Should you take ibuprofen if you are at risk of COVID- 19 infection?

Apr 20, 20207 min read

Updated: Apr 25, 2020

Should you take ibuprofen if you are at risk of COVID- 19 infection? Great question, hard answer. Here’s a (very) basic summary of the basic science.

Ibuprofen and acetaminophen are two different types of medications used to treat pain and fever. Ibuprofen though is an NSAID (non-steroidal anti-inflammatory drug) and has a more potent effect on both fever and pain, as well as a dampening of inflammation. Acetaminophen is not an NSAID: it treats pain (it is an “analgesic”) and reduces fever(an “antipyretic”) but doesn’t reduce inflammation the way that ibuprofen does.

Other NSAIDS you may recognize include aspirin, meloxicam, Aleve, Naprosyn, and Celebrex. Here’s a list of brand names and medical names of NSAIDs used in the US. Other anti-inflammatories you may recognize are steroids, Vitamin D, magnesium, fish oil, and many over-the-counter supplements. Being an anti-inflammatory does not make a substance “bad” for your health. In fact having natural anti-inflammatory compounds in our diet (like Vitamin D) is absolutely essential to our health. And some people rely on steroids and other prescribed/medical anti-inflammatories to manage their medical conditions: that’s a different situation and one to discuss with your doctor if you are concerned about a COVID infection. But let’s get back to how ibuprofen and other NSAIDs affect inflammation and how that may impact COVID and other viral infections.

COVID is a coronavirus and viral infections are fought off by a combination of what we call innate and acquired immunity. Innate immunity includes everything that exists in our body before an infection happens. Innate immunity includes (very simply) 1) barriers, 2) inflammation, and 3) the complement cascade.

So let’s review each step of innate immunity and how viruses get by them. And guess what?! The first step- barriers to infection- means we have to discuss hand washing again. Barriers to infection are simple but effective parts of the immune system: they include our skin, the mucous in our nose, saliva, tears, etc. But they don’t work if you place a heaping load of virus on your eyes, in your nose, or in your mouth. Wash your hands and don’t touch your face, people! Lather, rinse, repeat. I don’t care if you sing Baby Shark or Happy Birthday or use a timer, but lather away those viruses and don’t put them on your face. My favorite video for kids on this subject, by the way, compares touching your face with dirty hands to providing a free ride for germs to your Death Star Exhaust Port.

Having healthy barriers is definitely important. Yet it is also you why may be seeing so much spam right now touting miracle prevention of COVID by keeping your mouth moist and using humidified air. Sure, those are great, but you are getting inaccurate information if someone is telling you that drinking water every 20 minutes will prevent COVID infection. Barriers and your innate immunity are not going to work against a highly contagious virus if you are placing loads of virus on your face. Have we talked about hand washing yet? OK, Let’s move on.

The second part of innate immunity is the inflammatory response. The inflammatory response is exquisitely simple and yet unbelievably complex at the same time. In fact, the four parts of inflammation were described in the first century AD by Celsus: they include Rubor, Calor, Dolor et Tumor. My 2010 textbook on The Fundamentals of Inflammation- which is three inches thick- describes, you guessed it, the molecular details of redness(Rubor), heat (Calor), pain (Dolor), and swelling (Tumor).

Inflammation, the second part of innate immunity, is highly effective at fighting viral infection. Cells signal the body that they have been damaged with the release of prostaglandins (causing dolor). Swollen and leaky blood vessels(rubor) allow white cells to leave the blood to find the offending agent. Higher temperature triggers activation of different cells and proteins of the immune system to fight the virus(calor). Heat and fever also inhibits bacterial and viral growth. The arrival of immune cells during a viral infection triggers the second stage of the inflammatory response: the mass arrival of first nonspecific then specific white blood cells and fluids with protein (tumor) that know how to fight a particular infection. They initiate a second stage of chemical and cellular battle, all choreographed by prostaglandins, called acquired immunity. Ideally, once the infection is cleared, the inflammation stops and the tissue is healed up after the damage caused by the battle itself. And yes, I know, we skipped the third part of innate immunity: the complement cascade. Complement is a group of proteins that are activated by infection or by tissue stress, usually with inflammation, and poke holes in the surfaces of cell membranes(ideally, not our own). Let’s leave complement alone for now and get back to the part of the immune response that is most affected by NSAIDs.

Ibuprofen and other NSAIDs work by suppressing the innate chemical coordinators of inflammation, collectively known as the prostaglandins. But unfortunately, they do that by reducing the action of cyclooxygenase enzymes. Why is this unfortunate? Because cyclooxygenase enzymes regulate all prostaglandin production and prostaglandins regulate almost every chemical cascade in the human body. So when we use NSAIDs, we can cause some collateral damage to how the body functions. Ideally, it would be great to decrease just PGE2(prostaglandin Type E2) when it is involved in the production of pain. But,nobody has created that medication yet. PGE2 regulates pain, but also regulates gastric fluids, acid production, and blood clotting. Know someone who has migraines but now has higher blood pressure after taking NSAIDs? PGE2 inhibition helps a headache, but prostaglandins also regulate blood flow to the kidneys and retention of salts and water. Know someone who had a GI bleed from too much ibuprofen use? Their pain was probably well-controlled but their stomach acid balance and blood clotting was not normal.

