Inherited IFNAR1 Deficiency in a Child with Both Critical COVID-19 Pneumonia and Multisystem Inflammatory Syndrome.

Abolhassani H, Landegren N, Bastard P, Materna M, Modaresi M, Du L, Aranda-Guillén M, Sardh F, Zuo F, Zhang P, Marcotte H, Marr N, Khan T, Ata M, Al-Ali F, Pescarmona R, Belot A, Béziat V, Zhang Q, Casanova JL, Kämpe O, Zhang SY, Hammarström L, Pan-Hammarström Q

J Clin Immunol - (-) - [2022-01-28; online 2022-01-28]

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. To detect causal genetic variants in very rare cases with concomitant critical COVID-19 pneumonia and MIS-C. 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. 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. 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.

Category: Biochemistry

Category: Health

Type: Journal article

PubMed 35091979

DOI 10.1007/s10875-022-01215-7

Crossref 10.1007/s10875-022-01215-7

pii: 10.1007/s10875-022-01215-7

Publications 9.5.0