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

on behalf of the Overcoming COVID-19 Investigators

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1351-1358
Number of pages8
JournalClinical Infectious Diseases
Volume75
Issue number8
DOIs
StatePublished - Oct 15 2022

Funding

Financial support. This work was supported in part by a grant to N.R.P. from the Boston Children\u2019s Hospital Emerging Pathogens and Epidemic Response Cluster of Clinical Research Excellence. S-PLEX assays were provided as an in-kind service by Meso Scale Diagnostics. The US Centers for Disease Control and Prevention funded the referenced Overcoming COVID-19 Immunobiology Study (contract numbers 75D30119C05584 and 75D30120C07725; to A. G. R.). J. C. F is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) K23DK119463. A. B. M. is supported by NICHD K23HD096018. M. S. Z. is supported by NHLBI K23HL146936.

Keywords

  • COVID-19
  • SARS-CoV-2
  • antigen
  • antigenemia
  • ultrasensitive immunoassay

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases

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