Hoertel Nicolas, Rezaei Katayoun, Sánchez-Rico Marina, Delgado-Álvarez Alfonso, Kornhuber Johannes, Gulbins Erich, Olfson Mark, Ouazana-Vedrines Charles, Carpinteiro Alexander, Cougoule Céline, Becker Katrin Anne, Alvarado Jesús M, Limosin Frédéric
INSERM U1266, Université Paris Cité, F-75014 Paris, France.
Service de Psychiatrie et Addictologie de l'Adulte et du Sujet Agé, DMU Psychiatrie et Addictologie, Hôpital Corentin-Celton, GHU APHP.Centre, F-92130 Issy-les-Moulineaux, France.
Pharmaceuticals (Basel). 2023 Aug 4;16(8):1107. doi: 10.3390/ph16081107.
Prior evidence indicates the potential central role of the acid sphingomyelinase (ASM)/ceramide system in the infection of cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients with laboratory-confirmed SARS-CoV-2 infection who were admitted to 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 to 31 August 2022. We examined the association between the ongoing use of medications functionally inhibiting acid sphingomyelinase (FIASMA), which reduces the infection of cells with SARS-CoV-2 in vitro, upon hospital admission with 28-day all-cause mortality in a 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other medications (N = 9714). The univariate Cox regression model of the matched analytic sample showed that FIASMA medication use at admission was associated with significantly lower risks of 28-day mortality (HR = 0.80; 95% CI = 0.72-0.88; < 0.001). In this multicenter observational study, the use of FIASMA medications was significantly and substantially associated with reduced 28-day mortality among adult patients hospitalized with COVID-19. These findings support the continuation of these medications during the treatment of SARS-CoV-2 infections. Randomized clinical trials (RCTs) are needed to confirm these results, starting with the molecules with the greatest effect size in the study, e.g., fluoxetine, escitalopram, and amlodipine.
先前的证据表明酸性鞘磷脂酶（ASM）/神经酰胺系统在细胞感染严重急性呼吸综合征冠状病毒2（SARS-CoV-2）中可能发挥核心作用。我们进行了一项多中心回顾性观察研究，纳入了2020年5月2日至2022年8月31日期间在巴黎公共援助医院集团（AP-HP）的36家医院住院的72105例实验室确诊的SARS-CoV-2感染成年患者。我们以1:1的比例，基于临床特征、疾病严重程度和其他药物，对一个匹配分析样本（N = 9714）进行研究，考察入院时正在使用功能性抑制酸性鞘磷脂酶（FIASMA）的药物（该药物在体外可减少细胞感染SARS-CoV-2）与28天全因死亡率之间的关联。匹配分析样本的单变量Cox回归模型显示，入院时使用FIASMA药物与28天死亡率风险显著降低相关（风险比[HR] = 0.80；95%置信区间[CI] = 0.72 - 0.88；P < 0.001）。在这项多中心观察研究中，使用FIASMA药物与新冠肺炎住院成年患者28天死亡率显著且大幅降低相关。这些发现支持在SARS-CoV-2感染治疗期间继续使用这些药物。需要进行随机临床试验（RCT）来证实这些结果，首先从研究中效应量最大的分子开始，例如氟西汀、艾司西酞普兰和氨氯地平。
