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

Author:

Barzaghi Federica12ORCID,Visconti Camilla123,Pipitone Giovanni Battista4,Bondesan Simone4,Molli Giulia4,Giannelli Stefania2,Sartirana Claudia2,Lampasona Vito5,Bazzigaluppi Elena5ORCID,Brigatti Cristina5,Gervais Adrian67,Bastard Paul6789,Din Chiara Tassan10,Molinari Chiara5,Piemonti Lorenzo35ORCID,Casanova Jean-Laurent678911,Carrera Paola412,Casari Giorgio313ORCID,Aiuti Alessandro123ORCID

Affiliation:

1. Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute , Milan , Italy

2. San Raffaele Telethon Institute for Gene Therapy, IRCCS San Raffaele Scientific Institute , Milan , Italy

3. Vita-Salute San Raffaele University , Milan , Italy

4. Laboratory of Clinical Genomics, IRCCS San Raffaele Scientific Institute , Milan , Italy

5. San Raffaele Diabetes Research Institute, IRCCS San Raffaele Scientific Institute , Milan , Italy

6. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France

7. Paris Cité University, Imagine Institute , Paris , France

8. St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University , New York, USA

9. Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris , Paris , France

10. Clinic of Infectious Diseases, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute , Milan , Italy

11. Howard Hughes Medical Institute , Paris , France

12. Unit of Genomics for Human Disease Diagnosis, IRCCS San Raffaele Scientific Institute , Milan , Italy

13. Genomic Unit for the Diagnosis of Human Pathologies, IRCCS San Raffaele Scientific Institute , Milan , Italy

Abstract

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.

Funder

Fondazione Telethon, and Horizon Europe

Howard Hughes Medical Institute

Rockefeller University

St Giles Foundation

NIH

National Center for Advancing Translational Sciences

NIH Clinical and Translational Science Award

Fisher Center for Alzheimer's Research Foundation

Meyer Foundation

JPB Foundation

French government and implemented

Agence Nationale de la Recherche

Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence

French Foundation for Medical Research

ANR GENVIR

ANR AI2D

ANR AAILC

ANR-RHU COVIFERON Program

Square Foundation

French Ministry of Higher Education, Research, and Innovation

Publisher

Oxford University Press (OUP)

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