Periodic Reporting for period 1 - HERVCOV (SARS-CoV-2-induced activation of pathogenic endogenous retrovirus envelope HERV-W: towards personalized treatment of COVID-19 patients)
Reporting period: 2022-07-01 to 2023-12-31
Severe COVID-19 disease and the high frequency of its long-term complications are now a major health problem worldwide. As a result of an acute symptomatic COVID-19 episode, more than 30% of adult patients still have different clinical symptoms at 1-2 months and 10-15% at 6-8 months after the initial SARS-CoV-2 infection. Due to the significant heterogeneity of COVID-19 disease profiles, biomarkers that allow either the identification of patients at high risk for developing severe forms of COVID-19 and its long-term complications, or guide personalized treatment options, are scarce. The HERVCOV project aims to analyse the role of human endogenous retroviruses (HERVs), known for their high pro-inflammatory potential, in the immunopathogenesis of acute COVID-19 and its long-term complication, Long Covid, and to identify and evaluate a set of biomarkers which will be important for the diagnosis and follow-up of patients and their prioritization for targeted therapy. HERVCOV focuses on the biological pathways and functions that underlie the association of HERV expression and activation with severe COVID-19 forms and related complications. Results obtained from the project should help understanding the pathogenic role of HERV-W envelope protein in COVID-19 disease, and developing novel prognostic markers and therapeutic targets for personalized treatment of COVID-19-associated syndromes.
The project has started in summer 2022, putting together 8 partners with complementary experience from 5 European countries. This study has already produced first evidence for the induction of a specific protein during COVID-19 disease. Recent data from the consortium has demonstrated that HERV-W envelope protein is highly expressed in lymphocytes of COVID-19 patients and correlates with inflammatory markers and respiratory outcome of the disease, strongly suggesting the role of HERVs in COVID-19 pathogenesis. Plasma and/or sera of COVID-19 patients from different cohorts, infected with successive SARS-CoV-2 variants including the Omicron, had detectable HERV-W ENV, and peaked with the disease severity. HERV-W ENV was also found in post-mortem tissues of lungs, heart, gastrointestinal tract, brain olfactory bulb and nasal mucosa from COVID-19 patients. In addition, the HERVCOV project has started the analysis of patients who suffer from post COVID-19 condition (PCC), known also as Post-acute COVID sequelae (PACS) and more commonly as Long COVID. The first results suggest the presence of HERV-W envelope protein in the serum and plasma of these patients and the study of different other biomarkers specific for this disease is currently ongoing.
Biomarkers based on SARS-CoV-2-specific immune responses, cytokine production and mandatory medical blood analyses for COVID-19 clinical monitoring have been studied in samples from different forms of acute and long COVID patients. Parameters have been determined that allow biomarker-based diagnostics of Long COVID disease and allow potential clustering of different bio-clinical profiles of COVID-19 patients. Ongoing inclusion of biomarkers based on HERV pathogenic protein activation may improve diagnostics and bio-clinical profiles, allowing for future stratification of patients based on the clinical course (or clinical profile) of the disease and the severity of SARS-CoV-2-induced symptoms. A HERVCOV web site has been developed (https://www.hervcovproject.eu/(opens in new window)) and regularly updated with all the information relevant to the project.