Check thy evidence: ibuprofen menace (or not).

“Breaking news! Share urgently! WHO officially stated that drug X should/shouldn’t be administered in COVID-19!” — you could have read online in the last few days.

While humanity is on the way to overcome the pandemic infection, it seems that another evil spreads its vile roots, and its name is false and unproven news. Now it’s the time to calm down, take a slow breath, and do what every person with Internet access should do: the fact-checking. 

What’s up with ibuprofen?

On the 14th of March Dr. Olivier Véran, the French Minister for Solidarity and Health, tweeted:

“Taking anti-inflammatory drugs (ibuprofen, cortisone, …) could be an aggravating factor of the infection. In case of fever, take paracetamol. If you are already taking anti-inflammatory drugs or in case of doubt, ask your doctor for advice.” (translation from French, the original: http://bit.ly/2U4iAKR)

Earlier that day, a message with more detailed information was published on the website of the French Ministry of Solidarity and Health (http://bit.ly/2wlWRVk). It was noted that there were previously reported possible or confirmed cases of nonsteroidal anti-inflammatory drugs (NSAIDs)-related adverse events in patients with COVID-19. Unfortunately, the reference to the source of information was absent.

What was the reason?

The reason for it is not reliably known since neither the publication nor the tweet contained any references on this matter. If you Google search the keywords “France”, “ibuprofen”, and “COVID”, you may find the comments of a few French specialists stating the same position as mentioned above, without referring to any source. 

The recent BMJ publication (http://bit.ly/2UlbgJB) contained information about the reports of a few cases of young patients with COVID-19 who developed more severe symptoms after using NSAIDs during the early stage of their disease. Several opinions were cited, including the one of Paul Little, a professor of primary care research at the University of Southampton, who mentioned the existence of “good evidence” for prolonged illness or more severe complications in patients receiving NSAIDs, based on two randomized trials. 

No ibuprofen then?

Not so fast. In the material published by The Guardian (http://bit.ly/3b9GBWa) an additional message by Prof. Little was given: 

“The evidence in this area was “not 100% clear” and had not come directly from studies of patients with Covid-19, Little said. “I personally think that given there is plausible evidence for harm, the advice should be changed.”

However, the UK’s NHS claims that “there is currently no strong evidence that ibuprofen can make coronavirus (COVID-19) worse. But until we have more information, take paracetamol to treat the symptoms of coronavirus, unless your doctor has told you paracetamol is not suitable for you.” (http://bit.ly/2TYAw9A). In the article “Are Warnings Against NSAIDs in COVID-19 Warranted?” (https://wb.md/3d4VACR), published on Medscape, opinions of several specialists cited, highlighting the lack of evidence of the French government statement discussed above. At this point, that’s a topic of an ongoing debate and the only way to make it productive is to perform an adequate study.

Two words: ACE2 proteins

The New York Times publication “Is Ibuprofen Really Risky for Coronavirus Patients?” (https://nyti.ms/2IVJuOr) refers to a recent The Lancet letter (http://bit.ly/2WnsuIU) as to the possible reason for the above-discussed statement of the French government. The recent discovery revealed that SARS-CoV-2 requires binding to angiotensin-converting enzyme (ACE2), a membrane protein, in order to infect cells. The authors of The Lancet letter speculated about the role of some drugs which upregulate ACE2, including ibuprofen, to facilitate COVID-19 in infected patients. No additional studies were performed up to the moment to receive the final answer to this question. 

Where’s the proof, Lebowski?

Unfortunately, some media have distorted this situation. For example, ScienceAlert wrote in the related material: “The World Health Organization recommended Tuesday that people suffering COVID-19 symptoms avoid taking ibuprofen” (http://bit.ly/3b5Axy6). The name of the article is confusing, as no such recommendations were published by the WHO yet, and no source was cited in the article. Another big resource, Al Jazeera, published an article about this topic without mentioning that the position lacks strong evidence (http://bit.ly/2QvaSXU). Besides these sources, there is a myriad of resources without published editorial policy, spreading the misinformation on the topic.

More facts:

According to the published press-briefing with Christian Lindmeier, the WHO spokesperson (http://bit.ly/2TYxQsu), from the 17 of March:

  • WHO experts were looking into possible detrimental effects of ibuprofen for those infected with COVID-19; for the time being, the WHO recommended using paracetamol instead;
  • WHO is aware of the discussed concerns;

The next day more information was published: up to the current state, WHO does not recommend against the use of ibuprofen (tweet of the WHO from 18 of March, http://bit.ly/3a5jtbu). 

This means that there was no basis for articles claiming that “WHO recommends avoiding ibuprofen”, and the decision to publish them before the statement itself was hasty and wrong.

Brief summary & social media information hygiene:

  • When referring to any recommendations, the reliable source must be re-checked and cited;
  • In many clinical situations, paracetamol is preferred over NSAIDs;
  • However, there is no strong evidence that ibuprofen intake leads to facilitation of COVID-19 in infected patients;
  • While it still could be the case, it’s impossible to confirm or deny this hypothesis without adequate data; 
  • Personal opinions, based on in-vitro studies or interpretations of human physiology and disease biology are the weakest evidence in the hierarchy of evidence-based medicine (CEBM: http://bit.ly/3daifxn) and should not be considered as an immediate call for action or inaction, as well as for permission or prohibition of a medical approach or intervention;
  • Every person is responsible for sharing information on social media that may appear to be false because of the potential impact on those, who are not specialists in the field, or who may interpret the data incorrectly by the reason of unfamiliarity with the principles of evidence-based medicine;
  • When sharing any information, especially COVID-19-related, a thorough study of the source is the must. In the case of the slightest suspicion regarding the source or the completeness of the facts, the information should not be shared by you;
  • We should develop zero tolerance to the spread of therapeutic “author’s techniques”, not supported by research, which sometimes include the application of methods of alternative medicine or substances not previously reported to be effective in the specific clinical situation. These biased approaches may lead to potential harm to patients.

Unfortunately, some of my colleagues were affected by such fakes in the media. I wish all my colleagues to maintain a critical mindset and to prevent the distribution of potentially harmful information.

**Statement: **I have no conflict of interest and I do not have any financial relationships with the abovementioned media, or with companies that could benefit from the production or distribution of the abovementioned medicines. Opinions are my own and may not represent those of my colleagues or employer.

Oleksandr Petrenko
Oleksandr Petrenko
M.D., PhD student

A medical doctor and researher, studying rare diseases.