Which COVID-19 Variant Caused the Most Severe Disease in Children?

Our knowledge of COVID-19 has come a long way, especially regarding pediatric populations.

Children, initially believe to be immune to COVID-19, are now proven to benefit from COVID-19 vaccination. More than 14 million children have contracted COVID-19 since the beginning of the pandemic, representing 18.6% of all US cases.

Although pediatric populations are less likely to experience severe COVID-19 disease progression, this varied throughout the course of the pandemic. A recent study, published in The Lancet Regional Health, examined how children’s severe COVID-19 outcomes differed during Alpha, Delta, and Omicron variant predominance.

This multicenter, observational cohort study collected data from Beaumont Health, a large regional healthcare system in urban Detroit. The 8-hospital acute care system cares for approximately 2.2 million people.

The analysis included patients less than 18 years old who presented to one of Beaumont’s emergency departments with a principal diagnosis of COVID-19; children with a secondary diagnosis of COVID-19 were excluded. Pediatric COVID-19 hospital admissions were categorized by time intervals that coincided with Alpha (1/1/21-6/30/21), Delta (7/1/21-12/31/21), and Omicron (1/1/22-6/16/22) variant predominance.

Investigators defined “severe disease” as intensive care unit (ICU) admission at any time during hospitalization, need for mechanical ventilation, multisystem inflammatory syndrome in children (MIS-C), myocarditis, or in-hospital death. The primary outcome was severe disease, and secondary outcomes included viral coinfection and vaccination status.

Throughout the entire study period, there were 4517 emergency COVID-19 visits. Of these, 12.5% (n = 566) children were hospitalized. Broken down by variant, 24.4% of admissions occurred during Alpha, 31.6% during Delta, and 44.0% during Omicron.

Of the admitted children, 55.1% were male and 59.9% were white. The average age was 5 years, with 22.8% of the admitted classified as infants, 25.1% as toddlers, 23.0% as children, and 29.2% as teenagers. Over the progression of variants, the proportion of hospitalized infants increased while the proportion of hospitalized teenagers decreased.

Viral coinfection was most common during the Delta period and least common during Alpha. Coinfection most occurred in younger children (average age 1.2 years), and severe disease outcomes occurred in 45.6% of coinfection cases (compared to 22.1% of cases without coinfection).

After conducting multivariable logistic regression analysis, the investigators found the odds of severe composite disease decreased significantly from Alpha to Omicron. Children who were fully vaccinated, both with and without a booster dose, had low hospital admission rates throughout all variant periods.

It is notable that even though the Omicron period had the highest frequency of hospital admission, severe illness occurred less frequently than during the Alpha and Delta periods. Additionally, a small percentage of all inpatients had been vaccinated, and these vaccinated children had less severe outcomes.