Johns Hopkins study casts doubt on statins as COVID-19 treatment

Johns Hopkins University has published a new study in which researchers evaluated whether statins — a type of drug used to lower "bad" LDL cholesterol levels — may offer some protection against severe COVID-19 outcomes. Unlike previous smaller studies that reported evidence pointing toward a potential benefit, the new study reports statins don't seem to have any effect on the respiratory disease.

The data

The new study was led by Johns Hopkins Medicine; it involved 4,447 COVID-19 patients who were hospitalized in the Johns Hopkins Health System due to the disease. The patients were at least 18 years old and officially tested positive for SARS-CoV-2 between March 1, 2020, and June 30, 2020. Of those 4,447 patients whose data were used in this study, 13-percent of them had been prescribed statins before they were admitted to the hospital.

As far as demographics are concerned, the researchers note that the patients who received statins were 57-percent male, they primarily fell into the 52 to 78 years age group, 74-percent had high blood pressure, 53-percent had diabetes, and 47-percent of the patients were Black. Beyond that, the study considered a patient death as related to COVID-19 if the tragic event occurred while hospitalized for the virus.

Do statins help?

The researchers accounted for patient factors that may skew their final results, ultimately concluding that taking statins appears to neither hurt nor help the outcome of COVID-19 infections. The study's senior author Petros Karakousis, M.D., explained the results and how they conflict with previous smaller studies on the topic:

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. 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.

Though the study didn't find any sort of potentially beneficial or harmful link between taking statins and COVID-19 outcomes, the scientists say that hospitalized patients who take statins are at an 18-percent greater risk of developing a more severe infection compared to those who don't take the cholesterol-lowering drugs. Though one may assume this increased risk is due to statin patients' greater rates of known risk factors like diabetes and high blood pressure, Karakousis highlights a different potential explanation:

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. 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.

It's important to note that Johns Hopkins' new study, as well as the smaller ones on this topic that came before it, were all retrospective in nature, meaning it is possible that other risk factors may still skew the results despite efforts to eliminate them from the data. Karakousis points out the aforementioned reality that statin users are more likely to have known risk factors like diabetes, as well as the fact that many are overweight, and these complications are known to increase one's risk of developing a severe COVID-19 infection.

The researchers explain that a randomized clinical trial with a placebo group is necessary to determine whether statins do, in fact, offer any sort of benefits for hospitalized COVID-19 patients.

Past studies, conflicting results

This new retrospective study follows previous studies that involved far fewer patients — ones that came to different conclusions. In July, the American Heart Association highlighted the results from one related study, which had found that patients who were already taking statins before being hospitalized for COVID-19 had "significantly" lower death risk, with the benefits skewing toward patients who suffered from high blood pressure and heart disease.

The study published in July, which is available on PLOS One, involved data on 10,541 hospitalized COVID-19 patients that were enrolled in the AHA's COVID-19 Cardiovascular Disease Registry. In this study, 42-percent of the participants used statins before being hospitalized, though the majority were also taking medication to lower blood pressure, as well. Only 7-percent of the patients were taking statins alone, while the reduced death risk was assessed among the total group, including those who were taking both drugs.

Why it matters

Experts are scrambling to find existing drugs with the potential to help protect against severe COVID-19 infections and death. A number of existing drugs have been evaluated for this potential; this isn't the first time research has surfaced suggesting potential benefits, only for additional research calling the results into question later on.

The most notable instance of this occurred in summer 2020 when a study was published suggesting the anti-malarial drug hydroxychloroquine had potential as a COVID-19 treatment. The results quickly proved controversial, however, and more than 100 experts across the globe signed a letter [PDF] expressing doubt over the data and raising questions about factors that may have skewed the findings.

Hydroxychloroquine has since been fully dismissed as a potential COVID-19 treatment, but the early research combined with some political boosts have made it a persistent staple among those who are skeptical about the vaccines and accepted treatment protocols. The public should remain mindful about early studies indicating potential benefits related to the virus, keeping in mind that data on the disease and how to best treat it is still evolving. In addition, many early studies are often small in nature and may produce findings that don't hold up under further scrutiny.