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1.
Int J Mol Sci ; 22(8)2021 Apr 17.
Article in English | MEDLINE | ID: covidwho-1298166

ABSTRACT

The virus responsible for the current COVID-19 pandemic is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a new virus with high infectivity and moderate mortality. The major clinical manifestation of COVID-19 is interstitial pneumonia, which may progress to acute respiratory distress syndrome (ARDS). However, the disease causes a potent systemic hyperin-flammatory response, i.e., a cytokine storm or macrophage activation syndrome (MAS), which is associated with thrombotic complications. The complexity of the disease requires appropriate intensive treatment. One of promising treatment is statin administration, these being 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors that exert pleiotropic anti-inflammatory effects. Recent studies indicate that statin therapy is associated with decreased mortality in COVID-19, which may be caused by direct and indirect mechanisms. According to literature data, statins can limit SARS-CoV-2 cell entry and replication by inhibiting the main protease (Mpro) and RNA-dependent RNA polymerase (RdRp). The cytokine storm can be ameliorated by lowering serum IL-6 levels; this can be achieved by inhibiting Toll-like receptor 4 (TLR4) and modulating macrophage activity. Statins can also reduce the complications of COVID-19, such as thrombosis and pulmonary fibrosis, by reducing serum PAI-1 levels, attenuating TGF-ß and VEGF in lung tissue, and improving endothelial function. Despite these benefits, statin therapy may have side effects that should be considered, such as elevated creatinine kinase (CK), liver enzyme and serum glucose levels, which are already elevated in severe COVID-19 infection. The present study analyzes the latest findings regarding the benefits and limitations of statin therapy in patients with COVID-19.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Animals , COVID-19/complications , Endothelium/drug effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Inflammation/complications , Inflammation/drug therapy , Lipid Metabolism/drug effects , Macrophage Activation/drug effects , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , SARS-CoV-2/drug effects , Thrombosis/complications , Thrombosis/drug therapy
2.
Curr Opin Lipidol ; 32(4): 231-243, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1266229

ABSTRACT

PURPOSE OF REVIEW: Coronavirus Disease 2019 (COVID19) has caused significant global morbidity and mortality, especially in persons with underlying cardiovascular disease. There have been concerns that lipid-lowering therapy (LLT) increases angiotensin-converting enzyme 2 levels. Conversely, pleiotropic effects of statins can theoretically protect against severe COVID19 infection, supporting evidence from other respiratory illnesses in which statin use probably confers benefit. RECENT FINDINGS: There is an abundance of studies that show that statins are safe and potentially protect against severe COVID19 infection (critical illness and death), even when adjustment for potential confounders is undertaken. However, the evidence is limited to retrospective cohorts. The benefit for patients with diabetes is less clear. There is a paucity of evidence for other LLT agents. Available clinical guidelines recommend the ongoing use of LLT in patients with COVID19 (unless specifically contra-indicated) and the data from available studies support these. SUMMARY: In patients with COVID19 infection, LLT should be continued. However, the current findings need substantiating in larger prospective clinical studies with specific examination of the possible mechanisms by which LLT confers benefit from COVID19.


Subject(s)
Atherosclerosis/drug therapy , COVID-19/drug therapy , Cardiovascular Diseases/drug therapy , Dyslipidemias/drug therapy , Atherosclerosis/complications , Atherosclerosis/epidemiology , Atherosclerosis/virology , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Cardiovascular Diseases/complications , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/virology , Cholesterol, LDL/drug effects , Dyslipidemias/complications , Dyslipidemias/epidemiology , Dyslipidemias/virology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypolipidemic Agents/therapeutic use , SARS-CoV-2/pathogenicity
3.
Wien Klin Wochenschr ; 133(17-18): 958-965, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1155277

