealed an inflammatory signature associated with most of the post-COVID symptoms. No positive correlations were found between post-COVIDPCC symptoms and coagulation complexes. In conclusion, this study shows that at 24 months after acute COVID-19 infection patients experience a high prevalence of post-COVIDPCC symptoms which correlate with an inflammatory signature cytokine IL-1Ra and markers of endothelial dysfunction, especially endothelin-1. Our data may provide a rationale for the selection of treatment strategies for further clinical studies.