A little over a year ago, the AAP discussed the potential for the development of “post-COVID-19 conditions” in children in the release of guidance on follow-up care after infection with the SARS-CoV-2 virus. Post-COVID conditions, using CDC guidance, was defined as “physical and mental health consequences experienced by some patients that remained present for 4 or more weeks following a SARS-CoV-2 infection.” They further clarified that some children developed more significant and longer lasting complaints that impaired their quality of life, which fell into the category of post-acute sequelae of COVID (PASC):
The World Health Organization (WHO) recently developed a consensus definition of pediatric PASC, which is defined as the presence of one or more new, persistent physical symptoms, which may fluctuate and relapse, that lasts at least 12 weeks after confirmed initial SARS-CoV-2 infection and impairs daily function.
This part is confusing. The WHO had not, in fact, developed a definition of pediatric PASC at that time. The WHO has actually never used that term, instead choosing post-COVID condition (PCC), which they defined only for adults in 2021. It wasn’t until February of 2023 that the WHO finally released an updated definition specific to children, but nobody is perfect.
As I will get to shortly, the WHO definition of pediatric PCC would end up being a bit different from what was stated in the AAP guidance and mistakenly labelled as PASC. It appears that the AAP jumbled up the current (at the time) adult WHO definition of PCC with definitions of PASC used by other organizations, because the WHO didn’t put so much focus on impairment of daily function. It would, however, when eventually releasing a pediatric focused definition in 2023, include the fact that this is a typical component of PCC.
The NIH uses PASC as their preferred term. The CDC uses it as a subset of PCC. So any hardcore nationalists reading this in ‘Merica right now can go with that if they want. Personally I’m sticking with PCC because it feels right, and science cares about my feelings. Other individuals, groups, and professional organizations use a variety of terms to describe bad stuff that happens to some people after acute COVID-19, such as long COVID, long-haul COVID, chronic COVID, late sequelae of COVID-19, post-acute COVID-19, and post-acute sequelae of SARS-CoV-2 infection. Naturally because of the heterogeneity in terms, among other issues, data on prevalence has been a bit all over the place, especially in children.
As with adults suffering with post-COVID conditions, PASC, or whatever you want to call it this week, a wide variety of complaints and conditions affecting several body systems have been documented in children. Common symptoms are fatigue, headache, distorted sense of smell, abdominal pain, muscle aches, post-exertional malaise, and rashes. The list also includes mental health disturbances, impaired sleep, and even potentially life-threatening thromboembolic events such as pulmonary embolism. Multisystem inflammatory syndrome in children, a severe inflammatory response to recent SARS-CoV-2 infection resulting in organ dysfunction or shock, is technically a post-COVID condition but generally discussed separately as there is specific testing used for diagnosis and it tends to occur within 2 to 4 weeks of acute COVID-19.
In September of 2022, data was limited and the reported incidence of PCC in children ranged from 2% to 66%. A large meta-analysis published around that time had found that 25% of children continued to have symptoms one month after the initial infection and other studies investigating pediatric PASC determined a prevalence of 2% to 5% at 90 days. Using adult WHO criteria, the AAP estimated that PASC (again, not what WHO actually calls it) might impact anywhere from 2% to even 10% of kids. But in general, attempts to determine accurate numbers was hampered by differing definitions, populations, and study methods.
But what about now? Have we learned anything in the past 15 months or so? Authors of a Canadian paper recently published in JAMA Pediatrics set out to update our understanding:
To address the aforementioned limitations and to standardize pediatric PCC definitions, the World Health Organization (WHO) adopted a consensus definition that added several qualifiers, notably, that symptoms have an onset within 3 months of the infection, persist for a minimum of 2 months, and limit everyday function and ascertainment of developmental milestones. Use of this definition has the potential to advance our understanding of PCC in children. Thus, we sought to quantify the prevalence of PCC at 6 and 12 months after acute infection and to characterize symptoms among children evaluated in pediatric EDs across Canada using the WHO definition.
Even this requires the introduction of a little nuance. The WHO pediatric PCC criteria doesn’t state that limitation of everyday function or in meeting developmental milestones is absolutely required. According to the published clinical case definition, participants in the expert panel agreed that though symptoms should generally have a negative effect on daily function/development, this is challenging when caring for young children who rely on their caregivers to communicate for them. Ultimately, such a distinction must be made on a case by case basis.
