In the worldwide effort to battle SARS-CoV-2, the virus that causes COVID-19, researchers have often turned to medications used as therapies for other conditions in the hopes of finding ones that either kill the coronavirus or lessen the impacts from its infection.

Recent small-sample studies (fewer than 200 patients) have suggested that statins — drugs that lower levels of low-density lipoprotein (LDL), a form of cholesterol linked to heart disease and stroke — also may reduce the chances of severe disease or death from COVID-19.

However, the findings from a recent Johns Hopkins Medicine-led study of nearly 4,500 patients hospitalized with COVID-19 over a four-month period provide a stronger case for a very different conclusion: Statins likely do not confer any impact — positive or negative — on COVID-related mortality and may be associated with an significantly increased risk (nearly 1 chance in 5) of more serious illness.

The study was published Sept. 10 in the journal PLOS ONE.

“Despite the apparent beneficial effect of statins on the outcomes of various infectious diseases, our study revealed that their specific use to treat COVID-19 is probably not merited,” says senior study author Petros Karakousis, M.D., professor of medicine at the Johns Hopkins University School of Medicine.

“Compared with earlier research, we looked at a larger and more widely varied inpatient population and had better criteria for defining disease severity, thereby enabling our results to be more relevant for predicting the impact of statins on COVID-19 outcomes in hospitalized patients.”

Of the 4,447 patients, ages 18 years or older, who were studied, 594 (13%) were receiving statins at hospital admission. Statin users were mostly men (57%) and older (ages 52–78, compared with ages 29–62) than the non-statin users.

The largest percentage of statin users were Black (47%), had hypertension (74%) or diabetes (53%), and were more likely to take medications for lowering blood pressure — along with statins to reduce their LDL cholesterol.

After accounting for other known factors that might skew the data, the researchers found statin use had no significant effect on mortality from COVID-19.

However, they did find that patients hospitalized with COVID-19 and taking statins had an 18% increased risk for having a more severe form of the disease than patients who did not take cholesterol-lowering agents.

“One plausible explanation for this finding is that statins increase cellular production of angiotensin-converting enzyme 2 [commonly known as ACE2], the receptor on a cell’s surface through which SARS-CoV-2 gains entry,” says Karakousis.

“Therefore, statins may lower a cell’s resistance to infection and, in turn, increase the odds that the patient will have a more severe case of COVID-19.”

Karakousis says future studies should attempt to better define the relationship between statin use and COVID-19.

“All of the studies published to date, including ours, have been retrospective — and that means no matter how hard one tries to eliminate factors associated with poor COVID-19 outcomes other than statin use, some may still be at work,” says Karakousis.

“For example, there’s the fact that many statin users also are overweight, have diabetes, or experience high blood pressure — all things that can impact the severity of COVID-19 on their own.”

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