COVID-19 therapy and vaccination: a clinical narrative review.

The SARS-CoV-2 pandemic is the most globally impacting health issue our world has faced over the last century. As of January 7, 2022, around 300 million cases have been reported worldwide, with over 5 million deaths. The SARS-CoV-2 infection causes a hyperactive host immune response leading to an excessive inflammatory reaction with the release of many cytokines - cytokine storm - commonly noticed in acute respiratory distress syndrome, sepsis and fulminant multiorgan failure. Since the beginning of the pandemic, the scientific medical community has worked on therapeutic procedures that interfere with the exaggerated immune response. Thromboembolic complications are widespread in patients who are critically ill with COVID-19. Anticoagulant therapy was initially considered a cornerstone in hospitalized patients and even in the early post-discharge period; however, later trials have aborted the clinical benefits except for suspicion of or confirmed thrombosis. Immunomodulatory therapies are still crucial in moderate to severe COVID-19. Immunomodulator therapies include various medications from steroids to hydroxychloroquine, tocilizumab and Anakinra. Anti-inflammatory agents, vitamin supplements and antimicrobial therapy had initial encouraging evidence, but there are limited data to review. Convalescent plasma, immunoglobulins, eculizumab, neutralizing IgG1 monoclonal antibodies and remdesivir have positively impacted inpatient mortality and hospital length of stay. Eventually, wide population vaccination was proven to be the best tool to overcome the SARS-CoV-2 pandemic and help humanity return to regular life. Many vaccines and various strategies have been used since December 2020. This review discusses how the SARS-CoV-2 pandemic has progressed and surged, and summarizes the safety and efficacy of the most used therapies and vaccines in the light of recent evidence.

Mechanisms and management of prothrombotic state in COVID-19 disease.

The novel severe acute respiratory syndrome viral disease outbreak due to SARS-CoV-2 is a rapidly evolving disease and represents one of the greatest medical challenges in recent times. It is believed that SARS-CoV-2 has migrated from bats to an intermediate host and then to humans. This article aims at the mechanism and management of prothrombotic state in COVID-19 positive patients. We tried to present how the SARS-CoV-2 virus can induce thromboembolic events and the incidence of these thromboembolic events. We also tried to depict anticoagulation management in these patients as well as postdischarge plan and follow-up. Invasion of type 2 pneumocytes by the SARS-CoV-2 virus is critical in the course of illness because it results in activation of immune cells leading to elevation of cytokines. The subsequent activation of T cells and macrophages infiltrates the infected myocardial cells causing direct myocardiocyte toxicity and development of arrhythmia. Hypoxia or hypotension during the clinical course causes a mismatch between myocyte oxygen supply and workload demand resulting in cardiac distress. SARS-CoV-2 affects endothelial cells and pericytes that lead to severe micro and macrovascular dysfunction, and together with oxygen supply-demand mismatch, immune hyperresponsivity can potentially cause destabilization and plaque rupture causing acute coronary syndromes. Other mechanisms of injury include myocarditis, pericarditis, stress cardiomyopathy, vasculitis, and DIC (Disseminated intravascular coagulation)/microthrombi. SARS-CoV-2 enters the cells by the Spike protein S whose surface unit, S1, binds to the ACE2 receptor on the host cell. The type II transmembrane serine proteases TMPRSS2 and histone acetyltransferases (HAT) are host cell proteases that are recruited by the virus to cleave ACE2 surface protein S which facilitates the viral entry. Therefore, TMPRSS2 and HAT could be targeted for potential drugs against SARS-CoV-2. SARS-CoV-2 uses an RNA-dependent RNA polymerase for proliferation, which is targeted by remdesivir that is currently approved for emergency use by Food and Drug Administration (FDA). We need to adopt a multifaceted approach when combating SARS-CoV-2 because it presents several challenges including medical, psychological, socioeconomic, and ethical. COVID-19 is the biggest calamity during the 21st century, we need to have a keen understanding of its pathophysiology and clinical implications for the development of preventive measures and therapeutic modalities.

Current treatment in COVID-19 disease: a rapid review.

The world has faced the most challenging pandemic of the modern era, that of severe acute respiratory syndrome coronavirus 2 infection, causing coronavirus disease and affecting over 35 million people globally. The wide range of clinical manifestations associated with this viral disease is thought to be related to the overexpression of inflammatory markers. Due to a dysregulated host response, the most severe form involves multi-organ failure and thromboembolic complications. Immunomodulatory therapies may help prevent its progression and anticoagulation has been shown to reduce the risk of thrombotic complications. As this is a new entity for the medical world, there are no known therapeutic options nor has the prevention of complications been established. Anti-inflammatory agents, antimicrobial therapy, and vitamin supplements are short of clear benefits, but there is limited data to review. Other agents, such as convalescent plasma, eculizumab, immunoglobulins, neutralizing IgG1 monoclonal antibodies, remdesivir, steroids, and tocilizumab, have shown a possible impact on inpatient length of stay and mortality rate. This review aims to assess the efficacy and safety of these available therapies in light of current evidence. We compare these treatment options based on their impact on symptom management, inpatient length of stay, and overall morbidity and mortality.

COVID-19 and renin-angiotensin system modulators: what do we know so far?

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory system-coronavirus-2 (SARS-CoV-2), is an important medical problem worldwide. Increased risk of mortality has been reported in patients with cardiovascular disease, such as hypertension (HTN). SARS-CoV-2 invades the pulmonary alveolar epithelial cells by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2). Renin-angiotensin system (RAS) modulators can increase levels of ACE2. Thus, concerns have been raised regarding an increased risk of severe COVID-19 infection in patients receiving RAS antagonists. AREAS COVERED: We reviewed current literature about the potential association between the utilization of RAS inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-inhibitors) and angiotensin-receptor blockers (ARBs) and likelihood of developing severe COVID-19 infection and whether or not continuation of these medications is appropriate in patients with active disease. EXPERT OPINION: The joint statement from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC) and Heart Failure Society of America (HFSA), strongly recommends that physicians should not initiate or withdraw their usual RAS-related treatments (ACE-inhibitor/ARB) to COVID-19 infected patients with cardiovascular disease. The decision should be made based upon each patient's clinical presentation and hemodynamic status.