COVID-19: nonhospitalized youth may also experience persistent COVID symptoms

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A new study by researchers from The University of Texas (UT) Health Science Center at Houston-USA has found that children who contracted mild COVID-19 can still develop Long COVID symptoms after recovery.

The study findings were published in the peer reviewed The Pediatric Infectious Disease Journal. https://journals.lww.com/pidj/Fulltext/9900/Comparison_of_Persistent_Symptoms_Following.151.aspx

We report here one of the first population-based estimates of the prevalence of persistent COVID symptoms in children and adolescents in the United States, often called long COVID. Our findings show that 4.5% of the total sample reported persistent COVID symptoms beyond 4 weeks with more than twice the number reporting symptoms lasting >12 weeks (n = 58) versus 4–12 weeks (n = 27) and more than double did so during the pre-Delta (8.0%) versus Delta variant period and beyond (3.4%).

Regardless of length, all those reporting long COVID symptoms were symptomatic upon initial SARS-CoV-2 infection. In general, all pediatric age groups were significantly less at risk for persistent COVID symptoms than adults in the same study. Those who (1) reported symptomatic initial infection; (2) severe symptoms; (3) not being vaccinated and (4) had obesity were at higher risk for reporting persistent COVID symptoms versus their counterparts, although some of the associations did not meet statistical significance.

These findings contribute to a better understanding of the expected burden of long COVID disease in the pediatric population that was not hospitalized due to COVID-19 illness, and thus the pediatric healthcare resources that will be required.

Our overall prevalence estimate (4.5%) of persistent COVID symptoms findings in children and adolescents falls more toward the lower end of other studies that report prevalence estimates ranging from (1.8%–4%)11,2 to >30%.12 Our findings that children are less at risk for long COVID versus adults is similar to other recent studies. Specifically, a study that included 201 households (n = 507 participants, 56.4% children) in Italy showed children experienced long COVID months (77 days median follow-up post-SARS-CoV-2 diagnosis, interquartile range 47–169) after mild acute SARS-CoV-2 infection, but at less frequency and severity than co-habitant adults.29 The authors note the importance of continued need for population-based studies, such as the study sample here, to further characterize long COVID in children and its impact on their families and society as a whole.

Results here are some of the first to report by variant time period (pre-Delta defined as before July 1, 2021) and to include a control group. Indeed, to date, most pediatric studies only have included a few hundred subjects; a recent meta-analysis reported the mean sample size of long COVID studies in pediatric patients being about 238 subjects.30

Similarly, Zimmermann et al10 found that of 14 studies reviewed, only 5 (36.7%) studies included control groups with other significant limitations including lack of clear inclusion criteria, heterogeneity between studies and selection bias due to low response rate.8

Although severe symptoms of COVID are relatively rare, persistent COVID symptoms have the potential to debilitate a child’s day-to-day function and emotional well-being.31 One study reported that 7 months post-initial COVID-19 (mild) illness, lung single-photon emission computed tomography and cardiopulmonary exercise test results showed pulmonary circulation dysfunction with possible peripheral microvascular and endothelial damage in a 14-year-old girl.32

A multidisciplinary rehabilitation approach may be needed for those having more difficulty recovering from long COVID, offering age-specific coping strategies to target the distinct needs of children and adolescents. This includes optimizing daily cognitive functioning to facilitate academic performance as well as addressing mood and behavioral difficulties associated with persistent COVID symptom complications including anxiety and depression.14,32

Results here also showed that roughly a third of those reporting persistent COVID symptoms and those reporting no persistent symptoms reported their social/mental health status had been mildly/moderately impacted, while 6% of those who reported long symptoms lasting >12 weeks stated their mental/social health was severely impacted due to the pandemic.

A systematic review that analyzed the impact of COVID-19 and past pandemics on child and adolescent mental health suggested this population is more likely to experience high rates of depression and anxiety during and after a pandemic.8 Another national study reported 16 or more sick days (1205 [18.2%] vs. 2518 [11.6%]; P < 0.0001) and 16 or more days of school absence (695 [10.5%] vs. 1777 [8.2%]; P < 0.0001) among older adolescents with a positive SARS-CoV-2 test.33

While our results did not show mental health differences by persistent COVID symptom status, they highlight that well over 1 in 4 children have had some level of mental health impact during the pandemic. This may be compounded for those struggling with persistent COVID physical conditions as described here and suggest that not only clinical settings but schools and other community resources should be developed and be accessible to all families during COVID recovery.

Interestingly, 3 participants reported persistent COVID symptoms but were seronegative. The challenge of persistent or long COVID conditions being attributable to actual infection or pandemic fatigue has been mentioned by others. Again, our study design helps disentangle this by providing seroprevalence data but also calls attention to youth who may need post-pandemic support but did not experience COVID-19 illness.11

Risk factors for persistent COVID symptoms continue to be an area of interest. Specifically, the association between childhood obesity and persistent COVID symptoms has yet to be assessed. Our findings show that youth with obesity may be more likely to report persistent COVID symptoms >12 weeks compared with those at a healthy weight. Similarly, a retrospective analysis in adult patients (n = 2839) found that moderate and severe obesity (BMI ≥35 kg/m2) are associated with a greater risk of post-acute COVID-19.34 These similar findings may be a result of elevated inflammation from excess adipose tissue but are in need of more research.

Limitations of the findings reported here should be noted. The first limitation is that all responses regarding persistent COVID symptoms were self-reported and thus subject to selection bias. Additionally, the definition of long COVID requires exclusion of alternative conditions, which is not allowable with a survey. Secondly, because the study design was based on nonrandom sampling of participants, unweighted analysis cannot provide precise estimates of seroprevalence by age group in the general Texas population.

Population-level weights35 were calculated based on the Texas population and thus may not be generalizable to other states or the United States in general; however, the diverse population mirrors that of the United States. The third limitation due to the sampling frame is another selection bias; that is, parents who suspected their child or an adult in the household may have been infected with SARS-CoV-2 may have been more likely to participate. However, over half of those with positive antibody status reported no symptoms during the pre-Delta time period and slightly less than half when Delta became the dominant variant and beyond. Finally, the power to detect significant predictors of reported symptoms lasting 4–12 weeks was very low and thus may be driving the insignificant results.

Strengths of the current study include the inclusion of a comparison/control group of those with no SARS-CoV-2 antibodies. Our study may not be as subject as others to selection and misclassification bias given the high proportion who were asymptomatic, regardless of serostatus. Another strength is our ability to examine a wide age range among children, the impact of initial disease symptom severity and pre-Delta versus Delta variants on the prevalence of persistent COVID symptoms.

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