Severe West Nile Virus and Severe Acute Respiratory Syndrome Coronavirus 2 Infections in a Patient With Thymoma and Anti-Type I Interferon Antibodies

Abstract

Patients with severe West Nile virus and SARS-CoV-2 infections deserve accurate diagnosis of underlying diseases, determining possible anti-interferon autoantibody production, since they must receive antiviral and immunological therapies to enhance antiviral response. The current study aimed to investigate determinants of severity in a previously healthy patient who experienced 2 life-threatening infections, from West Nile Virus (WNV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). During coronavirus disease 2019 (COVID-19) hospitalization he was diagnosed with a thymoma, retrospectively identified as already present at the time of WNV infection. Heterozygosity for p.Pro554Ser in the TLR3 gene, which increases susceptibility to severe COVID-19, and homozygosity for CCR5 c.554_585del, associated with severe WNV infection, were found. Neutralizing anti-interferon (IFN)-α and anti-IFN-ω autoantibodies were detected, likely induced by the underlying thymoma and increasing susceptibility to both severe COVID-19 pneumonia and West Nile encephalitis.

Keywords: CCR5; COVID-19; TLR3; West Nile virus; anti-IFN autoantibodies; thymoma.

Figure 1.

Patient's clinical history and imaging. A, Timeline of viral infections and identification of the mediastinal mass, then diagnosed as thymoma. B, High-resolution chest computed tomography (CT) scan showing coronavirus disease 2019 (COVID-19) pneumonia, characterized by bilateral ground-glass areas associated with interstitial thickening, most extensively in the upper lung lobes and areas of pulmonary consolidation with dense streaks in the lower lobes bilaterally. C, CT scan showing right paracardiac mass with maximum transverse diameter of 5 cm (arrow). D, Low-dose positron emission tomography/CT scan with [¹⁸F]fluorodeoxyglucose showing medium accumulation in the right paracardiac mediastinal mass (arrow).

Figure 2.

Genetics and immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the patient and family. A, Pedigree and segregation of the TLR3 variant c.2660C > T, p.P554S and of the CCR5 variant c.554_585del, p.Ser185IlefsTer32 (CCR5Δ32). Proliferative response to SARS-CoV-2 spike protein peptides (B) and Wuhan spike receptor-binding domain immunoglobulin G levels (C) in the probands (I.1 and II.2) and 2 control cohorts; the assay cut-off is shown as a dashed line. D, Anti–type I interferon (IFN) autoantibodies: neutralization of type I IFNs (1 ng/mL of IFNs) detected in a luciferase-based cell reporter assay, in the patient plasma/serum (I.1) at different time points after coronavirus disease 2019 infection, before and after thymectomy, in the daughter (II.1) and in control groups (autoantibody-positive patients and healthy control without autoantibodies). Abbreviations: AAB, autoantibody; AU, arbitrary units; COVID-19, coronavirus disease 2019; IFN, interferon; IgG, immunoglobulin G; ISRE, interferon-stimulated response element; NS, not stimulated; RBD, receptor-binding domain; RLA, relative luciferase activity; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; SI, stimulation index; wt, wild type.