Ibuprofen Does Not Make COVID-19 More Severe, Study Finds

Ibuprofen is not linked to any harmful effects in people who test positive for SARS-CoV-2, the virus that causes COVID-19, new research shows.

A report published on September 8 in PLOS Medicine found no statistically significant outcomes between groups of people with confirmed cases of COVID-19 who took ibuprofen and those who did not take the medication.

This research dispels claims made at the beginning of the pandemic. In March, a report out of France published in BMJ raised concerns about the potential for ibuprofen to make COVID-19 more severe. As a result, the World Health Organization (WHO) warned people not to take ibuprofen if they became infected, suggesting acetaminophen as an alternative.

The WHO's warning drew criticism due to the lack of evidence. By April, the organization changed its stance, saying it no longer recommended against taking ibuprofen.

“I think the caution then was justified but the current data are clear: the worry is, in fact, not justified,” Ian Jones, PhD, a virology professor at University of Reading in the U.K., tells Verywell. Jones was not involved with either study.

Evaluating Ibuprofen in COVID-19 Patients

During the trial published in Plos Medicine, the scientists looked at data from 9,326 Danish residents who tested positive for SARS-CoV-2 between February 27 and April 29. Of the participants, 248 people (2.7%) filled a prescription for NSAIDs within 30 days of having a positive test.

Of those who tested positive and used the medications, 6.3% died, 24.5% were hospitalized, and 4.9% were admitted to an intensive care unit (ICU). In the group who tested positive and didn’t use ibuprofen, 6.1% died, 21.2% were hospitalized, and 4.7% went to the ICU. The figures from both groups were not statistically significant, the researchers say.

"Considering the available evidence, there is no reason to withdraw well-indicated use of NSAIDs during the SARS-CoV-2 pandemic," the authors write. There are well-known NSAID side effects, and that should be considered in any patient.

Anton Pottegårs, PhD, a clinical pharmacist in Denmark who authored the PLOS Medicine study, tells Verywell that more research to replicate the findings would be a positive addition. But because the initial theory about the danger of ibuprofen was based on a hypothetical situation, he believes his research provides enough data to alleviate concerns.

Ibuprofen and ACE2 Expression: Another COVID-19 Risk?

A study published in The Lancet in April added to initial concerns of taking ibuprofen with COVID-19. Researchers suggested that people taking certain medications for conditions like cardiovascular disease, hypertension, and diabetes may be more susceptible to severe COVID-19 if they additionally took ibuprofen. The reason? These medications in question—ACE inhibitors, angiotensin II type I receptor blockers (ARBs), or thiazolidinediones—increase the expression of angiotensin-converting enzyme 2 (ACE2) in the body, and ibuprofen can make that expression even stronger. SARS-CoV-2 enters the body by binding to that enzyme receptor.

The idea that ibuprofen boosts ACE2 expression and could therefore make COVID-19 worse in some people, however, comes from rat studies. It is not known if ibuprofen raises ACE2 levels in humans.

“While animal models suggested certain medications that raise ACE2 could permit easier entry of the COVID-19 virus, studies in humans taking ACE inhibitors or ARBs have not resulted in an increased risk of COVID-19,” Michael Miller, MD, a professor of cardiovascular medicine at the University of Maryland School of Medicine, tells Verywell.

Is There Enough Evidence to Safely Take Ibuprofen?

“It is hard for any single study to be definitive,” David M. Aronoff, MD, a professor at Vanderbilt University Medical Center, tells Verywell. “[But] unless people have a pre-existing reason to avoid ibuprofen—such as gastric ulcer disease or kidney problems—then ibuprofen and related NSAIDs are acceptable as fever-relieving and pain-relieving medications in the setting of COVID-19."

The Danish study was a retrospective epidemiological study that used pharmacy records to associate NSAID exposure to patients subsequently diagnosed with COVID-19, Aronoff explains.

"The investigators did not study the dose of the NSAID or frequency of NSAID use prior to infection, so we cannot be sure that patients took the medications they filled at the pharmacy, and we cannot know how often they took said medication," he says. “I think the study has several limitations. It is not the same as a prospectively conducted randomized and controlled trial."

That said, none of the studies published so far related to NSAID use and COVID-19 should change prescribing behavior, Aronoff says.

Miller notes that additional research is underway to further examine the role ibuprofen and other medications may have on the severity of COVID-19. In the meantime, anyone concerned about taking ibuprofen if they get COVID-19 should discuss it with their doctor.

"The evidence at this time does not appear to warrant discontinuation of this medication solely due to COVID-19." Miller says.

Jones agrees.

“I think this is enough to be sure we need not worry about ibuprofen use going forward,” Jones says.

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