Existing DFG portfolio offers funding opportunities in the context of long-COVID and long-COVID-related consequences across the entire breadth of academic disciplines

Existing DFG portfolio offers funding opportunities in the context of long-COVID and long-COVID-related consequences across the entire breadth of academic disciplines

Long-COVID* syndrome resulting from COVID disease is a multidisciplinary challenge that comprises the entire spectrum of science and the humanities. Understanding the underlying pathomechanisms, developing potential therapies and investigating the consequences for individuals, society and the economy requires a wide range of research initiatives and formats. In the view of the interdisciplinary Commission for Pandemic Research of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), this type of questions requires more than short-term approaches. For this reason, long-COVID syndrome will be taken as an example to illustrate how the DFG’s existing funding portfolio can be used to respond to such issues.

The long-term effects of a COVID infection can be complex and manifest themselves in various organ systems. The frequency of such long-term effects seems to be essentially independent of existing comorbidities, but it has been observed that similar somatic or psychosomatic symptoms or a significant psychosocial burden favour their occurrence (1). Furthermore, the incidence of post-COVID symptoms four weeks after symptom onset increases with age, body mass index and the number of initial symptoms, and tends to occur more frequently in women (2). Incident pulmonary, cardiovascular, thromboembolic, metabolic and neurological and cognitive impairments are among the most common long-term outcomes that occur, regardless of the initial severity of infection. The most commonly reported symptoms are fatigue, shortness of breath, headaches, decreased performance and anosmia. Symptom complexes are subsumed under the term “long-COVID” or “post-COVID” if they persist for more than four weeks in total, and as “long-COVID syndrome” if they persist for more than twelve weeks after initial symptom onset. The word “syndrome” reflects the fact that the clinical pattern is heterogeneous. The highly varied origins and the respective pathobiological backgrounds to the complications remain largely misunderstood to date. Consequently, current therapies focus on symptom relief and supportive measures. Based on current data, it is estimated that approximately 10 percent of SARS-CoV-2 positive individuals develop post-COVID symptoms and the incidence of long-COVID syndrome is approximately 2 percent of COVID sufferers (2).

The incidence of post-COVID symptoms in children and adolescents is unclear since there is currently a lack of prospectively collected population-based data with large case numbers. A study conducted in the UK showed persistent symptoms over a period of four and eight weeks respectively in 4 percent and 2 percent of children and adolescents who had contracted the disease (3).

The symptoms can significantly affect the daily life of the sufferer, for example in limiting mobility and social participation. The longer-term psychosocial consequences of these impairments can be considerable.

Fatigue is only one of the symptoms that occur, but it serves as a good example of how the topic area in general might be tackled by scientific investigation. Fatigue syndrome is known to be subject to a wide variety of triggers, including viral infections and life events. It also occurs after a variety of other infectious diseases, such as infectious mononucleosis (4). Due to the diversity of triggers and the uncertainty in whom it occurs, it is virtually impossible to carry out systematic studies on central aspects such as risk factors, pathomechanisms and long-term progression.

The current situation offers a unique opportunity to address a number of these issues based on the example of SARS-CoV-2 infection and set up investigative projects for this purpose. It also allows the heterogeneity of disease patterns to be analysed, as well as the initiation and establishment of cohort studies, registries and databases. This can potentially provide the basis for identification and characterisation of subgroups, also with regard to the pathomechanisms, determinants and risk factors involved. It offers the opportunity to simultaneously investigate analogous sequelae of other severe (respiratory) infections (e.g. influenza, bacterial pneumonia) which have not been systematically addressed in the past but may have similarly significant effects. This also applies to the clarification of underlying pathomechanisms and to clinical studies, as well as the observation of the long-term progression and the analysis of social, psychosocial and economic effects.

If there are increasing numbers of long-COVID sufferers, this could have far-reaching implications for the health system and the labour market. A reduction in the labour supply could exacerbate the shortage of skilled workers, for example – a phenomenon that is set to increase demographically in the coming years (5). Depending on the number of people with long-COVID, this development could also have implications for economic growth in the next years. These effects need to be systematically investigated.

In addition, it is to be expected that long-COVID syndrome is associated with psychological distress and – depending on severity and individual disposition – reactive mental disorders, the effects of which could be considerable due to the prevalence of long-COVID. Research is needed to identify factors that influence the development of reactive mental disorders so as to gain knowledge to inform their prevention and treatment. There is also a need for research and action on the consequences for individual and institutional teaching and learning associated with long-COVID and how these can be addressed. Since the long-term consequences of COVID is potentially relevant not only biomedically but also on a broad social and economic scale, multidisciplinary research approaches are needed that integrate other subject-specific perspectives such as those of epidemiology, psychology, sociology, economics and public health.

The questions outlined above show that long-COVID encompasses much more than just biomedical aspects and that various funding instruments will be required, depending on the objective. It is therefore worth taking a look at the DFG’s funding formats, since they allow a high degree of creative freedom in terms of proposal submission and conception: research into clearly defined aspects can take advantage of the flexibility in terms of duration, funding scope and funding modules offered by research grants, while the Clinical Trials programme offers opportunities to support phase II and III interventional designs, for example to evaluate therapeutic options. The aforementioned complexity of the topic of long-COVID is expected to require the intense pursuit of interdisciplinary or transdisciplinary approaches: these can be well addressed within the framework of a research consortia. Depending on the breadth and characteristics of the approach, (Clinical) Research Units or Collaborative Research Centres (CRC) are well suited to conducting research into complex scientific issues. In addition, Priority Programmes (PP) can be used to provide an impetus for the development, establishment and interlinking of research fields. In addition to funding for scientific projects, opportunities are available to support academic exchange at national and international level in the form of networks or the initiation of collaborative international ventures.

With its science-driven approach and peer-review based research funding, the DFG invites subject-specific communities to identify the questions and research approaches relevant to them in connection with long-COVID and address them in the relevant proposals. It might well be that many of the challenges and questions can only be tackled by means of multidisciplinary and interdisciplinary approaches, since these offer great potential for generating new insights. Here, the DFG offers a wide range of support options for addressing the various issues. Multidisciplinary approaches in particular are welcomed in this context.

*COVID is used synonymously with COVID-19.

Literature

(1) Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27(4):601–15.

(2) Sudre CH, Murray B, Varsavsky T, Graham MS, Penfold RS, Bowyer RC, et al. Attributes and predictors of long COVID. Nat Med. 2021;27(4):626–31.

(3) Molteni E, Sudre CH, Canas LS, Bhopal SS, Hughes RC, Antonelli M, et al. Illness duration and symptom profile in a large cohort of symptomatic UK school-aged children tested for SARS-CoV-2. medRxiv. 2021:2021.05.05.21256649.

(4) Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006;333(7568):575.

(5) Marjenko A, Müller M, Sauer S. Das KfW-ifo-Fachkräftebarometer: Jedes fünfte deutsche Unternehmen wird derzeit durch Fachkräftemangel beeinträchtigt. ifo Schnelldienst, 2021, 74, No. 04, 57–59.

Further Information

About the DFG’s Interdisciplinary Commission for Pandemic Research:

• www.dfg.de/foerderung/corona_informationen/pandemie_kommission

Specialist contacts at the DFG Head Office:

• Dr. Jan Christian
  Life Sciences 3: Medicine
  Tel. +49 228 885-2345
  jan.christian@dfg.de
• Dr. Katharina Hartmann
  Life Sciences 2: Microbiology, Immunology, Neurosciences
  Tel. +49 228 885-2342
  katharina.hartmann@dfg.de