The role of miRNAs in viral myocarditis, and its possible implication in induction of mRNA-based COVID-19 vaccines-induced myocarditis.

Background: Several reports of unheeded complications secondary to the current mass international rollout of SARS-COV-2 vaccines, one of which is myocarditis occurring with the FDA fully approved vaccine, Pfizer, and others. Main body of the abstract: Certain miRNAs (non-coding RNA sequences) are involved in the pathogenesis in viral myocarditis, and those miRNAs are interestingly upregulated in severe COVID-19. We hypothesize that the use of mRNA-based vaccines may be triggering the release of host miRNAs or that trigger the occurrence of myocarditis. This is based on the finding of altered host miRNA expression promoting virus-induced myocarditis. Short conclusion: In conclusion, miRNAs are likely implicated in myocarditis associated with mRNA vaccines. Our hypothesis suggests the use of miRNA as a biomarker for the diagnosis of mRNA vaccine-induced myocarditis. Additionally, the interplay between viral miRNA and the host immune system could alter inflammatory profiles, hence suggesting the use of therapeutic inhibition to prevent such complications.

Peroxisome proliferator-activated receptor agonists and reversal of vascular degeneration through DNA repair, a step toward drug-induced regenerative medicine.

Endothelial dysfunction with subsequent degeneration and vasoocclusive remodeling is the hallmark of many cardiovascular disorders including pulmonary vascular disease (PVD). To date, the available treatments slows disease progression but does not prevent deterioration. Reversing such pathologies would spare many patients risky surgeries and long waiting lists for a possible organ donor. Peroxisome proliferator-activated receptor agonists were first introduced as sole insulin sensitizers, however, there is increasing body of evidence that they have different actions on DNA which might help reverse vascular degeneration. This effect appears to be mainly achieved through enhancement of DNA damage responses (DDR). The aforementioned effect could offer new insights about repurposing drugs for achieving organ or tissue regeneration, an understudied field named drug-induced regenerative medicine.

Single cell sequencing unraveling genetic basis of severe COVID19 in obesity.

COVID-19 has shown a substantial variation in the rate and severity by which it impacts different demographic groups. Specifically, it has shown a predilection towards obese patients as well as well as other vulnerable groups including predilection of males over females, old age over young age and black races over Caucasian ones. Single cell sequencing studies have highlighted the role of cell polarity and the co-expression of proteases, such as Furin, along with ACE2 in the genesis of coronavirus disease rather than exclusively link tissue involvement with ACE2 levels thought previously. It has also forged a connection between the genetic and immune cellular mechanisms underlying COVID infection and the inflammatory state of obese patients, offering a more accurate explanation as to why obese patients are at increased risk of poor COVID outcomes. These commonalities encompass macrophage phenotype switching, genetic expression switching, and overexpression of the pro-inflammatory cytokines, depletion of the regulatory cytokines, in situ T cell proliferation, and T cell exhaustion. These findings demonstrate the necessity of single cell sequencing as a rapid means to identify and treat those who are most likely to need hospital admission and intensive care, in the hopes of precision medicine. Furthermore, this study underlines the use of immune modulators such as Leptin sensitizers, rather than immune suppressors as anti-inflammation therapies to switch the inflammatory response from a drastic immunological type 1 response to a beneficial type 2 effective one.

Is it infection or rather vascular inflammation? Game-changer insights and recommendations from patterns of multi-organ involvement and affected subgroups in COVID-19.

Coronavirus disease 2019 (COVID-19) is a serious illness that has rapidly spread throughout the globe. The seriousness of complications puts significant pressures on hospital resources, especially the availability of ICU and ventilators. Current evidence suggests that COVID-19 pathogenesis majorly involves microvascular injury induced by hypercytokinemia, namely interleukin 6 (IL-6). We recount the suggested inflammatory pathway for COVID-19 and its effects on various organ systems, including respiratory, cardiac, hematologic, reproductive, and nervous organ systems, as well examine the role of hypercytokinemia in the at-risk geriatric and obesity subgroups with upregulated cytokines' profile. In view of these findings, we strongly encourage the conduction of prospective studies to determine the baseline levels of IL-6 in infected patients, which can predict a negative outcome in COVID-19 cases, with subsequent early administration of IL-6 inhibitors, to decrease the need for ICU admission and the pressure on healthcare systems. Video abstract: http://links.lww.com/CAEN/A24.

Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications.

Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO. Despite being mainly a respiratory virus, cardiac complications have been described. These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19. The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins. It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes. It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively. Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction. The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications.

A multicenter consensus: A role of furin in the endothelial tropism in obese patients with COVID-19 infection.

Furin, a cleavage enzyme, is increasingly recognized in the pathogenesis of metabolic syndrome. Its cleavage action is an essential activation step for the endothelial pathogenicity of several viruses including SARS-CoV-2. This Furin-mediated endothelial tropism seems to underlie the multi-organ system involvement of COVID-19; which is a feature that was not recognized in the older versions of coronaviridae. Obese and diabetic patients, males, and the elderly, have increased serum levels of Furin, with its increased cellular activity; this might explain why these subgroups are at an increased risk of COVID-19 related complications and deaths. In contrast, smoking decreases cellular levels of Furin, this finding may be at the origin of the decreased severity of COVID-19 in smokers. Chinese herbal derived luteolin is suggested to be putative Furin inhibitor, with previous success against Dengue Fever. Additionally, Furin intracellular levels are largely dependent on concentration of intracellular ions, notably sodium, potassium, and magnesium. Consequently, the use of ion channel inhibitors, such as Calcium Channel blockers or Potassium Channel blockers, can prevent cellular transfection early in the course of the illness. Nicotine patches and Colchicine have also been suggested as potential therapies due to Furin mediated inhibition of COVID-19.