About eight percent of human genetic material comes from a virus and not from our ancestors, according to a new study. The research shows that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus.

Patients with COVID-19 may develop abnormal inflammatory response and lymphopenia, followed in some cases by delayed-onset syndromes, often long-lasting after the initial SARS-CoV-2 infection. As viral infections may activate human endogenous retroviral elements (HERV), we studied the effect of SARS-CoV-2 on HERV-W and HERV-K envelope (ENV) expression, known to be involved in immunological and neurological pathogenesis of human diseases. Our results have showed that the exposure to SARS-CoV-2 virus activates early HERV-W and K transcription but only HERV-W ENV protein expression, in an infection- and ACE2-independent way within peripheral blood mononuclear cell cultures from one-third of healthy donors. Moreover, HERV-W ENV protein was significantly increased in serum and plasma of COVID-19 patients, correlating with its expression in CD3+ lymphocytes and with disease severity. Finally, HERV-W ENV was found expressed in post-mortem tissues of lungs, heart, brain olfactory bulb and nasal mucosa from acute COVID-19 patients in cell-types relevant for COVID-19-associated pathogenesis within affected organs, but different from those expressing of SARS-CoV-2 antigens. Altogether, the present study revealed that SARS-CoV-2 can induce HERV-W ENV expression in cells from individuals with symptomatic and severe COVID-19. Our data suggest that HERV-W ENV is likely to be involved in pathogenic features underlying symptoms of acute and post-acute COVID. It highlights the importance to further understand patients’ genetic susceptibility to HERV-W activation and the relevance of this pathogenic element as a prognostic marker and a therapeutic target in COVID-19 associated syndromes.

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### Competing Interest Statement

HP, BC, JB, JP, NQ received compensation for their work from Geneuro Innovation (France)

### Funding Statement

This study was funded by the french National Agency for Researsch (ANR) - program RA-COVID-19 V15 (project name : COVERI)

### Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

- Ethics committee/IRB of SECRETARIA DE SALUD INSTITUTO NACIONAL DE ENFERMEDADES RESPIRATORIAS ISMAEL COSIO VILLEGAS (MEXICO)gave ethical approval for this work - Ethics committee/IRB of HOSPICES CIVILS DE LYON (HCL)/ BIOBANK OF CROIX ROUSSE HOSPITAL (FRANCE) gave ethical approval for this work - Ethics committee/IRB of SERVICIOS CIENTIFICO TECNICOS - SERVICIO DE BIOBANCO (BSSA)OF UNIVERSITY OF SARAGOZA (SPAIN) gave ethical approval for this work

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Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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All data produced in the present work are contained in the manuscript

[1]: pending:yes

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