Is the Final Word on Ibuprofen and COVID-19 Risk?

COVID-19 treatment guidelines issued by the NIH and the British health officials this week may ease concerns that nonsteroidal anti-inflammatory drugs (NSAIDs) - particularly ibuprofen - make people more vulnerable to infection by the SARS-Cov-2 virus that causes COVID-19 and, after infection with the virus, make increase serious illness more likely.

The NIH guidelines that came out Tuesday say there is no difference between acetaminophen and NSAIDs for reducing fever among patients with and without COVID-19. They also advise that people who are taking NSAIDs for another condition should keep on taking them in the way that they were prescribed.

On Wednesday, the National Institute for Health and Care Excellence (NICE), the British group that assesses the effectiveness and cost of health care interventions, added ibuprofen as an option for managing fever in COVID-19. In early April, according to BMJ, NICE had said paracetamol - the European name for acetaminophen - should be used in preference to NSAIDs.

Fever is one of the most common presenting symptoms of COVID-19; CNN viewers saw this firsthand when COVID-19-stricken Chris Cuomo was broadcastin from his basement. The choice of fever-reducing medication may not be loom as large other COVID-19 treatment issue, but it is a branch of the COVID-19 treatment decision tree and may be especially so for people with cases mild enough to stay home where they might wind up making some of their own medical decisions. 

The notion that NSAIDs might be dangerous and make people vulnerable to COVID-19 and its most serious consequences was put into circulation by the French Health Ministry mid-March when it issued a guidance that advised avoiding NSAIDs for COVID-19.

The French weren’t alone. As mentioned, NICE suggested acetaminophen. The British Medicines and Healthcare products Regulatory Agency - which has some of the powers and responsibilities of the FDA - issued an alert advising against the use of ibuprofen in patients with confirmed or suspected COVID-19. At about the same time, a World Health Organization (WHO) spokesman was quoted as saying that the international health organization was looking into the issue and that, in the meantime, people should take paracetamol, not ibuprofen. A few days later, WHO walked that back with a tweet of a qualified statement that said, “at present on currently available information, WHO does not recommend against the use of ibuprofen.”

Meanwhile, the social media cat was flying out of bag. As Factcheck.org reported, wildly misleading stories linking ibuprofen to dire COVID-19 outcomes were shared and reshared. Several respected organizations, including Factcheck.org, countered with stories that said there is no evidence linking ibuprofen - most of them focused on ibuprofen in particular - to COVID-19 or its worst outcomes.

Social media exaggeration and distortion aside, the concern about NSAIDs didn’t come out of nowhere. On March 16, when the COVID-19–ibuprofen question was being bandied about and getting media play, the respected Center for Evidence-Based Medicine at Oxford University issued an assessment of the use of NSAIDs by people with acute respiratory infections. Importantly, the assessment did not include COVID-19. Still, it said there is a “need for caution” when it comes to NSAIDs and patients with acute respiratory infection. The assessment cited a Taiwanese study that found that the use of NSAIDs during acute respiratory illness nearly tripled the risk of heart attack and another analysis that found a similarly increased risk of stroke. Of course the usual caveats about observational studies apply, but these are serious research findings, and the jump from general acuter respiratory infection to COVID-19 is not an illogic one. The center’s researchers said the five studies they found that examine whether NSAIDs worsen the outcomes of respiratory outcomes were difficult to interpret and possibly flawed by confounding. 

The NIH guidelines, which covered the full gamut of COVID-19 treatment issue not just the antipyretics, include a grading system for the strength of the recommendations, and the ones for NSAIDs were given the highest “A” grade. The guidelines also classify the underlying  evidence, and NSAIDs recommendations are based on “expert opinion,” not randomized trials or data from an observation study. That is not the least bit surprising because COVID-19 is a new disease, but expert opinion is opinion, not data, and therefore not as reliable as evidence from clinical trials or observational studies.

NICE’s position on NSAIDs and COVID-19 gets muddled if you drill down on the website. The landing page for the guidance on managing symptoms in the community says it has been updated on April 22 to include ibuprofen as an option for managing fever and other symptoms.

However, the evidence summary for NSAIDs, dated April 14 but with the proviso that it was up to date on March 24, says a literature search identified 156 references and that 13 were obtained and “assessed for relevance.” But even those 13 were not used and, as a result, there is “no evidence from published scientific studies” to determine whether acute use of NSAIDS is related to developing COVID-19 or more severe illness from it. The assessment goes on to say that NSAIDs may either have no effect on, or worsen, long-term outcomes possibly by masking the symptoms of worsening acute respiratory tract infection.