Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome
Hassan Abolhassani
(1, 2)
,
Nils Landegren
(3, 4)
,
Paul Bastard
(5, 6, 7)
,
Marie Materna
(6, 7)
,
Mohammadreza Modaresi
(8)
,
Likun Du
(1)
,
Maribel Aranda-Guillén
(3)
,
Fabian Sardh
(3, 4)
,
Fanglei Zuo
(1)
,
Peng Zhang
(5)
,
Harold Marcotte
(9)
,
Nico Marr
(10, 11)
,
Taushif Khan
(10)
,
Manar Ata
(10)
,
Fatima Al-Ali
(10)
,
Remi Pescarmona
(12, 13)
,
Alexandre Belot
(12, 14)
,
Vivien Béziat
(6, 7)
,
Qian Zhang
(5, 6)
,
Jean-Laurent Casanova
(5, 6, 7, 15)
,
Olle Kämpe
(4, 16)
,
Shen-Ying Zhang
(5, 6, 7)
,
Lennart Hammarström
(1)
,
Qiang Pan-Hammarström
(1)
1
BioNut -
Department of Biosciences and Nutrition [Karolinska Insitutet, Sueden]
2 IUMS - Iran University of Medical Sciences [Tehran, Iran]
3 Uppsala University
4 Department of medicine [Stockholm]
5 St. Giles Laboratory of Human Genetics of Infectious Diseases
6 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
7 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
8 Children’s Medical Center [Tehran, Liban]
9 Karolinska Institute
10 Sidra Medicine [Doha, Qatar]
11 HBKU - Hamad Bin Khalifa University
12 CIRI - Centre International de Recherche en Infectiologie
13 Service d'immunologie [Centre Hospitalier Lyon Sud - HCL]
14 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
15 HHMI - Howard Hughes Medical Institute [New York]
16 Karolinska University Hospital [Stockholm]
2 IUMS - Iran University of Medical Sciences [Tehran, Iran]
3 Uppsala University
4 Department of medicine [Stockholm]
5 St. Giles Laboratory of Human Genetics of Infectious Diseases
6 Equipe Inserm U1163 - Human genetics of infectious diseases : Mendelian predisposition
7 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
8 Children’s Medical Center [Tehran, Liban]
9 Karolinska Institute
10 Sidra Medicine [Doha, Qatar]
11 HBKU - Hamad Bin Khalifa University
12 CIRI - Centre International de Recherche en Infectiologie
13 Service d'immunologie [Centre Hospitalier Lyon Sud - HCL]
14 HFME - Hôpital Femme Mère Enfant [CHU - HCL]
15 HHMI - Howard Hughes Medical Institute [New York]
16 Karolinska University Hospital [Stockholm]
Hassan Abolhassani
- Function : Author
- PersonId : 783429
- ORCID : 0000-0002-4838-0407
Marie Materna
- Function : Author
- PersonId : 800325
- ORCID : 0000-0003-1180-6651
Peng Zhang
- Function : Author
- PersonId : 762416
- ORCID : 0000-0002-6129-567X
Nico Marr
- Function : Author
- PersonId : 762966
- ORCID : 0000-0002-1927-7072
Taushif Khan
- Function : Author
- PersonId : 802717
- ORCID : 0000-0002-7917-8965
Manar Ata
- Function : Author
- PersonId : 810093
- ORCID : 0000-0001-7111-5719
Alexandre Belot
- Function : Author
- PersonId : 781111
- ORCID : 0000-0003-4902-5332
- IdRef : 115823824
Vivien Béziat
- Function : Author
- PersonId : 778044
- ORCID : 0000-0002-4020-824X
- IdRef : 149613741
Qian Zhang
- Function : Author
- PersonId : 768070
- ORCID : 0000-0002-9040-3289
Jean-Laurent Casanova
- Function : Author
- PersonId : 756193
- ORCID : 0000-0002-7782-4169
- IdRef : 073388726
Shen-Ying Zhang
- Function : Author
- PersonId : 760020
- ORCID : 0000-0002-9449-3672
- IdRef : 144474549
Lennart Hammarström
- Function : Author
- PersonId : 794455
- ORCID : 0000-0002-8635-9609
Qiang Pan-Hammarström
- Function : Author
- PersonId : 804752
- ORCID : 0000-0003-1990-8804
Abstract
Abstract Background Inborn errors of immunity (IEI) and autoantibodies to type I interferons (IFNs) underlie critical COVID-19 pneumonia in at least 15% of the patients, while the causes of multisystem inflammatory syndrome in children (MIS-C) remain elusive. Objectives To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. Methods Whole exome sequencing was performed, and the impact of candidate gene variants was investigated. Plasma levels of cytokines, specific antibodies against the virus, and autoantibodies against type I IFNs were also measured. Results We report a 3-year-old child who died on day 56 of SARS-CoV-2 infection with an unusual clinical presentation, combining both critical COVID-19 pneumonia and MIS-C. We identified a large, homozygous loss-of-function deletion in IFNAR1 , underlying autosomal recessive IFNAR1 deficiency. Conclusions Our findings confirm that impaired type I IFN immunity can underlie critical COVID-19 pneumonia, while suggesting that it can also unexpectedly underlie concomitant MIS-C. Our report further raises the possibility that inherited or acquired dysregulation of type I IFN immunity might contribute to MIS-C in other patients.