Exploring the mechanisms of Long-COVID

An important aspect of the Corona pandemic is the long-term effects of COVID infection, also known as "long-COVID." Often, long-COVID is associated with damage to the brain and neurology. This damage may be related to extensive inflammation triggered by the infection with the SARS-CoV-2 virus. Recent findings have shown that there is an increased risk of neurological and psychiatric disorders in the six months following a COVID-19 diagnosis. The risk is especially higher if the patients have had to undergo hospitalization or intensive medical care. In addition, patients with pre-existing neurological conditions are more susceptible to SARS-CoV-2 infection and associated neurological damage.

Together with an international team, Prof. Paolo Carloni (JARA-BRAIN and JARA-CSD) and Prof. Rossetti (JARA-CSD) are investigating the neurological aspect of Long-COVID in the project "BRAVE ". In addition to the two researchers from Forschungszentrum Jülich, Prof. Rebecca Wade, University of Heidelberg, Prof. Francesca Spyrakis, University of Turin, and Prof. Giorgio Colombo, University of Pavia, are composing the team of scientist working in the project. The team received funding from the European Commission as a result of a call for proposals in the Human Brain Project.

The major mechanism involved in the development of psychiatric and neurodegenerative diseases is neuroinflammation. "The overall goal of our project is to develop computational approaches that complement and integrate EBRAINS tools and services," explains Prof. Giulia Rossetti, "In this way, we aim to advance the study of the mechanisms of COVID-19-related brain disorders. In addition, we will develop new drug candidates capable of blocking the excessive inflammatory responses in the brain triggered by SARS-CoV-2."

In particular, the team will focus on NLRP3, the key protein effector involved in the mechanisms that lead to brain disorders and neurodegeneration. "NLRP3 acts as a hub protein that activates and links different inflammatory pathways. This can occur in COVID-19, Alzheimer's pathology, and acute respiratory distress syndrome (ARDS). Survivors show an increased incidence of long-term depression, anxiety and cognitive impairment," adds Prof. Paolo Carloni. These observations suggest that inhibition of inflammasome activation could prevent COVID-related effects as well as neurological complications. Inhibition could be achieved by targeting NLRP3-centered mechanisms and protein-protein interactions.
Intervention in these mechanisms may fundamentally affect various COVID-related neurological manifestations that depend on either nonresolving inflammation or dysregulated immunity. Drugs developed in this context would help to avoid hospitalization for most people, especially those at risk, and prevent progression of severe COVID- and post-COVID-related neurological manifestations.

More information about the BRAVE project is available on the Human Brain Project website: https://www.humanbrainproject.eu/en/follow-hbp/news/2021/09/30/covid-19-and-mental-health-human-brain-project-welcomes-two-new-eu-funded-research-programmes/