Infants, children with comorbidities at greatest risk for critical COVID-19

The risk of critical COVID-19 is highest among infants and adolescents, children with multiple comorbidities, those with a history of prematurity, diabetes, obesity, severe immunocompromise, and those with cardiovascular, neurologic, or chronic lung diseases, reveals a study presented at PAS 2024.

“Nowadays, we have therapeutics agents such as remdesivir, Paxlovid, monoclonal antibodies, or convalescent plasma that can be used and have demonstrated to improve patient outcomes,” said lead author Camila Aparicio, postgraduate associate at Yale School of Medicine, Infectious Diseases Department, New Haven, Connecticut, US.

“However, not every child requires or benefits from these treatments, so knowing who to treat and who not to treat is key for optimal decision-making in the clinical setting. That is why risk stratification based on comorbidities and demographic factors was needed,” she added.

Aparicio and colleagues conducted an initial search in the databases of PubMed and Embase for studies published through 22 May 2023. They extended this through a manual search for studies published until 18 August 2023.

Studies with 30 or more children and young people with SARS-CoV-2 infection and with details on age, sex, and previously diagnosed underlying comorbidities and their association with critical outcomes (ie, intensive care unit admission, invasive ventilation, cardiovascular support, or death) due to COVID-19 were included in the analysis.

The investigators used a random effects model to estimate the effect size (odds ratio [OR], with 95 percent confidence interval [CI]) and I2 to test heterogeneity.

The initial screening identified a total of 10,178 studies. After removing duplicates, 8,749 articles were left. Of these, 136 met the eligibility criteria for systematic review, and 70 were included in the meta-analysis, with a total of 172,165 patients included.

The strongest risk factor for having critical COVID-19 disease was having one (pooled OR, 3.95, 95 percent CI, 2.78‒5.63) and at least two underlying comorbidities (pooled OR, 9.51, 95 percent CI, 5.62‒16.09). [PAS 2024, abstract 3095.4]

Children with cardiovascular (pooled OR, 3.48, 95 percent CI, 2.75‒4.41; I2, 62.8 percent), neurologic (pooled OR, 3.40, 95 percent CI, 2.70‒4.29; I2, 48.7 percent), and pulmonary diseases (pooled OR, 2.06, 95 percent CI, 1.61‒2.63; I2, 72.2 percent) showed the greatest risk for critical COVID-19.

The same was true for those with seizure disorders (pooled OR, 3.83, 95 percent CI, 2.13‒6.86; 78.8 percent), history of prematurity (pooled OR, 2.77, 95 percent CI, 2.17‒3.54; I2, 0.0 percent), diabetes (pooled OR, 2.85, 95 percent CI, 2.34‒3.46; I2, 29.8 percent), obesity (pooled OR, 2.26, 95 percent CI, 1.75‒2.92; I2, 74.7 percent), and severe immunocompromise (pooled OR, 2.15, 95 percent CI, 1.58‒2.91; I2, 64.9 percent).

Likewise, infants (age <1 year: pooled OR, 1.09, 95 percent CI, 0.81‒1.49; I2, 89.4 percent; age <1 month: pooled OR, 2.39, 95 percent CI, 1.42‒4.04; I2, 72.0 percent) and adolescents (age ≥12 years: pooled OR, 1.17, 95 percent CI, 1.04‒1.33; I2, 49.1 percent) showed an increased risk for critical COVID-19.

“However, age is only a modest risk factor when no other risk factors are present, with the exception of those younger than one month of age, for which evidence leans towards increased severity,” according to Aparicio.

“More robust evidence is needed to establish the risk for children with neurodisabilities, chronic gastrointestinal and kidney diseases, moderate immunocompromise, and sickle cell disease,” she said. “Further research is needed to address remaining gaps in understanding the extent to which sociodemographic factors, pre-existing immunity, and comorbidity control modify these risks.”