Yale Researchers Identify Blood Biomarkers That Can Actually Predict COVID-19 Severity And Outcomes
A multidisciplinary team of researchers from Yale University have actually identified a series of COVID-19 blood biomarkers
that can actually predict the disease severity and outcomes in COVID-19 patients.
Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood.
The study team carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients.
Utilizing Artificial intelligence or AI via a machine learning algorithm, the study team identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates.
The study findings suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.
The study findings were published in the peer reviewed journal: Blood Advances. https://ashpublications.org/bloodadvances/article/5/5/1164/475293/A-neutrophil-activation-signature-predicts
Typically when patients with COVID-19 arrive in emergency rooms, there are relatively few ways for doctors to predict which ones are more likely to become critically ill and require intensive care and which ones are more likely to enjoy a quick recovery.
The new Yale study could help them identify important early clues. In a recent study, researchers report that a series of biomarkers, or biological signals, associated with white blood cell activation and obesity can predict severe outcomes in COVID-19 patients.
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 told Thailand Medical News, "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."
In the past, 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.
The study team used proteomic profiling ie a screen for multiple proteins withi
n 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 study team also analyzed clinical data for over 3,000 additional patients with COVID-19 within the Yale New Haven Hospital system.
The team 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.
Importantly, 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.
Study author Dr Alfred Lee, associate professor of medicine in hematology, director of the Yale Medical Oncology-Hematology Fellowship Program, and a member of the Yale Cancer Center added, "This is one of the first demonstrations that a set of biomarkers in the blood of COVID patients can predict eventual ICU admission, even before such patients become critically ill."
The study team stressed that having early knowledge of these indicators could significantly improve patient treatment.
Dr Hyung Chun commented, “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."
The Yale research also underscores the connection between COVID-19 and obesity. The Centers for Disease Control and Prevention notes that obesity and severe obesity increase risk of severe illness from COVID-19. Obesity triples the risk of hospitalization from COVID-19, and levels of body mass index has been found to correlate with the risk of death from COVID-19.
Typically neutrophils are inflammatory cells, said Dr Lee, so it makes sense that they would be elevated in the context of both obesity which involves chronic, low-grade inflammation and COVID-19, which causes hyperinflammation in the most severe cases, leading to tissue damage and organ failure.
Dr Lee, added, "There are also signs that neutrophils might participate in thrombosis or blood clotting, another troubling hallmark of COVID-19.”
The study team will expand their study into the relationship between biomarkers and COVID-19 by looking at patients who have recovered from acute illness.
Dr Chun added, "We are hoping these findings motivate other groups to look at their own patient populations."
The study team that they'll need additional validation studies that would support developing diagnostic tests for these biomarkers.
The study involved collaborators from across many different Yale departments, including Dr Matthew L. Meizlish, an M.D.-Ph.D. student; Dr Alex Pine, an assistant professor of medicine in hematology and staff physician at the VA Medical Center in West Haven; Dr Jason Bishai, a graduate student; Dr Hanming Zhang and Dr C-Hong Chang, postdoctoral fellows; and D David van Djik, an assistant professor of medicine in cardiology.
Dr Lee added, "The evolution of our findings really shows the power of collaboration, which has emerged as one hopeful aspect of this devastating pandemic that we will continue to harness for the benefit of the patients.”
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