Discovery of biomarkers that can influence COVID-19 severity

The novel coronavirus, now called the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), is the causative agent of the dreaded coronavirus disease (COVID-19). It was first discovered in Wuhan City, China, back in late December 2019 and has since then spread throughout the globe.

The common symptoms of the illness include cough, fever, fatigue, and difficulty breathing. While most of the patients infected with the virus have no or minor symptoms, some develop severe pneumonia, acute respiratory distress syndrome (ARDS), multiple organ failure, and death.

Though the exact mechanism on why some people are spared from severe COVID-19, while others succumb to the infection, is still unclear, scientists at the University of Louisville have identified biomarkers that can predict a crisis in patients infected with SARS-CoV-2.

Levels of various immune cells in blood samples

An estimated 20 percent of COVID-19 patients experience severe disease. Some of these patients may experience the rapid influx of the immune cells to the lungs to fight the infection. As a result, they may cause inflammation and coagulation disorders, resulting in pulmonary embolism, heart attack, stroke, and deep vein thrombosis (DVT), which can be potentially fatal.

The team aimed to better understand the serious complications tied to COVID-19. To arrive at their findings, they evaluated the levels of many immune cells in blood samples from COVID-19 patients. They compared the levels to the blood samples taken from healthy people.

Based on the findings, published in the preprint journal MedRxiv*, the team has found that a specific type of immune cell, the low-density inflammatory neutrophils, became highly elevated in some patients who became severely-ill due to the novel coronavirus. The elevated levels of the immune cells have signaled a status of crisis, and a heightened risk of death within a few days.

Neutrophil, a white blood cell, 3D illustration Credit: Kateryna Kon / Shutterstock
Neutrophil, a white blood cell, 3D illustration Credit: Kateryna Kon / Shutterstock

Neutrophils are a type of white blood cell that aids in healing damaged tissues and resolving infection. During an infection, the blood levels of neutrophils increase. These cells serve as the first line of defense in the body when a person acquires an infection.

During infection, the neutrophils rush to the site to clear the pathogen. However, when elevated levels persist, they can cause adverse effects.

Just like what happens after infection with two other coronavirus conditions, the severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS), evidence shows that patients with severe COVID-19 may experience a cytokine storm syndrome. This triggers the production of too many cytokines in response to an infection, hence, attracting an excess of immune cells, such as neutrophils. As a result, the immune cells infiltrate into lung tissue and cause injury.

In worse scenarios, cytokine storms may cause excessive leakiness of the blood vessels, extremely low blood pressure, blood clotting, and lack of oxygen. Eventually, multi-organ system failure occurs.

Monitoring disease status and progression

The team believes that the discovery of the new biomarker can help clinicians monitor the progression of the disease in patients admitted to hospitals. Further, developing a simple test to predict disease severity can help mitigate the effects of the disease through proper monitoring and treatment.

“We conclude that the LDIB subset contributes to COVID-19-associated coagulopathy (CAC) and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards the LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients,” the team concluded in the study.

The researchers believe that the low-density inflammatory band neutrophil population drives COVID-19-associated coagulopathy (CAC), which can be used as a clinical marker to predict disease progression.

It is crucial to identify patients who may develop a cellular crisis. Implementing early and appropriate treatment could improve mortality rates for COVID-19 patients, the researchers emphasized. The team is now working with other scientists to test potential drugs and therapies.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Angela Betsaida B. Laguipo

Written by

Angela Betsaida B. Laguipo

Angela is a nurse by profession and a writer by heart. She graduated with honors (Cum Laude) for her Bachelor of Nursing degree at the University of Baguio, Philippines. She is currently completing her Master's Degree where she specialized in Maternal and Child Nursing and worked as a clinical instructor and educator in the School of Nursing at the University of Baguio.


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