Here is the exact breakdown straight from the WHO:
Post COVID-19 condition in children and adolescents occurs in individuals with a history of confirmed or probable SARS-CoV-2 infection, when experiencing symptoms lasting at least 2 months which initially occurred within 3 months of acute COVID-19.
Current evidence suggests that symptoms more frequently reported in children and adolescents with post-COVID-19 condition compared with controls are fatigue, altered smell/anosmia and anxiety. Other symptoms have also been reported.
Symptoms generally have an impact on everyday functioning such as changes in eating habits, physical activity, behaviour, academic performance, social functions (interactions with friends, peers, family) and developmental milestones.
Symptoms may be new onset following initial recovery from an acute COVID-19
episode or persist from the initial illness. They may also fluctuate or relapse over time.Workup may reveal additional diagnoses, but this does not exclude the diagnosis of post COVID-19
condition.This can be applied to children of all ages, with age-specific symptoms and impact on everyday function taken into consideration.
The study was prospective and involved subjects who required testing for SARS-CoV-2 infection at 14 Canadian pediatric emergency departments between the Summer of 2020 and early 2022. Data was collected during the initial ED visit and at 14 days in order to determine eligibility, and then at 90 days (if enrolled) in order to determine a diagnosis of PCC. At 6 and 12 months after the initial ED visit, caregivers answered questions on PCC symptoms and overall health/quality of life.
The authors chose persistence of PCC diagnosis (if diagnosed at 90 days) using the WHO definition at 6 and 12 months following COVID-19 diagnosis as the primary outcome. As secondary outcomes, they chose quality of life measurements using two approaches, a validated pediatric inventory tool and a 0- to 100-point scale. As a third secondary outcome, they looked at PCC symptom profiles at 12 months.
At the end of recruitment, 7,421 patients were screened with 7,263 deemed eligible for the study. Of these, 1,454 were SARS-CoV-2 positive and 5,809 were negative. Of these, 5,147 (1,152+, 3,995-) were evaluated at 6 months and 5,563 (1,192+, 4,371-) at 12 months. Most were young, with a median age of subjects of 2 years.
At 6 months, based on symptoms and quality of life changes meeting WHO criteria, 0.52% of children who had COVID-19 initially were diagnosed with PCC compared to 0.10% of those in the control group. At 12 months, 0.67% and 0.16% of children testing positive and negative at their initial ED visit respectively ended up meeting criteria for PCC. Furthermore, quality of life measurements at 6 and 12 months were equivalent (98.4 and 98.8) regardless of initial testing status.
It appears that chronic and severe COVID-related problems are less likely to impact children than previous reports estimated, which is good news. And this is a study that went to further lengths to focus in on clinically meaningful PCC than previous attempts, which likely lumped together PCC with milder presentations. The authors do point out, however, that these results may not generalize to older children and adolescents since the bulk of subjects were less than 8 years old. Also there were no methods used to determine any negative developmental impacts after COVID-19 in study subjects, so it is possible that PCC was underestimated in infants.
Though quality of life scores were essentially equivalent in both groups at 6 and 12 months, the study did find that there was a significant differences in caregiver perception of their child’s overall health at the 12-month mark. 24% of children with COVID-19 were felt to have worse overall health compared to 15% of those who tested negative initially. The authors point out that this particular assessment is more subjective than the tool used to measure quality of life and was potentially biased by specific beliefs within families.
As with all studies, there were some issues that potentially limit our ability to draw conclusions from this study. In addition to losing roughly 30% of subjects to follow up and the reliance on caregiver rather than direct patient report, which is obviously difficult with young children, the authors point out a few more interesting issues:
We did not perform antibody testing to confirm the absence of SARS-CoV-2 infection during the study period in control participants, and thus control group contamination could have occurred, which would minimize our ability to detect between-group differences. This is an important consideration as just over one-half of unvaccinated children had SARS-CoV-2 spike antibodies indicative of infection and/or vaccination following the peak of the Omicron wave. Additionally, as illness severity may be different among children with SARS-CoV-2 who visit the ED and those who do not, generalizing our findings to the latter population should be performed with caution. However, as illness severity is associated with PCC, children not requiring ED evaluation likely have a lower
PCC prevalence than we report.
Despite these limitations, I think this study still provides some reassurance to young patients and their families. Chronic debilitating health problems related to infection with SARS-CoV-2, while not impossible, do appear to be uncommon in children, particularly infants and toddlers. This shouldn’t be interpreted as a support for avoiding proven means of reducing the risk of acute infection, however. Proper precautions and vaccinations are still important tools in our toolbox.