Blood Plasma Biomarker Discovered in Hospitalized COVID-19 Patients May Predict ARDS Severity

The compounds, known as leukotoxins and leukotoxin diols, originate from linoleic acid, the body's most abundant dietary fat. The UC Davis scientists used clinical data collected from six hospitalized patients with laboratory-confirmed SARS-CoV-2 infection and 44 healthy samples carefully chosen from the healthy control arm of a recently completed clinical study.

“The hypothesis advanced in this paper is that because the leukotoxins have been associated with serious illness and death in humans and dogs and the symptoms are those of adult respiratory distress syndrome, these compounds are biomarkers of pulmonary involvement in COVID-19,” said UC Davis distinguished professor Bruce Hammock. “We also think that it is the conversion of leukotoxin to the toxic leukotoxin diol that causes pulmonary and perivascular edema and this could be leading to the respiratory complications.”

“So the leukotoxins and leukotoxin diols,” Hammock said, “are indicators of respiratory problems in COVID-19 patients as plasma biomarkers. They also present a pathway for reducing ARDS in COVID-19 if we could inhibit the soluble epoxide hydrolase, a key regulatory enzyme involved in the metabolism of immune resolving fatty acids.”

“Different outcomes from COVID-19 infections are both terrifying from a human health perspective and fascinating from a research perspective,” said UC Davis lead author and doctoral candidate Cindy McReynolds of the Hammock lab. “Our data provide an important clue to help determine what impacts the severity of COVID-19 outcomes. Initially, we focused on the immune response and cytokine profile as important drivers in severity, but considering what we now know from our study and others in the field, lipid mediators may be the missing link to answering questions such as why some people are asymptomatic while others die, or why some disease resolves quickly while others suffer from long-haul COVID.”

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