Monocyte anisocytosis corresponds with increasing severity of COVID-19 in children

Abigail S Kane; Brittany P Boribong; Maggie Loiselle; Anagha P Chitnis; Hector Chavez; Lyle L Moldawer; Shawn D Larson; Oluwakemi Badaki-Makun; Daniel Irimia; Lael M Yonker

doi:10.3389/fped.2023.1177048

Monocyte anisocytosis corresponds with increasing severity of COVID-19 in children

Front Pediatr. 2023 Jun 23:11:1177048. doi: 10.3389/fped.2023.1177048. eCollection 2023.

Authors

Abigail S Kane^{1

2}, Brittany P Boribong^{1

2

3}, Maggie Loiselle^{1

2}, Anagha P Chitnis², Hector Chavez^{4

5}, Lyle L Moldawer⁶, Shawn D Larson⁶, Oluwakemi Badaki-Makun^{7

8}, Daniel Irimia^{3

9

10}, Lael M Yonker^{1

2

3}

Affiliations

¹ Department of Pediatrics, Massachusetts General Hospital, Boston, MA, United States.
² Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA, United States.
³ Department of Pediatrics, Harvard Medical School, Boston, MA, United States.
⁴ Department of Pediatrics, Jackson Memorial Hospital, Miami, FL, United States.
⁵ Department of Pediatric Emergency Medicine, Holtz Children's Hospital, Miami, FL, United States.
⁶ Department of Surgery, University of Florida, Gainesville, FL, United States.
⁷ Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁸ Center for Data Science in Emergency Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United States.
⁹ Department of Surgery, Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA, United States.
¹⁰ Department of Surgery, Shriners Burn Hospital, Boston, MA, United States.

Abstract

Introduction: Although SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children.

Methods: We performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children.

Results: Monocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters.

Conclusion: Monocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.

Keywords: SARS-COV-2 infection; monocyte anisocytosis; monocyte distribution width; multisystem inflammatory syndrome; pediatric COVID-19.

Grants and funding

This research was supported in part with federal funds from the Department of Health and Human Services, including the National Heart Lung and Blood Institute (5K08HL143183 to LY), the National Institute of General Medical Sciences, and the National Institute of Child Health and Human Development (GM092804 and HD089939 to DI), and the Administration for Strategic Preparedness and Response: Biomedical Advanced Research and Development Authority, under Contract No 75A50120C00189. Beckman Coulter, Inc. provided cost share as part of BARDA contract #75A50120C00189.