NSAID Safety with COVID-19 Infection Save

NSAIDs do not affect COVID outcomes; here we are nearly 16 months into the pandemic, and this is the common sense conclusion of a recent trial published in Lancet Rheumatology.

Early in the pandemic there was an unfounded directive from the French government suggesting that non-steroidal anti-inflammatory drugs (NSAIDs) should be avoided in COVID-19 infected patients as they may contribute to increased disease severity.  Yet a search for evidence failed to provide support to this contention.

A prospective, cohort trial examined hospitalized (confirmed or highly suspected) COVID-19 patients and ascertained clinical outcomes and whether the subject had been exposed to NSAID use within the 2 weeks of hospital admission.

Amongst a total of 78 674 hospitalized UK patients, 5·8% were taking NSAIDs before hospital admission.  On admission there were no differences between NSAIDs users and NSAIDs non-users regarding COVID severity.

Moreover, NSAID use was not associated with higher rates of any of the following:

• in-hospital mortality (matched OR 0·95, 95% CI 0·84–1·07; p=0·35)
• critical care admission (1·01, 0·87–1·17; p=0·89)
• requirement for invasive ventilation (0·96, 0·80–1·17; p=0·69)
• requirement for oxygen (1·00, 0·89–1·12; p=0·97)
• acute kidney injury (1·08, 0·92–1·26; p=0·33)

NSAID use is not associated with higher mortality or increased severity of COVID-19. 

An accompanying discussion explains the concern and potential mechanisms for NSAID harm.  When so little was known about COVID, causes and comorbidities, it was thought NSAIDs could theoretically upregulate angiotensin-converting enzyme 2 (ACE2) receptors, thereby enhancing SARS-CoV-2 binding to ACE2 receptors in the lungs, arteries, heart, kidney, and intestines. To a lesser extent, some argued that NSAIDs might by mask inflammation or fever.

Multiple agencies have previously gone on record stating that NSAIDs were not a risk factor for COVID-19 infection - including the WHO, EMA, and thus, the current study supports these directives. 

Editor’s note: Interestingly, ACR guidance states that without COVID infection or exposure, NSAIDs can be safely used, but with rheumatic patients with COVID infection and severe respiratory symptoms, NSAIDS should be stopped (but the panel demonstrated low consensus with regards to stopping NSAIDs in the absence of severe symptoms). Also, the recently updated ACR COVID-19 vaccine guidance suggests "NSAIDs... should be (held) for 24 hours prior to vaccination (no restrictions on use post vaccination to treat symptoms)."

Where's the evidence or rationale for these two opinions from the ACR?