Critical Infections of West Nile Virus and SARS-CoV-2 in a Thymoma Patient with Anti-Type I Interferon Autoantibodies

Overview

A previously healthy patient experienced life-threatening infections from both West Nile Virus (WNV) and SARS-CoV-2, with underlying thymoma and presence of neutralizing anti-type I interferon autoantibodies. Genetic variants in TLR3 and CCR5 genes, combined with autoantibodies likely induced by thymoma, contributed to severe disease manifestations.

Background

Type I interferons (IFNs) are crucial in the innate immune response against viral infections. Defects in IFN signaling or the presence of neutralizing autoantibodies against IFN-α and IFN-ω have been linked to severe viral diseases including COVID-19. Thymoma is associated with a high prevalence of these autoantibodies, which impair antiviral defenses. West Nile Virus neuroinvasive disease is rare but can be severe in patients with genetic susceptibility such as CCR5 variants.

Data Highlights

The patient was heterozygous for the p.Pro554Ser variant in the TLR3 gene, increasing susceptibility to severe COVID-19, and homozygous for the CCR5 c.554_585del variant, associated with severe WNV infection. Neutralizing autoantibodies against IFN-α and IFN-ω were detected, likely induced by the thymoma diagnosed during COVID-19 hospitalization but retrospectively present at the time of WNV infection.

Key Findings

• Severe infections with WNV and SARS-CoV-2 occurred in a patient with an underlying thymoma.
• Neutralizing autoantibodies against type I IFNs (IFN-α and IFN-ω) were identified, impairing antiviral immunity.
• Genetic predisposition included heterozygosity for TLR3 p.Pro554Ser variant linked to severe COVID-19.
• Homozygosity for CCR5 c.554_585del variant was associated with severe West Nile virus infection.
• Thymoma likely induced the production of anti-IFN autoantibodies, increasing susceptibility to both viral infections.

Clinical Implications

Clinicians should consider screening for anti-type I IFN autoantibodies and relevant genetic variants in patients presenting with severe viral infections, especially when atypical or multiple infections occur. Identification of underlying thymoma or other causes of autoantibody production can guide immunological and antiviral therapies to improve patient outcomes.

Conclusion

This case highlights the interplay of genetic susceptibility and acquired autoantibodies in severe viral infections, emphasizing the importance of comprehensive immunological and genetic evaluation in patients with critical infections. Early detection of thymoma and anti-IFN autoantibodies may inform targeted therapeutic strategies.

References

1. Bastard et al. 2020 -- Autoantibodies against type I IFNs in patients with life-threatening COVID-19
2. Zhang et al. 2020 -- Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
3. Meisel et al. 2021 -- Neutralizing autoantibodies to type I IFNs in COVID-19 patients
4. Meisel et al. 2021 -- Anti-IFN autoantibodies in thymoma and myasthenia gravis
5. Lim et al. 2021 -- CCR5Δ32 variant and severe West Nile virus infection