Host factors contributing to susceptibility to COVID-19 disease

这些研究是NIAID，NIDCR，NCI和NIAMS的校内研究计划中多个主要研究者更广泛努力的一部分，以及与美国基因组中心/健康科学统一服务大学的研究人员的研究合作协议。我们已经组织了一项国际合作，研究在意大利中心入组的患者，后来扩展到包括东亚、中东和美洲的中心。IRB批准的COVID方案涉及发送样本，以便于在其他缺乏自己的COVID方案的中心进行研究。我们与COVID-人类遗传努力合作，并通过这种国际合作发表了多篇论文。 于2022财年，我们扩展了先前发现的I型IFN反应的遗传性和获得性缺陷是导致严重或危重COVID-19的原因。 我们的特点是对I型IFN的中和自身抗体的动力学，并发现这些是动态产生的急性感染，但在恢复期减少，这表明疾病的发病机制可能涉及的记忆反应与感染前检测个人与这种自身抗体的影响。在与NIAID COVID-19联盟和COVID人类遗传工作的各种合作中，我们还协助表征神经生物标志物和克隆造血在呼吸道COVID-19中的潜在作用，以及对其他形式的潜在遗传贡献SARS-CoV-2感染（MIS-C，pernio）。最后，由我们的研究小组领导的正在进行的工作正在调查dsRNA传感器的遗传变体在COVID-19结果中的潜在作用。

These studies have been organized as part of a broader effort among multiple principal investigators in the Intramural Research Programs of NIAID, NIDCR, NCI, and NIAMS, as well as a research collaborative agreement with investigators at the American Genome Center/Uniformed Services University of the Health Sciences. We have assembled an international collaboration to study patients enrolled at centers in Italy, which was later expanded to include centers in East Asia, the Middle East, and the Americas. An IRB-approved COVID protocol involving send-in samples was written to facilitate studies at other centers lacking their own COVID protocols. We have partnered with the COVID-Human Genetic Effort, and multiple papers have come out of this international collaboration. In FY 2022, we extended our previous discovery of genetic and acquired defects in type I IFN responses as a cause of severe or critical COVID-19. We characterized the kinetics of neutralizing autoantibodies against type I IFN and found that these were dynamically produced during acute infection but decreased during convalescence, suggesting that disease pathogenesis might involve a memory response with implications for detecting individuals with such autoantibodies before infection. In various collaborations with the NIAID COVID-19 Consortium and the COVID Human Genetic Effort, we have also assisted with the characterization of potential role of neurological biomarkers and clonal hematopoiesis in respiratory COVID-19, as well as potential genetic contribution to other forms of SARS-CoV-2 infection (MIS-C, pernio). Finally, ongoing work led by our research group is investigating the potential role of genetic variants of dsRNA sensors in COVID-19 outcome.