Vascular Dysfunction and Its Cardiovascular Consequences During and After COVID-19 Infection: A Narrative Review

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV2) has brought out changes in our daily life and has caused severe morbidity and mortality across the globe. Especially, post covid complications may remain a threat to the patient’s life. It may also increase the burden on existing health infrastructure and the country’s economy. This disease affects the respiratory system and other organ systems of the body, such as the cardiovascular system. The aim of the present narrative review is to understand how COVID-19 infection deranges vascular homeostasis, leading to endothelial dysfunction and arterial stiffness in the acute phase and following infection. To this effect, definite keywords were employed to obtain relevant information using PubMed database and Google Scholar search engines. It was documented that preexisting cardiovascular disease enhances morbidity in COVID-19 patients. Moreover, an elevated risk of development of new onset cardiovascular events has also been reported. Even a small amount of myocardial injury was significantly associated with death. The presence of virus in myocardial cells has also been documented. Furthermore, endothelial dysfunction and arterial stiffness were documented in the acute phase and 3–4 weeks to 4 months after COVID infection. The virus enters endothelial cells by binding with ACE2 “receptor” on its surface and deranges cellular machinery. It results in reduced conversion of Ang II to Ang (1–7). Accumulated Ang II then activates PI3K-Akt signaling pathway and regulates endothelial activation and production of IL-6 and reactive oxygen species (ROS). An imbalance between renin angiotensin aldosterone system (RAAS) and kallikrein kinin system (KKS) also occurs, which may cause endothelial dysfunction. It is understandable that the underlying pathophysiology of this altered arterial stiffness is multifactorial, involving various cellular and immunological biomolecules.

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs

“…CVD patients infected by SARS-CoV-2 tend to have more severe lung pathology compared to individuals without CVD. They also show elevated levels of inflammatory markers, such as C-reactive protein (CRP), interleukin (IL)-6, serum amyloid A (SAA), D-dimer, and fibrinogen, among others [9,39,70,[71][72][73][74][75].…”

“…In addition, it has been reported that COVID-19 patients can develop new cardiovascular events, such as right and left diastolic dysfunction, indicating the involvement of small coronary capillaries [ 11 , 231 ]. The observed diastolic dysfunction was also attributed to nonischemic myocarditis [ 39 , 232 ]. Even if the cardiac complications are associated with the various stages of EC dysfunction, the underlying mechanisms are not sufficiently understood.…”

“…Endothelial cells (ECs) at the interface between blood and the underlying vascular tissue have also been described to be involved in the COVID-19 pathologies [14,[28][29][30][31][32][33][34][35][36][37], possibly leading to inflammation and endothelial dysfunction. Currently, the clinical complications in COVID-19 patients with CVD are thought to be due to SARS-CoV-2 infection and subsequent dysregulation of ECs [12,36,38,39].…”

Vascular alterations among male elite athletes recovering from SARS-CoV-2 infection

“…SARS-CoV-2 itself, however, was shown to directly affect the cardiovascular system, leading to an increased risk of cardiovascular events, especially in men 8 , 9 , and endothelial dysfunction 10 – 12 . Even in healthy young individuals recovering from a SARS-CoV-2 infection, significant vascular alterations including increased arterial stiffness and decreased vascular function as assessed by flow-mediated dilation (FMD), were observed 13 , raising concerns about the long-term effects of the infection 14 . Further, another study 15 reported higher carotid stiffness and aortic stiffness among young adults (mean age 20 years) recovering from SARS-Cov-2 compared to uninfected age-matched controls.…”

Advances in Targeting ACE2 for Developing COVID-19 Therapeutics

“…This function is integral to the renin–angiotensin–aldosterone system (RAAS) pathway to regulate healthy cardiorespiratory functions. 37 Because of this high binding affinity and critical physiological and functional role, despite other receptors being identified as potential therapeutic targets, research has shown that targeting the ACE2 receptors is one of the most potent, smart, and effective ways of targeting and treating the SARS-CoV-2 viral infection. Therefore, significant efforts focus on developing therapeutic approaches that specifically target ACE2 receptors and expression.…”