COVID-19: Scientists identify biomarker to predict mortality risk

  • A new study identifies viral RNA as a blood biomarker that may help predict which patients with COVID-19 have the greatest risk of dying.
  • The team found the biomarker in blood samples collected from people hospitalized with COVID-19 and later confirmed it in two other hospitalized patient groups.
  • The scientists believe that their discovery could help medical professionals identify patients with the highest mortality risk.

Since the COVID-19 pandemic began, in December 2019, medical professionals have struggled to identify which groups have the highest risk of mortality.

Early research unveiled some common factors, including median age and underlying chronic conditions. However, much remains unknown.

Now, a new study from the University of Montreal Hospital Research Centre (CRCHUM) has found that a blood biomarker of SARS-CoV-2, the virus that causes COVID-19, may help doctors determine which patients are most likely to die from the disease.

The researchers believe that this finding will allow medical professionals to provide treatments faster to patients with the highest risk of mortality.

The study appears in the journal Science Advances.

COVID-19 and the blood

Earlier research into COVID-19 and its connection to human blood has investigated why the disease causes blood clots, how blood thinners may protect against complications, and how five protein blood biomarkers may predict which patients become critically ill.

The lead author of the new study, Dr. Daniel Kaufmann, a principal scientist at CRCHUM and medical professor at Université de Montréal, spoke with Medical News Today. He explained that the purpose of this study was to identify a simple, reliable blood marker that could pinpoint patients with the highest risk of fatal illness.

“The course of COVID-19 is extremely variable among patients,” Dr. Kaufmann explained. “From a clinical care perspective, it is important to be able to rapidly identify the persons who are at the highest risk of evolving toward critical disease and death.”

“A lot of different blood measurements have been associated with severe disease,” he continued, “but it is really impractical to work with a profusion of parameters, and some will be more reliable than others.”

In this study, Dr. Kaufmann and his team found that one blood biomarker — viral RNA — helped predict which patients had the greatest risk of dying from COVID-19.

SARS-CoV-2 is an RNA virus, which means that RNA, rather than DNA, is its genetic material. Once inside a human cell, the virus co-opts our cellular machinery to build the proteins coded by its RNA. Some of this viral RNA (vRNA) is detectable in the blood of people with the infection.

Searching for the biomarker

For their study, Dr. Kaufmann and his team collected blood samples from 279 patients hospitalized with COVID-19.

The disease severity ranged; some patients required no oxygen support, while others needed mechanical ventilation. The researchers took blood samples from each person 11 days after their symptoms had appeared.

They also followed the participants for 60 days after their symptoms had appeared. Of the 279 patients, 13 died. Almost half of those died between 30 and 60 days after the first onset of symptoms. Most were in the “critical” patient group.

The researchers initially measured three main biomarkers in the blood of the participants: inflammatory proteins, vRNA, and the level of SARS-CoV-2 antibodies.

They found that the amount of vRNA in a patient’s blood provided the best predictor of mortality risk — noncritical patients had less vRNA than critical patients. Also, those who died had high levels of vRNA in their blood, compared with participants who survived.

Importantly, the researchers reported that the other biomarkers did not help predict mortality rates.

To further examine their theory, the authors tested two additional COVID-19 patient groups — one from Montreal’s Jewish General Hospital and another from CRCHUM. Again, they found that their predictive model worked.

A new testing protocol? 

Dr. Kaufmann noted that the measurements of immunological and virological parameters used in the study are not currently part of standard clinical testing.

However, he said, measuring vRNA in the blood is routine for some other infections, such as HIV. Therefore, if more research data support a clinical application, doctors could rapidly implement this type of test.

“To determine if measurement of SARS-CoV-2 vRNA in plasma may have direct implications for clinical care, a critical research step is to determine how this indicator — and other parameters we measured in this study — varies with the new therapies that are now given to patients with severe COVID-19,” Dr. Kaufmann explained.

“The progress made has reduced the risk of fatal infection. A key question is: Can monitoring of blood vRNA be used to follow the impact of these new treatments in patients?”

MNT also spoke with Dr. Fady Youssef, a pulmonologist, internist, and critical care specialist at Long Beach Memorial Medical Center, in California. He said:

“A lot of times, I’ve had two patients next to each other, [of] similar age, similar ethnicity, similar symptoms, and one of them does OK and goes home, and the other one worsens and goes to the [intensive care unit] and sometimes passes away.”

“We don’t have any understanding of how can we tell which of those patients was going to worsen and which was going to improve. And so having a tool that lets us figure out that piece of the puzzle can help us with targeting therapies, especially when we’re having shortages with some of the therapies that we do use.”

In terms of next steps, Dr. Youssef said that he would like to see these findings applied in an outpatient setting, where the majority of COVID-19 care occurs.

“If we have better outpatient care and better ways to prevent patients from progressing, then that would minimize the demand on the inpatient setting,” he explained.

“If I had my wishes, I would say if somebody gets a diagnosis of COVID-19, they would get some lab work that would tell them what’s their risk of progressing to severe COVID-19. And then having some protocols that are done in the outpatient [setting], where the patients would receive treatments early on and help prevent the progression.”

According to Dr. Kaufmann, the next steps for his team involve examining how new therapies used to target excessive inflammation in COVID-19 might also affect the immune responses against the virus.

“In a new study,” he told MNT, “we are therefore currently investigating how these treatments given to patients with severe COVID-19 change these measurements, and if they keep their predictive capacity, with regard to disease outcome.”

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