NSAID use and clinical outcomes in COVID-19 patients: A 38-center retrospective cohort study

Abstract

BACKGROUND Cyclooxygenase (COX) inhibitors including non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community acquired pneumonia and other respiratory tract infections (RTIs). Conclusive data are not available about potential beneficial or adverse effects of COX inhibitors on COVID-19 patients. METHODS We conducted a retrospective, multi-center observational study by leveraging the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative (N3C). Potential associations of eight COX inhibitors with COVID-19 severity were assessed using ordinal logistic regression (OLR) on treatment with the medication in question after matching by treatment propensity as predicted by age, race, ethnicity, gender, smoking status, comorbidities, and BMI. Cox proportional hazards analysis was used to estimate the correlation of medication use with morbidity for eight subcohorts defined by common indications for COX inhibitors. RESULTS OLR revealed statistically significant associations between use of any of five COX inhibitors and increased severity of COVID-19. For instance, the odds ratio of aspirin use in the osteoarthritis cohort (n=2266 patients) was 3.25 (95% CI 2.76 - 3.83). Aspirin and acetaminophen were associated with increased mortality. CONCLUSIONS The association between use of COX inhibitors and COVID-19 severity was consistent across five COX inhibitors and multiple indication subcohorts. Our results align with earlier reports associating NSAID use with complications in RTI patients. Further research is needed to characterize the precise risk of individual COX inhibitors in COVID-19 patients.

NSAIDs and COVID-19: A Systematic Review and Meta-analysis

“…Two papers mentioning reviews in the title were identified: one related to ibuprofen and acute bacterial or viral respiratory lower tract infections [6], while the other was a narrative review of the issues involved [7]. We found no other systematic reviews on this topic, while some papers of potential interest provided no usable data [8,9]. In ClinicalTrials.gov, 22 studies cited COVID and NSAIDs, a few of which might be of interest when completed or published, i.e.…”

COVID-19 and Rheumatoid Arthritis Crosstalk: Emerging Association, Therapeutic Options and Challenges

“…Thus, the use of NSAIDs in the COVID-19 setting may delay in diagnosis of SARS-CoV-2 infection due to their antipyretic principle. However, treatment with selective COX-2 inhibitors (diclofenac, meloxicam, and celecoxib) was not found to be associated with an increase in COVID-19 severity [66]. Thus, it may be said that the effects of NSAIDs represent drug-specific risk profiles in the COVID-19 setting, and it is not worthy to mention their effects in a generalized way under a single class.…”

“…The French Society of Pharmacology and Therapeutics recommended that the use of NSAIDs be avoided for symptomatic treatment in non-severe COVID-19 cases [65]. In a recent retrospective multicentre observational study, non-selective COX inhibitors (aspirin and acetaminophen) were found to be associated with increased severity and mortality in COVID-19 patients including patients with pre-existing arthritis [66]. Fever is regarded as one of the indications of SARS-CoV-2 infection.…”

Targeting SARS-CoV-2-Platelet Interactions in COVID-19 and Vaccine-Related Thrombosis

“…A large retrospective study showed that use of COX inhibitors (aspirin, ibuprofen, naproxen, ketorolac) or paracetamol was significantly associated with more severe Covid-19 but only aspirin and paracetamol were associated with increased mortality (Reese et al, 2021). Another study found no effect on mortality with aspirin or NSAIDS but did find an increase in the combined endpoint of MI, stroke or venous thromboembolism (Sahai et al, 2020).…”