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

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  • Sigal, G.B.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Novak, T.
    • Other Affiliation: Boston Children's Hospital
  • Mathew, A.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Chou, J.
    • Other Affiliation: Boston Children's Hospital
  • Zhang, Y.
    • Other Affiliation: Boston Children's Hospital
  • Manjula, N.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Bathala, P.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Joe, J.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Padmanabhan, N.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Romero, D.
    • Other Affiliation: Meso Scale Diagnostics, LLC
  • Allegri-Machado, G.
    • Other Affiliation: Boston Children's Hospital
  • Joerger, J.
    • Other Affiliation: Boston Children's Hospital
  • Loftis, L.L.
    • Other Affiliation: Baylor College of Medicine
  • Schwartz, S.P.
    • Affiliation: School of Medicine, Department of Pediatrics
  • Walker, T.C.
    • Affiliation: School of Medicine, Department of Pediatrics
  • Fitzgerald, J.C.
    • Other Affiliation: University of Pennsylvania Perelman School of Medicine
  • Tarquinio, K.M.
    • Other Affiliation: Emory University School of Medicine
  • Zinter, M.S.
    • Other Affiliation: University of California, San Francisco
  • Schuster, J.E.
    • Other Affiliation: Children's Mercy Kansas City
  • Halasa, N.B.
    • Other Affiliation: Vanderbilt University Medical Center
  • Cullimore, M.L.
    • Other Affiliation: University of Nebraska Medical Center
  • Maddux, A.B.
    • Other Affiliation: University of Colorado School of Medicine
  • Staat, M.A.
    • Other Affiliation: Cincinnati Children's Hospital Medical Center
  • Irby, K.
    • Other Affiliation: Arkansas Children's Hospital
  • Flori, H.R.
    • Other Affiliation: University of Michigan
  • Coates, B.M.
    • Other Affiliation: Northwestern University
  • Crandall, H.
    • Other Affiliation: University of Utah
  • Gertz, S.J.
    • Other Affiliation: Saint Barnabas Medical Center
  • Randolph, A.G.
    • Other Affiliation: Harvard Medical School
  • Pollock, N.R.
    • Other Affiliation: Boston Children's Hospital and Harvard Medical School
  • Overcoming COVID-19 Investigators
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.
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  • Article
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  • In Copyright
Journal title
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Journal volume
  • 75
Journal issue
  • 8
Page start
  • 1351
Page end
  • 1358
Language
  • English
ISSN
  • 1537-6591

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