Endothelial cells and blood vessels are major targets for COVID-19-induced tissue injury and spreading to various organs

Abstract

The coronavirus disease 2019 (COVID-19) infected so far over 250 million people and caused the death of over 5 million worldwide. Aging, diabetes, and cardiovascular diseases, conditions with preexisting impaired endothelial functions predispose to COVID-19. While respiratory epithelium is the main route of virus entry, the endothelial cells (ECs) lining pulmonary blood vessels are also an integral part of lung injury in COVID-19 patients. COVID-19 not only affects the lungs and respiratory system but also gastrointestinal (GI) tract, liver, pancreas, kidneys, heart, brain, and skin. Blood vessels are likely conduits for the virus dissemination to these distant organs. Importantly, ECs are also critical for vascular regeneration during injury/lesions healing and restoration of vascular network. The World Journal of Gastroenterology has published in last two years over 67 outstanding papers on COVID-19 infection with a focus on the GI tract, liver, pancreas, etc. , however, the role of the endothelial and vascular components as major targets for COVID-19-induced tissue injury, spreading to various organs, and injury healing have not been sufficiently emphasized. In the present article, we focus on these subjects and on current treatments including the most recent oral drugs molnupiravir and paxlovid that show a dramatic, significant efficacy in controlling severe COVID-19 infection.

Tobacco smokers as target group for complicated coronavirus infection

“…This study also demonstrated an increased number of endothelial cells containing ACE2-receptors, as well as significant changes in the endothelial morphology of the lungs in autopsied patients with Covid-19 infection (Ackermann et al 2020). Under certain pathological conditions of existing endothelial dysfunction, the ACE/Ang II axis is overactivated, leading to vasoconstriction, thrombogenesis, fibrosis, coagulopathy, and thrombophilia (Tarnawski and Ahluwalia 2022).…”

“…Endothelial cells and blood vessels are targets, but also a mechanism for the spread of the SARS-CoV-2 virus, and associated tissue changes, as well as for its dissemination to various organs in the patient's body. Therefore, prior endothelial dysfunction could make endothelial cells more sensitive to the action of the virus, leading to the more severe systemic course of Covid-19 (Tarnawski and Ahluwalia 2022).…”

“…Although the initial "target" of the Covid 19 virus is the epithelium presented in the respiratory system, the high occurrence of vascular complications in the affected patients directs attention to the endothelial cells of the blood vessels, and their key role in the progression and deterioration of the coronavirus disease. SARS-CoV-2 causes endothelial dysfunction and increases the thrombogenic risk by two main mechanisms -by directly infecting the endothelium and compromising its antithrombotic and barrier function, and/or indirectly by inducing a local cytochrome storm, and systemic inflammatory response, which potentiate endothelial dysfunction (Tarnawski and Ahluwalia 2022). Ackerman and co-authors demonstrated the abnormalities of the pulmonary microcirculation expressed in vascular congestion and microthrombi in patients suffering from Covid-19, by objectifying using electron microscopy single-body lesions and vascular lumen, filled with cell fragments and degenerated cell organelles.…”

Advances and challenges in using nirmatrelvir and its derivatives against SARS-CoV-2 infection

“…6) COVID-19 damages not only the lungs and respiratory system but also other organs, such as the GI tract, liver, pancreas, kidneys, heart, brain, and skin. Notably, blood vessels and endothelial cells (ECs), which are the conduits for virus dissemination to these organs, can be injured by the virus [ 67 ]. However, the biological effects of paxlovid and nirmatrelvir on blood vessels and ECs have not been investigated.…”

hPSC-derived lung organoids: Potential opportunities and challenges

“…The innermost layer of blood vessels is comprised of endothelial cells (ECs) that are heterogeneous in nature [ 51 ]. ECs are critical for supplying oxygen and nutrients to cells and tissues, and are involved in coagulation and generation of vasoactive substances, hormones and growth factors [ 52 ]. There are three main lung ECs, pulmonary microvascular, pulmonary artery and pulmonary vein ECs [ 53 ].…”