Sigal George B, Novak Tanya, Mathew Anu, Chou Janet, Zhang Yubo, Manjula Navaratnam, Bathala Predeepthi, Joe Jessica, Padmanabhan Nikhil, Romero Daniel, Allegri-Machado Gabriella, Joerger Jill, Loftis Laura L, Schwartz Stephanie P, Walker Tracie C, Fitzgerald Julie C, Tarquinio Keiko M, Zinter Matt S, Schuster Jennifer E, Halasa Natasha B, Cullimore Melissa L, Maddux Aline B, Staat Mary A, Irby Katherine, Flori Heidi R, Coates Bria M, Crandall Hillary, Gertz Shira J, Randolph Adrienne G, Pollock Nira R
Meso Scale Diagnostics, LLC., Rockville, MD, USA.
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital and Department of Anesthesia, Harvard Medical School, Boston, MA, USA.
medRxiv. 2021 Dec 9:2021.12.08.21267502. doi: 10.1101/2021.12.08.21267502.
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).
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).
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.
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.
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.
在患有急性新冠肺炎的成年人中，检测血液中的新冠病毒2型（SARS-CoV-2）抗原具有较高的敏感性，但在儿科患者中的敏感性尚不清楚。近期数据表明，持续性SARS-CoV-2刺突抗原血症可能导致儿童多系统炎症综合征（MIS-C）。我们使用超灵敏免疫测定法（Meso Scale Discovery）对患有急性新冠肺炎或MIS-C的儿科患者血液中的SARS-CoV-2核衣壳（N）和刺突（S）抗原进行了定量。
从美国15个州15家医院收治的住院患者（<21岁）中采集血浆。急性新冠肺炎患者（n=36）疾病严重程度各异，且在采血后24小时内鼻咽SARS-CoV-2逆转录聚合酶链反应（RT-PCR）呈阳性。MIS-C患者（n=53）符合美国疾病控制与预防中心（CDC）标准，且SARS-CoV-2检测呈阳性（RT-PCR或血清学检测）。对照组为新冠肺炎疫情前的患者（n=67）或RT-PCR阴性后24小时内的患者（n=43）。
N和S检测的特异性分别为95%-97%和100%。在急性新冠肺炎患者中，N/S血浆检测的敏感性分别为89%/64%；鼻咽拭子循环阈值（Ct）≤35的患者中，敏感性分别为93%/63%。抗原浓度范围为1.28-3844 pg/mL（N）和1.65-1071 pg/mL（S），且与疾病严重程度相关。在MIS-C患者中，3/53（5.7%）的样本检测到抗原（3例N阳性：1.7、1.9、121.1 pg/mL；1例S阳性：2.3 pg/mL）；N值最高的患者在采血时鼻咽RT-PCR呈阳性（Ct 22.3）。
超灵敏血液SARS-CoV-2抗原检测在患有急性新冠肺炎的儿童中具有较高的诊断率。大多数MIS-C患者未检测到抗原，这表明持续性抗原血症并非MIS-C发病机制的常见因素。
在美国一个使用超灵敏免疫测定法检测的儿科队列中，大多数急性新冠肺炎患者可检测到SARS-CoV-2核衣壳抗原，刺突抗原也普遍可检测到。几乎所有MIS-C患者均未检测到这两种抗原。
