Association between long COVID and nonsteroidal anti-inflammatory drug use by patients with acute-phase COVID-19: A nationwide Korea National Health Insurance Service cohort study

Abstract

Introduction Long coronavirus disease (COVID) poses a significant burden following the coronavirus disease 2019 (COVID-19) pandemic. Debate persists regarding the impact of nonsteroidal anti-inflammatory drug (NSAID) administration during acute-phase COVID-19 on the development of long COVID. Hence, this study aimed to assess the potential association between NSAID use and long COVID using data from patients with COVID-19 in Korea's National Health Insurance Service. Methods This nested case-control study defined the study cohort as patients diagnosed with COVID- 19 for the first time between 2020 and 2021. The primary exposure investigated was NSAID prescriptions within 14 days of the initial COVID-19 diagnosis. We used propensity score matching to create three control patients matched to each patient in the NSAID exposure group. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after the adjustment for demographics, Charlson Comorbidity Index, and existing comorbidities. Results Among the 225,458 patients diagnosed with COVID-19, we analyzed data from 254 with long COVID. The adjusted OR (aOR) for NSAID exposure during acute-phase COVID-19 was higher in long COVID cases versus controls (aOR, 1.79; 95% CI, 1.00-3.19), suggesting a potential relationship. However, a sensitivity analysis revealed that the increased odds of NSAID exposure in the acute phase became statistically non-significant (aOR, 1.64; 95% CI, 0.90-2.99) when COVID-19 self-quarantine duration was included as a covariate. Additionally, acetaminophen exposure was not significantly associated (aOR, 1.12; 95% CI, 0.75-1.68), while antiviral drugs demonstrated a stronger association (aOR, 3.75; 95% CI, 1.66-8.48). Conclusion Although this study suggests a possible link between NSAID use in the acute COVID-19 infection stage and a higher risk of long COVID as well as both NSAID and acetaminophen use during the chronic COVID-19 period and a lower risk of long COVID, the association was not statistically significant. Further research is needed to determine the causal relationship between the various treatment options for acute COVID-19 and the development of long COVID.