Long COVID in children and adolescents: towards understanding the mechanisms underlying the persistence of ...

Long COVID is a syndrome characterised by the persistence of clinical signs and symptoms related to SARS-CoV-2 infection. To date, a clear understanding of the underlying immunopathogenic mechanisms is still lacking. Many patients describe long-term effects of the infection, such as fatigue, headache, dyspnoea, anosmia and gastrointestinal disorders.

In a new study published in the European Journal of Immunology, the result of a collaboration between Raphael Viscidi of the Johns Hopkins University in Baltimore and the research groups coordinated by Guido Antonelli of the Department of Molecular Medicine and Fabio Midulla of the Department of Paediatrics and Child Neuropsychiatry of Sapienza University, both working as Unit Directors at the AOU Policlinico Umberto I General Hospital, assessed the involvement of the interferon system - molecules naturally produced by cells in response to viral infections - in the development and persistence of symptoms associated with Long COVID in paediatric age, even some time after infection.

Alterations in the production of type I interferons at the mucosal and systemic level in the early phase of SARS-CoV-2 infection had already been associated with severe COVID-19 in adults; likewise, it had been shown that a pre-activation of innate immunity can lead to a more rapid and effective anti-SARS-CoV-2 response in the paediatric population. However, the fact that an increasing number of children and adolescents continue to experience debilitating symptoms even after the resolution of their SARS-CoV-2 infection has led researchers to consider a possible involvement of interferons in the development and persistence of symptoms associated with Long COVID even in paediatric age.

In this new work, differences in the expression of type I interferons were observed that were closely associated with age: whereas in adolescents (12-17 years) an increase in transcriptional I levels was found (particularly pronounced in those with neurological symptoms), a decrease was observed in children (6-11 years). It was possible to record this phenomenon both in those who were infected with SARS-CoV-2 but did not develop long COVID symptoms and in healthy controls.

"The importance of our research," says Guido Antonelli, "lies in the fact that we performed a detailed transcriptomic analysis of type I interferons on a large number of children and adolescents with Long COVID, observed 3-6 months after the acute phase of SARS-CoV-2 infection, who had not yet adhered to vaccination programmes. Possible co-factors that could alter interferon response analyses, such as the presence of type I interferon-neutralising autoantibodies, were also investigated and excluded”.

"Our study", says Carolina Scagnolari, Sapienza coordinator of the research, "adds new elements to our understanding of the immunopathogenetic mechanisms associated with long COVID”.

"Distinct and opposing interferon-related immunological scenarios", continues Matteo Fracella of the Department of Molecular Medicine of Sapienza, "could selectively influence the evolution of long COVID in different age groups".

"The identification of the immunopathogenic mechanisms underlying Long COVID may help in the better clinical therapeutic management of paediatric patients", concludes Fabio Midulla, head of the paediatric emergency department at Policlinico Umberto I General Hospital in Rome.

References:

Age-related transcript changes in type I interferon signaling in children and adolescents with long COVID - Fracella M, Mancino E, Nenna R, Virgillito C, Frasca F, D'Auria A, Sorrentino L, Petrarca L, La Regina D, Matera L, Di Mattia G, Caputo B, Antonelli G, Pierangeli A, Viscidi RP, Midulla F, Scagnolari C - Eur J Immunol. 2024. doi: 10.1002/eji.202350682. 

Further Information

Guido Antonelli Department of Molecular Medicineguido.antonelli@uniroma1.it 

Carolina ScagnolariDepartment of Molecular Medicinecarolina.scagnolari@uniroma1.it