Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2:...

Area of Science:

• Biochemistry
• Infectious Diseases
• Pharmacology

Background:

• The acid sphingomyelinase (ASM)/ceramide system is implicated in SARS-CoV-2 infection.
• In vitro studies suggest that inhibiting this system reduces viral entry into cells.

Purpose of the Study:

• To investigate the association between the use of medications functionally inhibiting acid sphingomyelinase (FIASMA) and 28-day all-cause mortality in hospitalized COVID-19 patients.

Main Methods:

• A multicenter retrospective observational study of 72,105 adult patients with laboratory-confirmed SARS-CoV-2 infection.
• A 1:1 matched analytic sample (N = 9714) was created based on clinical characteristics, disease severity, and other medications.
• Univariate Cox regression analysis was used to assess the association between FIASMA use and mortality.

Main Results:

• FIASMA medication use at hospital admission was associated with a significantly lower risk of 28-day all-cause mortality (HR = 0.80; 95% CI = 0.72-0.88; p < 0.001).
• The association remained significant and substantial in the matched cohort.

Conclusions:

• The use of FIASMA medications is associated with reduced 28-day mortality in adult patients hospitalized with COVID-19.
• These findings support the continued use of FIASMA medications during SARS-CoV-2 infection treatment.
• Randomized clinical trials, particularly with fluoxetine, escitalopram, and amlodipine, are warranted to confirm these results.