Blood Tests Can Predict ICU Admission Even Before COVID-19 Patients Become Critically Ill

Previously, a few laboratory studies had identified possible indicators of severe COVID-19, including D-dimer levels, a measure of blood coagulation, and levels of proteins known as cytokines, which are released as part of inflammatory responses in the body. However, until now, no laboratory marker could predict which patients with COVID-19 would eventually become critically ill prior to showing clinical signs and symptoms of severe disease.

For the new study, Yale researchers used proteomic profiling - a screen for multiple proteins within the blood — to analyze samples taken from 100 patients who would go on to experience different levels of COVID-19 severity. In all cases, the blood samples were collected on the patients’ first day of admission. The researchers also analyzed clinical data for over 3,000 additional patients with COVID-19 within the Yale New Haven Hospital system. They found that five proteins (resistin, lipocalin-2, HGF, IL-8, and G-CSF) that are associated with neutrophils, a type of white blood cell, were elevated in the COVID-19 patients who later became critically ill. Many of these proteins had previously been associated with obesity but not with COVID-19 or other viral illnesses.

Notably, the elevated neutrophil biomarkers for patients who would go on to experience more serious symptoms were evident before those symptoms appeared. All COVID-19 patients who were admitted or transferred to the ICU had elevated neutrophil activation markers, while these biomarkers remained low for patients who never developed severe illness. None of the patients with lower neutrophil biomarker levels died. Having early knowledge of these indicators could significantly improve patient treatment, the researchers said.

“Patients with high levels of these markers were much more like to require care in the intensive care unit, require ventilation, or die due to their COVID-19,” said Dr. Hyung Chun, the lead author, an associate professor of medicine in cardiovascular medicine and pathology and director of translational research at the Yale Pulmonary Vascular Disease Program. “If a diagnostic test [for these biomarkers] could be ordered early, it could give us a better sense of who is more likely to become critically ill and will benefit from a higher level of care and consideration for therapies that affect the immune system early on in their hospitalization. Many of these drugs do carry potential side effects, and these tests may help identify those patients who would benefit the most.”

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