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

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

Published Open-Access

yes

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

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.