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

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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.