On Tuesday, Christian Lindmeier, spokesperson for the World Health Organization (WHO), told reporters in Geneva that experts are looking into the matter, but seconded the advice of the French Health Ministry, saying: "In the meantime, we recommend using rather paracetamol, and do not use ibuprofen as a self-medication. That's important."
He quickly added that people whose use of ibuprofen is prescribed by a physician can still choose to take them. The popular non-steroidal anti-inflammatory drug (NSAID) is sold under several brand names, such as Motrin, Nurofen and Advil.
The French Health Minister's tweet over the weekend was prompted by an article published in The Lancet on March 11. In it, researchers proposed that certain medications that increase the production of a protein called angiotensin-converting enzyme 2 or ACE2 also increase the risk of severe coronavirus infection.
ACE2 is a protein produced by cells that cover the surfaces of major organs, such as the skin, the intestines, the kidneys and the lungs. These cells also serve as the outer lining of blood vessels. Previous studies have found that ACE2 acts as a receptor on the surfaces of these cells, and human pathogenic coronaviruses bind to this protein, so they can infect their targets. Because of scientific evidence supporting this interaction, the researchers proposed that increased production of ACE2 would facilitate infection with the novel coronavirus.
"We therefore [hypothesize] that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19 [the disease caused by the novel coronavirus]," the researchers wrote in their report. They also suggested that the necessity of these medications puts people with the conditions they mentioned at a greater risk of getting infected by the virus. (Related: Prestigious vaccine journal: Flu vaccine increases coronavirus infection risk 36%.)
Some notable examples of ACE2-increasing medications are anti-hypertensives like ACE inhibitors and angiotensin II type-I receptor blockers (ARBs), which are widely used by diabetics, and those with heart problems to lower their blood pressure. The researchers also listed thiazolidinediones, which are used for the treatment of Type 2 diabetes, and ibuprofen as medications that increase the levels of ACE2 in the body.
On March 19, two days after Lindmeier spoke to reporters, the WHO released a statement regarding the issue of whether or not ibuprofen should be avoided due to the coronavirus crisis. On its official Twitter account, the agency reversed its earlier statement and said that it "does not recommend against the use of ibuprofen," citing a lack of clinical data to support claims that it could worsen the disease caused by the novel coronavirus.
Reckitt Benckiser, the British pharmaceutical company responsible for Nurofen, also released a statement acknowledging the growing concerns over the use of ibuprofen, especially when addressing symptoms of coronavirus infection. Ibuprofen is one of the milder NSAIDs or painkillers used to address muscle pain and fever – two commonly reported symptoms that signify the onset of illnesses caused by viruses.
In a statement posted by the company's spokesperson, Reckitt Benckiser assured the public that their safety is its topmost priority and that the company "does not currently believe there is any proven scientific evidence linking over-the-counter use of ibuprofen to the aggravation of COVID-19." The spokesperson further said that the company would give the WHO, the European Medicines Agency (EMA) and other local health authorities "any additional information or guidance necessary" for the safe use of their products following evaluation, reported ScienceAlert.
Since the warnings about ibuprofen use surfaced on social media, some experts have voiced their disagreement with the issues raised against it. One of the most vocal was Angela Rasmussen, a virologist at Columbia University and one of the scientists who discovered the genetics behind a person's susceptibility or resistance to the Ebola virus. She said that there is, as yet, no evidence that anti-inflammatory drugs increase susceptibility to the novel coronavirus.
In a series of tweets posted on March 15, she explained that higher levels of ACE2 do not lead to more infected cells as viruses require more than just ACE2 to replicate. Rasmussen also said that more infected cells do not necessarily mean more virus either because "not all susceptible cells will produce the same amount of virus." Additionally, she cited the variability of individual responses to a particular virus as something that dictates susceptibility. Meanwhile, genetics, environment and overall health, according to Rasmussen, can influence the severity of COVID-19.
Warnings about the use of ibuprofen are not new to the French public. According to an online report posted on Wednesday by France24, authorities have raised concerns about the serious complications that may arise from the use of NSAIDs like ibuprofen even before the coronavirus pandemic. They said that taking anti-inflammatory drugs are risky for people with infectious diseases as these medications tend to weaken the body's immune response.
Studies also associate organ-related complications with the use of NSAIDs. In 2008, French researchers found that their use increased the risk of severe skin and soft tissue complications in children with chickenpox. Adults and the elderly who contract the same viral disease are also exposed to the same risk following the use of NSAIDs. The researchers attributed these complications to the activity of anti-inflammatory drugs, which can impair neutrophil blood cell function. Neutrophils are white blood cells that serve as the body's first line of defense against infections.
In an interview with CNN, Rupert Beale, a researcher at The Francis Crick Institute in London, also said that another good reason why people should avoid ibuprofen is that "it may exacerbate acute kidney injury brought on by any severe illness, including severe COVID-19 disease."