ABSTRACT

On 11 March 2020 the World Health Organization (WHO) declared a status of global pandemic caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019, COVID-19). The pandemic is currently underway, and to date has caused approximately 2.42 million deaths worldwide. The first vaccines have recently been licensed; however, research continues to identify therapeutic agents to prevent serious complications, such as anti-inflammatory, immunomodulatory, anticoagulant or antiviral agents authorized for other therapeutic indications. Epidemiological evidence shows that advanced age and comorbidities, such as diabetes, heart disease, and dyslipidemia may represent COVID-19 risk factors. In particular, in patients with hypercholesterolemia treated with statins, it is recommended that treatment should not be discontinued if COVID-19 infection occurs. The pleiotropic effects of statins are well known. In this brief review, we propose that the use of statins can potentially protect against SARS-CoV-2-induced tissue damage and improve lung function in COVID-19 patients through several pleiotropic effects. Pleiotropic effects of statins that may be a significant benefit in patients with hypercholesterolemia treated with statins and COVID-19 positive. Recent evidence shows promising results.


Subject(s)
COVID-19 , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Pharmaceutical Preparations , COVID-19/drug therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , SARS-CoV-2
4.
Prog Cardiovasc Dis ; 67: 53-64, 2021.
Article in English | MEDLINE | ID: covidwho-1091673

ABSTRACT

Myocarditis refers to the clinical and histological characteristics of a diverse range of inflammatory cellular pathophysiological conditions which result in cardiac dysfunction. Myocarditis is a major cause of mortality in individuals less than 40 years of age and accounts for approximately 20% of cardiovascular disease (CVD) events. Myocarditis contributes to dilated cardiomyopathy in 30% of patients and can progress to cardiac arrest, which has a poor prognosis of <40% survival over 10 years. Myocarditis has also been documented after infection with SARS-CoV-2. The most commonly used lipid-lowering therapies, HMG-CoA reductase inhibitors (statins), decrease CVD-related morbidity and mortality. In addition to their lipid-lowering effects, increasing evidence supports the existence of several additional beneficial, 'pleiotropic' effects of statins. Recently, several studies have indicated that statins may attenuate myocarditis. Statins modify the lipid oxidation, inflammation, immunomodulation, and endothelial activity of the pathophysiology and have been recommended as adjuvant treatment. In this review, we focus on the mechanisms of action of statins and their effects on myocarditis, SARS-CoV-2 and CVD.


Subject(s)
COVID-19/drug therapy , Cardiovascular Diseases/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Myocarditis/drug therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/chemistry , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Molecular Structure , Myocarditis/etiology
5.
Br J Pharmacol ; 177(21): 4873-4886, 2020 11.
Article in English | MEDLINE | ID: covidwho-998831

ABSTRACT

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has overwhelmed healthcare systems requiring the rapid development of treatments, at least, to reduce COVID-19 severity. Drug repurposing offers a fast track. Here, we discuss the potential beneficial effects of statins in COVID-19 patients based on evidence that they may target virus receptors, replication, degradation, and downstream responses in infected cells, addressing both basic research and epidemiological information. Briefly, statins could modulate virus entry, acting on the SARS-CoV-2 receptors, ACE2 and CD147, and/or lipid rafts engagement. Statins, by inducing autophagy activation, could regulate virus replication or degradation, exerting protective effects. The well-known anti-inflammatory properties of statins, by blocking several molecular mechanisms, including NF-κB and NLRP3 inflammasomes, could limit the "cytokine storm" in severe COVID-19 patients which is linked to fatal outcome. Finally, statin moderation of coagulation response activation may also contribute to improving COVID-19 outcomes. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.


Subject(s)
Coronavirus Infections/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Pneumonia, Viral/drug therapy , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/immunology , Coronavirus Infections/virology , Cytokines/immunology , Drug Repositioning , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Pandemics , Pneumonia, Viral/immunology , Pneumonia, Viral/virology , SARS-CoV-2 , Virus Internalization/drug effects
6.
Med Hypotheses ; 146: 110452, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-965499

