A tweet from France’s minister of health has divided scientists and doctors across the Atlantic. Olivier Véran, writing in French, tweeted on Saturday: “Taking anti-inflammatory drugs (ibuprofen, cortisone…) could be an aggravating factor of the infection [Covid-19]. If you have a fever, take paracetamol. If you are already on anti-inflammatory drugs or in doubt, ask your doctor for advice.”
American doctors were flummoxed by part of the French minister’s statement. Steroids, such as cortisone, are known immune suppressors, so this advice was unsurprising. But ibuprofen — the primary ingredient in over-the-counter painkillers such as Advil and Motrin — is a non-steroidal anti-inflammatory drug (NSAID) and has not been shown to significantly affect the body’s immune response. There’s also no solid research to back up the claim.
“As far as I’m aware, there’ve never been any studies to show that chronic NSAID use has anything to do with suppressing the immune system,” says Andrew White, MD, an immunologist at Scripps Health in San Diego. “Patients aren’t at increased risk of viral infections; they’re not at increased risk of any sort of health outcomes related to infection.”
“I don’t think the NSAID issue is credible at this point, and it doesn’t make a lot of sense,” agrees Warner Greene, MD, PhD, director of the Gladstone Center for HIV Cure Research and a professor of microbiology and immunology at the University of California, San Francisco. “I haven’t seen any data that’s really convincing about this link to worsening of disease course.”
However, a news article published on March 17 in BMJ quoting French and British doctors backed the minister’s claims that physicians should use paracetamol — also known as acetaminophen or Tylenol — instead of ibuprofen. According to Jean-Louis Montastruc, MD, PhD, a professor of medical and clinical pharmacology at the Central University Hospital in Toulouse, the French National Agency for the Safety of Medicines and Health Products told health professionals not to treat fever or infections with ibuprofen starting in 2019.
Paul Little, MD, a professor of primary care research at the University of Southampton in England, said there was evidence “that prolonged illness or the complications of respiratory infections may be more common when NSAIDs are used.” And Ian Jones, PhD, a professor of virology at the University of Reading in England, is paraphrased as saying “ibuprofen’s anti-inflammatory properties could ‘dampen down’ the immune system, which could slow the recovery process.”
“As far as I’m aware, there’ve never been any studies to show that chronic NSAID use has anything to do with suppressing the immune system.”
So why might these two over-the-counter painkillers have such different effects? Acetaminophen and ibuprofen both relieve pain and reduce fevers, but they work through different pathways. Ibuprofen blocks two versions of a protein called cyclooxygenase (COX). Doing so stops the production of prostaglandins, chemicals that are released as part of the body’s immune response and bring on fever and inflammation, as well as sensations of pain. Less prostaglandin means less pain, inflammation, and fever.
Scientists aren’t exactly sure how acetaminophen reduces fever and relieves pain, but at least one study shows that acetaminophen also inhibits one of the COX proteins, and at high doses (1,000 milligrams, or two extra-strength tablets) it can have an anti-inflammatory effect, although not as strong as ibuprofen’s.
There is some concern among physicians about whether blocking the body’s natural fever response to infection could in some way inhibit the immune system. This is a debate doctors have waged for decades — whether it’s better to treat fever and relieve suffering or ride it out in case the body can use the higher temperature to fight off the infection.
“Some people adamantly believe that the fever is the body’s response to kill the invader (virus, bacteria, whatever), while others view it as just a result of the mechanisms to fight the infection,” says Brandon Merritt, MD, MPH, a family medicine doctor in Charleston, West Virginia. “It’s surprisingly unsettled in medicine. I tend toward the latter, though. I just don’t think the evidence is there that fever is the mechanism that attacks infection… It’s not like your immune system doesn’t work until your body cranks up the temperature.”
There’s also no reason to think that stopping a fever with acetaminophen would be any different than stopping it with ibuprofen. In fact, doctors tend to think that acetaminophen is better at lowering the body’s temperature than ibuprofen because it acts more directly in the brain.
“If you’re going to discourage use of ibuprofen, my gut is that you should also discourage use of acetaminophen, at least at high doses,” says David Kroll, PhD, a professor of pharmacology at the University of Colorado. But, he adds, “There’s no direct evidence suggesting that ibuprofen, acetaminophen, any of these will enhance the lethality of Covid-19.”
In an interview Wednesday, Anthony Fauci, MD, the director of the National Institute of Allergy and Infectious Diseases who’s been leading the U.S. response to the novel coronavirus, weighed in on the debate, stating that Tylenol every six hours is the standard of care for fevers. In regards to the ibuprofen dilemma he says, “Bottom line is, I have not seen any firm data to indicate there’s a problem or to prove that there’s not a problem.”
Unfortunately, like lots of things related to the novel coronavirus, it’s not a very satisfactory answer, but it’s an honest one. In the meantime, if you’re concerned you have the virus and want to take a painkiller and fever reducer, either over-the-counter drug should work. Just make sure you do so in moderation — one dose every six hours.