by Tina McManus, ND
As confirmed cases continue to rise across the globe, we seem to all be collectively learning new information about this disease. We have gotten a couple questions about whether using NSAIDs or ACEi/ARBs are safe to use with COVID-19. Since there is conflicting information out there, we thought an article addressing these concerns would be helpful.
NSAIDs – Are These Ok to Take with COVID-19?
On Saturday, March 14, 2020, the French Minister of Health Olivier Véran tweeted https://twitter.com/olivierveran/status/1238776545398923264 that taking anti-inflammatory drugs like ibuprofen and cortisone could aggravate the COVID-19 infection. Instead, in case of fever, paracetamol or Tylenol should be used. While he mentioned two kinds of anti-inflammatory drugs (ibuprofen – NSAID, cortisone – steroid), it seems like most people have been focused on the NSAID part of his statement.
So, what exactly is an NSAID? NSAID stands for non-steroidal anti-inflammatory drug, and this class of drugs includes ibuprofen, naproxen, diclofenac, indomethacin, and aspirin to name a few. These are commonly used drugs to treat pain, inflammation, and fever, and they work by blocking certain enzymes which lower the production of prostaglandins, which are involved in inflammation.
It seems like Véran tweeted this information simply from a physiological point of view. Inflammation is a necessary part of combatting an infection and so therefore, it is counterproductive to block it with the use of anti-inflammatory drugs. Apparently, the health ministry added that paracetamol would lower the fever without affecting the inflammation. [1] (You can read more about whether or not we should try to lower fever here: https://drteresarichter.com/blog/should-i-stifle-a-fever However, the question is what is the evidence for his statement?
Evidence About Use of NSAIDs in People with COVID-19
Anthony Fauci, the head of the National Institute of Allergy and Infectious Disease, says there is no firm evidence to support Véran’s statement. The Canadian Pharmacists Association released a statement about this topic, and one of their key points is that there is “insufficient evidence that NSAIDs negatively impact morbidity or mortality of COVID-19.” [2] However, this statement also discussed potential risks and benefits associated with NSAIDs in this disease, which are listed below.
Potential Risk of NSAIDs
NSAIDs block COX enzymes, but B cells need COX-2 for sufficient antibody production, an important step in fighting an infection. There is in vitro evidence that showed that aspirin, naproxen, acetaminophen (Tylenol, aka not an NSAID), and especially ibuprofen reduced antibody production.
Potential Benefit of NSAIDs
On the other hand, indomethacin and naproxen have been shown to be antiviral properties. Indomethacin was studied in animals and was shown to be antiviral against SAR-CoV (the cause of SARS) by interfering with viral replication. Naproxen is antiviral against influenza A and B, and it is thought that since it interferes with the viral RNA replication, it might also be effective against the virus that causes COVID-19, which is also an RNA virus.
So, you can see that there is some evidence both for and against NSAID use in COVID-19, but there is no strong human evidence either way. There are other reasons to minimize the use of these drugs because they can be hard on the liver, kidneys and digestive system. They are also to be used with caution in the elderly.
Hypertension and Increased Risk of Serious COVID-19
Although about 80% of COVID-19 cases will be mild, roughly 20% will be severe or critical, requiring hospitalization. [3] There are a few populations particularly at risk for more serious disease. These include [4]:
- People 65 years and older
- People living in a nursing home or long-term care facility
- People with underlying medical conditions like chronic lung disease, cardiovascular disease and high blood pressure, diabetes, kidney or liver disease
- People who are immunocompromised
In a meta-analysis looking at the co-morbidities in serious COVID-19 infection, hypertension was found to be most prevalent. [5] Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are common medications used to reduce high blood pressure, and a question was raised recently whether these medications might put these patients at risk for more serious COVID-19 infection. [6] The rationale was that the SARS-CoV-2 virus, which causes COVID-19, uses the ACE2 receptor in the lower lung to gain entry to the cell. Both ACEi and ARBs seem to increase the expression of these receptors in animal studies. Therefore, the authors hypothesize that this may increase the potential of infection in people on these drugs.
Should ACEi and ARBs be Discontinued in COVID-19?
The official position of the American Heart Association, the Heart Failure Society of America and the American College of Cardiology is to continue ACEis or ARBs in all patients already taking these medications. [7] There is no human evidence that these drugs are harmful, and these drugs may, in fact, be protective. Dr. Roger Seheult, MD, a pulmonologist in Southern CA, does a great job of reviewing the evidence on both sides of the argument and showing how these drugs may be protective in COVID-19 in the following video:
References
[1] K. Willsher, “Coronavirus outbreak: Anti-inflammatories may aggravate Covid-19, France advises,” The Guardian, 14 Mar 2020. [Online]. Available: https://www.theguardian.com/world/2020/mar/14/anti-inflammatory-drugs-may-aggravate-coronavirus-infection. [Accessed 23 Mar 2020].
[2] “Use of NSAIDs in patients with COVID-19: what is the evidence?,” Canadian Pharmacists Association, 17 Mar 2020. [Online]. Available: https://www.pharmacists.ca/cpha-ca/assets/File/cpha-on-the-issues/Use-of-NSAIDs-in-patients-with-COVID-19-FINAL-EN.pdf. [Accessed 23 Mar 2020].
[3] “Coronavirus Symptoms (COVID-19),” Worldometer, 29 Feb 2020. [Online]. Available: https://www.worldometers.info/coronavirus/coronavirus-symptoms/#mild. [Accessed 24 Mar 2020].
[4] “People who are at higher risk for severe illness,” Centers for Disease Control and Prevention, 22 Mar 2020. [Online]. Available: https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/people-at-higher-risk.html. [Accessed 24 Mar 2020].
[5] J. Yang, Y. Zheng, X. Gou and K. Pu, “Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis,” Int J Infect Dis, no. 20, pp. S1201-9712, 2020.
[6] R. Sommerstein and C. Gräni, “Rapid response: re: preventing a covid-19 pandemic: ACE inhibitors as a potential risk factor for fatal Covid-19,” BMJ, 8 March 2020. [Online]. Available: https://www.bmj.com/content/368/bmj.m810/rr-2. [Accessed 24 Mar 2020].
[7] “Patients taking ACE-i and ARBs who contract COVID-19 should continue treatment, unless otherwise advised by their physician,” Heart Failure Society of America, 19 Mar 2020. [Online]. Available: https://www.hfsa.org/patients-taking-ace-i-and-arbs-who-contract-covid-19-should-continue-treatment-unless-otherwise-advised-by-their-physician/. [Accessed 24 Mar 2020].