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: COVID-19; SARS-CoV-2; antigen; antigenemia; ultrasensitive immunoassay.
【저자키워드】 COVID-19, SARS-CoV-2, Antigen, antigenemia, ultrasensitive immunoassay., 【초록키워드】 coronavirus disease, coronavirus, Pathogenesis, serology, children, disease severity, hospital, diagnostic, detection, RT-PCR, MIS-C, Nasopharyngeal swab, immunoassay, sensitivity, cycle threshold, nasopharyngeal, Patient, Control, plasma, SARS-CoV-2 RT-PCR, SARS-CoV-2 antigen, patients, Blood, SARS-CoV-2 spike, Concentration, Inflammatory, COVID-19 patient, Inpatient, acute respiratory syndrome, Pediatric patient, syndrome, CDC criteria, acute COVID-19, positive, SARS-CoV-2 nucleocapsid, blood collection, negative RT-PCR, Meso Scale Discovery, blood draw, recent, enrolled, highest, tested, the patient, was collected, contribute, correlated, ranged, quantified, 24 hour, undetectable, 【제목키워드】 coronavirus 2, respiratory, measurement,