Funding for Organo-Strat within the National University Medicine Research Network (NUM) ended on 31 December 2021. Some of the research work will be continued in various working groups. Publications are updated on an ongoing basis.
COVID-19 is a novel infectious disease that can affect other organ systems in addition to the respiratory tract, especially in severe cases. The extent and nature of this extra-pulmonary organ involvement has a direct influence on the individual clinical prognosis as well as on therapeutic strategies and options. Accordingly, the overarching goal of the "National Competence Network Organo-Strat" is to make a significant contribution to the understanding of COVID-19 and the multiple organ involvement associated with the disease and possible treatment options. In order to clarify these largely open and clinically highly relevant questions, a systematic, organ-specific stratification for COVID-19 is being established. "Organo-Strat" will use COVID-19 to establish a modular and flexible network structure that will be able to provide information on organ-specific stratification as soon as new pathogens emerge, in the sense of "pandemic preparedness". Organo-Strat will take on these important tasks as an integral part of the National University Medicine Research Network (NUM). The pooling of expertise from a wide range of disciplines within the NUM is as unique as it is necessary to cope with this and future pandemics.
Infrastructural development of a National Competence Network Organo-Strat
There are numerous expert groups for human, organ-representative model systems working nationwide, albeit in isolated cases, which have not yet worked in the context of infection. In addition, there are BSL3 laboratories specialising in SARS-CoV-2 infections that lack 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 is required for structural and effective implementation and the development of reliable results. The aim is to structurally establish a network with these groups and assigned roles, in which standards for organ models, targeted infections, native tissue and autopsy samples, analyses and data management become effective in the form of an agreed process chain for COVID-19 and beyond.
Clarification of the organo- and cell tropism of SARS-CoV-2
According to current knowledge, SARS-CoV-2 permissive (infectable) cells must have specific host factors that support viral entry, maturation and replication. However, the literature regarding the involvement of different organ systems and their cell types is so far ambiguous and fragmented. Reliable data that allow an inter-organ relation of permissivity-determining host factors at mRNA and protein level are urgently needed and must also be related to viral replication capacity and individual donor data. The determination of these factors and relationships is being pursued within "Organo-Strat" and compared in native or SARS-CoV-2-infected tissues. The establishment of donor-specific native tissue and organoid banks will also make it possible to examine questions of personalised medicine in the future.
Understanding organ-specific virulence in COVID-19
Virus-infected cells generally undergo defined damage mechanisms and release additional factors during this process and for the purpose of immune activation. The identification of affected cells, the analysis of the viral replication capacity and the estimation of the extent of damage (virulence) in each organ system are the primary objectives here.
Establishment of drug testing on human organ models
Re-purposing refers to the use of already authorised drugs and active substances in a new field of application. A prerequisite for both the preclinical testing of potentially anti-viral substances against SARS-CoV-2 and the assessment of the influence of concomitant medications such as antihypertensives on the course of infection is the identification of suitable infection models. Since it cannot be assumed that the various organ systems are equally permissive, these must first be identified. Ideally, suitable models should have a robust and reproducible viral replication 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 or reducing virulence and potential side effects. These models are identified and operated in "Organo-Strat" and the data obtained are made available in a timely manner for use in clinical studies.