Periodic Reporting for period 1 - EPIVINF (Epigenetic regulation of host factors in viral infections (EPIVINF))
Berichtszeitraum: 2022-09-01 bis 2024-02-29
In the case of SARS-CoV-2 infection, sometimes severe neurological disease has been noted from the earliest days of the Covid-19 pandemic. As the pandemic progressed, it became also evident that approximately 10-15% of the infected individuals may continue to experience Covid-19 related disease after the initial infection has resolved. This situation has been recognized by the WHO as the separate disease entity of “Long Covid” or “Post Covid-19 condition (PCC)”, which may affect in Europe alone 15+ million individuals. In a significant proportion of these individuals, disease manifestation includes neurological symptoms, which we here refer to as “Neuro Long Covid”. This disease spectrum includes a wide range of symptoms, which often are considered subjective perceptions, rather than representing objective measurements of some clinical parameter or biomarker. There is therefore common skepticism in the general public, among medical professionals, health insurances and among public health authorities as to the existence and nature of (Neuro) Long Covid. This has led to major frustration and medical abandonment of affected people and slowed progress in understanding the mechanisms, biomarkers and prognosis of this disease.
Disease persistence or progression in chronically persistent infections, such as HIV, have been linked to effects of ongoing viral replication and inflammation. The reasons for prolonged disease manifestation after supposedly only transient infections, such as SARS-CoV-2 infection, remain less well understood. The EPIVINF project is based on the hypothesis that immunological and epigenetic mechanisms triggered during the acute infection stages are determining the longer-term outcomes of these infections. Epigenetic regulation of host genes´ activity can be mediated by different mechanisms, which, as a general principle, lead to reduced amounts of the specific proteins being produced. Some of these mechanisms are considered to be stable over time, so that events during an acute infection could well persist long after the pathogen has been cleared from the body. Thus, our project centers especially on epigenetic dysregulation of host factors that are central for pathogen control and resolution of disease in the long term. We are thereby especially interested in mechanisms that are drivers of neurological long-term disease and how their identification could help develop novel therapeutic tools as the prevention and treatment of the neurological impact of these infections remains an enormous unmet medical need.