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.

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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DOI:
10.1093/cid/ciac160
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发表时间:
2022-10-12
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Overcoming COVID-19 Investigators
Overcoming COVID-19 Investigators
中科院分区:
其他
文献类型:
--
作者:
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;Overcoming COVID-19 Investigators

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血液中严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)抗原的检测在2019年急性冠状病毒病(COVID-19)成人患者中具有高灵敏度,但在儿科患者中的灵敏度尚不清楚。最近的数据表明,持续的SARS-CoV-2峰抗原血症可能有助于儿童多系统炎症综合征(MIS-C)。我们使用超灵敏免疫测定(Meso Scale Discovery)定量了急性COVID-19或MIS-C儿科患者血液中的SARS-CoV-2核衣壳(N)和刺突(S)抗原。从美国15个州的15家医院招募的住院患者(<21岁)中收集血浆。急性COVID-19患者(n = 36)在采血后24小时内有一系列疾病严重程度和鼻咽SARS-CoV-2 RT-PCR阳性。  MIS-C患者(n = 53)符合CDC标准,SARS-CoV-2检测呈阳性(RT-PCR或血清学)。  对照组为COVID-19前(n = 67)或RT-PCR阴性24小时内(n = 43)的患者。    N和S试验的特异性分别为95-97%和100%。在急性COVID-19患者中,N/S血浆检测的灵敏度为89%/64%;同时鼻咽拭子循环阈值(Ct)≤35的患者的灵敏度为93%/63%。抗原浓度范围为1.28-3844 pg/mL(N)和1.65-1071 pg/mL(S),与疾病严重程度相关。在MIS-C中,在3/53(5.7%)份样本中检出抗原(3份N阳性:1.7、1.9、121.1 pg/mL; 1份S阳性:2.3 pg/mL); N最高的患者在抽血时鼻咽RT-PCR(Ct 22.3)呈阳性。超灵敏血液SARS-CoV-2抗原测量在急性COVID-19儿童中具有较高的诊断率。在大多数MIS-C患者中检测不到抗原,表明持续性抗原血症不是MIS-C发病机制的常见因素。在一项使用超灵敏免疫测定法进行测试的美国儿科队列中,2019年大多数急性冠状病毒病患者均可检测到严重急性呼吸综合征冠状病毒2型核衣壳抗原,并且通常可检测到刺突抗原。在几乎所有的多系统炎性综合征患儿中,这两种抗原均检测不到。
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). 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). 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. 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, severe acute respiratory syndrome coronavirus 2 nucleocapsid antigens were detectable in most patients with acute coronavirus disease 2019, and spike antigens were commonly detectable. Both antigens were undetectable in almost all multisystem inflammatory syndrome in children patients.
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发表时间: 2021-02-24
影响因子: 120.7
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