Swiss neurology specialist GeNeuro SA present first data linking silent COVID-19-induced inflammations to neuropsyciatric diseases.
The results of a collaboration of GeNeuro with the FondaMental Foundation were presented at the Schizophrenia International Research Society (SIRS) congress from April 6 to 10 in Florence, Italy during the session entitled “Human Endogenous Retrovirus (HERV) as a Missing Link between Inflammation and Schizophrenia in the Context of COVID” with presentations by Prof. Marion Leboyer (Université Paris-Est-Créteil, Hôpital H. Mondor, FondaMental Fondation, Créteil, France), Dr. Livia de Picker (University of Antwerp, Belgium), Prof. Urs Meyer (University of Zurich, Switzerland) and Dr. Hervé Perron (GeNeuro), and concluded by Prof. Robert Yolken (Johns Hopkins University, Baltimore, USA).
The first results presented in Florence were based on the analysis of blood samples from 104 patients hospitalized between January and March 2021 for psychiatric disorders, either for the first time or because of relapses, in the psychiatry department of Prof. Leboyer in Créteil at Hôpital H. Mondor, and 63 controls.
The objective of this analysis was to measure the coronavirus infection rate in a population with no reported COVID-19 disease and to search for links between SARS-CoV-2 infection and the endogenous retroviral protein W-ENV. The analyses were performed by the INSERM “We-Met” platform at the Paul Sabatier University in Toulouse.
Serological analyses showed that 82% of the patients admitted to the psychiatric ward had been exposed to the COVID-19 virus. The detection of W-ENV protein was positive in the serum of 40% of the patients studied, but almost exclusively and very significantly in patients seropositive for SARS-CoV-2 (p=0.01). The presence of W-ENV protein in the blood was also strongly correlated with elevated levels of cytokines characteristic of innate inflammation such as TNF-alpha, IL-1beta or IL8 (p0.0001 for all three).
“We have repeatedly, in independent cohorts, shown the presence of W-ENV protein in blood samples of patients with psychotic spectrum disorders and chronic systemic inflammation,” said Prof. Marion Leboyer, Director of the Department of Psychiatry at Henri Mondor University Hospitals and Director of the FondaMental Foundation. “The results of our study in these patients hospitalised during the COVID-19 pandemic revealed that most of them had been exposed to SARS-CoV-2. These data reinforce the interest of a personalised therapeutic approach in W-ENV positive patients against neuropsychiatric syndromes in the post-COVID-19 context.”
Studies published last year demonstrated that W-ENV expression was triggered by SARS-CoV-2 in leukocytes and tissues of about 20% of healthy donors, suggesting individual susceptibility. The protein was also detected in the blood of hospitalised COVID-19 patients where the amount of expression in lymphocytes was associated with disease progression severity. The persistence of W-ENV expression long after the acute phase of the disease and its association with immunoinflammatory manifestations support the biological hypothesis of its importance in the long-term neuropsychiatric syndromes found in many post-COVID patients.
“The action of the W-ENV protein on innate inflammation and its deleterious action on cells of the nervous system have been documented over the last 20 years,” add Dr. Hervé Perron, Chief Scientific Officer of GeNeuro. “Post-COVID is characterized by a wide range of symptoms, with probably a multifactorial origin. But the ability to detect W-ENV in post-COVID patients with neuropsychiatric disorders allows to identify a well-defined group of patients that we can rapidly treat with the aim of improving their condition by neutralising this pathogenic protein.
GeNeuro has developed temelimab, a specific antibody against the W-ENV protein, which has shown promising results in Phase II trials in multiple sclerosis against MRI markers of neurodegeneration. Temelimab has shown excellent safety and tolerability in several hundred patients treated for two years and more. GeNeuro is preparing to launch a clinical trial in 200 W-ENV-positive patients with post-COVID neuropsychiatric syndromes. This clinical trial is co-financed by the Swiss Federal Office of Public Health.