TY - JOUR
T1 - Monocyte anisocytosis increases during multisystem inflammatory syndrome in children with cardiovascular complications
AU - Yonker, Lael M.
AU - Badaki-Makun, Oluwakemi
AU - Arya, Puneeta
AU - Boribong, Brittany P.
AU - Moraru, Gabriela
AU - Fenner, Brittany
AU - Rincon, Jaimar
AU - Hopke, Alex
AU - Rogers, Brent
AU - Hinson, Jeremiah
AU - Fasano, Alessio
AU - Lee, Lilly
AU - Kehoe, Sarah M.
AU - Larson, Shawn D.
AU - Chavez, Hector
AU - Levin, Scott
AU - Moldawer, Lyle L.
AU - Irimia, Daniel
N1 - Funding Information:
We would like to thank the following individuals for their work on this project: MGH: Eva J. Farkas, Maggie Loiselle, Jameson P. Davis, Madeleine Burns, Nicola Young, Rosie Lima, Andrea Edlow, MD, Blair A Parry, Nicole Russell, Ari Cohen, MD, Michael R. Filbin, MD, MS, Allison Fialkowski, Jameson P. Davis, Anika L. Marand, Elizabeth F. Gootkind, Sinan Muldur, PhD for ethics compliance, subject recruitment, and blood sample logistics. UF: Lara Nicolas, MD for ethics compliance, Ricardo Ungaro, Tera Thigpin for subject recruitment and blood sample logistics. JHU: Ben Henreid, Esosa Nosakhare, Ann Kane, Amyna Husain, Ted Kouo, Matt Lee, Aishwarya Pradeep for subject recruitment and blood sample logistics. Danaher Diagnostics: Lili Tejidor, PhD, Senior Director Clinical Affairs for discussions about cut-off value determination for cardiac complications of MIS-C. BARDA: Meghan Pennini, PhD, for discussions about cut-off value determination for cardiac complications of MIS-C. We also thank Beckman Coulter Inc. for providing research access to four DxH900 hematology analyzers.
Funding Information:
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, GM139690 to LLM), and the Office of the Assistant Secretary for 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.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. Methods: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. Results: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78–100%) and 80% specificity (95% CI 69–88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80–100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. Conclusions: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.
AB - Background: Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening complication that can develop weeks to months after an initial SARS-CoV-2 infection. A complex, time-consuming laboratory evaluation is currently required to distinguish MIS-C from other illnesses. New assays are urgently needed early in the evaluation process to expedite MIS-C workup and initiate treatment when appropriate. This study aimed to measure the performance of a monocyte anisocytosis index, obtained on routine complete blood count (CBC), to rapidly identify subjects with MIS-C at risk for cardiac complications. Methods: We measured monocyte anisocytosis, quantified by monocyte distribution width (MDW), in blood samples collected from children who sought medical care in a single medical center from April 2020 to October 2020 (discovery cohort). After identifying an effective MDW threshold associated with MIS-C, we tested the utility of MDW as a tier 1 assay for MIS-C at multiple institutions from October 2020 to October 2021 (validation cohort). The main outcome was the early screening of MIS-C, with a focus on children with MIS-C who displayed cardiac complications. The screening accuracy of MDW was compared to tier 1 routine laboratory tests recommended for evaluating a child for MIS-C. Results: We enrolled 765 children and collected 846 blood samples for analysis. In the discovery cohort, monocyte anisocytosis, quantified as an MDW threshold of 24.0, had 100% sensitivity (95% CI 78–100%) and 80% specificity (95% CI 69–88%) for identifying MIS-C. In the validation cohort, an initial MDW greater than 24.0 maintained a 100% sensitivity (95% CI 80–100%) and monocyte anisocytosis displayed a diagnostic accuracy greater that other clinically available hematologic parameters. Monocyte anisocytosis decreased with disease resolution to values equivalent to those of healthy controls. Conclusions: Monocyte anisocytosis detected by CBC early in the clinical workup improves the identification of children with MIS-C with cardiac complications, thereby creating opportunities for improving current practice guidelines.
KW - Monocyte distribution width
KW - Multisystem inflammatory syndrome in children
KW - Pediatric COVID-19
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U2 - 10.1186/s12879-022-07526-9
DO - 10.1186/s12879-022-07526-9
M3 - Article
C2 - 35725405
AN - SCOPUS:85132295483
SN - 1471-2334
VL - 22
JO - BMC Infectious Diseases
JF - BMC Infectious Diseases
IS - 1
M1 - 563
ER -