The project started in summer 2022, putting together 8 partners with complementary experience from 5 European countries. This study 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 envelope (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. Regarding the transcriptomic activity of HERVs, diverse sequencing technologies have been tested and the most efficient approach was selected for the quantitation of HERVs and characterization of different isoforms. We then analyzed placenta samples from uneventful pregnancies and samples from COVID-19 positive women. We also investigated publicly available datasets of placentas from women with COVID-19, preeclampsia and healthy controls, as well as frontal cortex post-mortem samples of COVID-19 patients and controls, to further enrich our understanding of HERV transcription in multiple tissues. After the abatement of the acute COVID-19 pandemic, the HERVCOV project has started the analysis of patients who suffer from post COVID-19 more commonly known as Long COVID. The first results suggest the presence of HERV-W ENV in the serum and plasma of these patients and the study of different other biomarkers specific for this disease is currently ongoing. Subgroups of Long COVID patients have now been identified, including those defined by HERV-W ENV. The presence of specific subgroups also defined by immunological, inflammatory, cardiovascular and serological markers, has been determined within three different cohorts. The presence of these subgroups across cohorts is now being established, and the underlying mechanisms are being addressed. Currently, we also conduct a preliminary bioinformatic analysis on HERV expression in publicly available datasets from Long COVID cohorts aiming to detect main trends in the expression of HERVs in Long COVID, starting from samples of olfactory epithelium. Finaly, the new cell line model has been developed within the consortium and should allow further analysis of the molecular and cellular mechanism of the regulation of HERV-W envelope protein expression
