Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone

Ganjali, Shiva; Bianconi, Vanessa; Penson, Peter E.; Pirro, Matteo; Banach, Maciej; Watts, Gerald F.; Sahebkar, Amirhossein

doi:10.1016/j.metabol.2020.154375

Cited by 43 publications

(44 citation statements)

References 49 publications

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“…The clinical utility of statins for the management of COVID-19 has been debated [ 86 ]. However, a recently published meta-analysis of 4 clinical studies involving a total of 8,990 COVID-19 patients concluded that statins reduce the hazard for severe or fatal COVID-19 cases [ 87 ].…”

Section: Putative Pharmacological and Dietary Approaches For The Prevmentioning

confidence: 99%

COVID-19 enters the expanding network of apolipoprotein E4-related pathologies

et al. 2021

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COVID-19 incidence and case fatality rates (CFR) differ among ethnicities, stimulating efforts to pinpoint genetic factors that could explain these phenomena. In this regard, the multiallelic apolipoprotein E (APOE) gene has recently been interrogated in the UK biobank cohort, demonstrating associations of the APOE ε4/ε4 genotype with COVID-19 severity and mortality. The frequency of the ε4 allele and thus the distribution of APOE ε4/ε4 genotype may differ among populations. We have assessed APOE genotypes in 1638 Greek individuals, based on haplotypes derived from SNP rs7412 and rs429358 and found reduced frequency of ε4/ε4 compared to the British cohort. Herein we discuss this finding in relation to CFR and hypothesize on the potential mechanisms linking APOE ε4/ε4 to severe COVID-19. We postulate that the metabolic deregulation ensued by APOE4, manifested by elevated cholesterol and oxidized lipoprotein levels, may be central to heightened pneumocyte susceptibility to infection and to exaggerated lung inflammation associated with the ε4/ε4 genotype. We also discuss putative dietary and pharmacological approaches for the prevention and management of COVID-19 in APOE ε4/ε4 individuals.

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Section: Putative Pharmacological and Dietary Approaches For The Prevmentioning

confidence: 99%

COVID-19 enters the expanding network of apolipoprotein E4-related pathologies

et al. 2021

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“…However, reverse causality—SARS-CoV-2 infection as a cause of LDL cholesterol reduction—instead of true causality, where LDL cholesterol reduction is a factor promoting the viral infection, might explain the association between low LDL cholesterol and severe COVID-19 manifestations. As previously discussed [51] , such an association may distract from refutations of the potential benefits of statin therapy in clinical settings of patients exposed to SARS-CoV-2 infection. In fact, every study included in the present meta-analyses failed to present results on blood lipid levels, and only a few [18] , [19] , [21] made clear mention of whether or not statin use identified at admission was maintained throughout the stay in hospital [16] .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, statins may exert anti-inflammatory [55] , immunomodulatory [64] and antioxidant properties [65] . As cytokine storms and consecutive bouts of inflammation play crucial roles in the development of poorer outcomes for COVID-19 [66] , positive effects may be expected from these pleiotropic effects of statins [11] , [51] , [67] . It should also be noted that statins have been described to have antiviral properties [68] .…”

Section: Discussionmentioning

confidence: 99%

“…In general, there are more arguments favouring the continued use of statin therapy rather than its interruption in patients exposed to SARS-CoV-2 [11] , [67] , [70] . While an in-depth description of these potential mechanisms is beyond the scope of the present report, such details may be found elsewhere [10] , [11] , [51] , [68] , [71] , [72] , [73] .…”

Section: Discussionmentioning

confidence: 99%

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Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies

Scheen

2021

Diabetes & Metabolism

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Aims People with cardiovascular disease or risk factors are at increased risk when exposed to SARS-CoV-2. Most are treated with statins, but the impact of these drugs on clinical outcomes of COVID-19 remains unclear. This report is therefore based on meta-analyses of retrospective observational studies aimed at investigating the impact of previous statin therapy in patients hospitalized for COVID-19. Methods In studies reporting on the clinical outcomes of COVID-19 in statin users vs non-users, two endpoints have been used—in-hospital death rates, and disease severity as assessed by admission to intensive care units (ICUs)—with a special focus on patients with diabetes. Results Regarding mortality, 13 studies were included in the meta-analysis for a total of 10,829 statin users (2517 deaths) and 31,893 non-users (7516 deaths): univariate analysis showed no statistically significant reduction in deaths (OR: 0.97, 95% CI: 0.92–1.03), although between-study heterogeneity was high (I² = 97%). As for disease severity, 11 studies were selected for a total of 3462 statin users (724 endpoints) and 10,560 non-users (1763 endpoints): here again, univariate analysis showed no reduction in severity (OR: 1.09, 95% CI: 0.99–1.22; I² = 93%). Collectively, in 10 studies using multivariable analysis adjusted for the more prevalent baseline risk factors among statin users, lower OR values were reported than with univariate analyses (0.73 ± 0.31 vs 1.44 ± 0.84, respectively; P = 0.0028; adjusted OR: P = 0.0237 vs non-users). Limited but conflicting findings were observed for diabetes patients. Conclusion Although no significant reductions in either in-hospital mortality or COVID-19 severity were reported among statin users compared with non-users after univariate comparisons, such reductions were observed after adjusting for confounding factors. These highly heterogeneous observational findings now require confirmation by ongoing randomized clinical trials.

