Epigenetic alterations in response to Covid-19 infection –correlation with severity, age, long-term effects and mycobacterial exposure

Bakgrund:

The Covid-19 pandemic has affected the world in an unprecedented way, and while coronaviruses are not new to the scientific community, the disease keeps puzzling with its different manifestations and the enigmatic behavior of the causative agent, SARS-CoV-2. Most studies on the immune response towards SARS-CoV-2 infection have followed a classical approach to map immunological events, including virus-specific antibody production and T cell responses.

However, epigenetic alterations may also be at play and to fill this gap, epigenomics should be added to systematic investigations of infectious diseases. We have discovered that epigenetic changes occur during infections such as tuberculosis and Covid-19 and these changes are reflected in altered DNA methylation patterns.

Målsättning:

To investigate how the DNA methylation signature identified in Covid-19 convalescents relates to Covid-19 disease severity, ageing, comorbidities and long-term effects of the disease, and whether this signature displays overlaps with the DNA methylation signature induced through mycobacterial exposure

Arbetsplan:

In the proposed project we will characterize the kinetics of the of DNA methylation alterations during Covid-19 and elucidate the relationship between reprogramming of the DNA methylome and disease severity, age, comorbidities and long-term effects. Furthermore, we will investigate how Covid-19 DNA methylome signatures correlate with those observed in subjects exposed to TB.

Since we are investigating epigenetic responses that are evolutionary conserved, we expect (corroborated in our previous studies) similar reactions in the different cell types composing peripheral blood. Such material is readily available to the project through the database-linked biobanks that have been built-up since the emergence of the pandemic.

Betydelse:

The project is unique in its kind in the endeavour to further characterize the epigenetic changes identified in covid-19 covlalescents and attempting to explain variations in relation to severity, age and comorbidities. The project can also give answer to how the epigenetic changes relates to persisting covid-19 symptoms and how they correlate with the epigenetic alterations induced through tuberculosis. Togehter, this research opens up a new avenue towards understanding infectious disease.