ABSTRACT

Statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors interfere with several pathophysiological pathways of coronavirus disease 2019 (COVID-19). Statins may have a direct antiviral effect on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by inhibiting its main protease. Statin-induced up-regulation of angiotensin-converting enzyme 2 (ACE2) may also be beneficial, whereas cholesterol reduction might significantly suppress SARS-CoV-2 by either blocking its host-cell entry through the disruption of lipid rafts or by inhibiting its replication. Available human studies have shown beneficial effects of statins and PCSK9 inhibitors on pneumonia and sepsis. These drugs may act as immunomodulators in COVID-19 and protect against major complications, such as acute respiratory distress syndrome and cytokine release syndrome. Considering their antioxidative, anti-arrhythmic, antithrombotic properties and their beneficial effect on endothelial dysfunction, along with the increased risk of mortality of patients at high cardiovascular risk infected by SARS-CoV-2, statins and PCSK9 inhibitors might prove effective against the cardiovascular and thromboembolic complications of COVID-19. On the whole, randomized clinical trials are needed to establish routine use of statins and PCSK9 inhibitors in the treatment of SARS-CoV-2 infection. In the meantime, it is recommended that lipid-lowering therapy should not be discontinued in COVID-19 patients unless otherwise indicated.


Subject(s)
COVID-19/drug therapy , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Serine Proteinase Inhibitors/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/therapeutic use , COVID-19/complications , COVID-19/physiopathology , Cardiovascular Diseases/prevention & control , Endothelium, Vascular/drug effects , Endothelium, Vascular/physiopathology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Immunity, Innate/drug effects , Models, Biological , Pandemics , Pneumonia, Viral/drug therapy , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , SARS-CoV-2/physiology , Safety , Sepsis/drug therapy , Serine Proteinase Inhibitors/adverse effects , Thromboembolism/prevention & control
7.
Front Med (Lausanne) ; 7: 584870, 2020.
Article in English | MEDLINE | ID: covidwho-963101

ABSTRACT

Background: Statins have multiple protective effects on inflammation, immunity and coagulation, and may help alleviate pneumonia. However, there was no report focusing on the association of statin use with in-hospital outcomes of patients with coronavirus disease 2019 (COVID-19). We investigated the association between the use of statins and in-hospital outcomes of patients with COVID-19. Methods: In this retrospective case series, consecutive COVID-19 patients admitted at 2 hospitals in Wuhan, China, from March 12, 2020 to April 14, 2020 were analyzed. A 1:1 matched cohort was created by propensity score-matched analysis. Demographic data, laboratory findings, comorbidities, treatments and in-hospital outcomes were collected and compared between COVID-19 patients taking and not taking statins. Result: A total of 2,147 patients with COVID-19 were enrolled in this study. Of which, 250 patients were on statin therapy. The mortality was 2.4% (6/250) for patients taking statins while 3.7% (70/1,897) for those not taking statins. In the multivariate Cox model, after adjusting for age, gender, admitted hospital, comorbidities, in-hospital medications and blood lipids, the risk was lower for mortality (adjusted HR, 0.428; 95% CI, 0.169-0.907; P = 0.029), acute respiratory distress syndrome (ARDS) (adjusted HR, 0.371; 95% CI, 0.180-0.772; P = 0.008) or intensive care unit (ICU) care (adjusted HR, 0.319; 95% CI, 0.270-0.945; P = 0.032) in the statin group vs. the non-statin group. After propensity score-matched analysis based on 18 potential confounders, a 1:1 matched cohort (206:206) was created. In the matched cohort, the Kaplan-Meier survival curves showed that the use of statins was associated with better survival (P = 0.025). In a Cox regression model, the use of statins was associated with lower risk of mortality (unadjusted HR, 0.254; 95% CI, 0.070-0.926; P = 0.038), development of ARDS (unadjusted HR, 0.240; 95% CI, 0.087-0.657; P = 0.006), and admission of ICU (unadjusted HR, 0.349; 95% CI, 0.150-0.813; P = 0.015). The results remained consistent when being adjusted for age, gender, total cholesterol, triglyceride, low density lipoprotein cholesterol, procalcitonin, and brain natriuretic peptide. The favorable outcomes in statin users remained statistically significant in the first sensitivity analysis with comorbid diabetes being excluded in matching and in the second sensitivity analysis with chronic obstructive pulmonary disease being added in matching. Conclusion: In this retrospective analysis, the use of statins in COVID-19 patients was associated with better clinical outcomes and is recommended to be continued in patients with COVID-19.

