Statin Use in Relation to COVID-19 and Other Respiratory Infections: Muscle and Other Considerations

Abstract

Statins have been widely advocated for use in COVID-19 based on large favorable observational associations buttressed by theoretical expected benefits. However, past favorable associations of statins to pre-COVID-19 infection outcomes (also buttressed by theoretical benefits) were unsupported in meta-analysis of RCTs, RR = 1.00. Initial RCTs in COVID-19 appear to follow this trajectory. Healthy-user/tolerator effects and indication bias may explain these disparities. Moreover, cholesterol drops in proportion to infection severity, so less severely affected individuals may be selected for statin use, contributing to apparent favorable statin associations to outcomes. Cholesterol transports fat-soluble antioxidants and immune-protective vitamins. Statins impair mitochondrial function in those most reliant on coenzyme Q10 (a mevalonate pathway product also transported on cholesterol)—i.e., those with existing mitochondrial compromise, whom data suggest bear increased risks from both COVID-19 and from statins. Thus, statin risks of adverse outcomes are amplified in those patients at risk of poor COVID-19 outcomes—i.e., those in whom adjunctive statin therapy may most likely be given. High reported rates of rhabdomyolysis in hospitalized COVID-19 patients underscore the notion that statin-related risks as well as benefits must be considered. Advocacy for statins in COVID-19 should be suspended pending clear evidence of RCT benefits, with careful attention to risk modifiers.

Cholesterol and COVID-19—therapeutic opportunities at the host/virus interface during cell entry

“…However, this also reduces production of coenzyme Q10, which is required for mitochondrial electron transport that drives the generation of ATP. Hence, statin-mediated reduction of coenzyme Q10 availability in patients with existing mitochondrial dysfunction may amplify the risk of poor COVID-19 outcomes ( Golomb et al, 2023 ).…”

Profound Rhabdomyolysis and Viral Myositis Due to SARS-CoV-2: A Case Report

“…Risk factors for SARS-CoV-2 rhabdomyolysis include pre-existing health conditions such as advanced age, hypertension, diabetes, cardiovascular disease, and underlying kidney disease [ 4 ]. Underlying musculoskeletal disorders and prescription medications such as statins, especially lipophilic varieties, and antipsychotics are thought to increase risk [ 5 ]. There may be a direct underlying interaction between the drug and the infection, causing oxidative stress and mitochondrial dysfunction, which impair energy supply, increase demand, and reduce reserves [ 5 ].…”

“…Underlying musculoskeletal disorders and prescription medications such as statins, especially lipophilic varieties, and antipsychotics are thought to increase risk [ 5 ]. There may be a direct underlying interaction between the drug and the infection, causing oxidative stress and mitochondrial dysfunction, which impair energy supply, increase demand, and reduce reserves [ 5 ]. Dehydration, fever, and respiratory distress can further heighten the body’s immune response, leading to muscle inflammation and damage [ 6 , 7 ].…”