Study suggests increased pediatric COVID-19 hospitalizations related to increased Delta variant incidence

The 2019 coronavirus disease (COVID-19) pandemic has dealt a severe blow to the health and prosperity of the world, but it is widely believed to have spared children. However, it is necessary to look at it with fresh eyes, given that vaccination of children with COVID-19 vaccines is still not widely approved, while more and more children are returning to group settings as schools and nurseries in different countries, even as new and potentially more serious viral variants begin to circulate.

Study: Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 variants of care in children: a retrospective cohort study in one center. Image Credit: MIA Studio/Shutterstock

A new preprint explores this area, comparing disease outcomes in children with COVID-19 caused by different strains of the virus to help frame future public health interventions.

Background

Newer variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have shown increased transmissibility, immune evasion and/or disease severity, leading to variants of concern (VOS). Genomic monitoring in the US by the Centers for Disease Control and Prevention (CDC) points to a rapid expansion of alpha and gamma VOCs in the country’s Midwest in winter-spring 2021, after which the Delta variant took over.

This appears to be related to an increased incidence of the disease in children, with higher hospital admissions, but the link between them is uncertain. This prompted the current study comparing disease severity in children infected with the wild-type strain with the VOC that is now common in terms of outcomes in this age group. The paper appeared on the medRxiv* preprint server.

What did the investigation reveal?

The researchers studied a 10-month period from October 15, 2020 to August 31, 2020, in which they identified approximately 500 patients, ages 0-18, who had whole-genome sequencing (WGS) performed. The median age was seven years.

More than half of the sequences were caused by a VOC, including nearly 38% Alpha, 47% Delta and 15% Gamma isolates. Only 1% was due to infection with a beta strain and these were not further investigated.

By time period, the Alpha and Gamma made up the majority of infections until May 2021, starting in January and February 2021 respectively. At that point, pediatric infections started to decline, but shot up again after June 2021 due to the rise of the Delta VOC, according to patterns of incidence in adults.

Further analysis shows that black patients are more likely to become infected with a VOC. At the same time, infection with the Gamma variant was associated with an increased risk of hospitalization, respiratory support and serious illness. Conversely, the single was death in a child with a non-VOC infection.

Older children also had a more serious disease, with a 10-20% higher chance per year. Children with high-risk medical conditions were also more prone to hospitalization. As noted above, Gamma VOC was a marker for approximately six times higher hospitalization rates, eight times higher risk of respiratory support, and approximately eight times higher risk of major illness.

What are the implications?

With its retrospective design, this study showed that COVID-19 in children remained largely mild despite the rise of VOCs. Infection with the Gamma VOC and its sublines was linked to a more serious disease, with a greater chance of hospitalization, but not the Alpha or Delta

In this one-center retrospective cohort study of children with COVID-19 in the Chicago area, serious illness was more common with Gamma VOC infection. A previous study in younger patients in Brazil showed an increased number of hospitalized younger patients with severe COVID-19 but no other underlying medical conditions caused by Gamma VOC infection.

In the US, a Delta spike led to a higher number of pediatric hospitalizations with COVID-19. Still, the percentage of such hospitalizations requiring intensive care (ICU) admission or mechanical ventilation did not change significantly. Conversely, in Canada, adults with COVID-19 caused by Alpha, Beta or Gamma VOCs were more prone to become seriously ill or die.

Although both Alpha and Gamma variants proliferated during the study period, meaning these strains caused the most infections in children, the absolute incidence in children and adults decreased simultaneously. This may indicate that the Gamma strain cannot spread at sustained high levels, even though most children remained unvaccinated and many schools reopened at the same time, with mitigation measures.

The increased severity of COVID-19 in children affected by the Gamma strain may mean that when this strain is common, monoclonal antibodies should be considered earlier and antibodies that are ineffective against this strain should not be used. The value of using tests that identify the strain of infection is also indicated.

However, the Gamma strain has now become a minor variant, with Chile, Brazil and Peru being the only place where it causes >1% of infections. Along with the Alpha, this variant is now considered a variant controlled and not a VOC by the CDC.

Further research is needed to understand why the Gamma strain causes more serious illness in children.

This study was a small, single-center study, involving only those patients who had the viral genomes sequenced, potentially limiting its generalizability. However, it implies that the Delta VOC does cause more infections, but not necessarily more serious infections in children.

Continued surveillance will be needed to identify new outbreaks of these and newer variants to inform public health responses to and clinical protocol for treating pediatric COVID-19.

*Important announcement

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, should guide clinical practice/health-related behavior or be treated as established information.