A Review on COVID-19: Primary Receptor, Endothelial Dysfunction, Related Comorbidities, and Therapeutics

Since December 2019, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic named coronavirus disease-19 (COVID-19) and resulted in a worldwide economic crisis. Utilizing the spike-like protein on its surface, the SARS-CoV-2 binds to the receptor angiotensin-converting enzyme 2 (ACE2), which highly expresses on the surface of many cell types. Given the crucial role of ACE2 in the renin–angiotensin system, its engagement by SARS-CoV-2 could potentially result in endothelial cell perturbation. This is supported by the observation that one of the most common consequences of COVID-19 infection is endothelial dysfunction and subsequent vascular damage. Furthermore, endothelial dysfunction is the shared denominator among previous comorbidities, including hypertension, kidney disease, cardiovascular diseases, etc., which are associated with an increased risk of severe disease and mortality in COVID-19 patients. Several vaccines and therapeutics have been developed and suggested for COVID-19 therapy. The present review summarizes the relationship between ACE2 and endothelial dysfunction and COVID-19, also reviews the most common comorbidities associated with COVID-19, and finally reviews several categories of potential therapies against COVID-19.

Vaccines against SARS-CoV-2 variants and future pandemics.

INTRODUCTION: Vaccination continues to be the most effective method for controlling COVID-19 infectious diseases. Nonetheless, SARS-CoV-2 variants continue to evolve and emerge, resulting in significant public concerns worldwide, even after more than 2 years since the COVID-19 pandemic. It is important to better understand how different COVID-19 vaccine platforms work, why SARS-CoV-2 variants continue to emerge, and what options for improving COVID-19 vaccines can be considered to fight against SARS-CoV-2 variants and future pandemics. AREA COVERED: Here, we reviewed the innate immune sensors in the recognition of SARS-CoV-2 virus, innate and adaptive immunity including neutralizing antibodies by different COVID-19 vaccines. Efficacy comparison of the several COVID-19 vaccine platforms approved for use in humans, concerns about SARS-CoV-2 variants and breakthrough infections, and the options for developing future COIVD-19 vaccines were also covered. EXPERT OPINION: Owing to the continuous emergence of novel pathogens and the reemergence of variants, safer and more effective new vaccines are needed. This review also aims to provide the knowledge basis for the development of next-generation COVID-19 and pan-coronavirus vaccines to provide cross-protection against new SARS-CoV-2 variants and future coronavirus pandemics.

SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients.

Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with ACE2 gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.