NSAIDS & Coronavirus: should we be worried?

Can taking NSAID medications like Ibuprofen (aka Motrin or Advil) really make COVID-19 infection worse? 

A possible correlation was noted by Olivier Veran, French Minister for Solidarity & Health, after doctors in France observed that young people presenting with more severe illness may have had NSAID use as a common risk factor. Mr. Veran then went on to recommend paracetamol (which is acetaminophen aka Tylenol) if you have a fever instead. Within 18 hours of posting this on his FB page on March 16, 2020, it has literally gone “viral” (no pun intended), and since then, I’ve been flooded with questions from concerned parents whether or not it’s safe to give their child ibuprofen if they suspect they may be infected with SARS-CoV-2.

On March 17, World Health Organization spokesman Christian Lindmeier stated at a Geneva press conference that UN Health Agency experts are “looking into this to give further guidance… In the meantime, we recommend using rather paracetamol, and do not use ibuprofen as self-medication.” Mr. Lindmeier notes, however, that if ibuprofen has been “prescribed by the healthcare professionals, then, of course, that’s up to them.”

Since Mr. Veran’s declaration, several respected health organizations and professionals have expressed concern over this sweeping statement. Public Health England (PHE) said, “There is not currently enough information on ibuprofen use and Covid-19 to advise people to stop using ibuprofen … Currently there is no published scientific evidence that ibuprofen increases the risk of catching Covid-19 or makes the illness worse. There is also no conclusive evidence that taking ibuprofen is harmful for other respiratory infections … Patients who have been prescribed NSAIDs for long-term health problems should continue to take them as directed by their healthcare professional”

So, how worried do we really need to be about NSAIDs and COVID-19?

Here are my opinions as a pediatrician, based on as much research I could gather on this newly-emerging concern …

Correlation キ Causation

Since we know so little about SARS-CoV-2, it’s observations like these, from doctors in the front lines, that may lead to research that provides breakthroughs for COVID-19 treatment dos and don’ts. However, these are still merely observations, and similar observations have not been noted in China or other countries. Correlation does not equal causation – meaning that when we observe x with y, it doesn’t mean that x causes y. So before we completely villainize ibuprofen, more observational and clinical research needs to be done – and it needs to be done ASAP given that in the US alone in 2017, over 24 MILLION prescriptions for ibuprofen were written (1), and this number does not include over-the-counter use! This matter needs to be especially elucidated for my patients with autoimmune illnesses such as PANS/PANDAS and juvenile arthritis, where NSAIDs are a mainstay of therapy. 

A theoretical cause for concern was fueled by an article that appeared in Lancet (2) that was published on March 11, 2020. We know that SARS-CoV-2 attaches to target cells (for instance, the epithelial cells of the lung) through angiotensin-converting enzyme 2 (ACE2) receptors. So theoretically, medications that increase ACE2 expression may allow more SARS-coV-2 particles to attach to lung cells and potentially lead to more invasive disease. In fact, one theory why children appear to be less affected with COVID-19 is that their lung cells may express less ACE2 and have fewer ACE2 receptor binding sites to allow SARS-CoV-2 to invade. ACE2 is increased by some medications, including ibuprofen, which led some to conclude that ibuprofen may be dangerous if you have SARS-CoV-2 infection. 

However, some studies have shown the exact opposite – that higher ACE2 levels may actually protect against acute respiratory distress syndrome (ARDS) and sepsis, what we’re all very concerned about with COVID-19 infection. One mouse study (3) of ARDS and sepsis that mimicked what is seen in human SARS coronavirus cases found that lower ACE2 worsened acute lung injury, while higher ACE2 actually protected lungs. Another mouse study (4) of acute respiratory distress syndrome (ARDS) induced by avian influenza H5N1 (aka “bird flu”) found that ACE2 administration could improve lung function and survival rates. ACE2 inactivates Angiotensin II. Elevated serum levels of Angiotensin II were found in patients with H7N9 avian influenza, with higher levels of Angiotensin II correlating with worse disease severity and outcome. The authors speculate that treatment with ACE2 could be beneficial for patients with SARS-CoV, which is very similar to the currently circulating SARS-CoV-2 that causes COVID-19.

NSAIDS May be Beneficial for Coronavirus Infection

There is some evidence that NSAIDs may actually be beneficial for coronavirus infections from what we’ve learned with SARS-CoV.  Indomethacin, also an NSAID, in one study (5) was actually found to have “potent antiviral activity” against SARS-coV, and “to dramatically inhibit virus replication and protect the host cell from virus-induced damage.” The authors conclude that “indomethacin, possessing both anti-inflammatory properties and a direct antiviral activity against SARS-CoV, could be effective in the treatment of SARS.” 

What Does This Mean for NSAIDs & COVID-19?

Given the above findings, I am not as ready to completely give up on NSAIDs if you have COVID-19, so please, if NSAIDs are a part of your or your child’s prescribed treatment protocol, please consult with your physician before stopping them.

Until more research is done, I do not recommend that patients who rely on NSAIDs to manage their disease go off without consultation with their physician. On the flip side, until more research is done, I would recommend exercising caution when using ibuprofen for symptomatic relief of fever and upper respiratory symptoms and be sure to consult with your physician before using NSAIDs for you or your child. 

