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In medRxiv : the preprint server for health sciences

There is an urgent need to identify cellular and molecular mechanisms responsible for severe COVID-19 disease accompanied by multiple organ failure and high mortality rates. Here, we performed untargeted/targeted lipidomics and focused biochemistry on 127 patient plasma samples, and showed high levels of circulating, enzymatically active secreted phospholipase A 2 Group IIA (sPLA 2 -IIA) in severe and fatal COVID-19 disease compared with uninfected patients or mild illness. Machine learning demonstrated that sPLA 2 -IIA effectively stratifies severe from fatal COVID-19 disease. We further introduce a PLA-BUN index that combines sPLA 2 -IIA and blood urea nitrogen (BUN) threshold levels as a critical risk factor for mitochondrial dysfunction, sustained inflammatory injury and lethal COVID-19. With the availability of clinically tested inhibitors of sPLA 2 -IIA, our study opens the door to a precision intervention using indices discovered here to reduce COVID-19 mortality.

Snider Justin M, You Jeehyun Karen, Wang Xia, Snider Ashley J, Hallmark Brian, Seeds Michael C, Sergeant Susan, Johnstone Laurel, Wang Qiuming, Sprissler Ryan, Zhang Hao Helen, Luberto Chiara, Kew Richard R, Hannun Yusuf A, McCall Charles E, Yao Guang, Del Poeta Maurizio, Chilton Floyd H