Prior Statin Use and Risk of Mortality and Severe Disease From Coronavirus Disease 2019: A Systematic Review and Meta-analysis

Abstract

Background Statins up-regulate angiotensin converting enzyme-2, the receptor of SARS-CoV-2, while also exhibiting pleiotropic antiviral, antithrombotic and anti-inflammatory properties. Uncertainties exist about their effect on the course of SARS-CoV-2 infection. Objectives We sought to systematically review the literature and perform a meta-analysis to examine the association between prior statins use and outcomes of patients with COVID-19. Methods We searched Ovid MEDLINE, Web of Science, Scopus, and the preprint server MedRxiv from inception to December 2020. We assessed the quality of eligible studies with the Newcastle-Ottawa quality scale. We pooled adjusted risk ratios (aRR) of the association between prior statins use and outcomes of patients with COVID-19 using the DerSimonian-Laird random effects model and assessed heterogeneity using the I 2-index. Results Overall, 19 (16 cohorts and 3 case-control) studies were eligible, with a total of 395,513 patients. Sixteen of 19 studies had low- or moderate-risk of bias. Among 109,080 patients enrolled in 13 separate studies, prior statins use was associated with a lower risk of mortality, (pooled aRR 0.65 (95% CI 0.56-0.77, I 2 = 84.1%) and a reduced risk of severe COVID-19 was also observed in 48,110 patients enrolled in 9 studies, (pooled aRR of 0.73 (95% CI 0.57-0.94, I 2 = 82.8%), with no evidence of publication bias. Conclusions Cumulative evidence suggests that prior statins use is associated with lower risks of mortality or severe disease in patients with COVID-19. These data support the continued use of statins medications in patients with an indication for lipid-lowering therapy during the COVID-19 pandemic.

Statins and Risk of Thrombosis in Critically ill Patients with COVID-19: A Multicenter Cohort Study

“…A meta-analysis of 19 observational studies showed that statins use prior to COVID-19 diagnosis was associated with lower mortality. 31 This aligns with findings observed by Lori et al in which prior use of statins reduced the risk of death in patients with CVD and HTN. 32 Similarly, a multicenter observational study in Italy conducted on 842 patients with COVID-19 failed to demonstrate a statistically significant reduction in mortality among statin users but highlighted that statin use was associated with more severe disease.…”

Metabolic Reprogramming in COVID-19

“…Statin-associated improved prognosis is partially attributed to the relieved inflammatory response [102]. A number of other researchers have confirmed the beneficial role of statin-use in COVID-19 infection [103][104][105][106][107][108][109][110][111]. Of note, an updated meta-analysis of 22 studies suggested stains use in COVID-19 patients were connected to an approximately 35% decrease in the adjusted risk of mortality [112].…”

Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity

“…The upregulatory effect of statins on KLF2 expression has been traced to inhibition of protein prenylation and consequent inhibition of Rho activation 74 79 80. It is reasonable to suspect that modulation of KLF2 is pertinent to the reported favourable impacts of concurrent metformin or statin therapy on COVID-19 prognosis 81 82…”