Determination of immunological deviations in post-COVID-19 syndromes by single cell omics

自大流行开始以来，已经明确的是，COVID-19是一种非常异质性的传染病，在疾病的急性阶段具有不同的病程，不仅限于肺部，而且涉及许多不同的器官系统，包括全身免疫反应。我们证明，通过单细胞rna测序等高分辨率、高通量的单细胞技术，可以解剖急性COVID-19的全身免疫反应，这使我们能够识别几乎所有免疫细胞区室中的巨大重编程。近几个月来，越来越明显的是，大量急性COVID-19患者并没有完全康复，轻度或重度急性感染患者也是如此。我们假设，在急性COVID-19中观察到的免疫偏差导致免疫重编程的慢性化，这可能与在未恢复的患者中观察到的异质性症状（也称为“长期COVID-19”）有因果关系。为了表征免疫系统内的细胞和分子基础，我们的目标是使用我们成功应用于表征COVID-19急性期的相同单细胞组学技术，研究长COVID-19患者的全身免疫反应。我们将把我们的研究结果与急性COVID-19、健康对照以及其他慢性炎症进行对比。与我们之前在急性COVID-19中的发现类似，我们期望通过这些基于单细胞的技术确定Long COVID-19的系统性免疫细胞区室，将使我们能够确定免疫病理，从而进一步纳入治疗开发和分子机制的背景下。

Since the start of the pandemic, it has become clear that COVID-19 is a very heterogenous infectious disease with different disease courses during the acute phase of the disease, which is not restricted to the lung, but with involvement of many different organ systems including a systemic immune response. We demonstrated that the systemic immune response in acute COVID-19 can be dissected by high-resolution, high-throughput single cell technologies such as single cell RNA-sequencing, which allowed us to identify the enormous reprogramming in almost all immune cellular compartments. In the last months, it become more and more clear that a large number of patients suffering from acute COVID-19 do not fully recover and this is similarly true for patients with mild or severe courses of the acute infection. We hypothesize that immune deviations observed in acute COVID-19 are leading to chronification of immune reprogramming, which might be causally linked to the heterogenous symptoms observed in patients that do not recover (also termed shortly ‘Long COVID-19’). To characterize the cellular and molecular underpinnings within the immune system we aim to study the systemic immune response in patients with long COVID-19 using the same single cell omics technologies we successfully applied to characterize the acute phase of COVID-19. We will contrast our findings to acute COVID-19, healthy controls, but also other chronic inflammatory conditions. Similar to our previous findings in acute COVID-19, we expect that the determination of the systemic immune cell compartment in Long COVID-19 by these single cell-based technologies will allow us to determine immune pathology that can be further put into context of therapy development and molecular mechanisms.