# Plasma Ceramides Levels in Severe COVID-19 Disease: Correlations with Survival

## TL;DR

This study found that plasma ceramides in severe COVID-19 patients show unique patterns linked to survival, differing from their role in chronic diseases.

## Contribution

The study reveals novel temporal patterns of ceramides in severe COVID-19 and their inverse correlation with inflammatory markers.

## Key findings

- Nonsurvivors had higher initial ceramide levels followed by a decline compared to survivors.
- Ceramides showed inverse trends with standard inflammatory markers like CRP and ferritin.
- Ceramide patterns in COVID-19 differ from those in chronic diseases like cardiometabolic disorders.

## Abstract

Dysregulated inflammatory processes have been associated with severe COVID-19 disease. Ceramides, bioactive lipids involved in inflammatory signaling, have been utilized to predict outcomes in chronic cardiometabolic diseases and pancreatic cancer, but their role in COVID-19 remains unknown.

This observational study prospectively enrolled patients with COVID-19 disease who required intubation and mechanical ventilation at a Midwestern academic hospital between August 2020 and March 2021. Plasma ceramides 16:0 (C16), 22:0 (C22), and 24:0 (C24) and inflammatory markers (CRP, ESR, D-Dimer, and ferritin) were collected and organized weekly from symptom onset for up to 6 weeks. Patients were grouped by in-hospital mortality status. Linear mixed-effects models assessed temporal trends and associations between ceramides, inflammatory markers, and clinical outcomes.

We enrolled 53 patients with COVID-19. Demographic and clinical characteristics were similar between survival groups, except nonsurvivors more frequently received convalescent plasma (77% vs 44%, P = .04). C16, C22, and C24 followed similar temporal trajectories to each other, but demonstrated an inverse pattern when compared with other inflammatory markers. Nonsurvivors demonstrated higher plasma levels of all the ceramide species in the first week of illness, followed by lower levels compared with survivors in subsequent weeks.

The synchronous trajectories of C16, C22, and C24 differ from patterns reported in chronic disease and suggest their behavior may vary with disease acuity. Their inverse trend with standard inflammatory markers resembles the behavior of negative acute-phase reactants. Further research into ceramide flux dynamics in the acute-to-subacute phase of disease is needed.

Plasma ceramides levels in severe COVID-19 display distinct patterns compared with those observed in chronic cardiometabolic diseases, where ceramides are established prognostic indicators. Further investigation is needed to understand their potential clinical and prognostic role as inflammatory biomarkers.