Pathogenic IgG from Long COVID Neurological Patients Induces Sensitivity in Mice

Overview

This study investigated whether IgG antibodies from long COVID patients with neurological symptoms can induce neuropsychiatric effects in mice. Passive transfer of purified IgG from these patients caused increased pain sensitivity but did not impair cognitive function in recipient mice.

Background

Long COVID affects approximately 10% of individuals after SARS-CoV-2 infection, with neurological symptoms including cognitive impairment and neuropathic pain. Autoimmunity has been proposed as a potential mechanism underlying these symptoms, with some evidence of autoantibodies targeting nervous system antigens in affected patients. However, the pathogenic role of such autoantibodies remains unclear. This study aimed to clarify whether IgG antibodies from long COVID patients with neurological symptoms can produce functional neurological effects when transferred to mice.

Data Highlights

Key Findings

• IgG antibodies purified from long COVID patients with neurological symptoms bind to central and peripheral nervous system epitopes.
• Passive transfer of these IgGs into mice induced increased pain sensitivity (allodynia/hyperalgesia) over two weeks.
• Cognitive, anxiety, and depressive-like behaviors in mice were not significantly affected by the transferred IgGs.
• IgG-depleted serum and enzymatically digested IgGs did not produce the sensitivity phenotype, implicating IgG as the active component.
• Findings support a potential autoimmune mechanism contributing to neuropathic pain symptoms in a subset of long COVID patients.

Clinical Implications

These results suggest that autoantibodies, specifically IgG, from long COVID patients with neurological symptoms may contribute to neuropathic pain but not cognitive dysfunction. This supports consideration of immunomodulatory therapies targeting pathogenic IgG in managing long COVID-related neuropathic pain. Further research is needed to identify specific autoantibody targets and validate these findings in larger cohorts.

Conclusion

The study provides evidence that pathogenic IgG from long COVID patients with neurological symptoms can induce pain sensitivity in mice without affecting cognition, highlighting a possible autoimmune contribution to long COVID neuropathic symptoms.

References

1. National Academies of Sciences, Engineering and Medicine 2021 -- Definition of Long COVID
2. Various cohort studies 2020-2023 -- Autoimmunity and Long COVID
3. Current Study Authors 2024 -- Transfer of Pathogenic IgG from Long COVID Patients