Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection-A Cross-Sectional Study

Philipp Jud; Paul Gressenberger; Viktoria Muster; Alexander Avian; Andreas Meinitzer; Heimo Strohmaier; Harald Sourij; Reinhard B Raggam; Martin Helmut Stradner; Ulrike Demel; Harald H Kessler; Kathrin Eller; Marianne Brodmann

doi:10.3389/fcvm.2021.750887

Evaluation of Endothelial Dysfunction and Inflammatory Vasculopathy After SARS-CoV-2 Infection-A Cross-Sectional Study

Front Cardiovasc Med. 2021 Oct 13:8:750887. doi: 10.3389/fcvm.2021.750887. eCollection 2021.

Affiliations

¹ Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
³ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
⁴ Department Center of Medical Research, Medical University of Graz, Graz, Austria.
⁵ Division of Endocrinology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁶ Division of Rheumatology and Immunology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
⁷ Diagnostic and Research Institute of Hygiene, Microbiology and Environmental, Medical University of Graz, Graz, Austria.
⁸ Division of Nephrology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.

Abstract

Background: Rising data suggest that COVID-19 affects vascular endothelium while the underlying mechanisms promoting COVID-19-associated endothelial dysfunction and inflammatory vasculopathy are largely unknown. The aim was to evaluate the contribution of COVID-19 to persisting vascular injury and to identify parameters linked to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy. Methods: In a cross-sectional design, flow-mediated dilation (FMD), nitroglycerine-related dilation (NMD), pulse-wave velocity (PWV), augmentation index, intima-media thickness (IMT), compounds of the arginine and kynurenine metabolism, homocysteine, von Willebrand factor (vWF), endothelial microparticles (EMP), antiendothelial cell antibodies, inflammatory, and immunological parameters, as well as nailfold capillary morphology were measured in post-COVID-19 patients, patients with atherosclerotic cardiovascular diseases (ASCVD) and healthy controls without prior or recent SARS-CoV-2 infection. Results: Post-COVID-19 patients had higher values of PWV, augmentation index, IMT, asymmetric and symmetric dimethylarginine, vWF, homocysteine, CD31+/CD42b- EMP, C-reactive protein, erythrocyte sedimentation rate, interleukin-6, and β-2-glycoprotein antibodies as well as lower levels of homoarginine and tryptophan compared to healthy controls (all with p < 0.05). A higher total number of pathologically altered inflammatory conditions and higher rates of capillary ramifications, loss, caliber variability, elongations and bushy capillaries with an overall higher microangiopathy evolution score were also observed in post-COVID-19 patients (all with p < 0.05). Most parameters of endothelial dysfunction and inflammation were comparably altered in post-COVID-19 patients and patients with ASCVD, including FMD and NMD. Conclusion: COVID-19 may affect arterial stiffness, capillary morphology, EMP and selected parameters of arginine, kynurenine and homocysteine metabolism as well as of inflammation contributing to COVID-19-associated endothelial dysfunction and inflammatory vasculopathy.

Keywords: COVID-19; capillary changes; endothelial dysfunction; inflammation; vasculopathy.