key: cord-0704117-ebv1s8rn
authors: Zhao, Tie; Peng, Liang
title: Letter in response to the article: Pros and cons for use of statins in 59 people with coronavirus disease-19 (COVID-19)(Ray, S et al.)
date: 2020-11-25
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.11.017
sha: d8d93041d5824c3bb530cd02c690832b524d2b04
doc_id: 704117
cord_uid: ebv1s8rn

nan

Statins may also serve as potential SARS-CoV-2 main protease inhibitors, thereby contributing to 18 the control of viral infection. However, the adverse effects of statins include muscle problems and 19

the most important one being muscle pain. Statin-related muscle problems include myopathy, 20 myalgias and rhabdomyolysis. The molecular mechanism of statin-induced muscle problems or 21 muscle pain is still unclear.

Statins can be metabolized by cytochrome CYP3A4 (such as simvastatin, lovastatin and 23 atorvastatin) or CYP2C9 (fluvastatin). Now, antiviral, and symptomatic treatments are still mainly 24 adopted for COVID-19 treatment. And the most frequent therapies used to treat lung viral are 25 antiviral and antibiotics. While dealing with COVID-19 patients on statins, we should take into 26 account drug-to-drug interactions. In fact, many antiviral drugs, such as tiranavir, ritonavir, 27

tranavir and other antiviral drugs, can significantly inhibit the biological activity of CYP3A4, 28 thereby slowing down the degradation of statins, resulting in increased blood concentration and 29

increasing the risk of myopathy. Macrolide antibiotics and antifungal drugs such as itraconazole, 30

ketoconazole and posaconazole are also potent inhibitors of CYP3A4. Therefore, atorvastatin and 31 cyclosporine, berberic acid, macrolide antibiotics, azole antifungal agents and nicotinic acid 32

increase the risk of myopathy. 33

In addition, great individual differences were found in the occurrence of untoward reaction in 34 statins therapy. In recent years, clinical studies indicated that individual differences are key to 35 statins therapy. Some protein polymorphism have been reported to be associated with the 36 untoward reaction of statins. SNPs of proteins involved in signal pathways of steroid metabolic 37 process and lipid transport were proved to be related to the curative effect of statins, thus affecting 38 the efficacy and safety. 39

Therefore, the main challenge of statins in COVID-19 treatment strategy is the possibility of fatal 40 adverse reactions caused by drug-drug interactions and the individual differences. The use of 41 statins should strictly screen patients with underlying diseases and control drug dosage to avoid 42 drug-drug interaction. However, as discussed earlier, statins have been shown to reduce the risk of 43 death and inflammation of COVID-19. Well designed clinical studies are essential to assess all 44 potential limitations, taking into account key factors such as the type of statin, the dose of the 45 combination therapy, the duration of treatment, and the patient's treatment plan. Further 46

investigation is needed on the use of statins amongst patients with COVID-19 infections. 47 48 49

Notes 50

Pros and cons for use of statins in people with 60 coronavirus disease-19 (COVID-19)

Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and 62 atorvastatin when coadministered with cyto-Chrome P450 inhibitors

Simvastatin-associated rhabdomyolysis after coadministration of 65 macrolide antibiotics in two patients

Rhabdomyolysis caused by comedication with simvastatin 67 and clarithromycin

Simvastatin-amiodarone interaction resulting in 69 thabdornyolysis, azotemia, and possible hepatotoxicity

The Fifth Affiliated Hospital of Guangzhou Medical University

Acknowledgments. This study is funded by the National Natural Science Foundation of China (No.

The authors declare that they have no conflict of interest.