8.
Curr Atheroscler Rep ; 22(11): 64, 2020 09 01.
Article in English | MEDLINE | ID: covidwho-738677

ABSTRACT

PURPOSE OF REVIEW: Statins are first-line therapy for lowering low-density lipoprotein (LDL) cholesterol in familial hypercholesterolemia (FH), particularly in heterozygous patients. We review advances and new questions on the use of statins in FH. RECENT FINDINGS: Cumulative evidence from registry data and sub-analyses of clinical trials mandates the value of statin therapy for prevention of atherosclerotic cardiovascular disease (ASCVD) in FH. Statins are safe in children and adolescents with FH, with longer term cardiovascular benefits. The potentially toxic effects of statins in pregnancy need to be considered, but no association has been reported in prospective cohort studies with birth defects. There is no rationale for discontinuation of statins in elderly FH unless indicated by adverse events. FH is undertreated, with > 80% of statin-treated FH patients failing to attain LDL cholesterol treatment targets. This may relate to adherence, tolerability, and genetic differences in statin responsiveness. Statin treatment from childhood may reduce the need for stringent cholesterol targets. Combination of statins with ezetimibe and PCSK9 inhibitors significantly improves the efficacy of treatment. Whether statin use could improve the clinical course of FH patients with COVID-19 and other respiratory infections remains an unsolved issue for future research. Statins are the mainstay for primary and secondary prevention of ASCVD in FH. Sustained long-term optimal statin treatment from an early age can effectively prevent ASCVD over decades of life. Despite their widespread use, statins merit further investigation in FH.


Subject(s)
Coronavirus Infections/epidemiology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hyperlipoproteinemia Type II , Medication Therapy Management , Pneumonia, Viral/epidemiology , Anticholesteremic Agents/classification , Anticholesteremic Agents/pharmacology , Betacoronavirus , COVID-19 , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Humans , Hyperlipoproteinemia Type II/drug therapy , Hyperlipoproteinemia Type II/epidemiology , Pandemics , SARS-CoV-2
9.
Diabetes Metab Syndr ; 14(5): 1225-1229, 2020.
Article in English | MEDLINE | ID: covidwho-640010

ABSTRACT

BACKGROUND AND AIMS: Morbidity and mortality from coronavirus disease 2019 (COVID-19) is higher among people with diabetes mellitus (DM), hypertension, and cardiovascular disease (CVD). Statins are used in the majority of people with DM and CVD. This mini-review discusses the current understanding of benefit-risk ratio of use of statins in COVID-19. METHODS: We searched PubMed database using specific keywords related to our aims till June 12, 2020. Full text of relevant articles published in English language were retrieved and reviewed. RESULTS: Statins, with their immunomodulatory, anti-inflammatory, anti-thrombotic, and anti-oxidant properties, have the potential to reduce severity of lung injury in, and mortality from, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infections. Statin-induced upregulation of angiotensin-converting enzyme-2 (ACE2) has the potential to reduce lung injury from excess angiotensin II. By disrupting lipid rafts, statins have the potential to reduce viral entry into cells. However, benefit-risk ratio of its complex interaction with MYD88 gene expression on outcomes in COVID-19, and the putative role of low serum LDL cholesterol in increasing severity of SARS-CoV2 infection need further clarification. CONCLUSIONS: People with COVID-19, who are already on statins for an underlying co-morbid condition, should continue on it unless there are specific contraindications. De-novo use of statins in people with COVID-19 with no underlying co-morbidity might be beneficial but awaits substantiation in clinical trials; till that time, de novo use of statins in COVID 19 should be limited to a clinical trial setting.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/epidemiology , Coronavirus Infections/prevention & control , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Pandemics/prevention & control , Pneumonia, Viral/epidemiology , Pneumonia, Viral/prevention & control , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Coronavirus Infections/virology , Humans , Incidence , India/epidemiology , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prognosis , SARS-CoV-2
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