Comprehensive metabolic modulations of sphingolipids are promising severity indicators in COVID‐19

Abstract

The COVID‐19 pandemic, caused by SARS‐CoV‐2, has had a significant worldwide impact, affecting millions of people. COVID‐19 is characterized by a heterogenous clinical phenotype, potentially involving hyperinflammation and prolonged tissue damage, although the exact underlying mechanisms are yet to be fully understood. Sphingolipid metabolites, which govern cell survival and proliferation, have emerged as key players in inflammatory signaling and cytokine responses. Given the complex metabolic pathway of sphingolipids, this study aimed to understand their potential role in the pathogenesis of COVID‐19. We conducted a comprehensive examination of sphingolipid modulations across groups classified based on disease severity, incorporating a time‐course in serum and urine samples. Several sphingolipids, including sphingosine, lactosylceramide, and hexosylceramide, emerged as promising indicators of COVID‐19 severity, as validated by correlation analyses conducted on both serum and urine samples. Other sphingolipids, such as sphingosine 1‐phosphate, ceramides, and deoxy‐dihydroceramides, decreased in both COVID‐19 patients and individuals with non‐COVID infectious diseases. This suggests that these sphingolipids are not specifically associated with COVID‐19 but rather with pathological conditions caused by infectious diseases. Our analysis of urine samples revealed elevated levels of various sphingolipids, with changes dependent on disease severity, potentially highlighting the acute kidney injury associated with COVID‐19. This study illuminates the intricate relationship between disturbed sphingolipid metabolism, COVID‐19 severity, and clinical factors. These findings provide valuable insights into the broader landscape of inflammatory diseases.