Controversy has arisen regarding use of ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) in treating COVID-19, according to correspondence published in The Lancet Respiratory Medicine. A subsequent message from France’s health ministry warned of “severe adverse events” related to NSAID use in patients with COVID-19.
David Aronoff, M.D., director of the Division of Infectious Diseases at Vanderbilt University Medical Center, says it is difficult to confirm a causal link between NSAIDs and worsening COVID-19 symptoms.
People older than 60 years or with chronic illness are at increased risk of developing severe COVID-19 infection or dying from it. Since NSAIDs are commonly taken by older or chronically ill adults to relieve persistent pain and inflammation, NSAID use could be a risk factor for developing severe COVID-19. “It becomes pretty easy to see that people who take NSAIDs are more likely to be the people who are sickest with COVID-19,” Aronoff said in a recent AARP article.
“It becomes pretty easy to see that people who take NSAIDs are more likely to be the people who are sickest with COVID-19.”
Guidance regarding NSAID use during COVID-19 infection is evolving. “As things stand now,” Aronoff said, “health experts shouldn’t advise people against taking a medicine that they take on a regular basis under the supervision of a health care provider like a physician.” This stance was echoed by the Lancet Respiratory Medicine authors.
The Food and Drug Administration (FDA) and World Health Organization (WHO) agree. On March 18, WHO stated on its Twitter account, “Based on currently available information, WHO does not recommend against the use of ibuprofen.” The FDA issued a March 19 statement that it “is investigating this issue further and will communicate publicly when more information is available.”
“Health experts shouldn’t advise people against taking a medicine that they take on a regular basis.”
COVID-19 patients of all ages may take NSAIDs to reduce the fever, sore throat, headache or body aches that arise during the infection. Those who feel worse are more likely to reach for NSAIDs, Aronoff said, which can result in a strong association between the use of these medications and infection severity. In addition, taking NSAIDs can suppress symptoms and may lead to delays in seeking medical attention.
“In these cases the NSAIDs are not, in and of themselves, worsening the infection but their use is a marker for disease severity,” Aronoff said.
NSAIDs and Fever
Aronoff has studied the clinical use of antipyretics such as aspirin, acetaminophen, and ibuprofen for over two decades and has previously reported on the connection between antipyretics and fever suppression. “There’s been a longstanding debate,” he said, “about whether to administer fever-suppressing drugs or to let the fever run its course. Fever may be an important window to clinically relevant information.”
Aronoff and colleagues reported that antipyretics “may not be indicated for all febrile conditions” because they may contribute to patient discomfort, interfere with accurate assessment, or predispose patients to adverse effects from other medications.
For fever and aches associated with COVID-19, people with kidney disease or stomach ulcers should be steered toward acetaminophen, Aronoff said. “On the flip side, if [the patient has] problems with hepatitis or liver trouble, then acetaminophen may not be the best choice.”
Need for More Research
The COVID-19 NSAID controversy is partly rooted in French studies from 2017 and 2019 reporting that NSAIDs may worsen the course of community-acquired pneumonia. “These are both retrospective ‘look-backs,’ and it’s difficult to disentangle the various factors and determine which is the cart and which is the horse,” Aronoff said. “There may be protopathic bias that occurs when a medication is taken in response to the first symptoms of the disease before it is actually diagnosed.”
“There may be protopathic bias that occurs when a medication is taken in response to the first symptoms of the disease before it is actually diagnosed.”
Aronoff says there is definitely a need for further research. Currently, he and colleagues at Vanderbilt Institute for Global Health and Vanderbilt Vaccine Center are engaged in multiple studies, including a rapid discovery of human antibodies for epidemics and COVID-19 antiviral strategies.