The Enigma of Endothelium in COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromerelated coronavirus-2 (SARS-CoV-2) has affected millions of people globally. Clinically, it presents with mild flu-like symptoms in most cases but can cause respiratory failure in high risk population. With the aim of unearthing newer treatments, scientists all over the globe are striving hard to comprehend the underlying mechanisms of COVID-19. Several studies till date have indicated a dysregulated host immune response as the major cause of COVID-19 induced mortality. In this Perspective, we propose a key role of endothelium, particularly pulmonary endothelium in the pathogenesis of COVID-19. We draw parallels and divergences between COVID-19-induced respiratory distress and bacterial sepsis-induced lung injury and recommend the road ahead with respect to identification of endothelium-based biomarkers and plausible treatments for COVID-19.

Endothelial cells and SARS-CoV-2: An intimate relationship

“…Consequently, the inflammation reaches endothelial levels and then intensifies. However, it is proposed that endothelial injury is due much more to inflammatory responses from the host due to epithelium infection rather than viral replication or increased viral load in EC [ 71 ]. In summary, direct or indirect activation of EC by SARS-CoV-2 infection culminates in pulmonary edema and triggers a coagulation cascade that is implicated in severe cases of COVID-19.…”

A Pictorial Review of the Role of Imaging in the Detection, Management, Histopathological Correlations, and Complications of COVID-19 Pneumonia

“…COVID-19 ARDS (CARDS) is diagnosed when someone with confirmed COVID-19 infection meets the Berlin 2012 ARDS diagnostic criteria that consist in the presence of these features: acute hypoxemic respiratory failure, presentation within 1 week of worsening respiratory symptoms, bilateral airspace disease on CXR or CT or LUS that is not fully explained by effusions, lobar or lung collapse, or nodules, and exclusion of cardiac failure. To date, the exact mechanism of CARDS remains unclear, and it has been shown to have different findings from typical ARDS [ 169 , 173 , 174 , 175 , 176 ]. Various studies have suggested that patients with CARDS have markedly higher lung compliance than patients with typical ARDS, and CARDS has frequently been associated with pulmonary thrombotic injury [ 143 , 169 , 173 , 174 , 175 , 176 , 177 , 178 ].…”

“…To date, the exact mechanism of CARDS remains unclear, and it has been shown to have different findings from typical ARDS [ 169 , 173 , 174 , 175 , 176 ]. Various studies have suggested that patients with CARDS have markedly higher lung compliance than patients with typical ARDS, and CARDS has frequently been associated with pulmonary thrombotic injury [ 143 , 169 , 173 , 174 , 175 , 176 , 177 , 178 ]. Chiumiello et al [ 177 ] showed that patients with CARDS exhibit normal pulmonary compliance with severe hypoxemia, probably sustained by a mismatch between hypoxic pulmonary vasoconstriction (HPV) and ventilation/perfusion (V/Q).…”

“…Various researchers are focusing on the vascular-centric pathogenesis of COVID-19 and whether the atypical features of CARDS can be due to vascular damage [ 143 , 172 , 173 , 174 , 175 , 176 , 177 , 178 , 179 , 180 ]. These findings were also confirmed in post-mortem studies [ 139 , 143 ].…”

COVID-19: A Challenge to Physiology of Aging

“…This very organ is recognized as the primary target of SARS-CoV-2 attack and the responder to the attack. The ubiquity of changes caused by SARS-COV-2 in the endothelium contributes to the proneness of COVID-19 patients to multi-organ failure, as it is acknowledged in publications starting from Sardu et al (2020) up to the latest ( Froldi and Dorigo, 2020 ; Kaur et al, 2020 ).…”