ABSTRACT
BACKGROUND: Prior research suggests that psychiatric disorders could be linked to increased mortality among patients with COVID-19. However, whether all or specific psychiatric disorders are intrinsic risk factors of death in COVID-19, or whether these associations reflect the greater prevalence of medical risk factors in people with psychiatric disorders, has yet to be evaluated. METHODS: We performed an observational multicenter retrospective cohort study to examine the association between psychiatric disorders and mortality among patients hospitalized for laboratory-confirmed COVID-19 at 36 Greater Paris University hospitals. RESULTS: Of 15,168 adult patients, 857 (5.7%) had an ICD-10 diagnosis of psychiatric disorder. Over a mean follow-up of 14.6 days (SD=17.9), death occurred in 326/857 (38.0%) patients with a diagnosis of psychiatric disorder versus 1,276/14,311 (8.9%) in patients without such a diagnosis (OR=6.27; 95%CI=5.40-7.28; p<0.01). When adjusting for age, sex, hospital, current smoking status, and medications according to compassionate use or as part of a clinical trial, this association remained significant (AOR=3.27; 95%CI=2.78-3.85; p<0.01). However, additional adjustments for obesity and number of medical conditions resulted in a non-significant association (AOR=1.02; 95%CI=0.84-1.23; p=0.86). Exploratory analyses following the same adjustments suggest that a diagnosis of mood disorders was significantly associated with reduced mortality, which might be explained by the use of antidepressants. CONCLUSIONS: These findings suggest that the increased risk of COVID-19-related mortality in individuals with psychiatric disorders hospitalized for COVID-19 might be explained by the greater number of medical conditions and the higher prevalence of obesity in this population, but not by the underlying psychiatric disease.
ABSTRACT
Sphingosine has been shown to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown whether sphingosine can be also employed to prevent viral infections. To test this hypothesis, we analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivo human epithelial cells with pseudoviral particles expressing SARS-CoV-2 spike (pp-VSV-SARS-CoV-2 spike) that served as a bona fide system mimicking SARS-CoV-2 infection. We demonstrate that exogenously applied sphingosine suspended in 0.9% NaCl prevents cellular infection with pp-SARS-CoV-2 spike. Pretreatment of cultured Vero epithelial cells or freshly isolated human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with pp-VSV-SARS-CoV-2 spike. Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS-CoV-2, and prevents the interaction of the receptor-binding domain of the viral spike protein with ACE2. These data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor. Our data also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for coronavirus disease-19.