Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS‐CoV‐2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID‐19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID‐19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time‐to‐event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow‐up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58‐0.87; p<0.001) and primary IPW (HR=0.58; 95%CI=0.46‐0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID‐19 and support the continuation of FIASMA medications in these patients. Double‐blind controlled randomized clinical trials of these medications for COVID‐19 are needed.

Objective: Preliminary data from different cohorts of small sample size or with short follow-up indicate poorer prognosis in people with obesity compared with other patients. This study aims to precisely describe the strength of association between obesity in patients hospitalized with coronavirus disease 2019 (COVID-19) and mortality and to clarify the risk according to usual cardiometabolic risk factors in a large cohort. Methods: This is a prospective cohort study including 5,795 patients aged 18 to 79 years hospitalized from February 1 to April 30, 2020, in the Paris area, with confirmed infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adjusted regression models were used to estimate the odds ratios (ORs) and 95% CIs for the mortality rate at 30 days across BMI classes, without and with imputation for missing BMI values. Results: Eight hundred ninety-one deaths had occurred at 30 days. Mortality was significantly raised in people with obesity, with the following ORs for BMI of 30 to 35 kg/m 2 , 35 to 40 kg/m 2 , and >40 kg/m 2 : 1.89 (95% CI: 1.45-2.47), 2.79 (95% CI: 1.95-3.97), and 2.55 (95% CI: 1.62-3.95), respectively (18.5-25 kg/m 2 was used as the reference class). This increase holds for all age classes. Conclusions: Obesity doubles mortality in patients hospitalized with COVID-19.

Background:We aimed to compare the efficacy of steroids alone or associated with immunosuppressive drugs for the prevention of relapse in cardiac sarcoidosis (CS). Methods: In this monocentric multidisciplinary retrospective single center study, all consecutive patients with histologically proven sarcoidosis hospitalized from January 2012 to December 2016 were considered. All patients with symptomatic CS were studied. Patients received steroids or steroids plus immunosuppressive drugs (IS) for CS treatment at diagnosis. The efficacy of each treatment strategy (steroids vs steroids + IS) was assessed by the cardiac relapse rate over follow up.Results 326 consecutive patients with histologically proven sarcoidosis were screened.Among them, 36 (11%) had symptomatic CS (20 (55.5%) men, median age at diagnosis 48.5 [22.8-76]). Twenty-four patients received steroids and 12 received steroids + IS (azathioprine n=5, methotrexate n=5, cyclophosphamide n=2) at CS diagnosis. Over a median follow up of 3.6 [1-15.2] years, 13 (36.1%) patients suffered a cardiac relapse including reduced left ventricular ejection fraction (LVEF, n=4), third degree heart block (n=2), atrio-ventricular (n=1) or ventricular (n=1) tachycardia and sudden cardiac death (n=1). Except for a higher frequency of black patients in patients receiving IS, CS features at diagnosis and median time to relapse did not significantly differ between patients who did or did not receive IS. Relapse rate was 45.8% in the steroids group versus 16.7% in the steroids+IS group (p=0.048). Conclusions:In cardiac sarcoidosis, the combination of steroids with immunosuppressive drugs might reduce the risk of cardiac relapse, as compared to steroids alone.