Male sex, obesity among risk factors for severe COVID-19 in children

A large study by the US National COVID Cohort Collaborative (N3C) has identified factors associated with the risk of severe disease among children with SARS-CoV-2 infection as well as factors tied to an increased risk of multisystem inflammatory syndrome in children (MIS-C) as compared to acute COVID-19.

“[T]here were observed differences in demographic characteristics, pre-existing comorbidities, and initial vital sign and laboratory values between severity subgroups,” the authors said.

This prospective study, conducted at 56 N3C centres, included 1,068,410 children aged <19 years when first tested for SARS-CoV-2 before September 24, 2021. Of these, 15.6 percent of children tested positive (n=167,262; median age 11.9 years, 49.6 percent female).

About 6 percent of patients (n=10,245) required hospitalization, of whom 13.9 percent (n=1,423) were categorized as having severe disease. Mechanical ventilation was warranted in 7.8 percent, vasoactive-inotropic support in 8.5 percent, and extracorporeal membrane oxygenation in 0.4 percent. A total of 131 patients (1.3 percent) died.

Among hospitalized children, several factors were identified as being associated with a greater likelihood of severe disease including male sex (odds ratio [OR], 1.37, 95 percent confidence interval [CI], 1.21–1.56; p<0.001), Black/African American race (OR, 1.25, 95 percent CI, 1.06–1.47; p=0.008), and obesity (OR, 1.19, 95 percent CI, 1.01–1.41; p=0.04). [JAMA Network Open 2022;5:e2143151]

Certain paediatric complex chronic conditions (PCCCs) were also tied to an increased risk of severe disease including cardiovascular (OR, 1.76; p<0.001), cancer (OR, 1.82; p<0.001), and neuromuscular (OR, 1.36; p=0.002) PCCCs.

Risk factors for MIS-C

Of the 707 children with MIS-C, 36.9 percent were considered to have severe disease. The risk of being diagnosed with MIS-C as compared with acute COVID-19 was greater in boys (OR, 1.59, 95 percent CI, 1.33–1.90) and patients of Black/African American race (OR, 1.44, 95 percent CI, 1.17–1.77), aged <12 years (OR, 1.81, 95 percent CI, 1.51–2.18), or obese (OR, 1.76, 95 percent CI, 1.40–2.22; p<0.001 for all).

Patients with MIS-C were significantly more likely to require invasive ventilation (16.5 percent vs 6.2 percent) or vasoactive-inotropic support (27.0 percent vs 5.2 percent; p<0.001 for both) compared with those with acute COVID-19.

“Although most children were aged 12–17 years, more aged 1–5 and 5–12 years were hospitalized over time,” said the authors. Antibody testing, a potential surrogate for MIS-C testing, suggested that the risk of MIS-C may be greatest in the 2–5 weeks post–SARS-CoV-2 infection, they added.

Lab values, vital signs, treatments differ by severity

The values and laboratory test results on day 0 for blood pressure, oxygen saturation, heart and respiratory rate, and organ dysfunction were more likely abnormal for children with severe than moderate disease. The results for most vital signs and values significantly improved by day 7 in children with moderate or severe disease, “likely reflect[ing] the low mortality rate and high recovery rate of the children,” the authors noted.

“[T]hese results suggest that early identification of children likely to progress to a more severe phenotype could be achieved using readily available data from the day of admission,” they commented.

More children with severe than moderate disease received antimicrobial treatment (69.4 percent vs 30.4 percent; p<0.001). Antibacterials and antivirals were the most common treatments (67.1 percent vs 29.1 percent and 13.2 percent vs 2.7 percent, respectively; p<0.001 for both comparisons), though systemic antibacterial use decreased with time owing to the low incidence of concomitant bacterial infections. More children with severe than moderate disease received remdesivir (8.3 percent vs 1.7 percent) or immunomodulatory treatments (52.9 percent vs 13.9 percent), including systemic corticosteroids (48.1 percent vs 12.9 percent; p<0.001 for all).

Difference according to era?

Hospitalization rates did not differ between the Delta and pre-Delta strain seasons (beginning and before June 26, 2021, respectively; 6.0 percent vs 6.2 percent; p=0.18). However, the rates of severe disease were lower during the Delta vs pre-Delta season (10.3 percent vs 14.6 percent; p<0.001). “This decrease may reflect that more previously healthy children were hospitalized in the Delta era,” the authors said.

They acknowledged that some hospitalizations may have been due to other conditions rather than SARS-CoV-2 infection. “We also were not able to account for the differing reference ranges for vital signs and many laboratory findings known to vary throughout childhood,” they said.