Some letters published in medical journals raised the question of NSAIDs increasing the risk of COVID-19 infection based on the increase in cell-bound ACE2 induced by drugs in this class. However, this extrapolation from “statistically significant” findings in animal models does not translate directly to humans with any of a variety of acute or chronic health conditions. These enzymes do serve as a binding site for the S protein of SARS-CoV-2 virus, allowing viral entry into cells by endocytosis. However, some data suggests that increased ACE2 may actually be useful for treating COVID-19.
Concern was also raised by prior studies suggesting that NSAID use is associated with a statistically significant increase in complications in the treatment of a mixture of infectious diseases (majority bacterial in origin). However, this does not necessarily indicate there will be a problem with SARS-CoV-2, and there is potential confounding in prior studies based on delay to care with symptomatic use of NSAIDs. Known potential risks of renal dysfunction or gastrointestinal symptoms/hemorrhage, and blood pressure elevation in some patients, as well as potential alterations in thrombosis risk and increased leukotriene expression as class effects of NSAIDs do suggest the need for caution in use of this drug class.
The importance of analgesia and fever control in managing fluid balance and sleep quality/quantity might argue for NSAID symptomatic use in those with mild-moderate symptoms managed at home. Acetaminophen (paracetamol) would be a reasonable alternative, although its limited analgesia and the tendency of patients to exceed recommended doses increase the risk of untoward (primarily hepatotoxic) effects with this choice.
Patients who have tolerated NSAIDs in the past or are currently on chronic NSAID therapy should continue in the face of COVID-19. Certainly, patients taking low dose aspirin for cardiovascular protection should continue to do so, although these low doses (81-325mg daily) may be insufficient for symptomatic COVID-19 treatment.
At this time, avoiding NSAIDs in higher risk patient categories, such as the elderly, those with a history of gastrointestinal hemorrhage, asthma, or renal disease, and those with prior thromboembolic events, or perhaps those COVID-19 patients with elevated d-dimers, is a reasonable course.
When beginning NSAID therapy, please refer to the FDA-approved label of the individual drug at the Daily Med Web Portal from the National Library of Medicine.
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Diaz JH. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19. J Travel Med 2020; DOI: 10.1093/jtm/taaa041 [letter]
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet 2020;8:621. Accessed May 11, 2020 at: https://www.thelancet.com/action/showPdf?pii=S2213-2600%2820%2930116-8
Little P. Non-steroidal anti-inflammatory drugs and covid-19. BMJ 2020.368m1185. Accessed May 11, 2020 at: https://www.bmj.com/content/368/bmj.m1185
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