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Published on: February 7, 2025
Normoblastemia in COVID-19 patients is associated with more severe disease and adverse outcome
Kenneth Ofori1, Diane Chen1, Jorge Sepulveda2
1Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center New York, NY, USA.
Insights
Normoblastemia, the presence of nucleated red blood cells, is common in COVID-19 patients. This finding indicates severe disease and is an independent predictor of mortality.
Area of Science:
- Hematology
- Infectious Diseases
- Critical Care Medicine
Background:
- Normoblastemia's clinical significance in COVID-19 remains under-explored.
- Understanding its associations can improve patient management.
Purpose of the Study:
- To determine the frequency of normoblastemia in COVID-19 patients.
- To assess its correlation with disease severity markers and clinical outcomes.
Main Methods:
- Retrospective cohort analysis of 2501 COVID-19 patients.
- Review of automated complete blood counts (aCBC) and acute phase response markers.
- Evaluation of histologic features in deceased patients.
Main Results:
- Normoblastemia occurred in 28.6% of patients.
- Associated with higher WBC, neutrophil counts, ESR, ferritin, INR, D-dimer, and IL-6.
- Linked to lower hemoglobin and lymphocyte counts.
- Higher rates of intubation, ventilation, and mortality in normoblastemic patients.
Conclusions:
- Normoblastemia in COVID-19 signifies severe disease.
- It is linked to extramedullary erythropoiesis and adverse outcomes.
- Normoblastemia is an independent predictor of short-term mortality.
Objectives:
The clinical, pathological, and laboratory correlates of normoblastemia in COVID-19 patients have not been adequately explored. We sought to assess the frequency of normoblastemia in COVID-19, its association with other markers of disease, as well as other clinical outcomes.
Methods:
All COVID-19 patients seen at our institution with at least one automated complete blood count (aCBC) evaluation from March to May 2020 were included in this retrospective cohort analysis. Results of aCBC and tests for markers of the acute phase response performed within 5 days before the first COVID-19 positive test and 14 days after the last positive test were reviewed. We also evaluated histologic features of the reticuloendothelial system of COVID-19 decedents.
Results:
Among a total of 2501 COVID-19 patients, 715 (28.6%) were found to have normoblastemia. Patients with this abnormality had significantly higher (median, (1st quartile, 3rd quartile) WBC (15.7 (11.2, 23.1) u/L vs. 8.3 (6.2, 11.5) u/L), absolute neutrophil count (7.0 (5.1, 10.1) u/L vs. 5.1 (3.7, 7.3) u/L), immature granulocyte percentage (0.8 (0.5, 1.3)% vs. 0.5 (0.3, 0.8)%), ESR (76.0 (60.5, 100.0) mm/hr vs. 66.0 (45.0, 87.0) mm/hr), ferritin (1404.5 (645.0, 2871.0) ng/mL vs. 672.7 (313.4, 1348.0) ng/mL), INR (1.4 (1.2, 1.7) vs. 1.2 (1.1, 1.3)), D-dimer (8.2 (2.8, 20.0) ug/mL FEU vs. 1.5 (0.8, 3.7) µg/mL FEU), and IL-6 (216.6 (77.7, 315.0) pg/mL vs. 54.3 (23.2, 127.8) pg/mL) levels, and lower hemoglobin (12.5 (10.7, 14.2) g/dL vs. 13.2 (11.8, 14.6) g/dL) and absolute lymphocyte count (1.0 (0.7, 1.3) u/L vs. 1.1 (0.8, 1.5) u/L). The incidence of intubation and ventilation support (61.3% (65/106) vs. 10.5% (31/263)) and mortality rates (37.9%, 271/715 vs. 11.8%, 210/1786), were higher in normoblastemic patients. Multivariable logistic regression revealed normoblastemia to be an independent predictive biomarker of short-term mortality in COVID-19.
Conclusion:
Normoblastemia in COVID-19 is associated with markers of severe disease, extramedullary erythropoiesis, and adverse clinical outcome.
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