Do NSAIDs exacerbate coronavirus severity: Myth or reality?

March 31, 2020
Does the consumption of nonsteroidal anti-inflammatory drugs put individuals at higher risk for a more severe disease response to COVID-19? Dr. Scott Froum examines the research.

As the coronavirus (COVID-19) pandemic grows exponentially, information bombards us daily. Because this is a novel virus, information we receive is, at best, extrapolation of data. Unfortunately, this can often lead to faulty predictions and advice.

One topic recently presented to the public is that the consumption of nonsteroidal anti-inflammatory drugs (NSAIDs) puts patients who otherwise might have mild or asymptomatic infection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—the virus that causes COVID-19—at risk of more severe disease. We are told that individuals taking NSAIDs for other reasons should stop doing so for fear of increasing their COVID-19 risk.1

This short article aims to evaluate the evidence and ascertain whether or not this claim is correct.

The biological reasoning behind this statement

Coronaviruses bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels.2 NSAIDs such as ibuprofen increase levels of ACE2 on the surface of cells that theoretically will give this virus more binding sites in which to enter the cell.3

This information was published in a letter to the Lancet with the recommendation that people avoid NSAIDs such ibuprofen in favor of acetaminophen. In addition, the letter suggests that patients with diabetes and hypertension who are treated with ACE inhibitors should consult with their physician about switching this medication during the current pandemic as they are “at risk for a more severe COVID-19 infection.”4

What does the evidence suggest?

Regrettably, there is not much evidence to back up this proposed mechanism of virulence. Both the US Food & Drug Administration (FDA) and the World Health Organization (WHO) issued similar statements: “The FDA is not aware of scientific evidence connecting the use of NSAIDs, like ibuprofen, with worsening COVID-19 symptoms. The agency is investigating this issue further and will communicate publicly when more information is available.”5

In addition, because many patients who acquired the virus were taking NSAIDs to reduce fever, confounding correlation may have been confused as causation.6

Conclusion

The current evidence does not support the thought that NSAIDs exacerbate the symptoms of the coronavirus. Individuals who take these medications for arthritis and other pain should not stop. There are some concerns, however, that those who take NSAIDs to lower fever during infection may be at increased risk for kidney problems. Because these drugs affect the kidneys, if a person is dehydrated due to fever during viral infection and takes NSAIDs, a greater strain may be placed on the kidneys.

Finally, according to Paul A. Offit, MD, an infectious disease expert at the University of Pennsylvania and the Children’s Hospital of Philadelphia, the immune system works better when body temperature is higher, enabling it to more efficiently kill viruses and bacteria.7 Therefore, by taking any medication to reduce fever, you are decreasing your body’s natural defense system against viral agents and increasing both the length of time you will be sick as well as the time you are actively shedding the virus.

References

1. Willsher K. Anti-inflammatories may aggravate COVID-19, France advises. The Guardian. March 14, 2020. https://www.theguardian.com/world/2020/mar/14/anti-inflammatory-drugs-may-aggravate-coronavirus-infection

2. Wan Y, Shang J, Graham R, Baric RS, Li F. Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade-long structural studies of SARS coronavirus. J Virol. 2020;94(7):e00127-e00220. doi:10.1128/JVI.00127-20

3. Wu K, Li W, Peng G, Li F. Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor. Proc Natl Acad Sci USA. 2009;106(47):19970-19974. doi:10.1073/pnas.0908837106

4. Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? [published online March 11, 2020] Lancet Respir Med. doi:10.1016/S2213-2600(20)30116-8

5. FDA advises patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. U.S. Food & Drug Administration. March 19, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19

6. Melville NA, Nainggolan L. Are warnings against NSAIDs in COVID-19 warranted? Medscape. March 17, 2020. Updated March 18, 2020. https://www.medscape.com/viewarticle/926940

7. Kolata G. Is ibuprofen really risky for coronavirus patients? N Y Times Web. March 17, 2020. Updated March 19, 2020. https://www.nytimes.com/2020/03/17/health/coronavirus-ibuprofen.html

Editor’s note: This article originally appeared in Perio-Implant Advisory, a newsletter for dentists and hygienists that focuses on periodontal- and implant-related issues. Perio-Implant Advisory is part of the Dental Economics and DentistryIQ network. To read more articles, visit perioimplantadvisory.com, or to subscribe, visit dentistryiq.com/subscribe.

MORE CLINICAL TIPS FROM DR. SCOTT FROUM . . .

Scott Froum, DDS, a graduate of the State University of New York, Stony Brook School of Dental Medicine, is a periodontist in private practice at 1110 2nd Avenue, Suite 305, New York City, New York. He is the editorial director of Perio-Implant Advisory and serves on the editorial advisory board of Dental Economics. Dr. Froum, a diplomate of the American Board of Periodontology, is a clinical associate professor at SUNY Stony Brook School of Dental Medicine in the Department of Periodontology. He serves on the board of editorial consultants for the Academy of Osseointegration's Academy News. Contact him through his website at drscottfroum.comor (212) 751-8530.