Kerfuffle Over NSAIDs in COVID Finally Resolved?

There was no association between use of non-steroidal anti-inflammatory drugs (NSAIDs) and increased disease severity or mortality among patients with COVID-19 requiring hospitalization, a U.K. cohort study found.

After adjusting for confounders, in-hospital mortality for patients who were taking NSAIDs prior to admission was no different from those who were not (matched OR 0.95, 95% CI 0.84-1.07), reported Ewan Harrison, PhD, of the University of Edinburgh in Scotland, and colleagues.

Moreover, NSAID use was not associated with critical care admission (matched OR 1.01, 95% CI 0.87-1.17), or the need for invasive (matched OR 0.96, 95% CI 0.80-1.17) or non-invasive ventilation (matched OR 1.12, 95% CI 0.96-1.32), the authors wrote in The Lancet Rheumatology.

NSAIDs were implicated in the severity of COVID-19 back in March 2020, when the French health ministry cited unpublished data showing they could increase disease severity, but later research found no associations between the drug and worse outcomes.

“We now have clear evidence that NSAIDs are safe to use in patients with COVID-19, which should provide reassurance to both clinicians and patients that they can continue to be used in the same way as before the pandemic began,” Harrison said in a statement.

In the largest study to date, Harrison’s group examined data from a cohort of around 79,000 patients from 255 healthcare facilities in the U.K. from January to August 2020. Participants included hospitalized patients with confirmed or suspected SARS-CoV-2 infection. In-hospital mortality was the primary outcome.

Of these patients, 72,179 had death outcomes available for matching. There were 4,211 patients (5.8%) who took systemic NSAIDs prior to hospital admission, who were more likely to be women and significantly more likely to have pre-existing rheumatological disease.

About 30% of patients in the NSAID cohort died versus 31.3% of patients who did not receive NSAIDs. The most common NSAID was ibuprofen. Use of ibuprofen was not associated with increased mortality versus either those not taking NSAIDs (matched OR 0.90, 95% CI 0.71-1.13) or those taking any other NSAID (matched OR 0.82, 95% CI 0.66-1.03).

“We found no evidence of harm caused by NSAID use in patients admitted to hospital with severe COVID-19,” the authors argued.

An accompanying editorial by Kristian Kragholm, MD, of Aalborg University Hospital in Denmark, and colleagues, agreed, noting that the clinical statements from the World Health Organization, FDA, and European Medicines Agency on the “lack of harmful effects of NSAID use in COVID-19 infection are supported by the current study.”

“Ultimately, based on current knowledge, clinicians should not refrain from or discontinue NSAIDs in patients with COVID-19 if NSAID treatment is indicated,” the editorialists wrote.

Harrison and colleagues noted limitations to the data, namely that it did not contain information about dosages or adherence, as well as that it was unclear the NSAID indication and duration of use (that is, if it was for a long-term condition or relief of COVID-19 symptoms). It is also unclear if patients continued to take NSAIDs while in the hospital or not.