A standard test that assesses variations in red blood cell volume can identify hospitalized patients with COVID-19 who are at elevated risk of becoming critically ill and succumbing to the disease, according to newly published research led by a team of Harvard Medical School investigators at Massachusetts General Hospital’s Center for Systems Biology.

The findings, described in JAMA Network Open, are based on a retrospective analysis of blood samples and medical records from 1,641 adult individuals diagnosed with SARS-CoV-2 infection and admitted to one of four hospitals in the Boston area between March 4 and April 28, 2020.

The test, known as red cell distribution width, or RDW, is part of the complete blood count profile routinely used by physicians to screen, diagnose and monitor a variety of conditions. The RDW test measures variation in the volume of red blood cells. While the test is not used in isolation as a diagnostic tool, variations in the ranges of RDW could herald a number of abnormalities, ranging from anemia to diabetes.

In the current study, the researchers identified that variations in RDW above normal range portended higher mortality risk among those hospitalized for COVID-19.

Indeed, patients who had RDW values above the normal range when they were admitted to the hospital had a mortality rate of 31 percent compared with 11 percent in patients with normal RDW values.

Notably, a subsequent increase in RDW after admission was linked with an even higher risk of dying, indicating that RDW could be tracked during hospitalization to help determine whether patients are responding to treatment or getting worse.

The link persisted even when the researchers accounted for the possible influence of other factors, including patient age, preexisting conditions and variations in other laboratory findings.

“We wanted to help find ways to identify high-risk COVID patients as early and as easily as possible—who is likely to become severely ill and may benefit from aggressive interventions, and which hospitalized patients are likely to get worse most quickly,” said senior author John Higgins, associate professor of systems biology at HMS and an investigator in the Department of Pathology at Mass General. 

Higgins noted that early reports from China indicated an inflammatory response that was extremely intense in some patients but very mild in others. His own group’s previous work revealed that certain changes in the numbers and types of blood cells during inflammation are associated with poor health outcomes in patients with illnesses such as heart disease, cancer and diabetes.

“We quickly refocused our computational infrastructure towards analysis of the COVID-19 patient cohort that was growing rapidly in the Boston area last spring,” explained first author Brody Foy, a research fellow in systems biology at HMS and Mass General.

The results of the study could help clinicians treating patients use this common blood test as a tool to monitor patients being treated for COVID-19 and react promptly if they notice any telltale changes.

“Our broader goal is to understand the ensemble of intrinsic risk factors and clinical events that dictate the severity of this infection, which can vary profoundly from person to person, but in the meantime we hope that the findings of our analysis can be of immediate clinical utility for those on the frontlines of caring for patients with COVID-19,” said study co-author Jonathan Carlson, a hematologist and researcher at Mass General and HMS.

The investigators are currently seeking to uncover the mechanisms that cause RDW elevations in severe COVID-19 cases.

“Such discoveries could point to new treatment strategies or identify better markers of disease severity,” noted co-author Aaron Aguirre, assistant professor of medicine at HMS and a cardiologist and critical care physician at Mass General.