We read with interest the recent meta-analysis assessing the clinical efficacy and safety of nirmatrelvir plus ritonavir (NMV-r) in the treatment of patients with COVID-19. 1 Based on the analysis of 13 studies involving 186,306 patients, the authors concluded that NMV-r was effective in reducing the mortality (odds ratio [OR], 0.12; 95% CI, 0.04-0.36) and the risk of hospitalization (OR, 0.32; 95% CI, 0.13-0.75) for patients with COVID-19. 1 These findings indicated that NMV-r could be a useful antiviral treatment for COVID-19. However, it was also noted that a significant proportion of individuals who have recovered from acute COVID-19 may experience long-term complications, a phenomenon referred to as long COVID. 2, 3 Moreover, long COVID has been shown to have a negative impact on both physical and mental well-being. 2, 3 Therefore, how to prevent the development of long COVID has become a serious concern. In fact, one study showed the promising role of NMV-r in reducing the risks of post-acute COVID-19 sequelae, such as dysrhythmia and ischemic heart disease, deep vein thrombosis, pulmonary embolism, fatigue, liver disease, acute kidney disease, muscle pain, neurocognitive impairment, and shortness of breath. 4 Study from Taquet et al. showed that compared to a matched cohort with influenza, COVID-19 patients had a higher incidence of new seizures or epilepsy diagnoses in the six months following their illness, particularly among those who were not hospitalized. 5 However, the preventive effect of NMV-r on the risk of longterm complications–epilepsy and seizure remained unknown. Therefore, we conducted this retrospective cohort study to evaluate the impact of NMV-r on the long-term risks of epilepsy and seizure.

This study utilized the database from the TriNetX Research Network-a global health-collaborative clinical-research platform, which provided real-time multi-healthcare organization (HCO) and multinational healthcare-associated information. 6 The search and data curation was conducted on January 7, 2023. Initially, we created a cohort of non-hospitalized patients with COVID-19 from 74 HCOs, as previously described. 7 The inclusion criteria were (a) they had at least two times of medical encounters with healthcare organizations from March 1, 2020, to January 1, 2022;(b) people who were older than 18 years old;(c) they had a new diagnosis of COVID-19. Exclusion criteria included (a) the patients who had a prior history of epilepsy or seizure,(b) patients who ever received remdesivir, molnupiravir, monoclonal antibody or convalescent plasma, and (c) COVID-19 patients requiring hospitalization. Thereafter, we divided this population into two cohorts based on