Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.
Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study.
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DOI：
10.3389/fmed.2021.639970
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发表时间：
2021
影响因子：
3.9
通讯作者：
COVID-19 RISK and Treatments (CORIST) Collaboration
中科院分区：
文献类型：
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作者：
Di Castelnuovo A;Costanzo S;Antinori A;Berselli N;Blandi L;Bonaccio M;Bruno R;Cauda R;Gialluisi A;Guaraldi G;Menicanti L;Mennuni M;My I;Parruti A;Patti G;Perlini S;Santilli F;Signorelli C;Stefanini GG;Vergori A;Ageno W;Aiello L;Agostoni P;Al Moghazi S;Arboretti R;Aucella F;Barbieri G;Barchitta M;Bartoloni A;Bologna C;Bonfanti P;Caiano L;Carrozzi L;Cascio A;Castiglione G;Chiarito M;Ciccullo A;Cingolani A;Cipollone F;Colomba C;Colombo C;Crosta F;Dalena G;Dal Pra C;Danzi GB;D'Ardes D;de Gaetano Donati K;Di Gennaro F;Di Tano G;D'Offizi G;Filippini T;Maria Fusco F;Gaudiosi C;Gentile I;Gini G;Grandone E;Guarnieri G;Lamanna GLF;Larizza G;Leone A;Lio V;Losito AR;Maccagni G;Maitan S;Mancarella S;Manuele R;Mapelli M;Maragna R;Marra L;Maresca G;Marotta C;Mastroianni F;Mazzitelli M;Mengozzi A;Menichetti F;Milic J;Minutolo F;Molena B;Mussinelli R;Mussini C;Musso M;Odone A;Olivieri M;Pasi E;Perroni A;Petri F;Pinchera B;Pivato CA;Poletti V;Ravaglia C;Rossato M;Rossi M;Sabena A;Salinaro F;Sangiovanni V;Sanrocco C;Scorzolini L;Sgariglia R;Simeone PG;Spinicci M;Trecarichi EM;Veronesi G;Vettor R;Vianello A;Vinceti M;Visconti E;Vocciante L;De Caterina R;Iacoviello L;COVID-19 RISK and Treatments (CORIST) Collaboration
背景：蛋白酶抑制剂被认为是COVID-19患者可能的治疗药物。目的：描述COVID-19患者洛匹那韦/利托那韦（LPV/r）或达那韦/共存司他（DRV/c）使用与住院死亡率的关系。研究设计：对意大利33家医院收治的COVID-19患者进行多中心观察性研究。从医疗记录中提取药物、既往疾病、临床措施和结果。根据LPV/r、DRV/c或均不使用，将患者回顾性分为三组。时间-事件分析的主要结局是死亡。我们使用Cox比例风险模型，通过多项倾向得分获得治疗权重的逆概率。结果：在3451例患者中，33.3%的LPV/r和13.9%的DRV/c接受治疗。接受LPV/r或DRV/c治疗的患者更可能是年轻男性，c反应蛋白水平较高，而高血压、心血管、肺部或肾脏疾病的可能性较低。在调整倾向评分后，LPV/r的使用与死亡率无关（HR = 0.94, 95% CI 0.78至1.13），而DRV/c治疗与更高的死亡风险相关（HR = 1.89, 1.53至2.34，e值= 2.43）。这种风险增加在女性、老年人、COVID-19严重程度较高的患者和接受其他COVID-19药物治疗的患者中更为明显。结论：在现实生活中因COVID-19住院的意大利患者的大型队列中，使用LPV/r治疗不会改变死亡率，而DRV/c与死亡率增加相关。在观察性研究范围内，这些数据不支持在COVID-19患者中使用LPV/r或DRV/c。
Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients.