Molecular Insights of SARS-CoV-2 Antivirals Administration: A Balance between Safety Profiles and Impact on Cardiovascular Phenotypes.

The COVID-19 pandemic has resulted in a complex clinical challenge, caused by a novel coronavirus, partially similar to previously known coronaviruses but with a different pattern of contagiousness, complications, and mortality. Since its global spread, several therapeutic agents have been developed to address the heterogeneous disease treatment, in terms of severity, hospital or outpatient management, and pre-existing clinical conditions. To better understand the rationale of new or old repurposed medications, the structure and host-virus interaction molecular bases are presented. The recommended agents by EDSA guidelines comprise of corticosteroids, JAK-targeting monoclonal antibodies, IL-6 inhibitors, and antivirals, some of them showing narrow indications due to the lack of large population trials and statistical power. The aim of this review is to present FDA-approved or authorized for emergency use antivirals, namely remdesivir, molnupinavir, and the combination nirmatrelvir-ritonavir and their impact on the cardiovascular system. We reviewed the literature for metanalyses, randomized clinical trials, and case reports and found positive associations between remdesivir and ritonavir administration at therapeutic doses and changes in cardiac conduction, relatable to their previously known pro-arrhythmogenic effects and important ritonavir interactions with cardioactive medications including antiplatelets, anti-arrhythmic agents, and lipid-lowering drugs, possibly interfering with pre-existing therapeutic regimens. Nonetheless, safety profiles of antivirals are largely questioned and addressed by health agencies, in consideration of COVID-19 cardiac and pro-thrombotic complications generally experienced by predisposed subjects. Our advice is to continuously adhere to the strict indications of FDA documents, monitor the possible side effects of antivirals, and increase physicians' awareness on the co-administration of antivirals and cardiovascular-relevant medications. This review dissects the global and local tendency to structure patient-based treatment plans, for a glance towards practical application of precision medicine.

COVID-19 Pathogenesis: From Molecular Pathway to Vaccine Administration.

The Coronavirus 2 (SARS-CoV-2) infection is a global pandemic that has affected millions of people worldwide. The advent of vaccines has permitted some restitution. Aside from the respiratory complications of the infection, there is also a thrombotic risk attributed to both the disease and the vaccine. There are no reliable data for the risk of thromboembolism in SARS-CoV-2 infection in patients managed out of the hospital setting. A literature review was performed to identify the pathophysiological mechanism of thrombosis from the SARS-CoV-2 infection including the role of Angiotensin-Converting Enzyme receptors. The impact of the vaccine and likely mechanisms of thrombosis following vaccination were also clarified. Finally, the utility of the vaccines available against the multiple variants is also highlighted. The systemic response to SARS-CoV-2 infection is still relatively poorly understood, but several risk factors have been identified. The roll-out of the vaccines worldwide has also allowed the lifting of lockdown measures and a reduction in the spread of the disease. The experience of the SARS-CoV-2 infection, however, has highlighted the crucial role of epidemiological research and the need for ongoing studies within this field.

Thromboembolic Complications of SARS-CoV-2 and Metabolic Derangements: Suggestions from Clinical Practice Evidence to Causative Agents.

Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 is a recently identified positive sense single-strand RNA (ssRNA) ß-coronavirus. The viral spike proteins infect human hosts by binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2). The infection causes a systemic illness involving cell metabolism. This widespread involvement is implicated in the pathophysiology of the illness which ranges from mild to severe, requiring multi organ support, ranging from oxygen supplementation to full cardiovascular and respiratory support. Patients with multiple co-existing comorbidities are also at a higher risk. The aim of this review is to explore the exact mechanisms by which COVID-19 affects patients systemically with a primary focus on the bleeding and thrombotic complications linked with the disease. Issues surrounding the thrombotic complications following administration of the ChAdOx1 nCoV-19 (Astra-Zeneca-Oxford) vaccine have also been illustrated. Risk stratification and treatment options in these patients should be tailored according to clinical severity with input from a multidisciplinary team.