Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation

Epidemiology has repeatedly associated certain infections with a risk of further developing psychiatric diseases. Such infections can activate retro-transposable genetic elements (HERV) known to trigger immune receptors and impair synaptic plasticity of neuroreceptors. Since the HERV-W ENV protein was recently shown to co-cluster with pro-inflammatory cytokines in a subgroup of patients with schizophrenia or bipolar disorder, we questioned the influence of the COVID-19 pandemic on patients with psychosis spectrum disorders (PSD). Present results revealed that (i) SARS-CoV-2 serology shows high prevalence and titers of antibodies in PSD, (ii) HERV-W ENV is detected in seropositive individuals only and (iii) SARS-CoV-2 and HERV-W ENV positivity co-clustered with high serum levels of pro-inflammatory cytokines in psychotic patients. These results thus suggest that SARS-CoV-2 infection in many patients with psychotic disorders now admitted in the psychiatry department did not cause severe COVID-19. They also confirm the previously reported association of elevated serum pro-inflammatory cytokines and HERV-W ENV in a subgroup of psychotic patients. In the context of the COVID-19 pandemic, this cluster is only found in SARS-CoV-2 seropositive PSD cases, suggesting a dominant influence of this virus on HERV-W ENV and cytokine expression, and/or patients' greater susceptibility to SARS-CoV-2 infection. Further investigation on an interplay between this viral infection and the clinical evolution of such PSD patients is needed. However, this repeatedly defined subgroup of psychotic patients with a pro-inflammatory phenotype and HERV expression calls for a differential therapeutic approach in psychoses, therefore for further precision medicine development.

Automated summary

Epidemiological studies have shown a link between certain infections and an increased risk of developing psychiatric disorders. These infections can activate retro-transposable genetic elements (HERV), which in turn impact immune receptors and synaptic plasticity. Recent research has found an association between the HERV-W ENV protein and pro-inflammatory cytokines in patients with schizophrenia or bipolar disorder. The COVID-19 pandemic's influence on patients with psychosis spectrum disorders (PSD) was investigated, revealing a high prevalence of SARS-CoV-2 antibodies in PSD patients, with HERV-W ENV detected only in seropositive individuals. SARS-CoV-2 infection and HERV-W ENV positivity were found to co-cluster with high levels of pro-inflammatory cytokines in psychotic patients. These findings suggest a dominant influence of the virus on HERV-W ENV and cytokine expression, and the need for further investigation into the interplay between viral infection and the clinical evolution of PSD patients.