More Good News on Statins and COVID-19

We read with interest the meta-analysis (4 studies, 8,990 coronavirus disease 2019 (COVID-19) patients) by Kow et al¹ reporting that statin use was associated with a significantly lower risk of fatal or severe COVID-19 (pooled hazard ratio: 0.70, 95% confidence intervals 0.53 to 0.94) compared with nonuse. This finding strongly supports the clinical importance of continuing or initiating (according to current guidelines²) statin treatment in the COVID-19 era. The authors mention some pathophysiological mechanisms that could explain this beneficial impact of statins, including anti-inflammatory actions and upregulation of angiotensin-converting enzyme 2 expression. There are also other mechanisms that have been described, including the degradation of lipid rafts, directly affecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-protein, and reducing the cholesterol important for viral entry into host cells.^{3 , 4}

Another mechanism could involve acute kidney injury and acute cardiac injury, both of which are predictors of COVID-19 mortality.^{5 , 6} Statins have been shown to prevent contrast-induced acute kidney injury^{7 , 8} and stabilize atherosclerotic plaques,⁹ thus protecting from acute adverse events from the cardiac and renal system. Furthermore, statins may favorably affect immunomodulation, oxidative stress, and thrombosis.¹⁰

It should be noted that a combination of statins/angiotensin II receptor blockers improved outcomes and increased survival of patients infected during the 2014 Ebola virus disease epidemic in Sierra Leone.¹¹

Drug-drug interactions should also be considered when treating COVID-19 patients on statins with antibiotics (e.g., macrolides) and antiviral drugs, due to an increased risk of statin-associated muscle symptoms.^{12 , 13} Furthermore, the use of lovastatin and simvastatin is contraindicated in patients on ritonavir/lopinavir therapy since they might increase the risk of rhabdomyolysis.¹⁴ Specific drugs used to combat SARS-CoV2 infections could have pharmacokinetic interactions with statins that affect plasma concentrations and toxicity of both statins and/or antiviral medication.¹² Knowledge in this field might help prescribers to use suitable doses and preparations and thus avoid treatment discontinuation for COVID-19 infection and prevent its complications.

Overall, statins can exert beneficial effects on the heart, vascular, and lung function, as well as inflammation,¹⁵ thus strongly supporting their continuation or initiation, based on recommendations,² during the COVID-19 pandemic.

Conflict of interest

NK has given talks, attended conferences and participated in trials sponsored by Astra Zeneca, Bausch Health, Boehringer Ingelheim, Elpen, Mylan, Novo Nordisk, Sanofi and Servier. MB speakers bureau: Abbott/Mylan, Abbott Vascular, Actavis, Akcea, Amgen, Biofarm, KRKA, MSD, Polpharma, Sanofi-Aventis, Servier and Valeant; consultant to Abbott Vascular, Akcea, Amgen, Daichii Sankyo, Esperion, Freia Pharmaceuticals, Lilly, MSD, Polfarmex, Resverlogix, Sanofi-Aventis; Grants from Sanofi and Valeant. DPM has given talks and attended conferences sponsored by Amgen, Novo Nordisk, and Libytec.