Kids’ Risk of Severe Respiratory Infection Rises With Comorbidity Count

Having multiple comorbidities or being transferred from a referring hospital was linked to a greater risk of severe illness in children hospitalized with acute respiratory tract infections (RTIs), according to a Canadian retrospective cohort study.

Nearly one in four of the study’s 2,585 hospitalized acute RTI pediatric patients (21.3%) developed severe disease, according to Haifa Mtaweh, MD, PhD, of the Hospital for Sick Children in Toronto, and colleagues.

Those with two or more underlying conditions were 62% more likely than kids with none to develop severe disease (adjusted relative risk [aRR] 1.62, 95% CI 1.36-1.93), an association not seen for the children with one or more preexisting conditions.

And those who were transferred from a hospital to one of the study’s two children’s hospitals were 4.7 times more likely to have their acute RTI lead to severe illness (aRR 4.73, 95% CI 4.01-5.59), they reported in JAMA Network Open.

“These findings suggest that children with chronic conditions represent a high-risk group who should be prioritized for preventive strategies and emerging prophylactic treatments,” Mtaweh and colleagues wrote. “Despite low mortality, the complication burden remained high, underscoring the need for targeted prevention and ongoing surveillance.”

RTIs continue to be a substantial cause of mortality globally in children under 5 and contribute to morbidity, hospitalizations, and healthcare costs. Studies on factors linked to severe outcomes have mostly focused on kids younger than 2 years with single viral infections, while other research on pediatric RTIs has similarly concentrated on narrow age ranges or had limited detail on outcomes.

To offer a broader understanding of RTIs in children of all ages, the READAPT-Kids Study Group conducted a retrospective, observational cohort study at two Canadian children’s hospitals from July 2022 to June 2023. Patients included all children up to 18 years who were hospitalized with an acute RTI caused by suspected or confirmed bacterial or viral pathogens.

The study’s primary outcome was the proportion of patients who developed severe illness, defined as death, cardiac arrest, or the need for noninvasive mechanical ventilation, invasive ventilation, or extracorporeal therapy.

Median patient age was 2.5 years, and 59.7% were male. Half of the patients (50.6%) had chronic comorbid conditions, including 25.3% who had neurological, developmental, or genetic disorders; 16.9% who had asthma or used puffers or inhalers at home; and 13.9% who had a pulmonary disease that wasn’t asthma.

Children with neurological or genetic disorders were 79% more likely to develop severe disease than those without underlying conditions (aRR 1.79, 95% CI 1.52-2.08), while those with pulmonary conditions including asthma and wheezing were 67% more likely (aRR 1.67, 95% CI 1.41-1.98).

Among the 2,332 patients who underwent viral testing, 70.7% had a viral pathogen identified. The predominant viruses were respiratory syncytial virus (RSV; 30.4%) and enterovirus-rhinovirus (EV-RV; 25.6%). Influenza was identified in 7.2% of patients, parainfluenza in 7.3% of patients, and human metapneumovirus in 8.4% of patients.

RSV and EV-RV were more common in children younger than 1 year, at 48.5% and 19.1%, respectively. No specific viral cause was linked to increased risk of severe disease, however. Only 6.8% of patients received antiviral therapy.

Nearly two-thirds (63.9%) of children tested had one virus, 12.5% had two viruses, and 2% had three viruses. Compared with no detected virus, presence of two viruses was not significantly linked to a greater risk of severe illness — but those with only one virus were at 65% greater risk (aRR 1.65, 95% CI 1.30-2.08).

“Our observation that coinfections were not associated with disease severity could be explained by biological mechanisms, such as rhinovirus modulating the course of influenza, as proposed by recent studies,” Mtaweh and colleagues noted.

One in four patients (24.8%) ended up in a pediatric intensive care unit (PICU), and nearly all of those patients (93.3%) had severe disease.

Median length of stay overall was 3 days, though the median for children with severe disease was twice that. Among those admitted to the PICU, median stay was 3 days. More than one-third of patients with RSV (34.1%) and those with SARS-CoV-2 (36%) spent time in the PICU.

Severity risk by age was bimodal, with those younger than 1 year or older than 10 years seeing greater risk. The mortality rate was 1.4%; 43.2% of patients who died had more than one pathogen. Only one patient death was caused by bacterial infection.

Study limitations included a lack of comparison with patients at community hospitals, and a lack of data on oxygenation or organ dysfunction scores. In addition, the study’s time span may have seen epidemiological shifts, with future seasons potentially seeing different viral distributions and burdens.

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