The PostAcute Sequelae of SARSCoV-2 (PASC)
The COVID-19 pandemic has caused widespread devastation, with the immediate and short-term effects of SARS-CoV-2 infection now well described. While most people recover, many experience longer-lasting effects known as long COVID, post-COVID condition, or post-acute sequelae of SARSCoV-2 (PASC). PASC encompasses a diverse range of symptoms that can impact nearly any organ system, with common issues including fatigue, cough, malaise, and pain. These symptoms can last for weeks, months, or even years after the initial infection resolves, often significantly affecting quality of life. Experts estimate that around 65 million people globally are living with PASC, with long-term consequences expected to affect population health for decades.
Certain groups are at a greater risk of developing long COVID, including females, individuals hospitalized with acute COVID-19, and those with pre-existing comorbidities. While the exact causes of PASC are still being studied, several factors are thought to contribute, including immune system dysregulation, autoimmunity and immune printing, microvascular clotting with endothelial dysfunction, and impaired neurological signaling.
Limited Research Data on Long COVID in Children
Most research on PASC has focused on adults, leading to a misconception that paediatric PASC is rare or presents in the same way as it does in adults. This misunderstanding may cause clinicians to overlook or misdiagnose long COVID in children. Currently, there is little information on how PASC symptoms differ between school-aged children (6-11 years) and adolescents (12-17 years). A lack of standardised methods for identifying PASC in children further complicates research into the underlying mechanisms and potential treatment targets.
The RECOVER Pediatric Observational Cohort Study (RECOVER-Pediatrics) is a combined retrospective and prospective longitudinal study that aims to fill this gap. Its goals are to identify (1) common long-term symptoms in children aged 6 to 17 after SARS-CoV-2 infection, (2) how symptoms vary by age group (school-aged vs adolescents), (3) how symptoms cluster into distinct phenotypes, and (4) which combinations could be used to create an index to consistently assess the likelihood of PASC in children.
The study involved 751 infected and 147 uninfected school-aged children, as well as 3,109 infected and 1,369 uninfected adolescents. In this cohort, 20% of infected school-aged children and 14% of adolescents had probable PASC, with prolonged symptoms affecting nearly every organ system. Most children experienced multisystem involvement.
Both age groups exhibited a cluster with a high symptom burden (similar to adults) and a cluster dominated by fatigue and pain. However, other symptom patterns varied by age, with four symptom clusters identified in school-aged children, and three in adolescents. School-aged children had one cluster involving neuropsychological and sleep issues, an another one involving gastrointestinal problems. In contrast, adolescents had a cluster primarily involving the loss of taste and smell – similar to adults – that was not observed in younger children. Respiratory symptom clusters were not identified, possibly due to the community-based recruitment or the small number of participants with severe acute illness.
The strongest factors distinguishing infection history in adults (based on the RECOVER-Adult study) and adolescents were similar. However, there was less overlap between adults and school-aged children.
More Clinical Trials Are Needed
Despite four years of research into long COVID, much remains to be learned about its trajectory and effective strategies for prevention and management, particularly in children.
The RECOVER-Pediatrics study has shown clear differences in PASC symptoms between school-aged children and adolescents, highlighting the importance of treating these two age groups separately. Understanding the pathophysiology behind these differences is crucial, especially given the significant growth, developmental, immunological, and hormonal changes that occur throughout childhood and adolescence. Futhermore, demonstrating that paediatric symptom clusters are associated with different underlying mechanisms than those in adults will be essential for identifying the right treatment targets for future clinical trials.
Véronique Ropion,
Strategic Projects Director, Pharmalys Ltd
Bibliography:
- Gross R.S. et al. Characterizing Long COVID in Children and Adolescents. JAMA | Original Investigation. doi:10.1001/jama.2024.12747 Published online August 21, 2024.
- Rao S. Uncovering Long COVID in Children. Editorial. JAMA Published online August 21, 2024
