On The Shelf
Mary Warner
After a research article published in Lancet on March 11 indicated that use of ibuprofen may worsen COVID-19 symptoms, and the subsequent media attention, patients are wary of taking NSAIDs in case they may be infected with coronavirus. It’s important to note, however, that there is no scientific evidence connecting use of NSAIDs like ibuprofen with worsening COVID-19 symptoms.
According to Dan Zlott, PharmD, vice president of professional education at APhA, the recommendations regarding use (or avoidance) of NSAIDs in COVID-19 disease are entirely anecdotal and hypothetical.
“There is currently no data whatsoever regarding the use (or avoidance) of NSAIDs in COVID-19 disease,” said Zlott in an APhA-produced educational resource for pharmacists on COVID-19 issues (available on APhA’s coronavirus resource page at www.pharmacist.com/coronavirus).
“The recommendations to avoid NSAIDs are based on hypotheses and extrapolations of inconclusive data in other viral/respiratory illnesses,” Zlott continued.
Timeline of the controversy (and confusion)
In their Lancet letter, Fang and colleagues hypothesized that because SARS-CoV-2 (the virus that causes COVID-19) binds to ACE2 on the cell surface to gain entry into cells, and because ibuprofen has been shown to increase ACE2, use of ibuprofen could worsen symptoms in patients with COVID-19 by making it easier for the virus to get into cells.
A few days later, on March 14, French Health Minister Olivier Véran tweeted that taking anti-inflammatory drugs such as ibuprofen and cortisone “could be an aggravating factor for the infection” and recommended that French citizens take paracetamol (acetaminophen) if they have a fever.
The warning was also included in a bulletin from the French health ministry, which counseled that patients should use acetaminophen rather than NSAIDs like ibuprofen.
Then on March 17, the World Health Organization (WHO) issued a warning against use of ibuprofen in patients with COVID-19, again based on the letter in Lancet.
But then on March 18, a day later, WHO tweeted that “At present, based on currently available information, WHO does not recommend against the use of ibuprofen” in patients with COVID-19. WHO continued that it “is not aware of published clinical or population-based data on this topic.” Use of the double negative in the second WHO recommendation caused significant concern among Twitter users and confusion among patients.
Finally, on March 19, FDA issued a statement clarifying its stance on use of NSAIDs for patients with COVID-19, saying that “FDA is not aware of scientific evidence connecting the use of NSAIDs, like ibuprofen, with worsening COVID-19 symptoms.” The agency also stated that it is investigating further and will communicate publicly when more information is available.
Basis for concern?
In his educational resource, Zlott compared the hypotheticals for the effects of NSAIDs on COVID-19. On the one hand, the inflammatory response is an important component of the immune response, and suppression of inflammation may inhibit immune response, resulting in more severe infection or increased risk of morbidity and mortality.
On the other hand, it has been documented that some of the severe complications from COVID-19 are the result of immune-mediated organ damage, and suppression of the inflammatory response may prevent or decrease immune-mediated organ damage.
What to tell your patients
Until there is sufficient scientific evidence to support NSAID use or avoidance in patients with COVID-19, pharmacists should use their best judgment about use of NSAIDs. Consider the risks and benefits to each patient, such as these patient-specific factors, and advise accordingly:
Is the patient on chronic NSAID therapy?
Does the patient have comorbidities or risk factors that would cause you to avoid NSAID use?
What is the goal of NSAID therapy in a patient with COVID-19? Are there alternatives that may accomplish the same goal?