Measurement of Severe Acute Respiratory Syndrome Coronavirus 2 Antigens in Plasma of Pediatric Patients With Acute Coronavirus Disease 2019 or Multisystem Inflammatory Syndrome in Children Using an Ultrasensitive and Quantitative Immunoassay

Author:

Sigal George B1,Novak Tanya2,Mathew Anu1,Chou Janet3,Zhang Yubo4,Manjula Navaratnam1,Bathala Pradeepthi1,Joe Jessica1,Padmanabhan Nikhil1,Romero Daniel1,Allegri-Machado Gabriella5,Joerger Jill5,Loftis Laura L6,Schwartz Stephanie P7,Walker Tracie C7,Fitzgerald Julie C8,Tarquinio Keiko M9,Zinter Matt S10,Schuster Jennifer E11,Halasa Natasha B12,Cullimore Melissa L13,Maddux Aline B14,Staat Mary A15,Irby Katherine16,Flori Heidi R17,Coates Bria M18,Crandall Hillary19,Gertz Shira J20,Randolph Adrienne G2,Pollock Nira R21,

Affiliation:

1. Meso Scale Diagnostics, LLC , Rockville, Maryland , USA

2. Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children’s Hospital, and Department of Anesthesia, Harvard Medical School , Boston, Massachusetts , USA

3. Department of Pediatrics, Boston Children’s Hospital and Harvard Medical School , Boston, Massachusetts , USA

4. Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital , Boston, Massachusetts , USA

5. Department of Laboratory Medicine, Boston Children’s Hospital , Boston, Massachusetts , USA

6. Division of Critical Care Medicine, Department of Pediatrics, Baylor College of Medicine , Houston, Texas , USA

7. Department of Pediatrics, University of North Carolina at Chapel Hill Children’s Hospital , Chapel Hill, North Carolina , USA

8. Division of Critical Care, Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine , Philadelphia, Pennsylvania , USA

9. Division of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta , Atlanta, Georgia , USA

10. Divisions of Critical Care and Bone Marrow Transplantation, Department of Pediatrics, University of California, San Francisco , San Francisco, California , USA

11. Division of Pediatric Infectious Diseases, Department of Pediatrics, Children’s Mercy Kansas City , Kansas City, Missouri , USA

12. Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center , Nashville, Tennessee , USA

13. Department of Pediatrics, College of Medicine, University of Nebraska Medical Center , Omaha, Nebraska , USA

14. Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children’s Hospital Colorado , Aurora, Colorado , USA

15. Department of Pediatrics, University of Cincinnati, Division of Infectious Diseases, Cincinnati Children’s Hospital Medical Center , Cincinnati, Ohio , USA

16. Section of Pediatric Critical Care, Department of Pediatrics, Arkansas Children’s Hospital , Little Rock, Arkansas , USA

17. Division of Pediatric Critical Care Medicine, Department of Pediatrics, Mott Children’s Hospital and University of Michigan , Ann Arbor, Michigan , USA

18. Division of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago , Chicago, Illinois , USA

19. Division of Pediatric Critical Care, Department of Pediatrics, University of Utah, Salt Lake City , Utah , USA

20. Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center , Livingston, New Jersey , USA

21. Department of Laboratory Medicine, Boston Children’s Hospital and Harvard Medical School , Boston, Massachusetts , USA

Abstract

Abstract Background Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in blood has high sensitivity in adults with acute coronavirus disease 2019 (COVID-19), but sensitivity in pediatric patients is unclear. Recent data suggest that persistent SARS-CoV-2 spike antigenemia may contribute to multisystem inflammatory syndrome in children (MIS-C). We quantified SARS-CoV-2 nucleocapsid (N) and spike (S) antigens in blood of pediatric patients with either acute COVID-19 or MIS-C using ultrasensitive immunoassays (Meso Scale Discovery). Methods Plasma was collected from inpatients (<21 years) enrolled across 15 hospitals in 15 US states. Acute COVID-19 patients (n = 36) had a range of disease severity and positive nasopharyngeal SARS-CoV-2 RT-PCR within 24 hours of blood collection. Patients with MIS-C (n = 53) met CDC criteria and tested positive for SARS-CoV-2 (RT-PCR or serology). Controls were patients pre–COVID-19 (n = 67) or within 24 hours of negative RT-PCR (n = 43). Results Specificities of N and S assays were 95–97% and 100%, respectively. In acute COVID-19 patients, N/S plasma assays had 89%/64% sensitivity; sensitivities in patients with concurrent nasopharyngeal swab cycle threshold (Ct) ≤35 were 93%/63%. Antigen concentrations ranged from 1.28–3844 pg/mL (N) and 1.65–1071 pg/mL (S) and correlated with disease severity. In MIS-C, antigens were detected in 3/53 (5.7%) samples (3 N-positive: 1.7, 1.9, 121.1 pg/mL; 1 S-positive: 2.3 pg/mL); the patient with highest N had positive nasopharyngeal RT-PCR (Ct 22.3) concurrent with blood draw. Conclusions Ultrasensitive blood SARS-CoV-2 antigen measurement has high diagnostic yield in children with acute COVID-19. Antigens were undetectable in most MIS-C patients, suggesting that persistent antigenemia is not a common contributor to MIS-C pathogenesis.

Funder

Boston Children’s Hospital Emerging Pathogens and Epidemic Response Cluster of Clinical Research Excellence

Meso Scale Diagnostics

Centers for Disease Control and Prevention

National Institute of Diabetes and Digestive and Kidney Diseases

Eunice Kennedy Shriver National Institute of Child Health and Human Development

National Heart, Lung, and Blood Institute

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

Cited by 20 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3