Understanding Co-morbidities: COVID-19 in individuals living with HIV/AIDS

摘要 虽然新冠肺炎仍然是一个健康挑战，但人们对新冠肺炎如何影响人们知之甚少 艾滋病毒携带者(PLHIV)。然而，根据疾控中心和世卫组织的最新报告，似乎 艾滋病毒携带者感染后患严重新冠肺炎疾病的可能性可能增加30% 与SARS-CoV-2有关。我们将利用已建立的SARS-CoV-2感染猕猴模型 在新冠肺炎和SIV感染中表征潜在SIV感染对两者表现的影响 急性和急性后新冠肺炎后遗症。我们团队是为数不多的建立恒河猴的组织之一。 在大流行期间早期的新冠肺炎感染模型。我们的模型已经被用来研究 预防SARS-CoV-2感染以及加速发展的免疫学机制 新冠肺炎的疫苗和治疗方法。在这里，我们建议将这种模式与长期存在的、高度 在SIV感染的恒河猴中验证致病艾滋病NHP模型，以研究一个中心假设 潜在的SIV感染和由此产生的免疫缺陷/免疫激活促进了 因SARS-CoV-2感染而出现更严重的新冠肺炎症状。作为推论，我们假设艺术可以 不能完全抑制SIV引起的慢性免疫激活的不良影响，也不能完全预防 非典冠状病毒2型感染致严重新冠肺炎猕猴模型的进展。我们有经验 在用SIV感染恒河猴并用ART治疗这些动物以抑制病毒复制和 研究免疫机制。通过描绘病毒滴度、诱导组织病理学和 潜在的免疫紊乱，我们将提供关于SIV感染恒河猴 猕猴对严重新冠肺炎表现出更高的易感性。此外，我们的研究也将能够暗示 导致这种易感性的具体机制。描绘出这些共病的免疫因素 驾驶敏感性将使更好的临床监测和患者护理的知情决定。机械论 这项研究得出的见解对于发展宿主导向的免疫治疗也是必不可少的 抗击新冠肺炎感染艾滋病的干预措施。

Summary While COVID-19 continues to be a health challenge, very little is known about how COVID-19 affects people living with HIV (PLHIV). Based on the most recent reports originating from CDC and WHO, however, it appears that people with HIV may have a 30% greater likelihood of developing severe COVID-19 disease when infected with SARS-CoV-2. We will leverage the established rhesus macaque models of SARS-CoV-2 infection resulting in COVID-19 and SIV infection to characterize the effects of underlying SIV infection on the manifestation of both acute and post-acute COVID-19 sequelae. Our group was amongst few that established the rhesus macaque models of COVID-19 infection early on during the pandemic. Our model has been utilized to both study the immunological mechanisms of protection from SARS-CoV-2 infection, as well as for accelerated development of vaccine and therapeutics against COVID-19. Here we propose to couple this model with the long-standing, highly validated, pathogenic AIDS NHP model in SIV infected rhesus macaques to study a central hypothesis that underlying SIV infection and the resulting immunodeficiency/immune activation promotes the progression of a more severe COVID-19 presentation due to SARS-CoV-2 infection. As corollary, we hypothesize that ART does not completely suppress the ill effects of chronic immune activation due to SIV, it will not completely prevent the progression of severe COVID-19 due to SARS-CoV-2 infection in the macaque model. We have the experience in infecting rhesus macaques with SIV and treating these animals with ART to suppress viral replication and study immune mechanisms. By profiling the differences in dynamics of viral titers, induced tissue pathology, and underlying immunological perturbations, we will provide definitive knowledge in whether SIV infected rhesus macaques exhibit higher susceptibility to severe COVID-19. Furthermore, our studies will also be able to hint at the specific mechanisms which result in this susceptibility. Delineating these comorbid immunological factors driving susceptibility will enable better clinical monitoring and informed decisions for patient care. Mechanistic insights developed by this study is also imperative for the development of host-directed immunotherapeutic interventions for combating COVID-19 in PLHIV.