PDF(Pubmed)
Abstract：
BACKGROUND: There is an urgent need for therapeutic strategies for inpatients with severe or critical COVID-19. The evaluation of the clinical benefits of nirmatrelvir and ritonavir (Nmr/r) for these patients beyond five days of symptom onset is insufficient.
METHODS: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated.
RESULTS: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited.
CONCLUSIONS: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.
METHODS: A new propensity score-matched cohort was constructed by using multicenter data from 6695 adult inpatients with COVID-19 from December 2022 to February 2023 in China after the epidemic control measures were lifted across the country. The severity of disease of the inpatients was based on the tenth trial edition of the Guidelines on the Diagnosis and Treatment of COVID-19 in China. The symptom onset of 1870 enrolled severe or critical inpatients was beyond five days, and they received either Nmr/r plus standard treatment or only standard care. The ratio of patients whose SOFA score improved more than 2 points, crucial respiratory endpoints, changes in inflammatory markers, safety on the seventh day following the initiation of Nmr/r treatment, and length of hospital stay were evaluated.
RESULTS: In the Nmr/r group, on Day 7, the number of patients with an improvement in SOFA score ≥ 2 was much greater than that in the standard treatment group (P = 0.024) without a significant decrease in glomerular filtration rate (P = 0.815). Additionally, the rate of new intubation was lower (P = 0.004) and the no intubation days were higher (P = 0.003) in the first 7 days in the Nmr/r group. Other clinical benefits were limited.
CONCLUSIONS: Our study may provide new insight that inpatients with severe or critical COVID-19 beyond five days of symptom onset benefit from Nmr/r. Future studies, particularly randomized controlled trials, are necessary to verify the above findings.
摘要：
背景：对于重症或危重症COVID-19的住院患者，迫切需要治疗策略。对这些患者症状发作五天后使用尼马特雷韦和利托那韦（Nmr/r）的临床益处的评估不足。
方法：使用2022年12月至2023年2月在中国取消疫情控制措施后的6695名COVID-19成年住院患者的多中心数据，构建了一个新的倾向评分匹配队列。住院患者的病情严重程度根据中国《COVID-19诊断和治疗指南》第十期试验。1870名重症或危重住院患者的症状发作超过五天，他们要么接受Nmr/r加标准治疗，要么只接受标准治疗。SOFA评分提高2分以上的患者比例,关键的呼吸终点，炎症标志物的变化，在开始Nmr/r治疗后的第七天的安全性，并评估住院时间。
结果：在Nmr/r组中，第7天,SOFA评分改善≥2的患者数量远大于标准治疗组(P=0.024),肾小球滤过率无显著下降(P=0.815).此外,Nmr/r组前7天的新插管率较低(P=0.004),无插管天数较高(P=0.003).其他临床获益有限。
结论：我们的研究可能提供新的见解，即症状发作超过五天的重症或重症COVID-19患者可从Nmr/r中受益。未来的研究，特别是随机对照试验，有必要验证上述发现。
方法：使用2022年12月至2023年2月在中国取消疫情控制措施后的6695名COVID-19成年住院患者的多中心数据，构建了一个新的倾向评分匹配队列。住院患者的病情严重程度根据中国《COVID-19诊断和治疗指南》第十期试验。1870名重症或危重住院患者的症状发作超过五天，他们要么接受Nmr/r加标准治疗，要么只接受标准治疗。SOFA评分提高2分以上的患者比例,关键的呼吸终点，炎症标志物的变化，在开始Nmr/r治疗后的第七天的安全性，并评估住院时间。
结果：在Nmr/r组中，第7天,SOFA评分改善≥2的患者数量远大于标准治疗组(P=0.024),肾小球滤过率无显著下降(P=0.815).此外,Nmr/r组前7天的新插管率较低(P=0.004),无插管天数较高(P=0.003).其他临床获益有限。
结论：我们的研究可能提供新的见解，即症状发作超过五天的重症或重症COVID-19患者可从Nmr/r中受益。未来的研究，特别是随机对照试验，有必要验证上述发现。
