Persistent HERV expression in patients with post-COVID symptoms


Karen Giménez-Orenga, Justine Pierquin, Joanna Brunel, Benjamin Charvet, Eva Martín-Martínez, Hervé Perron and Elisa Oltra


Universidad Católica de Valencia San Vicente Mártir, Spain


Frontiers in Immunology, 2022 October 27; 13:1020064


ME Research UK

Key points

  • Human endogenous retroviruses (HERVs), which are contained within the human genome, may have a role in triggering diseases such as ME/CFS and long COVID.
  • One hypothesis is that activation of dormant HERVs could cause an innate immune response leading to the development of symptoms.
  • A pro-inflammatory HERV envelope protein (HERV-W ENV) has been shown to be expressed in the blood of patients with acute COVID-19, and the current study investigated whether this protein remains active in individuals with post-COVID symptoms (i.e. long COVID).
  • The HERV-W ENV protein was detected in 58% of patients with post-COVID symptoms, compared with 41% of those with acute COVID-19.
  • In addition, high levels of anti-SARS-CoV-2 immunoglobulins (antibodies produced to fight off the virus) were associated with deteriorated physical function in patients with post-COVID symptoms.
  • These findings support the potential role of the HERV-W ENV protein in the development of post-COVID conditions, at least in a subgroup of patients.
  • The presence of HERV-W ENV protein and high anti-SARS-CoV-2 immunoglobulin levels may help identify patient subgroups and target effective therapies.


Due to the wide scope and persistence of COVID-19 ́s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient ́s symptom severity. Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other.

The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01).

These results indicate that HERV-W ENV antigenemia and anti- SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID- 19 condition.

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