In the middle of public health emergencies, doctors and scientists often turn to existing therapies and medications and apply them to new diseases in the hopes they play a helpful role in reducing illness severity or death.

However, just one of the many drugs that have been explored during the COVID-19 pandemic continues to produce conflicting results: statins, or medications that lower cholesterol.

Some studies show statins are associated with — but do not directly cause — improved COVID-19 outcomes, such as reduced risks of severe disease and death. Others show the opposite, including a new study researchers with Johns Hopkins Medicine shared Oct. 26.

The study of nearly 4,500 people hospitalized with COVID-19 found statins were not associated with either a positive or negative effect on risk of coronavirus-related death over four months while admitted.

Meanwhile, the drugs were associated with an 18% increased risk of severe COVID-19, defined as infections that required patients to stay in the hospital for over a week or receive mechanical ventilation.

The patients included in the new research published in September in the journal PLOS One were adults hospitalized for COVID-19 at five medical facilities in the Johns Hopkins Health System between March and June 2020. Thirteen percent of patients were taking statins upon hospital admission and some were also taking medications to lower their blood pressure.

A separate analysis of nine studies conducted in the U.S. and China found statins were not associated with reduced COVID-19 severity or death among hospitalized patients.

And what appears to be the only randomized controlled clinical trial on the drugs — the standard for determining if a medication or therapy offers clinical benefits — also found statins weren’t associated with reduced COVID-19 mortality in patients in Iran.

Statins did, however, appear to help reduce coronavirus-related death and blood clots in a smaller group of patients who were admitted to the intensive care unit within a week of showing symptoms.

Researchers of the new study say statins boost the production of ACE2 — receptors on cells’ surfaces that act as entry points for the coronavirus.

“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,” senior study author Dr. Petros Karakousis, a professor of medicine at the Johns Hopkins University School of Medicine in Maryland, said in a news release.

Studies that have found statins help COVID-19 patients improve instead focused on the drugs’ anti-inflammatory properties.

Inflammation is often to blame for many serious COVID-19 outcomes, including acute respiratory distress syndrome and heart or kidney injury, but the immune response is complicated, according to Dr. Michael Tran, a vascular medical internist at Cleveland Clinic.

“Inflammation in itself is a really complex topic, because there are so many different pathways of inflammation, and different medications affect different pathways, and they might not cross over,” Tran told Everyday Health in June. “I may use a statin medication for a plaque disease, which does have something to do with inflammation, but not for thrombosis, because those inflammation pathways can really be different in how they come about.”

Some studies show statins help reduce COVID-19 risks, but it’s complicated

A study published in July showed statins together with blood pressure drugs reduced in-hospital COVID-19 death by 40% among those who took them prior to being admitted.

The reduced risk of death was slightly higher for those taking statins alone (46%) compared to people only taking high blood pressure medication (27%). The analysis included more than 10,000 people admitted to more than 140 hospitals across the country.

The same held true of COVID-19 patients’ odds of severe disease: those only taking statins benefited from a 25% lower risk of developing severe disease and those taking blood pressure medications had an 11% lower risk.

Another paper published in February found that about 27% of COVID-19 patients who had not been taking statins died within 30 days of hospitalization compared to about 15% who were taking the drugs.

More research among COVID-19 patients in Massachusetts showed statin use during hospitalization reduced mortality over 28 days for people ages 65 and older but not for those younger than 65.

“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,” Karakousis, senior author of the new Johns Hopkins study, said. “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.”

The true relationship between statins and COVID-19 risks could only be revealed with the help of controlled randomized clinical trials, experts say. Until then, people who normally take statins to lower their cholesterol should continue to do so, regardless of whether they contract the coronavirus.

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