PMC:7534795 / 1971-8036 JSONTXT

{"target":"http://pubannotation.org/docs/sourcedb/PMC/sourceid/7534795","sourcedb":"PMC","sourceid":"7534795","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7534795","text":"1 Introduction\nThe first outbreak of the novel coronaviruses was triggered by severe and acute respiratory syndrome coronavirus (SARS-CoV) in China in 2002, which was followed in 2012 by the Middle East respiratory syndrome-related coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV are infectious, lethal and accounted for thousands of deaths over the past two decades (de Wit, van Doremalen, Falzarano, \u0026 Munster, 2016; Zaki, van Boheemen, Bestebroer, Osterhaus, \u0026 Fouchier, 2012). The Coronavirus Study Group of the International Committee on Taxonomy of Viruses evaluated the novelty of the coronavirus responsible for the recent outbreak in 2019 (COVID-19) and formally considered it related to SARS-CoV, as they share about 79% nucleotide identity and accordingly named it as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019-novel coronavirus (Coronaviridae Study Group of the International Committee on Taxonomy of, 2020; Ren et al., 2020; Zhou et al., 2020). The recent eruption of COVID-19 was first reported in Wuhan, Hubei Province, China in late December 2019 when a series of pneumonia cases of unknown cause were detected (Wang et al., 2020). Highly contagious, COVID-19 spread rapidly throughout China and most countries across the world. On March 11th, the spread of COVID-19 was declared by the World Health Organization as a global pandemic and by October 9, 2020, the cumulative number of diagnosed patients internationally was 36,577,872 with 1,062,677 global deaths (https://coronavirus.jhu.edu/map.html, 2020).\nCoronaviruses infect both animals and humans affecting their respiratory, gastrointestinal, cardiovascular and central nervous systems (Cui, Li, \u0026 Shi, 2019). Consistently, SARS-CoV-2 primarily targets the lungs but it can affect many other organs and systems, including the kidneys, heart, blood vessels, gastrointestinal tract and brain (Wadman, Couzin-Frankel, Kaiser, \u0026 Matacic, 2020). Symptoms of COVID-19 are manifested as myalgia, fatigue, fever and dry cough, together with lower respiratory tract disease. In some cases, the severe progression of the disease leads to acute lung injury (ALI), acute respiratory distress syndrome (ARDS), respiratory failure, sepsis, heart failure (HF) and sudden cardiac arrest within a few days. Importantly, there is significant morbidity and mortality in the elderly and individuals with underlying health conditions (Chen et al., 2020; Huang et al., 2020). Although treatment with corticosteroids, antiviral therapy and mechanical respiratory support have been employed, there is still no specific treatment for COVID-19 and therefore supportive care is of paramount importance (Huang et al., 2020; Wu \u0026 McGoogan, 2020) (Table 1 ).\nTable 1 Overview of some proposed pharmacological agents with potential beneficial effects in COVID-19 patients.\nPharmacological intervention Conclusion Reference\nAntioxidants including Vitamin C and E • Antioxidant effects may ameliorate cardiac injuries of critically ill COVID-19 patients (Wang, Zhang, \u0026 Bai, 2020)\nMelatonin • May have preventive effect against septic cardiomyopathy\n• Has benefits in myocardial infarction, cardiomyopathy, hypertensive heart diseases, and pulmonary hypertension (Zhang et al., 2020)\nAnti-interleukin-6 • Tocilizumab (anti-IL-6 receptor), siltuximab (anti-IL-6), and sirukumab (anti-IL-6) are proposed as possible treatments to manage cytokine storm and elevated IL-6 levels (Akhmerov \u0026 Marban, 2020; Hendren, Drazner, Bozkurt, \u0026 Cooper Jr., 2020; Rizk et al., 2020)\nAnti-TNFα • Infliximab, adalimumab, etanercept, golimumab, certolizumab as TNFα neutralizing therapies suggested as potential agents for COVID-19 hyperinflammatory state which may ameliorate organ damage including acute cardiac injury (Convertino et al., 2020)\nJanus kinase (JAK) inhibitors • Ruxolitinib, tofacitinib, baricitinib are proposed to be beneficial in controlling excessive IL-6 signaling through STAT-1 and STAT-3 pathways (Alijotas-Reig et al., 2020; Convertino et al., 2020; Richardson et al., 2020; Rizk et al., 2020)\nAnti-interleukin-1 • Anakinra, a modified IL-1 receptor antagonist protein, is suggested to have therapeutic potential in cytokine storm, given its effectiveness on patient survival in severe sepsis (Alijotas-Reig et al., 2020; Rizk et al., 2020)\nGranulocyte-macrophage-colony stimulating factor (GM-CSF) inhibition • GM-CSF can play a pro-inflammatory role signaling to macrophages\n• COVID-19 patients have been demonstrated to have elevated GM-CSF levels\n• Literature proposes that targeting GM-CSF upstream of inflammatory cytokines ex. gimsilumab, may be useful to blunt cytokine storm (Rizk et al., 2020)\nStatins • Anti-inflammatory properties, including reduction in cytokines, may benefit in COVID-19 hyperinflammatory states in addition to their conventional cardioprotective properties (Alijotas-Reig et al., 2020; Rizk et al., 2020)\nACEi/ARBs • Proposed that treatment with RAAS antagonists may theoretically be beneficial by upregulating ACE2 and compensating for ACE2 receptors lost due to COVID-19 (Akhmerov \u0026 Marban, 2020)\nN-acetylcysteine (NAC) • Anti-oxidant and anti-inflammatory properties of NAC proposed as an adjuvant therapy for COVID-19 and secondary cardiovascular complications\n• Suggested role for NAC in prevention of hypertension, atherosclerosis-associated inflammation, acute heart failure, thrombo-inflammation, and myocardial ischemia (De Flora, Balansky, \u0026 La Maestra, 2020; Guglielmetti et al., 2020)\nEicosanoids and soluble epoxide hydrolase (sEH) inhibitors • Epoxyeicosatrienoic acids (EETs) are cardioprotective, anti-inflammatory and pro-resolving\n• Inhibition of their metabolizing enzyme, sEH, may be beneficial by maintaining eicosanoid levels and reducing endoplasmic reticulum (ER) stress\n• Potential to limit inflammatory storm and resolve inflammation in addition to their established cardioprotective properties\n• Co-treatment with sEH inhibitors and omega-3 fatty acids may provide synergistic effects (Hammock, Wang, Gilligan, \u0026 Panigrahy, 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