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

Authors

George B Sigal
Tanya Novak
Anu Mathew
Janet Chou
Yubo Zhang
Navaratnam Manjula
Pradeepthi Bathala
Jessica Joe
Nikhil Padmanabhan
Daniel Romero
Gabriella Allegri-Machado
Jill Joerger
Laura L Loftis
Stephanie P Schwartz
Tracie C Walker
Julie C Fitzgerald
Keiko M Tarquinio
Matt S Zinter
Jennifer E Schuster
Natasha B Halasa
Melissa L Cullimore
Aline B Maddux
Mary A Staat
Katherine Irby
Heidi R Flori
Bria M Coates
Hillary Crandall
Shira J Gertz
Adrienne G Randolph
Nira R Pollock
Overcoming COVID-19 Investigators

Language

English

Publication Date

10-12-2022

Journal

Clinical Infectious Diseases

DOI

10.1093/cid/ciac160

PMID

35213684

PMCID

PMC8903440

PubMedCentral® Posted Date

2-25-2022

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Adult, Antigens, Viral, COVID-19, Child, Humans, Immunoassay, SARS-CoV-2, Systemic Inflammatory Response Syndrome, SARS-CoV-2, COVID-19, antigen, ultrasensitive immunoassay, antigenemia

Published Open-Access

yes

Recommended Citation

Sigal, George B; Novak, Tanya; Mathew, Anu; et al., "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" (2022). Center for Medical Ethics and Health Policy Staff Publications. 53.
https://digitalcommons.library.tmc.edu/med_ethics/53