Severe West Nile virus and Sars-CoV-2 infections in a patient with thymoma and anti-type I IFN antibodies

Federica Barzaghi; Camilla Visconti; Giovanni Battista Pipitone; Simone Bondesan; Giulia Molli; Stefania Giannelli; Claudia Sartirana; Vito Lampasona; Elena Bazzigaluppi; Cristina Brigatti; Adrian Gervais; Paul Bastard; Chiara Tassan Din; Chiara Molinari; Lorenzo Piemonti; Jean-Laurent Casanova; Paola Carrera; Giorgio Casari; Alessandro Aiuti

doi:10.1093/infdis/jiae321

Severe West Nile virus and Sars-CoV-2 infections in a patient with thymoma and anti-type I IFN antibodies

J Infect Dis. 2024 Jul 8:jiae321. doi: 10.1093/infdis/jiae321. Online ahead of print.

Authors

Federica Barzaghi^{1

2}, Camilla Visconti^{1

2

3}, Giovanni Battista Pipitone⁴, Simone Bondesan⁴, Giulia Molli⁴, Stefania Giannelli², Claudia Sartirana², Vito Lampasona⁵, Elena Bazzigaluppi⁵, Cristina Brigatti⁵, Adrian Gervais^{6

7}, Paul Bastard^{6

7

8

9}, Chiara Tassan Din¹⁰, Chiara Molinari⁵, Lorenzo Piemonti^{3

5}, Jean-Laurent Casanova^{6

7

8

9

11}, Paola Carrera^{4

12}, Giorgio Casari^{3

13}, Alessandro Aiuti^{1

2

3}

Affiliations

¹ Pediatric Immunohematology and Bone Marrow Transplantation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
² San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Milan, Italy.
³ Università Vita-Salute San Raffaele, 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, NY, USA.
⁹ Pediatric Hematology-Immunology and Rheumatology Unit, Necker Hospital for Sick Children, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France, EU.
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.

PMID: 38976510
DOI: 10.1093/infdis/jiae321

Abstract

The current study aimed to investigate determinants of severity in a previously healthy patient who experienced two life-threatening infections, from West Nile Virus and SARS-CoV2. During COVID19 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 to severe WNV infection, were found. Neutralizing anti-IFN-α and anti-IFN-ω auto-antibodies 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.