Role of Endothelium in Cardiovascular Sequelae of Long COVID

Abstract

The global action against coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, shed light on endothelial dysfunction. Although SARS-CoV-2 primarily affects the pulmonary system, multiple studies have documented pan-vascular involvement in COVID-19. The virus is able to penetrate the endothelial barrier, damaging it directly or indirectly and causing endotheliitis and multi-organ injury. Several mechanisms cooperate to development of endothelial dysfunction, including endothelial cell injury and pyroptosis, hyperinflammation and cytokine storm syndrome, oxidative stress and reduced nitric oxide bioavailability, glycocalyx disruption, hypercoagulability, and thrombosis. After acute-phase infection, some patients reported signs and symptoms of a systemic disorder known as long COVID, in which a broad range of cardiovascular (CV) disorders emerged. To date, the exact pathophysiology of long COVID remains unclear: in addition to the persistence of acute-phase infection mechanisms, specific pathways of CV damage have been postulated, such as persistent viral reservoirs in the heart or an autoimmune response to cardiac antigens through molecular mimicry. The aim of this review is to provide an overview of the main molecular patterns of enduring endothelial activation following SARS-CoV-2 infection and to offer the latest summary of CV complications in long COVID.

The Relationship between Post-COVID Syndrome and the Burden of Comorbidities Assessed Using the Charlson Comorbidity Index

“…It has been found that endothelial dysfunction plays a pivotal role in the development of many of the immediate complications associated with COVID-19, including acute cardiovascular events and thrombosis. Additionally, it is also linked to the onset of various post-COVID-19 signs and symptoms [ 6 , 24 ]. Finally, patients with pre-existing comorbidities may have lower functional organ reserve and, therefore, be more likely to develop post-COVID-19 syndrome.…”

“…In particular, patients with cardiac and cardiovascular diseases are more likely to develop post-COVID-19 syndrome [ 5 ]. Several authors underlined that both comorbidities and COVID-19 itself worsen endothelial dysfunction, which is currently deemed to be one of the most important determinants in the development of severe COVID-19 and in the persistence of several post-COVID-19 signs and symptoms [ 6 ].…”

New Insights into Endothelial Dysfunction in Cardiometabolic Diseases: Potential Mechanisms and Clinical Implications

“…In such a context, a higher prevalence of acute coronary syndromes, acute pulmonary embolism, deep veinous thrombosis and ischemic stroke has been reported as a consequence of the persistence of inflammation, cytokine storm, microvascular damage, and stress-induced cardiomyopathy [ 95 ].…”

Qualidade de Vida Relacionada à Saúde e Resultados em Longo Prazo após Covid-19 Levemente Sintomático: Explorando o Protocolo

“…1 , 2 O efeito citopático do vírus no endotélio, juntamente com o dano endotelial como consequência da inflamação sistêmica, tem sido associado a eventos cardiovasculares como miocardite, infarto do miocárdio, arritmias, e eventos tromboembólicos. 3 …”

“…1 , 2 The cytopathic effect of the virus on the endothelium, along with endothelial damage as a consequence of systemic inflammation, has been associated with cardiovascular events such as myocarditis, myocardial infarction, arrhythmias, and thromboembolic events. 3 …”