Acetaminophen May Worsen Viral Infections

Unlike Dr. Veran and WHO, I have significant concerns with using acetaminophen (Tylenol or paracetamol) during any viral illness.. Overdosage or prolonged usage of acetaminophen can lead to liver toxicity and failure, and maximum daily limits must be followed. And most importantly, acetaminophen depletes our levels of glutathione, our “master antioxidant,” which plays a crucial role in fighting and recovering from viral infections. In fact, studies have shown that acetaminophen may actually prolong the duration and severity of viral infections like varicella. (6) To tell you the truth – we don’t even have any acetaminophen in our household, I’m that concerned about glutathione depletion…

Should Fever be Treated Anyway?

This perhaps is the most important question …

This study from 2014 (7) is an important reminder to trust our body’s natural response to infection – fever. To cut to the chase, this study used statistical models to confirm that using antipyretics (fever-reducing medicine like acetaminophen or ibuprofen) could lead to larger influenza epidemics and greater morbidity and mortality! This was based on the facts that: 

1. When you reduce fever, people feel better and are more likely to interact with other people (i.e., go to work, send their kids to school, go out and do “normal” things because let’s face it – no one has time to be sick), EVEN THOUGH they’re still contagious. 
2. Suppressing fever actually INCREASES the amount of the influenza flu virus a person sheds (and therefore spreads to others), and PROLONGS the duration of that shedding (i.e., they stay contagious for longer!)
3. Therefore, fever reducers actually lead to a higher influenza transmission rate which will in general lead to larger epidemics with greater morbidity and mortality.

The authors conclude that “the population-level effects of antipyretic treatment during influenza pandemics could be especially dramatic. It has been suggested that widespread use of aspirin in 1918 may have increased disease severity, and consequently death rates, during the pandemic, and… research in humans… suggests that antipyretic use may increase the risk of death from serious infections.”

Not only that, but “exceptionally high rates of antipyretic treatment in CHILDREN might contribute to the disproportionate role that children play in influenza transmission.”

So while we’re waiting for research to clear up whether or not ibuprofen really can worsen COVID-19 illness, I believe that the most important consideration should really be whether or not we should be suppressing fever in the first place … 

Please, don’t give into fever phobia! Here are some important facts to know about fever:

• As stated above, fever can actually help your child get over their illness faster.
• Unless your child has a neurologic disorder or is overbundled, fever can’t get “too high” and cause brain damage
• How your child is acting is much more important than the number on the thermometer

So, What Should We Do When Our Kids have a Fever?

If your child has a fever, the first thing is to NOT PANIC. Take a deep breath, and remind yourself that fever is helping your child get better faster and also be less contagious to others. But, you do NOT have to just sit idly by while your child suffers. There are many evidence-based natural medicines that I know, from personal experience with my patients and my own kids, may work to help keep your child comfortable, support their immune system, and resolve their illness faster without artificially reducing their fever. 

Certain acupuncture points have been found in studies to have antipyretic effects, including Large Intestine 11, Large Intestine 4, Governing Vessel 14, Stomach 36 (8). Lavender essential oil has been proven to have pain-relieving and anti-inflammatory effects (9). 

I love teaching parents how to use acupressure to provide loving yet therapeutic touch when their kids are sick. Acupressure uses gentle but firm touch on specific acupuncture points to help provide relief for many of your child’s symptoms. Use the flat pads of your fingers or thumb to apply firm pressure to the appropriate acupuncture point(s) for 1-5 minutes. You can apply continuous pressure, or massage the point in a circular motion. And better yet, apply essential oils like lavender directly to those acupressure points for even more benefit.

The best acupressure point to massage when your child has a fever is “Large Intestine 4”: 

Large Intestine 4 is located on the back of the hand, in the web space between your thumb and index finger. You can massage this point by putting your thumb on the back of your child’s hand just on top of the web space, and your index finger on the palm-side just opposite of your thumb, and massaging vigorously.

If you’d like to learn more of my integrative pediatric tips to support your child when they have a fever, feel free to download my FREE guide: The Top 5 Mistakes Parents Make When Their Child Has a Fever – and what you can do instead! (10)

And please note, fever reducers aren’t completely off the table. As I always say, there’s a time and a place for everything. I do recommend that parents give their kids fever reducers if their fever is making them so uncomfortable that they don’t want to drink and are at risk for getting dehydrated, or if they can’t fall asleep – because when we’re sick, sleep is  one of the most healing things we can do. 

Stay well. We’re in this together. To help you further separate out facts from fear, please read and share my article: Coronavirus: What a Pediatrician Wants You to Know. I will continue to keep you informed of any new information I have, so be sure to sign up for my newsletter if you’d like the latest updates.

xo Elisa Song, MD

References:

1. https://clincalc.com/DrugStats/Drugs/Ibuprofen
2. https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30116-8/fulltext
3. https://www.nature.com/articles/nature03712
4. https://www.nature.com/articles/ncomms4594
5. https://www.researchgate.net/publication/6503810_Indomethacin_has_a_potent_antiviral_activity_against_SARS_coronavirus
6. https://www.ncbi.nlm.nih.gov/pubmed/2656959
7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906934/ 
8. May Loo. (Elsevier Health Sciences, 2009).  Integrative Medicine for Children.
9. https://www.ncbi.nlm.nih.gov/pubmed/26247152
10. FREE guide: The Top 5 Mistakes Parents Make When Their Child Has a Fever – and what you can do instead!