Age‐related transcript changes in type I interferon signaling in children and adolescents with long COVID

SARS‐CoV‐2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN‐I) response in children and adolescents with LC symptom...

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Published in:European journal of immunology 2024-05, Vol.54 (5), p.e2350682-n/a
Main Authors: Fracella, Matteo, Mancino, Enrica, Nenna, Raffaella, Virgillito, Chiara, Frasca, Federica, D'Auria, Alessandra, Sorrentino, Leonardo, Petrarca, Laura, La Regina, Domenico, Matera, Luigi, Di Mattia, Greta, Caputo, Beniamino, Antonelli, Guido, Pierangeli, Alessandra, Viscidi, Raphael P., Midulla, Fabio, Scagnolari, Carolina
Format: Article
Language:English
Subjects:
Adolescent
Adolescents
Age Factors
Child
Children
COVID-19
COVID-19 - immunology
Female
Gene expression
Humans
Immunity, Innate
Innate immunity
Interferon
Interferon Type I - genetics
Interferon Type I - immunology
Interferon Type I - metabolism
ISGs
Long COVID
Male
Neutralizing autoantibodies to interferon
Post-Acute COVID-19 Syndrome
RNA, Messenger - genetics
SARS-CoV-2 - immunology
SARS‐CoV‐2
Severe acute respiratory syndrome coronavirus 2
Signal transduction
Signal Transduction - immunology
Teenagers
Type I interferon
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Summary:SARS‐CoV‐2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN‐I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age‐matched SARS‐CoV‐2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN‐I (IFN‐α/β/ε/ω), IFN‐I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3–6 months after COVID‐19. LC adolescents (12–17 years) had higher transcript levels of IFN‐β, IFN‐ε, and IFN‐ω than HC, whereas LC children (6–11 years) had lower levels than HC. In adolescents, increased levels of IFN‐α, IFN‐β, and IFN‐ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN‐α/β mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age‐related changes in the expression of transcripts involved in the IFN‐I signaling pathway in children and adolescents with LC. Age‐related changes in the expression of transcripts associated with the IFN‐I signaling pathway have been observed in children and adolescents with long COVID symptoms, occurring at 3‐ to 6‐month intervals from the acute phase of SARS‐CoV‐2 infection.
ISSN:0014-2980
1521-4141
DOI:10.1002/eji.202350682