Scientists are investigating how epigenetic mechanisms, which regulate gene expression without changing DNA sequences, influence HIV’s long-term effects and how these mechanisms can be targeted to improve treatment for HIV disease
One of the major goals of the EPIVINF project is the investigation of the epigenetic changes associated with Long COVID-19, aiming to understand the lasting neurological symptoms that some patients experience after SARS-CoV-2 infection. To identify predictive biomarkers of Long COVID disease and disease progression and to identify potential therapeutic targets for people affected by Long COVID, it is fundamental to understand the mechanisms involved in the pathological processes of the Central Nervous System (CNS) seen in Long COVID). The uniqueness of the study lies in the comprehensive neuro-evaluation and multi-omics analysis of Long Covid, including simultaneous brain MRI, CSF and peripheral blood analyses.
Symptoms that persist for months
Long COVID refers to a clinical condition where patients continue to experience symptoms weeks or even months after recovering from the acute phase of SARS-CoV-2 infection. These symptoms are variable and can include fatigue, muscle pain, and cognitive impairments such as memory loss and concentration issues, commonly referred to as “brain fog.” Around 10% of COVID-19 patients are affected by these symptoms.
IrsiCaixa in collaboration with Fundació Lluita contra les Infeccions, are analysing how SARS-CoV-2 infection may trigger long-term changes in gene expression through epigenetic mechanisms and how these processes contribute to LongCovid. Researchers aim to understand how these alterations contribute to neurological manifestations, such as headaches, anosmia (loss of smell), dizziness, and cognitive difficulties. Moreover, the study differentiates between individuals infected before and after the OMICRON variant, to understand the impact of vaccination and viral variants on neurological effects.
Lumbar punctures are essential for this study
To date, the research team has enrolled 41 participants, aged 40-50, who have undergone an extensive battery of tests, including cognitive evaluations, electroencephalograms (EEGs), and challenging lumbar punctures to extract the volume of 30ml of cerebrospinal fluid (CSF). These CSF samples, which contain important soluble and cellular signals from the central nervous system, are critical to understand the immunological components of LongCovid in the CNS. Thus, the investigation derived from CSF samples and brain imaging will provide a direct window into potential changes in the CNS that are not resolved after acute SARS-CoV-2 infection.
By analysing these very unique biological samples using an equally innovative set of analyses, the study aims to determine whether epigenetic changes, such as DNA methylation, contribute to long-term neurological symptoms in COVID-19 patients. These changes could explain why some individuals experience persistent symptoms even after the virus has been cleared from their bodies and offer novel opportunities for treatment.
Integrating Multi-Omics to uncover Long COVID mechanisms
In collaboration with Centre Nacional d’Anàlisi Genòmica (CNAG), the project is now using advanced methods of single cell sequencing, TCR analyses and proteomics to investigate epigenetic, immune, and proteomic changes in Long Covid.
