- A study indicates that the blood levels of five proteins among people hospitalized for COVID-19 are higher in those in need of critical care.
- These proteins are associated with a type of immune cell that can promote excessive inflammation and blood clotting in the lungs.
- Some of the same proteins are at elevated levels in people with obesity.
- If further studies confirm the findings, the discovery could lead to new tests and treatments for severe COVID-19.
According to the Centers for Disease Control and Prevention (CDC), approximately 81% of people with COVID-19 develop only mild or moderate symptoms, such as fever and cough.
However, about 14% of all patients develop breathing problems and low oxygen levels in the blood.
About 5% become critically ill and may need treatment in an intensive care unit for acute respiratory distress and multiple organ failure.
Previous research has implicated the following risk factors in the development of severe COVID-19:
- immune signaling molecules called cytokines
- two types of immune cells: monocytes and macrophages
- a blood clotting factor
However, it remains unclear why some people recover with serious illnesses, while others become critically ill.
In a new study, researchers at the Yale School of Medicine in New Haven, CT, showed that levels of five protein biomarkers in the blood of COVID-19 patients in the hospital strongly predict who will become critically ill.
All five proteins play a role in activating another type of immune cell, known as a neutrophil.
‘As a diagnostic test [for these biomarkers] ‘can be ordered early, it can give us a better idea of who is more likely to become critically ill and will benefit from a higher level of care and treatment for therapies that affect the immune system early in their hospitalization,’ ‘says lead author Dr. Hyung Chun, MD, associate professor of cardiovascular medicine and pathology and director of translational research at the Yale Pulmonary Vascular Disease Program.
“Many of these drugs have potential side effects, and these tests can help identify the patients who will benefit the most,” he adds.
The study paper appears in the journal Blood transfusion.
The researchers used ‘proteomic profiling’ to examine proteins in 85 blood samples, including 13 asymptomatic controls. At least 23 of these individuals gave a blood sample on their first day of hospitalization with COVID-19.
Some of the participants needed treatment in the intensive care unit, while others did not.
The researchers used a machine learning algorithm to identify five proteins that were the best predictors for whom critics would become ill.
These protein biomarkers were better predictors of critical illnesses than some cytokines linked to severe COVID-19, the scientists say.
They were also good predictors of deaths. None of the individuals with a low level of these biomarkers are dead.
All five proteins are associated with the activation of neutrophils that begin life in the bone marrow before entering the bloodstream.
To confirm the importance of these immune cells for predicting worse outcomes in COVID-19, the researchers also analyzed blood test results from more than 3,000 people admitted to the Yale New Haven hospital system.
This analysis revealed that people with increased neutrophil counts shortly after being admitted to the hospital were more likely to die from the disease.
The authors write:
“This signature of neutrophil activation was predictive of hospital deaths, and most compelling, was increased during hospitalization in patients who only later progressed to critical illness, which preceded and predicted the onset of critical illness.”
Neutrophils are the first reaction of the immune system at the site of infection and injury, but they can also cause collateral damage due to excessive inflammation.
Previous research has linked some of the protein biomarkers that the new study identified to obesity.
According to the CDC, the risk of hospitalization with COVID-19 is a doubling of obesity, and the body mass index (BMI) correlates positively with the deaths due to the disease.
The researchers note that COVID-19, although obesity involves chronic, low-grade inflammation, causes hyperinflammation that can lead to tissue damage and organ failure.
There is also evidence, according to the researchers, that neutrophils may play a role in the excessive thrombosis, or blood clotting, that doctors see in critically ill patients with the disease.
The authors write that one limitation of their study was that it did not show that neutrophils are the source of the five protein biomarkers.
However, they add that there is several other pieces of evidence to support this hypothesis.
For example, four of the proteins are established products of neutrophils. The new study also found that the levels of each of the five proteins closely correlated with the concentration of neutrophils in the bloodstream of the participants.
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