Organo-Strat

Clarifying the direct or indirect involvement of central organ systems in COVID-19 is a particular challenge that Organo-Strat addressed on the basis of four specific objectives:

1. Infrastructural development of a national competence network Organo-Strat
2. Clarification of the organo- and cell tropism of SARS-CoV-2
3. Essential understanding of organ-specific virulence in COVID-19
4. Establishment of drug testing using preclinical human organ model systems

Ad 1) Throughout Germany, there were numerous but isolated expert groups for both human, organ-representative model systems that had not previously worked in the context of infection. In addition, there were BSL3 laboratories specialising in SARS-CoV-2 infections that lacked access to corresponding meaningful organ-specific infection models. In order to establish a systematic, organ-specific stratification for COVID-19, national cooperation in the form of a new network consisting of the aforementioned actors and other partners was required for structural and effective implementation and the development of reliable results. The aim was to structurally establish a network with the aforementioned groups and assigned roles, in which standards for organ models, targeted infections, native tissue and autopsy samples, analyses and data management could become effective in the form of an agreed process chain for COVID-19 and beyond.

Ad 2 ) According to the state of knowledge at the start of the project, cells permissive for SARS-CoV-2 had to have specific host factors that support viral entry, maturation and replication. However, the literature on the involvement of different organ systems and their cell types has so far been ambiguous and fragmented. Reliable data allowing an inter-organ relation of permissivity-determining host factors on mRNA and protein level were urgently needed and also had to be related to viral replication capacity and individual donor data. The determination of these factors and relationships was pursued within "Organo-Strat" and compared in native and COVID-19 tissues. The establishment of donor-specific native tissue and organoid banks also created the opportunity to examine questions of personalised medicine in the future.

Ad 3) Virus-infected cells generally undergo defined damage mechanisms and release other factors during this process for the purpose of immune activation. The identification of affected cells, the analysis of the viral proliferation capacity and the assessment of the extent of damage (virulence) in each organ system were the primary objectives here.

Ad 4) A prerequisite both for the preclinical testing of potentially anti-viral substances against SARS-CoV-2 and for the assessment of the influence of concomitant medications such as antihypertensives on the course of infection is to identify suitable infection models. Since it could not be assumed that the various organ systems were equally permissive, these first had to be identified, as mentioned in 2) and 3). Ideally, suitable models should have a robust and reproducible viral propagation capacity and allow the investigation of aspects of pharmacokinetics (e.g. absorption) and dynamics (e.g. dose-response relationship, mechanism of action). Furthermore, they allow conclusions to be drawn about influencing/reducing virulence and potential side effects. These models were identified and operated in "Organo-Strat", and the data obtained were promptly made available for use in clinical studies.