Long COVID
Corey Diamond, PharmD
Post–COVID-19 conditions (better known as long COVID) have taken clinicians by surprise. Since the onset of the pandemic, post–COVID-19 conditions have been well documented in adults, often manifesting as persistent fatigue, post-exertional malaise, and cognitive dysfunction months after an acute COVID-19 infection, often without correlation to severity of illness.
But there is still a scarcity of information about the effects of long COVID within the pediatric population. A new study published in JAMA from July 2022, reveals the best snapshot to date on how long COVID typically manifests in children 90 days after infection. The results of the study provide a basis for identifying key pediatric risk factors associated with COVID-19 infection.
The snapshot
Funk and colleagues conducted a prospective cohort analysis that included children younger than 18 years old who underwent testing for COVID-19 at over 20 pediatric emergency departments (EDs) from March 7, 2020, to January 20, 2021, across 8 countries, including the United States. At the 90-day follow-up mark, the analysis included over 1,800 children.
Researchers found that 9.8% of hospitalized pediatric patients with a confirmed COVID-19 infection reported post–COVID-19 conditions at 90 days. Conversely, the proportion of children infected with COVID-19 who were not hospitalized and reported post–COVID-19 conditions at 90 days was about half, at 4.6%.
In order to compare the rates of post–COVID-19 conditions against the background rates of similar symptoms after a general pediatric infection, the authors frequency matched the children who tested positive for COVID-19 with a virus-negative control participant. The authors found that 5% of the hospitalized virus-negative control participants and 2.7% of the nonhospitalized controls reported similar long COVID symptoms.
According to the study, the most common long COVID symptoms that were reported in children were respiratory problems (e.g., cough, difficulty breathing, or shortness of breath), as well as fatigue or weakness. Additionally, the authors used an adjusted regression analysis to identify key risk factors associated with childhood long COVID-19 symptoms within their cohort.
Their regression model found that children who tested positive for COVID-19 hospitalized for more than 48 hours had an over 2.5-fold stronger association with post–COVID-19 conditions compared to nonhospitalized children. These conditions were also strongly associated with symptom quantity at the index ED visit. Compared to children with 3 or fewer symptoms on ED presentation, children who tested positive for COVID-19 with 7 or more symptoms and 4 or more symptoms had about a 4.5-fold and 2.5-fold stronger association with post–COVID-19 conditions at 90 days, respectively.
The final risk factor they reported was age: Children who tested positive for COVID-19 who were 14 years or older had about a 2.5-fold stronger association with post–COVID-19 conditions at 90 days compared to children younger than one year.
Strength of the design
As a result of limitations in study methodology early in the pandemic, the literature has presented conflicting evidence of whether children were at risk of manifesting long COVID after acute COVID-19 infection. Early reports from 2020 and 2021 estimated that post–COVID-19 conditions occurred in up to 58% of pediatric patients with COVID-19, while other reports describe no disparity.
Funk and colleagues’ study now provides important insights into the characterization of COVID-19 in children as it is the first large prospective cohort study to investigate long COVID in children seeking ED care with advanced methodology that significantly mitigates bias.
“Our PCC [post-COVID-19 conditions] assessment approach, which clarifies the presence of the reported symptoms prior to the index ED visit, represents a methodological advance compared with prior assessments that focused on the presence or absence of symptoms in the preceding 7 days,” stated the authors.
They go on to say that by including children with repeat COVID-19 test results within 14 days of the index ED visit, the researchers were able to eliminate the risk of false-negative tests results. “Thus, our evaluation provides a realistic estimate of PCC prevalence along with a comparator group.” ■