Leveraging genomic data to dissect the association of internalizing disorders with the risk, onset, and vulnerability of COVID-19

抽象的。尽管我们对COVID-19及其传染因子SARS-Cov-2的了解， 虽然疫苗已经研制成功，但仍存在许多不确定性。 如何以及何时结束这场大流行此外，还有许多 由于COVID-19对个人和社会的广泛影响，我们 将继续面临的挑战。这是一个方面，这是强烈有助于 持续的危机是系统性地缺乏可靠的信息来指导医疗保健专业人员 和政策制定者。为了将网络方法应用于COVID-19研究，我们应该优先考虑 连接COVID-19后果不同领域的“枢纽”。心理健康肯定是 这是受COVID-19影响最大的卫生领域之一。 COVID-19限制导致的隔离、心理压力和“空闲时间”无聊， 一直与内化症状增加有关，包括焦虑和 萧条此外，与COVID-19相关的创伤经历（例如，严重的症状， 住院治疗和亲人的死亡）也与创伤后压力有关 disorder.在一个恶性循环中，内化障碍与风险增加有关。 SARS-Cov-2感染和COVID-19严重症状、住院和死亡率。为 例如，SARS-Cov-2感染和COVID-19严重程度可能是由于一种减弱的 与内在化障碍相关的免疫系统。近年来，基因研究 被证明是一个非常宝贵的工具，可以剖析与内化相关的潜在动态， 紊乱和特征事实上，遗传信息可以作为因果推理的锚 测试人类特征和疾病之间的关系，并调查 基因组调控机制对疾病风险的影响。基于我们的专业知识和支持 通过我们的研究结果，我们提出了一个多变量的调查，以确定潜在的 与内化谱（焦虑、重性抑郁症和创伤后精神障碍）相关的因素 应激障碍）和COVID-19结果（感染、住院和危重病）。然后， 我们将在多个组学中研究这些潜在因素的调节机制 结构域、组织和细胞类型。与此同时，我们也将测试内部化的相互作用， 与COVID-19相关的基于血液的转录组学和表观基因组学变化谱 发病率和心理压力。我们的研究结果将提供一个多维度的视角， COVID-19结果与内在化之间关联的潜在过程 紊乱

Abstract. Although our understanding of the COVID-19 and its infectious agent, SARS-Cov-2, is greatly improved and effective vaccines have been developed, there are many uncertainties regarding how and when the pandemic is going to end. Additionally, there are many consequences due to the pervasive impact of COVID-19 on individuals and societies that we will continue to face in the post-pandemic world. An aspect that is strongly contributing to the ongoing crisis is the systematic lack of reliable information to guide healthcare professionals and policymakers. To apply a network approach to COVID-19 research, we should prioritize the “hubs” connecting the different domains of COVID-19 consequences. Mental health is surely one of the health domains that are being more strongly affected by COVID-19 outcomes. Isolation, psychological stress, and “free-time” boredom induced by COVID-19 restrictions have been consistently associated with increased internalizing symptoms, including anxiety and depression. Additionally, traumatic experiences related to COVID-19 (e.g., severe symptoms, hospitalization, and death of a loved one) have been also linked to posttraumatic stress disorder. In a vicious circle, internalizing disorders have been associated with an increased risk of SARS-Cov-2 infection and COVID-19 severe symptoms, hospitalization, and mortality. For instance, SARS-Cov-2 infection and COVID-19 severity can be due to the effect of a weakened immune system associated with internalizing disorders. In recent years, genetic research has demonstrated to be an invaluable tool to dissect the underlying dynamics related to internalizing disorders and traits. Indeed, genetic information can be used as an anchor for causal inference to test the relationships linking human traits and diseases and to investigate the effect of genomic regulatory mechanisms on disease risk. Based on our expertise and the supporting findings generated by our studies, we propose a multivariate investigation to identify the latent factors linking the internalizing spectrum (anxiety, major depressive disorder, and posttraumatic stress disorder) and COVID-19 outcomes (infection, hospitalization, and critical illness). Then, we will investigate the regulatory mechanisms of these latent factors across multiple omics domains, tissues, and cell types. In parallel, we will also test the interaction of the internalizing spectrum with blood-based transcriptomic and epigenomic changes associated with COVID-19 morbidity and psychological stress. Our findings will provide a multi-dimensional perspective on the processes underlying the associations between COVID-19 outcomes and internalizing disorders.