Qiu Ye, Wen Hao, Wang Haoru, Sun Wenjun, Li Guangchao, Li Shaoqiang, Wang Yan, Zhai Jingnan, Zhan Yangqing, Su Yutian, Long Zhiwei, Li Zhengtu, Ye Feng
State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Gastroenterology and Respiratory Internal Medicine Department, Guangxi Medical University Cancer Hospital, Nanning, China.
Front Pharmacol. 2024 Aug 19;15:1401658. doi: 10.3389/fphar.2024.1401658. eCollection 2024.
Nirmatrelvir-ritonavir (Paxlovid) has received emergency use authorization from the US Food and Drug Administration owing to its effectiveness and safety. However, data on the effectiveness and safety of Paxlovid use in COVID-19 patients with onset of more than 5 days are lacking.
A real-world retrospective study was performed during the outbreak involving the SARS-CoV-2 BA.5.2 subvariant. Hospitalized COVID-19 patients (including mild, moderate, severe and critical cases) were divided into three groups: Paxlovid treatment within (Group A) or more than (Group B) 5 days of COVID-19 onset and no Paxlovid treatment during more than 5 days of COVID-19 onset with only basic symptomatic treatment (Group C). Endpoints were all-cause 28-day mortality, improvement in clinical classification, and a composite endpoint of disease progression, viral load and virus elimination time. Safety was assessed by comparing adverse events reported during treatment in each group.
During the period, 248 hospitalized COVID-19 patients, including 55 in Group A, 170 in Group B, and 23 in Group C, were enrolled. There were no significant differences in the clinical classification improvement rate [80.0% (16/20) vs. 81.3% (52/64), = 1.000; 60.0% (21/35) vs. 55.7% (59/106), = 0.653, respectively] or all-cause 28-day mortality [0% (0/20) vs. 1.6% (1/64), = 1.000; 11.4% (4/35) vs. 6.6% (7/106), = 0.576, respectively] between Groups A and B for nonsevere and severe cases. However, the clinical classification improvement rate in Group B was markedly higher than that in Group C [81.3% (52/64) vs. 50.0% (6/12), = 0.049] among nonsevere cases. Cycle threshold values of the N and ORF genes in Group B were significantly increased after Paxlovid treatment [31.14 (IQR 26.81-33.93) vs. 38.14 (IQR 36.92-40.00), < 0.001; 31.33 (IQR 26.00-33.47) vs. 38.62 (IQR 35.62-40.00), < 0.001, respectively]. No significant differences in reported adverse events of neurological disease ( = 0.571), liver injury ( = 0.960) or kidney injury ( = 0.193) between Group A and Group B were found.
Paxlovid treatment within 10 days of onset can shorten the disease course of COVID-19 by reducing the viral load. Paxlovid is effective and safe in treating COVID-19 with onset of more than five or even 10 days when patients have a high viral load.
奈玛特韦-利托那韦（帕罗韦德）因其有效性和安全性已获得美国食品药品监督管理局的紧急使用授权。然而，缺乏关于帕罗韦德用于新冠病毒感染发病超过5天患者的有效性和安全性数据。
在涉及严重急性呼吸综合征冠状病毒2型BA.5.2亚型的疫情期间进行了一项真实世界回顾性研究。将住院的新冠病毒感染患者（包括轻症、中症、重症和危重症病例）分为三组：新冠病毒感染发病5天内接受帕罗韦德治疗（A组）、发病超过5天接受帕罗韦德治疗（B组）以及新冠病毒感染发病超过5天未接受帕罗韦德治疗仅进行基本对症治疗（C组）。观察终点为全因28天死亡率、临床分类改善情况以及疾病进展、病毒载量和病毒清除时间的复合终点。通过比较每组治疗期间报告的不良事件评估安全性。
在此期间，共纳入248例住院新冠病毒感染患者，其中A组55例，B组170例，C组23例。非重症和重症病例中，A组和B组的临床分类改善率[80.0%（16/20）对81.3%（52/64），P = 1.000；60.0%（21/35）对55.7%（59/106），P = 0.653]或全因28天死亡率[0%（0/20）对1.6%（1/64），P = 1.000；11.4%（4/35）对6.6%（7/106），P = 0.576]均无显著差异。然而，非重症病例中B组的临床分类改善率明显高于C组[81.3%（52/64）对50.0%（6/12），P = 0.049]。B组接受帕罗韦德治疗后N基因和开放阅读框基因的循环阈值显著升高[分别为31.14（四分位间距26.81 - 33.93）对38.14（四分位间距36.92 - 40.00），P < 0.001；31.33（四分位间距26.00 - 33.47）对38.62（四分位间距35.62 - 40.00），P < 0.001]。A组和B组报告的神经系统疾病不良事件（P = 0.571）、肝损伤（P = 0.960）或肾损伤（P = 0.193）无显著差异。
发病10天内使用帕罗韦德可通过降低病毒载量缩短新冠病毒感染病程。当患者病毒载量较高时，帕罗韦德用于治疗发病超过5天甚至10天的新冠病毒感染有效且安全。
