Tissue and organ specific human B cell immunity: Supplement - Metabolic Risk Factors and Inflammation in PASC Development

尽管冠状病毒通常被认为是引起急性呼吸道感染的原因，但新出现的证据表明， 病毒抗原或甚至完整的病毒可能在呼吸系统外被发现， 急性感染后的一段时间。此外，数据显示，许多非呼吸道组织， 包括脂肪组织，可以作为病毒的储存库，这表明这种感染可能具有长期性。 对身体多个器官系统的影响。现在人们认识到， 被诊断患有COVID-19的人将继续表现出各种各样的衰弱症状，统称为 作为SARS-CoV-2（PASC或长COVID）的急性后遗症，在感染后数周至数月。鉴于 大量的SARS-CoV-2感染者可能发展为PASC，因此迫切需要 为了更好地了解与不同PASC表现相关的风险因素， 采取适当的干预措施来治疗这些患者。到目前为止，我们对PASC的原因知之甚少， 不了解预先存在的健康问题（风险因素）是否可以用来预测是否 是否有人会发展PASC，或者具有特定风险因素的个体是否会发展具有特定风险因素的PASC。 一系列症状。这种补充的目的是确定是否与前代谢相关的代谢变化， 现有的肥胖症和II型糖尿病（T2 D）导致特定的PASC相关免疫表现。在 本补充，我们将测试假设，代谢危险因素可用于确定患者与 炎性PASC综合征，其特征在于持续的免疫激活。为了实现这些目标，我们 已经聚集了超过4000名同意参与者（企业队列），他们之前因COVID住院， 19感染我们可以访问他们的电子医疗记录，可以纵向跟踪他们的症状， 在线调查问卷，并可以从中获得生物样本。我们收集了生物银行的血液样本 在急性感染期间，来自>1700人，其中许多人被诊断为PASC， 在我们的PASC诊所进行纵向随访。使用这些样本以及额外的血液样本， 从企业队列中的PASC患者中收集，我们建议：（i）确定肥胖和T2 D是否 PASC患者表现出持续的抗病毒T和B细胞应答;（ii）检查代谢危险因素是否 与肥胖和T2 D相关的炎症介质与炎性PASC的发展相关; 和（iii）评估预先存在的肥胖和相关的代谢疾病是否预测肥胖症的发展。 炎症性PASC综合征。这些研究很重要，因为它们将使我们能够具体地询问 代谢和免疫因素影响PASC的病理生理学在个人的慢性co- 影响到南方腹地大部分人口的疾病在未来，我们希望 这些研究结果有助于提高PASC的诊断和治疗水平。

Although coronaviruses are typically believed to cause acute respiratory infections, emerging evidence suggests that viral antigen or perhaps even intact virus may be found outside of the respiratory system for extended periods of time following acute infection. Moreover, the data show that numerous non-respiratory tract tissues, including adipose tissue, can serve as a reservoir for the virus, suggesting that this infection may have long-term effects on multiple organ systems of the body. It is now recognized that a significant fraction of individuals diagnosed with COVID-19 will continue to exhibit a wide array of debilitating symptoms, collectively referred to as Post-Acute Sequalae of SARS-CoV-2 (PASC or Long-COVID), for weeks to months after infection. Given the enormous number of SARS-CoV-2 infected individuals who are likely to develop PASC, there is a critical need to better understand the risk factors associated with the different PASC manifestations and to develop appropriate interventions to treat these patients. To date, we know very little about the causes of PASC and do not have any understanding of whether pre-existing health issues (risk factors) can be used to predict whether someone will develop PASC or whether individuals with particular risk factors will develop PASC with a specific set of symptoms. The goal of this supplement is to determine whether metabolic changes associated with pre- existing obesity and Type II Diabetes (T2D) contribute to specific PASC-associated immune manifestations. In this supplement, we will test the hypothesis that metabolic risk factors can be used to identify patients with an inflammatory PASC syndrome that is characterized by persistent immune activation. To meet these goals, we have assembled >4000 consented participants (Enterprise cohort) who were previously hospitalized for COVID- 19 infection. We have access to their electronic medical records, can follow their symptoms longitudinally with on-line questionnaires and can obtain biologic samples from them. We have bio-banked blood samples, collected during the acute infection, from >1700 individuals, many of whom were diagnosed with PASC and have been followed longitudinally in our PASC clinic. Using these samples as well as additional blood samples that will be collected from PASC patients in the Enterprise cohort, we propose to: (i) determine whether obese and T2D PASC patients exhibit sustained anti-viral T and B cell responses; (ii) examine whether metabolic risk factors and inflammatory mediators linked to obesity and T2D correlate with the development of inflammatory PASC; and (iii) assess whether pre-existing obesity and associated metabolic disease predict the development of an inflammatory PASC syndrome. These studies are important as they will allow us to specifically interrogate the metabolic and immunologic factors that influence the pathophysiology of PASC in individuals with chronic co- morbidities that affect a large proportion of the population in the Deep South. In the future, we expect that insights gained from these studies may improve the PASC diagnosis and treatment.