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“…Yet another work showed that statins may be effective in reducing in-hospital mortality among diabetic patients 21 . Potential mechanisms for the protective actions of statins have been discussed elsewhere 24-26 . It has been postulated that besides reducing CVD risks, statins may reduce risk/severity of infection by inhibiting inflammation and excessive immune response, producing direct antiviral effects, improving endothelial function and exerting an antithrombotic effect, among other actions 24-26 .…”

Section: Discussionmentioning

confidence: 99%

Exploring drugs and vaccines associated with altered risks and severity of COVID-19: a UK Biobank cohort study of all ATC level-4 drug categories

Xiang

Wong

2020

Preprint

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BackgroundCOVID-19 is a major public health concern, yet its risk factors are not well-understood and effective therapies are lacking. It remains unclear how different drugs may increase or decrease the risks of infection and severity of disease.MethodsWe studied associations of prior use of all level-4 ATC drug categories (including vaccines) with COVID-19 diagnosis and outcome, based on a prospective cohort of UK Biobank(UKBB). Drug history was based on general practitioner(GP) records. Effects of prescribed medications/vaccinations on the risk of infection, severity of disease and mortality were investigated separately. Hospitalized and fatal cases were categorized as ‘severe’ infection. We also considered different study designs and conducted analyses within infected patients, tested subjects and the whole population respectively, and for 5 different time-windows of prescriptions. Missing data were accounted for by multiple imputation and inverse probability weighting was employed to reduce testing bias. Multivariable logistic regression was conducted which controls for main confounders.ResultsWe placed a greater focus on protective associations here, as (residual) confounding by indication and comorbidities tends to bias towards harmful effects. Across all categories, statins showed the strongest and most consistent protective associations. Significant protective effects against severe infection were seen among infected subjects (OR for prescriptions within a 12-month window, same below: 0.50, 95% CI:0.42-0.60), tested subjects (OR=0.63, 0.54-0.73) or in the general population (OR=0.49, 0.42-0.57). A number of top-listed drugs with protective effects were also cardiovascular medications, such as angiotensin converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blocker and beta-blockers. Some other drugs showing protective associations included biguanides (metformin), estrogens, thyroid hormones and proton pump inhibitors, among others.Interestingly, we also observed protective associations by numerous vaccines. The most consistent association was observed for influenza vaccines, which showed reduced odds of infection (OR= 0.73 for vaccination in past year, CI 0.65-0.83) when compared cases to general population controls or test-negative controls (OR=0.60, 0.53-0.68). Protective associations were also observed when severe or fatal infection was considered as the outcome. Pneumococcal, tetanus, typhoid and combined bacterial and viral vaccines (ATC code J07CA) were also associated with lower odds of infection/severity.Further subgroup and interaction analyses revealed difference in protective effects in different clinical subgroups. For example, protective effects of flu and pneumococcal vaccines were weaker in obese individuals, while we observed stronger protective effects of statins in those with cardiometabolic disorders, such as diabetes, coronary artery disease, hypertension and obesity.ConclusionsA number of drugs, including many for cardiometabolic disorders, may be associated with lower odds of infection/severity of infection. Several existing vaccines, especially flu vaccines, may be beneficial against COVID-19 as well. However, causal relationship cannot be established due to risk of confounding. While further studies are required to validate the findings, this work provides a useful reference for future meta-analyses, clinical trials or experimental studies.

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Commentary: Statins, COVID-19, and coronary artery disease: killing two birds with one stone

Cited by 43 publications

References 49 publications

COVID-19 enters the expanding network of apolipoprotein E4-related pathologies

COVID-19 enters the expanding network of apolipoprotein E4-related pathologies

Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies

Exploring drugs and vaccines associated with altered risks and severity of COVID-19: a UK Biobank cohort study of all ATC level-4 drug categories

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