BMFTR – Collaborative Interdisciplinary Research into the Pathomechanisms of Post-Infectious Diseases

Funding is provided for interdisciplinary research consortia in Germany that investigate the pathomechanisms of post-acute infection syndromes (PAIS).

The funding initiative ‘Collaborative Interdisciplinary Research into the Pathomechanisms of Post-Infectious Diseases‘ (Förderung interdisziplinärer Verbünde zur Erforschung der Pathomechanismen von postinfektiösen Erkrankungen) by Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR – Federal Ministry of Research, Technology and Space) is part of the BMFTR’s ‘National Decade against Post-Infectious Diseases‘ (Nationale Dekade gegen Postinfektiöse Erkrankungen) and its overarching Health Research Framework Programme.

The aim of the National Decade campaign is to strengthen research into the causes and mechanisms of post-acute infection syndromes (PAIS) and to systematically investigate new possibilities for their diagnosis, treatment, rehabilitation and prevention. In this context, the investigation of disease-relevant pathomechanisms of PAIS is intended to contribute to a better understanding of the aetiology of PAIS, from which new approaches to improving prevention, diagnosis and treatment can be derived.

Funding is provided for interdisciplinary collaborative projects aimed at further elucidating, validating and functionally characterising the pathomechanistic processes in PAIS that are already broadly understood, as well as investigating the potential for therapeutic intervention. The focus is on Long/Post-COVID syndrome and post-infectious ME/CFS. Comparative studies of these clinical presentations with PAIS caused by other pathogens are also permissible.

Research approaches should be based on clinically relevant symptoms such as post-exertional malaise (PEM) or postural tachycardia syndrome (POTS), as well as on defined organ-specific damage. They must be based on a hypothesis with a clear mechanistic basis that is experimentally testable, for which there is already robust evidence, and which can be tested within the scope of the project.

The initiative supports all stages of pre-clinical and clinical research necessary to further elucidate the pathomechanisms of PAIS and to identify potential approaches for their application in prevention, diagnosis and treatment. This may include:

• Basic mechanistic research:
  • Mechanistic analysis and functional characterisation of disease-relevant pathomechanisms at the genetic, cellular and molecular levels.
  • Elucidation of the mechanisms underlying the dysregulation of various organ systems (eg the immune system, metabolism, the cardiovascular system, the autonomic nervous system).
  • Investigation of viral persistence or reactivation mechanisms.
  • Gender-dependent pathogenesis of PAIS.
• Identification of new predictive, diagnostic or prognostic biomarkers relevant to the stratification of patient groups:
  • Derivation of mechanistically grounded, clinically relevant disease endotypes.
  • Validation of meaningful biomarkers or biomarker signatures for distinguishing between relevant disease endotypes.
• Preclinical research into the development of new therapeutic approaches:
  • Validation of novel target molecules.
  • Demonstration of the feasibility of a novel therapeutic approach through exploratory and/or confirmatory studies in animal models, as well as further investigations in disease-relevant preclinical models.
• Research into relevant preclinical disease models, provided they are relevant to the pathomechanistic questions under investigation:
  • Further development and validation of suitable experimental model systems (animal models, organoids, human-derived cell and tissue systems).
  • Functional investigation of mechanistic questions and causal biological relationships in suitable preclinical model systems.
• Systems biology and data-driven approaches:
  • Analysis of various existing, harmonised data sources and material collections to investigate genetic, cellular and molecular pathomechanisms and their interactions with one another.
  • Systems biology modelling of pathophysiological processes.
  • AI-supported analysis of existing datasets to support and validate hypothesis-driven mechanistic research approaches.

Given the varying manifestations of PAIS, funded projects must carry out as comprehensive a clinical phenotyping as possible. Modifying factors such as gender, age group or comorbidities must also be taken into account.

Age- and development-related differences in the manifestation and dynamics of disease-relevant pathomechanisms in children and adolescents also should be taken into account where relevant. These include, in particular, changes in biological mechanisms over the long term, as well as the potential influence of hormonal and developmental changes during the transition from prepuberty to puberty.