Multiple early factors anticipate post-acute COVID-19 sequelae.
Multiple early factors anticipate post-acute COVID-19 sequelae.
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DOI：
10.1016/j.cell.2022.01.014
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发表时间：
2022-03-03
期刊：
影响因子：
64.5
通讯作者：
Heath JR
中科院分区：
文献类型：
--
作者：
Su Y;Yuan D;Chen DG;Ng RH;Wang K;Choi J;Li S;Hong S;Zhang R;Xie J;Kornilov SA;Scherler K;Pavlovitch-Bedzyk AJ;Dong S;Lausted C;Lee I;Fallen S;Dai CL;Baloni P;Smith B;Duvvuri VR;Anderson KG;Li J;Yang F;Duncombe CJ;McCulloch DJ;Rostomily C;Troisch P;Zhou J;Mackay S;DeGottardi Q;May DH;Taniguchi R;Gittelman RM;Klinger M;Snyder TM;Roper R;Wojciechowska G;Murray K;Edmark R;Evans S;Jones L;Zhou Y;Rowen L;Liu R;Chour W;Algren HA;Berrington WR;Wallick JA;Cochran RA;Micikas ME;ISB-Swedish COVID-19 Biobanking Unit;Wrin T;Petropoulos CJ;Cole HR;Fischer TD;Wei W;Hoon DSB;Price ND;Subramanian N;Hill JA;Hadlock J;Magis AT;Ribas A;Lanier LL;Boyd SD;Bluestone JA;Chu H;Hood L;Gottardo R;Greenberg PD;Davis MM;Goldman JD;Heath JR
COVID-19急性后遗症（PASC）代表着一场新兴的全球危机。然而，PASC的可量化的风险因素及其生物学相关性尚不清楚。我们对309名COVID-19患者从最初诊断到恢复期（2-3个月后）进行了深入的多组学纵向调查，结合临床数据和患者报告的症状。我们在最初诊断COVID-19时解决了四个PASC预期风险因素：2型糖尿病，SARS-CoV-2 RNA血症，EB病毒病毒血症和特异性自身抗体。在胃肠道PASC患者中，SARS-CoV-2特异性和CMV特异性CD 8 + T细胞在COVID-19恢复期间表现出独特的动态。分析与免疫相关的免疫特征显示，协调的免疫极化成四种内型，表现出不同的急性严重程度和PASC。我们发现PASC因子之间的免疫关联随着时间的推移而减少，导致不同的恢复期免疫状态。在COVID-19诊断时大多数PASC因素的可检测性强调了早期疾病测量对于了解紧急慢性疾病的重要性，并建议了PASC治疗策略。纵向多组学将PASC与自身抗体、病毒血症和合并症相关联初始感染期间潜伏病毒的再活化可能导致PASC亚临床自身抗体与抗SARS-CoV-2抗体负相关胃肠道PASC独特地存在于细胞毒性T细胞的急性后扩增通过将患者症状与整个COVID-19感染期间血细胞和血浆成分的深入分析相关联，这项研究确定了可能预测持续疾病的因素。
Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2–3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies. Longitudinal multi-omics associate PASC with auto-antibodies, viremia, and comorbidities Reactivation of latent viruses during initial infection may contribute to PASC Subclinical auto-antibodies negatively correlate with anti-SARS-CoV-2 antibodies Gastrointestinal PASC uniquely present with post-acute expansion of cytotoxic T cells By correlating patient symptoms with in-depth profiling of blood cells and plasma components throughout COVID-19 infection, this study identifies factors that may predict sustained disease.
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影响因子：
30.8
作者：
Emerson, Ryan O.;DeWitt, William S.;Robins, Harlan S.
通讯作者：
Robins, Harlan S.
影响因子：
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通讯作者：
Casanova JL
影响因子：
14.2
作者：
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通讯作者：
Romagnani, Sergio
影响因子：
13.8
作者：
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通讯作者：
Chinchilli VM