Periodic Reporting for period 1 - HDM-FUN (Host directed medicine in invasive fungal infection) Reporting period: 2020-01-01 to 2021-06-30 Summary of the context and overall objectives of the project Despite novel treatment options and diagnostic tools, invasive fungal infections are still associated with an unacceptably high mortality and morbidity. Experts believe that a host-directed approach is needed to overcome this clinical challenge. No study to date in invasive fungal infection has integrated a host-directed strategy into a clinical trial. This consortium proposes for the first time a trans-disciplinary approach to identify personalized therapeutic and prophylactic strategies based on host-pathogen factors. We believe that we need such a personalized medicine approach in order to advance the aim of improved outcome in invasive fungal infection, and that, together with the exponential knowledge that has been gained in host-fungal interaction over the last two decades, it is time to move towards proof-of-principle clinical trials that can save lives of patients.To this aim two clinical trials of host-directed medicine approaches will be performed: an immunotherapy trial with interferon gamma (IFNγ in patients with candidemia and a prospective observational trial in patients with influenza to identify patients at risk for aspergillosis that might benefit from antifungal prophylaxis. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far Despite the plans settled in the Annex I of Grant Agreement, the clinical studies have not started yet due to closure of clinical centres to face with Covid-19 pandemic. The preparation of documents for ethical clearance has been delayed by the Covid-19 emergency. Overall, the first reporting period was focused on several key objectives that could be carried out during the pandemic. We have setup the centralized biobank as described in WP4 in Nijmegen and established the routes and logistics for handling the samples that will be sent in batches from the clinical trial centres. We have focussed on establishing the legal contracts between RUMC, the Sponsor of both clinical studies (WP2-3), and the clinical centres involved in the two clinical studies. The protocols for the clinical trials have had extensive discussions and revisions which have been made possible by meetings with the two clinical teams that are responsible for carrying out the trial. During the pandemic we have organized this structure with 2-monthly meeting per clinical trial with the PIs involved in that trial. This gave us room to stay connected during the pandemic but also made it possible to prepare a more adapted plan to carry out the trials in the coming years. Although the timelines for starting the trials have both been delayed for 12 months the preparation allowed us to adapt the project in these uncertain times. For the basic science that will be performed in WP5,6,7 several partners have prepared and optimized the protocols and experimental measures that will be performed on the samples from the clinical trials.Besides, we have started to communicate project activities and also raising awareness about novel treatments in fungi infections in the scientific community and general public. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) HDM-FUN is a unique project with the ambition to change treatment of fungal infection and influence daily clinical practice. It has the ambitious goal of introducing a new paradigm in host-directed medicine, namely the personalization of treatment and prevention of fungal infections by stratification based on host and pathogen factors. At this moment, all clinical trials on immunotherapy in infectious diseases have had a ‘one size fits all’ approach. Because the immune status of ICU patients is substantially different, such an approach is eventually deemed to fail. HDM-FUN has setup its design of clinical trials and research in such a way that we will be able to overcome this hurdle after completion of the current proposal. HDM-FUN will contribute to (i) creating societal impact by changing clinical practice to better control infectious diseases and reduce their burden, thereby ensuring health and well-being for all, at every stage of life; (ii) reducing antimicrobial resistance; and (iii) developing HPF-based targeted treatments and preventive measures, HPF-biomarker based diagnostics and novel standards with respect to clinical trials and protocols. Project Logo HDM-FUN small teams HDM-FUN Management scheme
