Long-term N-Acetylcysteine Treatment Accelerates Improvement in Patient-Reported Outcomes for COVID-19 Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

ObjectivesThe coronavirus disease 2019 (COVID-19) pandemic has necessitated the urgent investigation of effective long-term therapeutic agents. This study aimed to evaluate the definitive, long-term causal effect of N-acetylcysteine (NAC) treatment on patient-reported outcomes (PRO) in patients with COVID-19 from hospital admission to six months after discharge. DesignProspective, multi-center, randomized, double-blind, placebo-controlled trial (RCT). SettingFive COVID-19-designated hospitals, including the Fourth Peoples Hospital, Taiyuan City, China. ParticipantsSixty-three confirmed COVID-19 patients were randomly assigned (1:1 ratio) to the NAC-treatment group (n=32) or the placebo control group (n=31). Both groups received conventional treatment. The NAC group received 600 mg oral NAC twice/day, while the control group received an identical-looking placebo. Both regimens were continued post-discharge for a total of six months. Main Outcome MeasuresPatients were followed up at discharge and at 1, 3, and 6 months after discharge. Patient-reported outcome was evaluated using the St. Georges Respiratory Questionnaire (SGRQ). ResultsBaseline characteristics were balanced between the two groups. Multivariate analysis using the Generalized Estimation Equation (GEE) indicated that NAC treatment, disease severity, and follow-up duration significantly influenced the total SGRQ score. Crucially, the interaction between NAC treatment and follow-up duration was statistically significant ({beta}=-0.436, P=0.004). ConclusionNAC treatment leads to a significantly more rapid decrease in the total SGRQ patient score compared to placebo. This RCT provides causal evidence that the long-term use of NAC accelerates the improvement in the health-related quality of life (HRQoL) of patients recovering from COVID-19. Trial RegistrationEvaluation of clinical effect of NAC on lung protection in COVID-19 patients. (www.chictr.org.cn; number: ChiCTR2100049355).