Therapeutic effect of N-acetylcysteine in severe or critical coronavirus disease 2019 pneumonia: A retrospective cohort study

Xin Jin; Yu Zhao; Xiaofei Jiang

Abstract: Observational study Therapeutic effect of N-acetylcysteine in severe or critical coronavirus disease 2019 pneumonia: A retrospective cohort study Xin Jin 1,# , Yu Zhao 2,# and Xiaofei Jiang 1 Abstract Background: Severe or critical coronavirus disease 2019 pneumonia is associated with a high mortality rate and considerable treatment cost. Although a few reports have shown that N-acetylcysteine may shorten recovery time in patients with severe acute respiratory syndrome coronavirus 2 infection, its effect on mortality or disease progression in patients with severe or critical coronavirus disease 2019 pneumonia has not been investigated. This study aimed to evaluate the effect of N-acetylcysteine on mortality or disease progression, hospital stay, and hospitalization costs in patients with severe or critical coronavirus disease 2019 pneumonia. Methods: This single-center, retrospective cohort study included 221 patients with severe or critical coronavirus disease 2019 pneumonia who were hospitalized at the Department of Respiratory and Critical Care Medicine, Huashan Hospital from December 2022 to January 2023. After 1:1 propensity score matching, 176 patients were divided into two groups based on whether oral N-acetylcysteine was administered for at least 3 days. Binary logistic regression was used to analyze the effect of N-acetylcysteine on mortality or disease progression, whereas its effect on 28- or 90-day mortality was analyzed using Cox regression. Results: Binary logistic regression analysis showed that N-acetylcysteine was associated with a reduced risk of the composite endpoint of mortality or disease progression during hospitalization (odds ratio = 0.288, 95% con fi dence interval: 0.147 -0.793, p = 0.011). However, N-acetylcysteine was not signi fi cantly associated with hospitalization costs, length of hospital stay, or the use of high- fl ow oxygen or mechanical ventilation. In addition, no signi fi cant association was observed between N-acetylcysteine use and 28- or 90-day mortality. Given the retrospective design and potential residual confounding, these fi ndings should be interpreted as exploratory. Conclusions: In this retrospective cohort study, treatment with N-acetylcysteine for at least 3 days was associated with a possible reduction in mortality or disease progression during hospitalization in patients with severe or critical coronavirus disease 2019 pneumonia. Prospective studies are needed to con fi rm these observations. Keywords N-acetylcysteine, coronavirus disease 2019 pneumonia, severe acute respiratory syndrome coronavirus 2 Received: 18 January 2026; revised: 3 June 2026; accepted: 8 June 2026 1 Emergency Department, Huashan Hospital, Fudan University, China 2 Department of Pulmonary and Critical Care Medicine, Huashan Hospital, Fudan University, China # These authors contributed equally to this study. Corresponding author: Xiaofei Jiang, Emergency Department, Huashan Hospital, Fudan University, No.12 Urumqi Middle Road, Shanghai, China. Email: sule\_jiang@126.com Journal of International Medical Research 2026, Vol. 54(6) 1 -9 © The Author(s) 2026 Article reuse guidelines: sagepub.com/journals-permissions DOI: 10.1177/03000605261463447 journals.sagepub.com/home/imr

DOI record: { "DOI": "10.1177/03000605261463447", "ISSN": [ "0300-0605", "1473-2300" ], "URL": "http://dx.doi.org/10.1177/03000605261463447", "abstract": "\n Background\n Severe or critical coronavirus disease 2019 pneumonia is associated with a high mortality rate and considerable treatment cost. Although a few reports have shown that N-acetylcysteine may shorten recovery time in patients with severe acute respiratory syndrome coronavirus 2 infection, its effect on mortality or disease progression in patients with severe or critical coronavirus disease 2019 pneumonia has not been investigated. This study aimed to evaluate the effect of N-acetylcysteine on mortality or disease progression, hospital stay, and hospitalization costs in patients with severe or critical coronavirus disease 2019 pneumonia.\n \n \n Methods\n This single-center, retrospective cohort study included 221 patients with severe or critical coronavirus disease 2019 pneumonia who were hospitalized at the Department of Respiratory and Critical Care Medicine, Huashan Hospital from December 2022 to January 2023. After 1:1 propensity score matching, 176 patients were divided into two groups based on whether oral N-acetylcysteine was administered for at least 3 days. Binary logistic regression was used to analyze the effect of N-acetylcysteine on mortality or disease progression, whereas its effect on 28- or 90-day mortality was analyzed using Cox regression.\n \n \n Results\n \n Binary logistic regression analysis showed that N-acetylcysteine was associated with a reduced risk of the composite endpoint of mortality or disease progression during hospitalization (odds ratio = 0.288, 95% confidence interval: 0.147–0.793,\n p\n = 0.011). However, N-acetylcysteine was not significantly associated with hospitalization costs, length of hospital stay, or the use of high-flow oxygen or mechanical ventilation. In addition, no significant association was observed between N-acetylcysteine use and 28- or 90-day mortality. Given the retrospective design and potential residual confounding, these findings should be interpreted as exploratory.\n \n \n \n Conclusions\n In this retrospective cohort study, treatment with N-acetylcysteine for at least 3 days was associated with a possible reduction in mortality or disease progression during hospitalization in patients with severe or critical coronavirus disease 2019 pneumonia. 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