Sphingolipid and glycerophospholipid profiling in post-acute sequelae of SARS-CoV-2 infection

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 infection (PASC) is a heterogeneous multisystemic condition with unclear pathogenesis. Emerging evidence suggests that the disruption in metabolism, including lipid metabolism, can be involved in the pathogenesis of coronavirus disease 2019 (COVID-19). We previously measured the bioactive lipids in acute COVID-19, and we hypothesized that bioactive lipid dysregulation play a role in PASC pathogenesis. We conducted targeted LC-MS/MS analysis of sphingolipids and glycerophospholipids in serum samples from individuals with acute-phase COVID-19, including those who developed PASC, alongside healthy controls. We systematically examined lipidomic changes in serum samples, including analyses using linear mixed model, and found that no sphingolipid or glycerophospholipid species differed between the COVID-19 and PASC groups. Although these results are exploratory, the group x time interaction in the linear mixed model suggested that phosphatidylglycerol (PG) may represent a bioactive lipid distinguishing the COVID-19 and PASC groups. Given the small PASC sample size and that the signal was detected only at specific time points, these findings are hypothesis generating and should be confirmed in larger, adequately powered, and independently validated cohorts.