COVID-19 & Ibuprofen: Yes Or No?

Everyone seems to have an opinion on the use of ibuprofen in the setting of COVID-19 – both lay people and experts –  so what is the answer? Should you take it – or not? Spoiler alert – it depends.

As a doctor of clinical pharmacy, the topic of ibuprofen and its cousins, nonsteroidal anti-inflammatory agents (NSAIDs), is within my area of expertise. NSAIDs are fantastic over-the-counter (OTC) medications to treat pain, fever, and inflammation, and provide safer alternatives to more potent medications like oral steroids or opioids. Acetaminophen, another OTC medication, is an effective option to treat pain and fever but not inflammation, due to its different mechanism of action.

Every decision in medicine, from prescribing medication to performing surgery to doing nothing, is grounded in the concept of risk versus benefit. No matter how risky the decision, it remains an option in those scenarios where the benefit is worth it. Since ibuprofen is an OTC medication that practically every person has purchased at some point in their life, it’s critical to understand the risk versus benefit profile of NSAIDs. This article is my opinion on the class overall, including its use in the treatment of symptoms of COVID-19.

So how does this apply to ibuprofen and COVID-19? As I previously explained in my article “COVID-19: The Facts”, there is no definitive science to say that ibuprofen increases susceptibility to COVID-19 or the severity of its infection. Ibuprofen remains an effective treatment option when appropriately indicated, but I also suggest avoiding it, if possible. Here is why.

Absence of evidence is not evidence of absence. There is evidence in rats that ibuprofen increases the amount of the protein that COVID-19 uses to attach to the lungs. The protein, called angiotensin I converting enzyme 2 (ACE2), is also increased by certain medications for diabetes and high blood pressure. For these people, increased ACE2 is favorable.

That being said, these patients are also experiencing worse outcomes if infected with COVID-19. One theory is that the increased density of ACE2 increases overall viral load; however, diabetes, hypertension, and cardiovascular disease are independent risk factors for more severe disease with any viral infection. So is it the chicken or the egg?

Lastly, to make it clear as mud, some patients report that ibuprofen made their symptoms worse (which makes sense), and other reports where ibuprofen effectively prevented the inflammatory storm caused by COVID-19 (which also makes sense).

We are just beginning to learn about the virus, much less how diseases or medications influence infection severity. The preliminary – and sometimes conflicting – information explains why if medication is indicated in the setting of COVID-19, it makes sense to use alternatives like acetaminophen, if possible, as well as prescribe ibuprofen, if needed.

This is true any time you reach for ibuprofen. Keep in mind I am talking to the person self-treating. If you are prescribed ibuprofen or another NSAID by a clinician, this is simply information to add to your discussion with them when making that decision.

It is unfortunate that most physicians receive only a few semesters of pharmacology, versus the four years received in a PharmD program. As a result, the complete risk profile of NSAIDs is often misunderstood – even by the average pharmacist. Rarely do I see this perspective included in the news and posts on this subject.

We all agree on the well-documented, acceptable risks of NSAIDs, which could include damage to the stomach lining, kidneys and cardiovascular system. Such side effects are reason enough to cautiously use NSAIDs for COVID-19 treatment, independent of their effect on ACE2. Organs like the heart and kidneys can be compromised in severe viral illness.

In the general population, these risks are of particular concern with long-term and/or high dose NSAID use. You can find this information in those long package inserts everyone reads when they pick up their medication…

Let’s take a deeper dive at the side effect profile of NSAIDs. NSAIDs inhibit cells called prostaglandins (PGs), reducing their associated fever, inflammation, and pain. But NSAIDs also deplete PGs in the gut, where these cells help maintain the protective barrier and microbiome homeostasis. Some evidence suggests ibuprofen use within the last 30 days can negatively impact your healthy gut buddies.

If you know anything about the gut microbiome, this should stop you right there. Given that 90+ percent of the healthcare burden is chronic, inflammatory disease, it’s imperative to use gut destroying medication only when necessary, one of the first issues a functional medicine practitioner would address. Even though NSAIDs are excellent anti-inflammatory agents, we do not yet fully understand the long term consequences of their potential to cause – not treat – inflammation by destroying the gut microbiome.

Avoiding NSAIDs may be ideal, but if you struggle with daily, inflammatory pain – sometimes so severe you cannot function – you may not think about your kidneys or gut years down the line. You care about being able to live and enjoy life now, making the benefit worth the risk. Avoiding NSAIDs may also be ideal in the setting of COVID-19, but not if it means dying of the fever the infection is causing. As always – is the benefit worth the risk?

In conclusion, although I agree OTC ibuprofen is an effective option to treat signs and symptoms of pain, fever, and inflammation associated with COVID-19, it should be used only when the benefit outweighs the risk. If possible, alternative options should be considered; please discuss this with your clinician. I make this statement regarding its use for all indications, not just for signs and symptoms of COVID-19 infection.

References 

1. Mary A.M. et al. The Influence of Nonsteroidal Anti-Inflammatory Drugs on the Gut Microbiome Clin Microbiol Infect. 2016;22(2): 178.e1–178.e9.
2. Hirofumi M. et al. The pathophysiology of nonsteroidal antiinflammatory drug (NSAID) induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr 2011;48(2): 107–111
3. Introduction to the Human Gut Microbiota. Biochem J 2017;474(11): 1823-36.
4. Role of the Gut Microbiota in Nutrition and Health. BMJ. 2018; 361: k2179.
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6. Immune Gate of Psychopathology- The Role of Gut Derived Immune Activation in Major Psychiatric Disorders. Front Psychiatry. 2018; 9:205.
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