用富含新合成抗体的培养基 MENSA 鉴别 SARS-CoV-2 在长期慢性阻塞性肺病患者中的持续存在和潜伏病毒再活化情况

Natalie S. Haddad, Andrea Morrison-Porter, Hannah Quehl, Violeta Capric, Pedro A. Lamothe, Fabliha Anam, Martin C. Runnstrom, Alex D. Truong, Adviteeya N. Dixit, Matthew C. Woodruff, Anting Chen, Jiwon Park, Doan C. Nguyen, Ian Hentenaar, Caroline Y. Kim, Shuya Kyu, Brandon Stewart, Elizabeth Wagman, Hannah Geoffroy, Daniel Sanz, Kevin S. Cashman, Richard P. Ramonell, Monica Cabrera-Mora, David N. Alter, John D. Roback, Michael C. Horwath, James B. O'Keefe, Alexandra W. Dretler, Ria Gripaldo, Samantha M. Yeligar, Ted Natoli, Viktoria Betin, Rahulkumar Patel, Kennedy Vela, Mindy Rodriguez Hernandez, Sabeena Usman, John Varghese, Anum Jalal, Saeyun Lee, Sang N. Le, R. Toby Amoss, John L. Daiss, Ignacio Sanz, F. Eun-Hyung Lee
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引用次数: 0

摘要

SARS-CoV-2(SARS2)感染的急性后遗症(PASC)是一种异质性疾病,但主要的病毒驱动因素尚不清楚。在这里,我们使用完全由循环中的人类浆细胞分泌的 MENSA(富含新合成抗体的培养基)来提供免疫快照,以确定潜在的病毒触发因素。我们提供的概念验证测试表明,MENSA 技术可以捕捉新的宿主免疫反应,在已知存在 SARS2 病毒或蛋白质的情况下,准确诊断急性原发性和突破性感染。在接种疫苗后,当尖峰蛋白引起急性免疫反应时,该技术也具有阳性反应。将同样的原理应用于长期 COVID 患者,40% 的 PASC 患者的 MENSA 对 SARS2 呈阳性,而没有任何后遗症的 COVID 康复 (CR) 患者的 MENSA 均不呈阳性,这表明只有 PASC 患者的 SARS2 病毒炎症仍在持续。此外,在 PASC 患者中,37% 的 MENSA 对 Epstein-Barr Virus (EBV) 呈阳性,23% 的 MENSA 对人类巨细胞病毒 (CMV) 呈阳性,15% 的 MENSA 对单纯疱疹病毒 2 (HSV2) 呈阳性,而 CR 对照组的阳性率分别为 17%、4% 和 4%。加在一起,共有 60% 的 PASC 患者的 MENSA 检测结果呈 SARS2、EBV、CMV 和/或 HSV2 阳性。MENSA 提供了一个独特的抗体快照,揭示了长期 COVID 的潜在病毒驱动因素,从而证明了 60% 的 PASC 患者体内 SARS2 的持续存在和病毒性疱疹的再活化。
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MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID
Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present. It is also positive after vaccination when spike proteins elicit an acute immune response. Applying the same principles for long-COVID patients, MENSA is positive for SARS2 in 40% of PASC vs none of the COVID recovered (CR) patients without any sequelae demonstrating ongoing SARS2 viral inflammation only in PASC. Additionally, in PASC patients, MENSAs are also positive for Epstein-Barr Virus (EBV) in 37%, Human Cytomegalovirus (CMV) in 23%, and herpes simplex virus 2 (HSV2) in 15% compared to 17%, 4%, and 4% in CR controls respectively. Combined, a total of 60% of PASC patients have a positive MENSA for SARS2, EBV, CMV, and/or HSV2. MENSA offers a unique antibody snapshot to reveal the underlying viral drivers in long-COVID thus demonstrating the persistence of SARS2 and reactivation of viral herpes in 60% of PASC patients.
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