In their Review article in The Lancet Infectious Diseases, Norberto Perico and colleagues1 recommend administration of non-steroidal anti-inflammatory drugs (NSAIDs) at the first sign of respiratory infection, without waiting for a confirmation of COVID-19. This recommendation contradicts both the ritual assertion that inflammation initially plays a defensive role against infections, and the results of two large randomised controlled trials showing an unfavourable and unsafe role of ibuprofen in managing respiratory infections.2
The authors acknowledge the more convincing data available for indometacin, the only NSAID to be successfully tested in a randomised controlled trial (against paracetamol),3 with in-vitro antiviral effects against several viruses and SARS-CoV-2,1 and outperforming a matched group of celecoxib users in a real-world dataset.4 Nevertheless, their recommended NSAIDs for early COVID-19 symptoms in adults include nimesulide, celecoxib (which has not been successfully tested in randomised controlled trials), ibuprofen (with unfavourable results in randomised controlled trials for respiratory infections),2 and aspirin (for which an ineffective randomised controlled trial is cited,1 which was associated with safety problems, as well as other uncited null randomised controlled trials), rather than indometacin.
Finally, the authors support their recommendations by citing two observational studies. Unfortunately, the first retrospective study5 did not meet its primary outcome; time to resolution of major symptoms was not significantly shorter with their algorithm, but significantly longer (18 days vs 14 days, p=0·033), suggesting that the recommendation of full-dose NSAIDs at onset of viral multiplication is not suitable for all patients, although it can be useful for a subgroup of patients with a high inflammatory state. Incidentally, the Bonferroni adjustment for the 18 comparisons shown in the study by Gordon and colleagues5 leads to a p value cutoff of 0·0050, which means the difference reported in the secondary outcome of hospitalisation is not statistically significant either.5
Therefore, the authors correctly conclude that randomised controlled trials are required to consolidate their positive observational findings.1
I declare no competing interests.
References
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