Are you really curious about *all* the cellular receptors involved with prostaglandins? Then take a look at the bottom of this article. If I put that graphic here, nobody will keep reading.

And don’t panic: but here is a more basic schematic of where and how NSAIDs work. Notice that it is shaped like a rake: we use ibuprofen and other NSAIDs to block the top of the reaction sequence, at the top of the rake, which means we block all of the lower arms. The right side arms produce prostaglandins, with NSAIDs we reduce them all. The left side regulates the production of thromboxanes, so we reduce them as well. Most of the side effects and problems with using ibuprofen and other NSAIDs are related to this “big gun” effect. We’d like to be able to reduce just pain caused by PGE2, but because we suppress all the products of the reaction, we can cause reduced platelet binding, blood pressure effects, fluid retention, confusion, increased inflammation, etc., etc. One of the great steps forward in regulating this pathway, was the recognition that there are COX-1 and COX-2 inhibitors and the synthesis of NSAID medications that affect only one type of COX receptor. Once we have more specific medications for specific prostaglandins, the medications will be better.

And now back to COVID. COVIS is a highly contagious virus that is spread in droplet form and tends to live for long periods of time on surfaces. Get those on your face and it starts. COVID-19 first causes what seems like a cold, then a cough and fever, then worsening cough, chest pain and shortness of breath. That is when the virus has settled in the lungs. Injured cells in the lungs produce prostaglandins at their cell membrane(as per the picture) and then immune cells and proteins, first of the innate and then the infection-specific acquired parts of the inflammatory immune response are triggered.

Patients who are taking steroids, NSAIDs, or ACE-inhibitors(another story) seem to have a maladjusted and less effective inflammatory response to the virus. When that happens, the virus blooms in the lung tissues but also seems to be associated with marked inflammation then prolonged inflammation, both of which impair our ability to breathe easily.

So should you avoid ibuprofen and other NSAIDs right now? Here are the most recent summaries I can find of what the best of the scientists among us think.

Ibuprofen has not been proven to have deleterious effects during COVID infection. This is the view of the American scientists at our prestigious Science magazine.

https://science.sciencemag.org/content/367/6485/1434.1

Key points in this article include: There has not been a formal trial that shows more serious COVID disease is caused by ibuprofen. There are several cases of clusters of severe COVID in young people who were taking NSAIDs but the causality hasn’t been shown. The article also points out the following: 1- should you stop taking your prescribed NSAIDs and switch to opiates? No, and 2- should you stop taking your ACE inhibitors or steroids without taking to your doctor? Absolutely no.

European observations studies bring up the possibility of causality. Enough observational and anecdotal evidence exists that one should avoid NSAIDS before or during a COVID infection.

https://www.bmj.com/content/368/bmj.m1086.full

And here’s my take on it all, as of Sunday March 29th 2020.

The data in this pandemic is moving so fast, though, a good answer may be more clear or less clear in 48-72 hours.

As a pediatrician and mother, I appreciate the chance to discuss again how and when to use over-the-counter medications when your child has an infection:

---Don’t treat fever just because it’s there.

---Don’t give the old-fashioned Tylenol alternating with ibuprofen method of treating fever before discussing with your doctor.

---Remember that we treat pain if needed and fever only if children are too uncomfortable. Your grandma treated fever with warm baths in a warm room, cool water compresses, drinking cool fluids, extra fluids. These non-medicinal treatments often keep children comfortable enough that you may not need medication, which is always better.

---And never trust a doctor who says, “We’ve always done it this way.”

I used to recommend ibuprofen much more liberally than I do now, for example. Thanks to many studies here and in other parts of the world in the last three years, I have a new appreciation for recommending acetaminophen only. And I’m sure my understanding may change with all the new science happening in 2020. If I’m doing a good job, I’ll stay informed, relate the data to you effectively, encourage you to make healthy choices, and let you know when a good basic understanding of the science behind ibuprofen and COVID changes again.

But will I give ibuprofen to my family in this next few months? No, unless a doctor tells me that it is absolutely necessary. For home treatment of minor aches or pains that can’t be managed without a dose of medication, I’ll be giving my kids acetaminophen. I am very aware that I am blessed with health and with a healthy family that doesn’t *need* NSAIDs right now. But health is like happiness: it’s a lot easier to appreciate once it’s gone unless you make an attempt to live a consciously thoughtful and grateful life. Hang in there everyone and stay safe.

References

Have I mentioned yet that I love Khan Academy for patient learning? Here’s