AP-HP, Hôpital Corentin-Celton, DMU Psychiatrie et Addictologie, Département de Psychiatrie, Issy-les-Moulineaux, France.
Université de Paris, Paris, France.
Transl Psychiatry. 2022 Mar 3;12(1):90. doi: 10.1038/s41398-022-01804-5.
The acid sphingomyelinase (ASM)/ceramide system may provide a useful framework for better understanding SARS-CoV-2 infection and the repurposing of psychotropic medications functionally inhibiting the acid sphingomyelinase/ceramide system (named FIASMA psychotropic medications) against COVID-19. We examined the potential usefulness of FIASMA psychotropic medications in patients with psychiatric disorders hospitalized for severe COVID-19, in an observational multicenter study conducted at Greater Paris University hospitals. Of 545 adult inpatients, 164 (30.1%) received a FIASMA psychotropic medication upon hospital admission for COVID-19. We compared the composite endpoint of intubation or death between patients who received a psychotropic FIASMA medication at baseline and those who did not in time-to-event analyses adjusted for sociodemographic characteristics, psychiatric and other medical comorbidity, and other medications. FIASMA psychotropic medication use at baseline was significantly associated with reduced risk of intubation or death in both crude (HR = 0.42; 95%CI = 0.31-0.57; p < 0.01) and primary inverse probability weighting (IPW) (HR = 0.50; 95%CI = 0.37-0.67; p < 0.01) analyses. This association was not specific to one FIASMA psychotropic class or medication. Patients taking a FIASMA antidepressant at baseline had a significantly reduced risk of intubation or death compared with those taking a non-FIASMA antidepressant at baseline in both crude (HR = 0.57; 95%CI = 0.38-0.86; p < 0.01) and primary IPW (HR = 0.57; 95%CI = 0.37-0.87; p < 0.01) analyses. These associations remained significant in multiple sensitivity analyses. Our results show the potential importance of the ASM/ceramide system framework in COVID-19 and support the continuation of FIASMA psychotropic medications in these patients and the need of large- scale clinical trials evaluating FIASMA medications, and particularly FIASMA antidepressants, against COVID-19.
酸性鞘磷脂酶 (ASM)/神经酰胺系统可能为更好地理解 SARS-CoV-2 感染以及重新利用在功能上抑制酸性鞘磷脂酶/神经酰胺系统的精神药物（称为 FIASMA 精神药物）提供有用的框架，以对抗 COVID-19。我们在巴黎大区大学医院进行的一项观察性多中心研究中，检查了 FIASMA 精神药物在因严重 COVID-19 住院的精神障碍患者中的潜在用途。在 545 名成年住院患者中，有 164 名（30.1%）在因 COVID-19 入院时接受了 FIASMA 精神药物治疗。我们在时间事件分析中比较了在基线时接受精神药物 FIASMA 治疗的患者和未接受治疗的患者的插管或死亡的复合终点，这些分析针对社会人口统计学特征、精神和其他医学合并症以及其他药物进行了调整。在未调整和主要逆概率加权（IPW）分析中，基线时使用 FIASMA 精神药物与插管或死亡风险降低显著相关（未调整 HR=0.42；95%CI=0.31-0.57；p<0.01；主要 IPW HR=0.50；95%CI=0.37-0.67；p<0.01）。这种关联并不是特定于一种 FIASMA 精神药物类别或药物。与基线时服用非 FIASMA 抗抑郁药的患者相比，基线时服用 FIASMA 抗抑郁药的患者插管或死亡的风险显著降低，在未调整（HR=0.57；95%CI=0.38-0.86；p<0.01）和主要 IPW（HR=0.57；95%CI=0.37-0.87；p<0.01）分析中均如此。在多项敏感性分析中，这些关联仍然显著。我们的结果表明 ASM/神经酰胺系统框架在 COVID-19 中的重要性，并支持在这些患者中继续使用 FIASMA 精神药物，以及需要进行大规模临床试验来评估 FIASMA 药物，特别是 FIASMA 抗抑郁药，以对抗 COVID-19。
