Association Between Ibuprofen Exposure and Severe COVID-19 Infection: A Nationwide Register-Based Study

<p>Background: Initially, the World Health Organization (WHO) and national health boards issued a warning against NSAID use in corona virus disease 2019 (COVID-19) patients and recommended that paracetamol or acetaminophen instead should be administered. However, later and current WHO and European Medicine Agency recommendations do not call for avoidance of ibuprofen in COVID-19 patients. Given the current uncertainty of drug safety for NSAID use in patients with COVID-19, we performed a nationwide register-based study on the association of recent ibuprofen exposure and COVID-19 severity. </p><p>Methods: Using national administrative databases, we identified COVID-19 patients in Denmark between end of February 2020 and April 2, 2020. Patients <30 years of age and heart failure, for whom ibuprofen is not recommended, were excluded. Ibuprofen exposure was defined using the Danish National Prescription Registry, where we had information until January 31, 2020. Endpoint was a composite of severe COVID-19 diagnosis with acute respiratory syndrome, intensive care unit admission or death. </p><p>Results: Among 1,872 patients, 46 (2.5%) were exposed to ibuprofen prior to COVID-19 infection. Patients with recent ibuprofen exposure tended to be older and more likely to have hypertension, diabetes, myocardial infarction, chronic obstructive pulmonary disease, and cancer, though all insignificant (P>0.05). When adjusting for these covariates, odds ratio was 1.57 [95% CI 0.72-3.38], with 12 ibuprofen-exposed patients meeting the endpoint (26.1% [95% CI 13.4-38.8%]) versus 272 unexposed patients (14.9% [95% CI 13.4-16.4%]), P=0.15. </p><p>Conclusion: The association between ibuprofen and severe COVID-19 was insignificant, although with a trend towards increased disease severity risk.</p>