Temporal associations of plasma levels of the secreted phospholipase A₂ family and mortality in severe COVID-19

Previous research suggests that group IIA-secreted phospholipase A₂ (sPLA₂-IIA) plays a role in and predicts lethal COVID-19 disease. The current study reanalyzed a longitudinal proteomic data set to determine the temporal relationship between levels of several members of a family of sPLA₂ isoforms and the severity of COVID-19 in 214 ICU patients. The levels of six secreted PLA₂ isoforms, sPLA₂-IIA, sPLA₂-V, sPLA₂-X, sPLA₂-IB, sPLA₂-IIC, and sPLA₂-XVI, increased over the first 7 ICU days in those who succumbed to the disease but attenuated over the same time period in survivors. In contrast, a reversed pattern in sPLA₂-IID and sPLA₂-XIIB levels over 7 days suggests a protective role of these two isoforms. Furthermore, decision tree models demonstrated that sPLA₂-IIA outperformed top-ranked cytokines and chemokines as a predictor of patient outcome. Taken together, proteomic analysis revealed temporal sPLA₂ patterns that reflect the critical roles of sPLA₂ isoforms in severe COVID-19 disease.