A prior meta-analysis showed that antidepressant use in major depressive disorder was associated with reduced plasma levels of several pro-inflammatory mediators, which have been associated with severe COVID-19. Recent studies also suggest that several antidepressants may inhibit acid sphingomyelinase activity, which may prevent the infection of epithelial cells with SARS-CoV-2, and that the SSRI fluoxetine may exert in-vitro antiviral effects on SARS-CoV-2. We examined the potential usefulness of antidepressant use in patients hospitalized for COVID-19 in an observational multicenter retrospective cohort study conducted at AP-HP Greater Paris University hospitals. Of 7230 adults hospitalized for COVID-19, 345 patients (4.8%) received an antidepressant within 48 h of hospital admission. The primary endpoint was a composite of intubation or death. We compared this endpoint between patients who received antidepressants and those who did not in time-to-event analyses adjusted for patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications. The primary analysis was a multivariable Cox model with inverse probability weighting. This analysis showed a significant association between antidepressant use and reduced risk of intubation or death (HR, 0.56; 95% CI, 0.43-0.73, p < 0.001). This association remained significant in multiple sensitivity analyses. Exploratory analyses suggest that this association was also significant for SSRI and non-SSRI antidepressants, and for fluoxetine, paroxetine, escitalopram, venlafaxine, and mirtazapine (all p < 0.05). These results suggest that antidepressant use could be associated with lower risk of death or intubation in patients hospitalized for COVID-19. Double-blind controlled randomized clinical trials of antidepressant medications for COVID-19 are needed.

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.