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The COVID Science Express: Ibuprofen Versus Acetaminophen

Confused about the use of ibuprofen to treat a COVID fever? This week’s mixed public messages did not help.

While whispered rumours and bellowed balderdash about COVID-19 cures spread, scientists and medical doctors are actually studying the virus and the people it infects to gain actionable knowledge about this pandemic. I hope to make this information more accessible to the public and to qualify it as necessary, because data collected from a few patients in one country are not as robust as results from a multi-centre clinical trial. Before we dive into recent discussions, let’s refresh our minds on what the enemy is.

We are dealing with viruses. Whether viruses are alive or not is a long-standing philosophical question, but the bottom line is that these infectious particles cannot replicate on their own. They attach to our cells, enter, and release their genetic blueprint. The “construction workers” inside our own cells use the blueprint to make more viruses. These newborn viruses burst out of our cells and repeat the process.

There’s a new virus out there and it belongs to a group called coronaviruses, because the spike proteins at the surface of these viruses look like a crown, and “corona” is Latin for crown. Coronaviruses have been around for a while: in fact, they are responsible for a minority of cases of the common cold each year. But once in a while, a coronavirus that was infecting animals makes the leap into humans and manages to replicate successfully. It happened with SARS. It happened again with MERS. And now it’s happening once more with a virus called SARS-CoV-2, which hit us like a bat out of hell. The disease it causes is referred to as COVID-19 (COronaVIrus Disease 2019).

Scientists are studying the virus in laboratories and working on possible vaccines, while healthcare professionals are documenting who COVID-19 patients are and how they are responding to treatments. Here are some of the things we have learned recently.

The fight between ibuprofen and acetaminophen

You may have heard that France’s health minister, Olivier Véran, tweeted that anti-inflammatory drugs—meaning medications that will reduce inflammation caused by your immune system, drugs like ibuprofen (trade names Advil and Motrin)—could make COVID-19 symptoms worse. He recommended the use of acetaminophen (trade name Tylenol) to bring down a concerning fever due to COVID-19 instead, as acetaminophen can fight the fever without reducing the inflammation.

There’s a simple mechanistic explanation for this theory. The spikes at the surface of the virus are like keys. Our own cells have certain locks at their surface. If the key matches the lock, the virus enters, hijacks our construction workers, and replicates. So it makes sense to minimize the number of these locks at the surface of our cells to protect ourselves. These locks—called ACE2 in the present case—are claimed by some to be made in larger quantities when ibuprofen is used (though the evidence for this is almost nonexistent according to a virologist). Hence the reasoning that using ibuprofen could lead to more ways for the virus to enter our cells.

However, and this is a big “however”, we do not know at the moment if this simple theory holds true for humans with COVID-19. It sounds superficially plausible but it hasn’t been tested so we don’t really know. There is also evidence of ibuprofen (and acetaminophen but to a lesser extent) reducing the production of protective antibodies, though this was done in cells in a laboratory setting. To add to our collective confusion, the World Health Organization first recommended against ibuprofen out of an abundance of caution… then reversed course and said they were no longer recommending against its use for COVID-19.

The Canadian Pharmacists Association weighed in on this debate by asking for further research. They issued a statement declaring that either ibuprofen or acetaminophen can be used to treat a COVID-19 fever. The use of ibuprofen, however, is a little tricky with people older than 60 and those with preexisting medical conditions, as it can increase the risk of ulcers and kidney toxicity and lead to high blood pressure. It may thus be wise to favour acetaminophen over ibuprofen in the case of COVID-19 fever to play it safe.

There was a related brouhaha over ACE inhibitors (drugs like perindopril and ramipril) and angiotensin receptor blockers (like losartan and candesartan) for heart conditions. These medications also increase production of ACE2, so the social media rumour mill got to work, telling people to stop taking these drugs in light of COVID-19. Many cardiological societies issued strong statements that this was pure speculation and that patients should continue their therapy. Biology is a lot more complex than “virus has key to lock, so don’t make more lock”: indeed, as the European Society of Cardiology pointed out in their statement, there is even evidence in animals (not humans) that these medications might actually protect COVID-19 patients against serious lung complications!

Collaboration is unprecedented

Scientists and doctors around the world are banding together in exceptional ways, sharing their data, opining, interpreting and modelling. The speed of knowledge acquisition is also unusual: after learning of this new disease in last December, scientists published the virus’ genetic code in early January of this year. As information races in, journalists and social media influencers will be quick to share the data but don’t be surprised if it changes rapidly. Science is like a dog on a leash, sniffing left, sniffing right, but eventually moving in one clear direction. With COVID-19, that dog is on rollerblades. Hang on to something. It’s going to be quite a ride.

Take-home message:
- There is no solid scientific evidence to say that ibuprofen (Advil) should not be used in the treatment of COVID-19 fever, but it may be wise to prefer acetaminophen (Tylenol)
- Cardiological societies issued statements for patients to continue taking their heart medication in the face of social media speculation that it would make things worse for people with COVID-19


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