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Anti-inflammatory agents for home treatment of COVID-19

Several recommendations on how to treat people at home with COVID-19 with mild to moderate symptoms have been proposed, starting with the use of anti-inflammatory drugs.

The main recommended NSAIDs are relatively selective COX-2 inhibitors, Indometacin, Ibuprofen, and Aspirin, often as part of a multipharmacological protocol.

Some of the recommendations have suggested Paracetamol as a safe therapy for the early management of pain and fever in people with COVID-19. However, one should consider that ( besides being a negligible anti-inflammatory drug ) at relatively low doses Paracetamol reduces plasma and tissue glutathione concentrations, which might exacerbate COVID-19.

Very few researchers have formally tested their proposed recommendations for outpatients with symptomatic COVID-19 through observational studies.
In particular, findings from the studies have corroborated the protocol recommendations for early outpatient treatment of COVID-19.
These treatment recommendations are based on three pillars: intervene at the very onset of symptoms at home; start therapy as early as possible after the family doctor has been contacted by the patient ( without waiting for the results of a nasopharyngeal swab ); and rely on NSAIDs, especially relatively selective COX-2 inhibitors.

The overlap in COX-2 selectivity between Celecoxib and Nimesulide was the rationale for recommending these two drugs for the early outpatient treatment of COVID-19 symptoms.
Aspirin or Ibuprofen are the alternative treatments to these relatively selective COX-2 inhibitors, if these COX-2 inhibitors are not available or when signs of toxicity or contraindications to these drugs are evident according to clinical characteristics and the medical history of the patient.

Treatment with NSAIDs should continue for 3–4 days, but if symptoms persist it could be extended for a maximum of 8–12 days, if not contraindicated.
Moreover, given the metabolic pathway of these NSAIDs involving, among others, the cytochrome 3A4, family physicians should consider the risk of potential drug interactions, especially for patients with COVID-19 who started antiviral therapy with Remdesivir or Ritonavir-boosted Nirmatrelvir.
In this case, potential strategies include adjusting the NSAID dose, increasing monitoring for potential adverse reactions, or temporary NSAID withholding.
These NSAIDs should be given to treatment-naive patients who are older than 65 years for the shortest time possible, and under adequate hydration.
They can be prescribed to pregnant women but only in the first few months of gestation, according to the summary of product characteristics.

Celecoxib, Ibuprofen, and Nimesulide should be avoided in children younger than 12 years, whereas Aspirin should be taken only under prescription and at the dose recommended by the family doctor.

Overall, the studies have indicated that anti-inflammatory therapy, especially NSAIDs, is crucial for the management of outpatients with early symptoms of COVID-19, since the mitigation of these symptoms protects against progression towards a more severe illness that would eventually require hospitalisation. ( Xagena )

Perico N et al, Lancet Infectious Diseases, 2022