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A scoring system based on 10 parameters in a complete blood count (CBC) with differential within 3 days of hospital presentation predict those with COVID-19 who are most likely to progress to critical illness, new evidence shows.
Advantages include prognosis based on a common and inexpensive clinical measure, as well as automatic generation of the score along with CBC results, note investigators in the observational study conducted throughout 11 European hospitals.
“COVID-19 comes along with specific alterations in circulating blood cells that can be detected by a routine hematology analyzer, especially when that hematology analyzer is also capable to recognize activated immune cells and early circulating blood cells, such as erythroblast and immature granulocytes,” senior author Andre van der Ven, MD, PhD, infectious diseases specialist and professor of international health at Radboud University Medical Center’s Center for Infectious Diseases in Nijmegen, the Netherlands, told Medscape Medical News.
Furthermore, van der Ven said, “these specific changes are also seen in the early course of COVID-19 disease, and more in those that will develop serious disease compared to those with mild disease.”
The study was published online December 21 in the journal eLife.
The study is “almost instinctively correct. It’s basically what clinicians do informally with complete blood count…looking at a combination of results to get the gestalt of what patients are going through,” Samuel Reichberg, MD, PhD, associate medical director of the Northwell Health Core Laboratory in Lake Success, New York, told Medscape Medical News when asked to comment.
“This is something that begs to be done for COVID-19. I’m surprised no one has done this before,” he added.
Van der Ven and colleagues created an algorithm based on 1587 CBC assays from 923 adults. They also validated the scoring system in a second cohort of 217 CBC measurements in 202 people. The findings were concordant — the score accurately predicted the need for critical care within 14 days in 70.5% of the development cohort and 72% of the validation group.
The scoring system was superior to any of the 10 parameters alone. Over 14 days, the majority of those classified as noncritical (NC) within the first 3 days remained clinically stable, whereas the “clinical illness” (CI) group progressed. Clinical severity peaked on day 6.
Most previous COVID-19 prognosis research was geographically limited, carried a high risk for bias and/or did not validate the findings, Van der Ven and colleagues note.
Early Identification, Early Intervention
The aim of the score is “to assist with objective risk stratification to support patient management decision-making early on, and thus facilitate timely interventions, such as need for ICU or not, before symptoms of severe illness become clinically overt, with the intention to improve patient outcomes, and not to predict mortality,” the investigators note.
Van der Ven and colleagues developed the score based on adults presenting from February 21 to April 6, with outcomes followed until June 9. Median age of the 982 patients was 71 years and approximately two thirds were men. They used a Sysmex Europe GmbH XN-1000 (Hamburg, Germany) hemocytometric analyzer in the study.
Only 7% of this cohort was not admitted to a hospital. Another 74% were admitted to a general ward and the remaining 19% were transferred directly to the ICU.
The scoring system includes parameters for neutrophils, monocytes, red blood cells and immature granulocytes, and when available, reticulocyte and iron bioavailability measures.
The researchers report significant differences over time in the neutrophil-to-lymphocyte ratio between the critical illness and non-critical groups (P < .001), for example. They also found significant differences in hemoglobin levels between cohorts after day 5.
The system generates a score from 0 to 28. Sensitivity for correctly predicting the need for critical care increased from 62% on day 1 to 93% on day 6.
A More Objective Assessment of Risk
The study demonstrated that SARS-CoV-2 infection is characterized by hemocytometric changes over time. These changes, reflected together in the prognostic score, could aid in the early identification of patients whose clinical course is more likely to deteriorate over time.
The findings also support other work that shows men are more likely to present to the hospital with COVID-19, and that older age and presence of comorbidities add to overall risk. “However,” the researchers note, “not all young patients had a mild course, and not all old patients with comorbidities were critical.”
Therefore, the prognostic score can help identify patients at risk for severe progression outside other risk factors and “support individualized treatment decisions with objective data,” they add.
Reichberg called the concept of combining CBC parameters into one score “very valuable.” However, he added that incorporating an index into clinical practice “has historically been tricky.”
The results “probably have to be replicated,” Reichberg said.
He added that it is likely a CBC-based score will be combined with other measures. “I would like to see an index that combines all the tests we do [for COVID-19], including complete blood count.”
Van der Ven shared the next step in his research. “The algorithm should be installed on the hematology analyzers so the prognostic score will be automatically generated if a full blood count is asked for in a COVID-19 patient,” he said. “So implementation of score is the main focus now.”
Andre J van der Ven disclosed an ad hoc consultancy agreement with Sysmex Europe GmbH. Sysmex Europe provided the reagents in the study free of charge; no other funders were involved. Reichberg has disclosed no relevant financial relationships.
eLife. Published online December 21, 2020. Full text
Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology and critical care. Follow Damian on Twitter: @MedReporter.