Display options
Cite
Sigal GB, Novak T, Mathew A, et al. Measurement of SARS-CoV-2 antigens in plasma of pediatric patients with acute COVID-19 or MIS-C using an ultrasensitive and quantitative immunoassay. medRxiv. 2021;doi: 10.1101/2021.12.08.21267502.
Sigal, G. B., Novak, T., Mathew, A., Chou, J., Zhang, Y., Manjula, N., Bathala, P., Joe, J., Padmanabhan, N., Romero, D., Allegri-Machado, G., Joerger, J., Loftis, L. L., Schwartz, S. P., Walker, T. C., Fitzgerald, J. C., Tarquinio, K. M., Zinter, M. S., Schuster, J. E., Halasa, N. B., Cullimore, M. L., Maddux, A. B., Staat, M. A., Irby, K., Flori, H. R., Coates, B. M., Crandall, H., Gertz, S. J., Randolph, A. G., & Pollock, N. R. (2021). Measurement of SARS-CoV-2 antigens in plasma of pediatric patients with acute COVID-19 or MIS-C using an ultrasensitive and quantitative immunoassay. medRxiv : the preprint server for health sciences, . https://doi.org/10.1101/2021.12.08.21267502
Sigal, George B, et al. "Measurement of SARS-CoV-2 antigens in plasma of pediatric patients with acute COVID-19 or MIS-C using an ultrasensitive and quantitative immunoassay." medRxiv : the preprint server for health sciences vol. (2021). doi: https://doi.org/10.1101/2021.12.08.21267502
Sigal GB, Novak T, Mathew A, Chou J, Zhang Y, Manjula N, Bathala P, Joe J, Padmanabhan N, Romero D, Allegri-Machado G, Joerger J, Loftis LL, Schwartz SP, Walker TC, Fitzgerald JC, Tarquinio KM, Zinter MS, Schuster JE, Halasa NB, Cullimore ML, Maddux AB, Staat MA, Irby K, Flori HR, Coates BM, Crandall H, Gertz SJ, Randolph AG, Pollock NR. Measurement of SARS-CoV-2 antigens in plasma of pediatric patients with acute COVID-19 or MIS-C using an ultrasensitive and quantitative immunoassay. medRxiv. 2021 Dec 09; doi: 10.1101/2021.12.08.21267502. PMID: 34909787; PMCID: PMC8669854.
Copy Download .nbib Format: NLM
Share it on

medRxiv. 2021 Dec 09; doi: 10.1101/2021.12.08.21267502.

Measurement of SARS-CoV-2 antigens in plasma of pediatric patients with acute COVID-19 or MIS-C using an ultrasensitive and quantitative immunoassay.

medRxiv : the preprint server for health sciences

George B Sigal, Tanya Novak, Anu Mathew, Janet Chou, Yubo Zhang, Navaratnam Manjula, Predeepthi 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

PMID: 34909787 PMCID: PMC8669854 DOI: 10.1101/2021.12.08.21267502

Abstract

BACKGROUND: Detection of SARS-CoV-2 antigens in blood has high sensitivity in adults with acute 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 24h 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, respectively; sensitivity in patients with concurrent nasopharyngeal swab cycle threshold (Ct) ≤ 35 were 93%/63%. Antigen concentrations ranged from 1.28-3,844 pg/mL (N) and 1.65-1,071 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.

KEY POINTS: In a U.S. pediatric cohort tested with ultrasensitive immunoassays, SARS-CoV-2 nucleocapsid antigens were detectable in most patients with acute COVID-19, and spike antigens were commonly detectable. Both antigens were undetectable in almost all MIS-C patients.

References

  1. N Engl J Med. 2020 Jul 23;383(4):334-346 - PubMed
  2. Proc Natl Acad Sci U S A. 2020 Oct 13;117(41):25254-25262 - PubMed
  3. J Med Virol. 2021 Oct;93(10):5729-5741 - PubMed
  4. Nat Commun. 2021 Mar 26;12(1):1931 - PubMed
  5. JAMA. 2021 Mar 16;325(11):1074-1087 - PubMed

Publication Types

Grant support