When the infection is over and the disease is just beginning

• Post-infectious diseases are on the rise. Infections such as COVID-19 can lead to chronic conditions such as Long COVID or ME/CFS months or even years later, affecting hundreds of thousands of people in Germany.
• As part of the National Decade Against Post-Infectious Diseases, the Federal Ministry of Research, Technology, and Space (BMFTR) is investing approximately 500 million euros over the next decade to systematically research causes, disease mechanisms, diagnostics, and therapies and to improve care.
• The NAKO Health Study, with 200,000 participants, provides crucial long-term data and enables a rare before-and-after comparison with data and biosamples from before, during, and after infection.
• The aim of research is to determine the actual prevalence of post-infectious diseases more accurately, to better understand the underlying biological processes, and to effectively support those affected through targeted interventions in the future.

The problem sometimes only begins once the danger has been averted and defeated. Individuals become infected with viruses or other microorganisms; their immune system becomes active, they may develop a fever and feel somewhat weakened while the battle rages inside their body. Eventually, the intruders are defeated, the infection is largely overcome, and things should actually start to improve. Instead, sometimes after a break of a few days to many years, depending on the disease, a new disease develops, presumably caused by immune dysregulation or pathophysiological processes during the infection. Such a disease is referred to as a post-infectious disease.

One particular form has been on everyone's lips since the coronavirus pandemic and has reached new proportions: Long COVID, characterized by fatigue, reduced resilience, cognitive impairment ("brain fog "), and shortness of breath persisting for weeks to months after a SARS-CoV-2 infection. The incidence of myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) has also skyrocketed. ME/CFS refers to a severe, chronic multisystem disease that often occurs after an infection and is characterized primarily by pronounced exhaustion that worsens significantly after exertion. According to expert estimates, approximately 870,000 people in this country were living with Long COVID and 650,000 with CFS by the end of 2024.

Ten years of research into the long-term effects of infections

Since the pandemic, post-infectious diseases have become an increasingly important issue, not only medically but also socially, with far-reaching consequences for those affected and the healthcare system. To counteract this, the Federal Ministry of Research, Technology, and Space, together with the Federal Ministry of Health and other partners, launched the "National Decade Against Post-Infectious Diseases " at the beginning of this year. The aim is to systematically research the causes, disease mechanisms, diagnostics, and therapies of post-infectious diseases, including Long COVID and ME/CFS, over the course of a decade, while also developing new care pathways. A total of around 500 million euros, or about 50 million per year, has been earmarked for this purpose, which will be invested in interdisciplinary projects, data infrastructures, and clinical studies.

"The better we understand the causes and disease mechanisms, the better we can prevent and treat them. This is especially true for post-infectious diseases: their disease mechanisms are still poorly understood, so there is a lot to do and discover, " explains Annette Peters, Chair of the NAKO Health Study and Director of the Institute of Epidemiology at Helmholtz Munich. 

The NAKO- Health Study is involved in several important projects as part of the National Decade Against Post-Infectious Diseases. This is hardly surprising, given that NAKO is particularly well-positioned to contribute its strengths effectively in this area. It is Germany's largest population-based long-term study to date. Since 2014, approximately 200,000 men and women aged 20 to 69 have undergone medical examinations throughout Germany and are regularly asked about their state of health, lifestyle habits, and environmental factors.  

A valuable before-and-after view

"In order to better understand post-infectious diseases, it is ideal to be able to make a before-and-after comparison. This is exactly what NAKO enables us to do: we have data and biological samples, such as blood samples, from our participants from before, during, and after the pandemic, " explains Peters. This is precisely the advantage offered by EpiPAIS (Epidemiology of Post-Acute Infection Syndromes), a central project of the Decade based at NAKO. EpiPAIS is conducting in-depth examinations of approximately 4,500 NAKO participants, for whom a before-and-after comparison is particularly feasible. 

The researchers are trying to keep the comparisons as broad as possible. This is because the exact mechanisms that cause a recovered infection to develop into a chronic disease have not yet been conclusively clarified. Among other things, they are discussing persistent dysregulation of the immune system, including chronic inflammatory activity, autoimmune reactions against the body's own structures, and viral components that remain in the body even after infection and continue to stimulate the immune system. Vascular dysfunction, microthrombi, changes in the autonomic nervous system, and metabolic and mitochondrial dysfunction are also suspected of contributing to symptoms such as fatigue, cognitive impairment, and shortness of breath. "It is probably not a single trigger, but rather an interaction of several factors that varies depending on the infection and individual predisposition, " says Peters.