This is a summary from a rapid evidence search and review (see evidence table in other doc if interested) and an analysis paper by the Oxford EBM group.

Are there specific harms of use in COVID?

There is no evidence at present linking NSAIDS with worsening symptoms of COVID

There are other risks of using NSAIDs in ARI to consider

There is a need for caution when using NSAIDs in the context of acute respiratory infections (ARI), especially in some groups.

1 NSAIDs increase the risk of acute MI even with very short term use.  

The risk of AMI is rapid onset within the first week of use. Taking any dose of NSAIDs for one week or more was associated with a 50% increased risk of a heart attack. The Odds Ratio is around 1.5 and there is no evidence that any NSAID is safer. (Bally et al meta-analysis)

There is a dose-response with increasing risk for AMI with increasing dose. Risk of AMI reduces over time after last dose. (Bally)

2 The risk of acute MI is also increased in ARI and influenza Odds ratio 2.7. NSAIDs further increase the risk of acute MI in ARI Odds Ratio 3.4.(Wen 2017)

3 NSAIDs make hypertension worse. They also make heart failure worse, so there is good reason already not to use them in people with these conditions. Some early COVID studies suggested an association of hypertension with higher risk of more serious COVID illness however these were not adjusted for confounders so hypertension may be a marker for other things that increase risk. Regardless, hypertension increases the risk of MI.

4 NSAIDs increase the risk of kidney injury in combination with other drugs (esp diuretics and ACE/ARB)

5 There are a few studies suggesting that bacterial infection complication rates are higher with NSAIDs, in particular suggesting that NSAIDs can worsen the course of a bacterial CAP. It is unclear whether this has any relevance to COVID. Some suggested this is due to symptom masking as studies show patients taking NSAIDs have a longer time to antibiotic initiation. (Basille 2017, Voirot 2011, Kotsiou 2017, Messika 2014)

Are there indications for taking an antipyretic in Covid-19?

Adults: For most adults, there is no convincing evidence that fever is itself detrimental and does not automatically require suppression.

In addition

NSAIDs do not significantly reduce total symptoms or duration of respiratory infections. Primary care studies show acetaminophen is just as effective for symptom relief in viral illness (Little et al)

Clinical Implications

If symptoms are significant enough to require relief then it seems sensible to recommend against use in:

  • Adults with CVD or CVD risk including hypertension and CHF should preferentially use acetaminophen.
  • Older adults with kidney disease or taking one of the other kidney risk classes should also preferentially use acetaminophen.
  • The usual other cautions around NSAIDs and any older adult also apply.

If used, the lowest effective dose should be used for the shortest period of time. Parenteral use of NSAIDs during an ARI should be avoided.

What about patients who are taking NSAIDs long term for significant other conditions

There is no scientific evidence to suggest this group have to stop NSAIDs if they are offering significant benefit however if they can easily stop or reduce the dose without compromising symptoms this seems sensible as some adverse effects are dose related.

See also full text of CEBM paper

Prepared by Dee Mangin, March 31, 2020

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