How is long-COVID different from other post-viral infection syndromes?

In a recent review published in eClinicalMedicine, researchers reviewed the symptoms, illness duration, long-term clinical traits, and possible healthcare burden of post-viral conditions in children and adolescents under 20 years.

Specifically, they evaluated the effects of post-acute infection syndromes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), otherwise known as Long COVID (coronavirus disease 2019/COVID-19) and other viruses that infect children, such as Varicella, Influenza, Epstein–Barr virus (EBV), Ebola, etc.

Study: How does post COVID differ from other post-viral conditions in childhood and adolescence (0–20 years old)? A systematic review. Image Credit: Starocean/Shutterstock.com

Background

Even though viral infections are common in children, children do not typically suffer from severe disease. However, post-viral infection syndromes sharing common etiopathogenesis, irrespective of the causal pathogen, occur in children and adolescents. 

Fortunately, their prevalence is lower in children and young adults relative to adults, e.g., post-viral fatigue syndrome, also medically known as myalgic encephalomyelitis.

Moreover, data from studies with adult subjects suggest that despite prolonged duration and persistence of symptoms, post-infection virus syndromes generally resolve within six months or even less, e.g., long COVID. 

However, evidence of their pathogenesis and long-term clinical manifestations in the pediatric population is lacking.

An understanding of this is crucial because it represents a considerable healthcare burden with socioeconomic consequences for the patients and their families.

About the study

In the present study, researchers systematically searched multiple databases, such as Google Scholar and Embase, adhering to the PRISMA guidelines to identify relevant studies on post-viral conditions in children.

In this way, they identified randomized controlled trials (RCTs), cross-sectional, observational, cohort, and case-control studies describing post-viral conditions (at least one) in children, adolescents, and young adults, i.e., the population of interest.

The screening process involved an independent assessment of titles, abstracts, and full texts of select studies by four investigators, who resolved disagreements through discussion and assessed the risk of bias in included studies using a quality rating system.

Additionally, they performed a descriptive analysis of continuous and categorical variables in data synthesis.

The primary study outcomes were symptom duration and type in post-COVID and other syndromes, the proportion of children developing chronic symptoms (e.g., fatigue), and full recovery alongside the differences between these two entities.

Secondary outcomes, if feasible to assess, were lost school days, difficulty in doing day-to-day tasks, and emergency department (ED) evaluations undertaken.

Results

The authors retrieved 35 studies with data on 42,934 children, adolescents, and adults under 20 who had post-viral infection symptoms.

Of these 35 studies, 28 studies focused on post-COVID conditions, five were on other respiratory viruses, mainly RSV and Rhinovirus, while the remaining two were respectively on EBV and gastrointestinal viruses, namely Adenovirus and Norovirus. 

These studies reported both physical and psychological symptoms, with similar symptom duration for post-COVID-19 and post-EBV/gastrointestinal virus syndromes, ranging between 10 days to 18 months.

However, post-acute syndromes after RSV/Rhinovirus infection were of even longer duration (average three years). Post-COVID chronic symptoms occurred among 36.8% of patients within the follow-up time of studies, while 63.2% attained recovery.

Intriguingly, two studies by Kikkenborg Berg et al. showed that the burden of symptoms in patients experiencing Long COVID was comparable to seronegative controls, highlighting a temporal association with infection and not causality.

They evaluated children from zero to 14 years and adolescents from 15 to 18 years in these studies. Further in-depth analysis may help clarify these observations in cases and controls.

As expected, fatigue was a dominant persistent symptom of the post-EBV and post-COVID conditions in older children and adolescents, which likely hindered their everyday tasks and activities.

Another noteworthy symptom shared by both post-COVID and post-gastrointestinal virus syndromes was persistent diarrhea, especially in younger children.

Likewise, studies on RSV and Rhinovirus showed that wheezing was common in children and infants younger than three years.

However, neurocognitive symptoms, such as the lack of concentration and loss of taste and smell, were specific to post-COVID conditions, and even their underlying mechanisms remain unestablished.

Even though data relating to secondary outcomes was scarce, they deserve attention as post-infectious conditions (in general) have a high morbidity burden on the population scale.

Conclusions

Studies have not comprehensively compared the severity and duration of post-COVID symptoms to the symptoms of post-infection syndromes due to other respiratory viruses.

In the present study, the authors found that their symptom duration was similar; however, recovery was achieved in more than half of the children with post-COVID and post-EBV conditions, with a smaller proportion of children developing chronic symptoms. 

Future studies should focus on definite age sub-groups and gastrointestinal and cardio-respiratory symptoms for post-viral infection syndromes other than post-COVID. 

Other areas worthy of further investigation might be the recurrence rate of symptoms post-recovery, the socioeconomic consequences of these conditions for children and their families, and the comparison of persistent symptoms developed after an asymptomatic acute infection.

Together, these measures could help effectively evaluate pediatric patients experiencing post-COVID or similar conditions and contribute towards preparedness for future pandemics.