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It's easy to think the COVID-19 pandemic is in the rearview mirror, especially for children who are often considered at low risk for severe disease.

For kids who do get severe COVID-19, treatment is now more nuanced and the spectre of multisystem inflammatory syndrome in children (MIS-C) has all but vanished. However, recent data point to some concerning trends in COVID-related hospitalization rates.

Spikes in Hospitalization Rates

Recent data has challenged the assumption that children are less likely to be hospitalized for COVID-19 compared with adults.

From October 2022 to April 2024, COVID-associated hospitalization rates among infants younger than 6 months were higher than rates among any other age group, except adults ages 75 and older, CDC researchers detailed in a recent .

In this age group, weekly COVID-19 hospitalization rates peaked at 23.0 per 100,000 infants during the weeks ending December 17 in the 2022-2023 respiratory virus season and at 20.3 per 100,000 infants during the weeks ending January 13 in the 2023-2024 season. From October 2022 to April 2024, there were 1,470 COVID-associated hospitalizations among infants under 6 months of age.

Moreover, of 1,148 hospitalized young infants with COVID-19, approximately one in five required admission to the intensive care unit (ICU), nearly one in 20 required mechanical ventilation, and nine died.

Of note, only one in four had any underlying conditions.

Infants younger than 6 months are at increased risk of becoming infected with SARS-CoV-2 because they are ineligible for COVID-19 vaccination. Any protection against the virus depends upon transplacental transfer of maternal antibodies from vaccination or infection.

High hospitalization rates among infants may have been tied to a substantial drop in the percentage of mothers getting vaccinated during pregnancy. From October 2022 to September 2023, 18% of mothers had been vaccinated against SARS-CoV-2 during pregnancy, but this dropped to less than 5% from October 2023 to April 2024.

COVID's Summer Surge

COVID-19-related hospitalizations for infants and children were high during the most recent COVID surge this summer, compared with adults under the age of 50.

According to for the week ending August 10, there were 10.0 COVID-related hospitalizations per 100,000 infants younger than 1 year and 3.4 per 100,000 children younger than 4 years, compared with 1.7 per 100,000 adults ages 18-49. Hospitalization rates among children have since decreased.

Colleen Nash, MD, MPH, of Rush University in Chicago, witnessed this latest increase in hospitalizations firsthand. "We saw after a bit of a break quite a few kids with more severe COVID, requiring just hospitalization and several in the ICU requiring supplemental oxygen," she told 乌鸦传媒. "I hadn't treated anyone for COVID in a long time."

Although the risk of severe COVID-19 is higher among children with underlying conditions, most of the kids at Nash's institution didn't have any such conditions. "Younger kids who didn't otherwise have a well-established chronic condition were coming in and requiring maybe brief admission, even potentially ICU admission -- which is a big deal in an otherwise healthy kid," she said.

These increases in COVID-19 hospitalizations may have been due to waning immunity in the general population, ineligibility for vaccination among infants under 6 months of age, and less motivation for parents to have their children vaccinated, she explained.

However, not all clinicians agreed that they saw more children with severe outcomes from COVID-19 over the summer.

"Disease severity in children was still relatively mild," Neil Rellosa, MD, of Nemours Children's Health in New Castle, Delaware, told 乌鸦传媒. "In our hospital during this past summer, there were many children admitted who tested positive for COVID-19, but may have been admitted for other unrelated medical reasons."

What About MIS-C?

MIS-C is a serious complication of COVID-19, typically occurring 2 to 6 weeks after SARS-CoV-2 infection, and is characterized by fever, elevation in inflammatory markers, and multi-organ involvement.

Over the last few years, cases of MIS-C have, thankfully, become a rare occurrence. Early in the pandemic, MIS-C incidence was 6.79 cases per million person-months, but by 2023 had decreased by 98% to 0.11 cases per million person-months, according to CDC data.

"At the beginning of the COVID outbreak, and probably for the first year, we were seeing two to four cases of MIS-C a week," Stephen Aronoff, MD, of Temple Health in Philadelphia, told 乌鸦传媒. "I don't believe I've seen one in the last 2 years."

The exact reasons why there are fewer cases of MIS-C isn't clear, physicians said, but it may have to do with overall immunity, vaccination, or alterations in the virus over time.

Which Kids Are at Highest Risk?

Children with compromised immune systems, such as those undergoing chemotherapy, with organ transplants, or taking other immunosuppressants, are at increased risk for severe COVID-19.

In addition, "children with pre-existing lung conditions, such as prematurity-related lung disease and asthma, can have more complications from SARS-CoV-2 infections," Megan Freeman, MD, PhD, of the UPMC Children's Hospital of Pittsburgh, told 乌鸦传媒.

According to the , children ages 12 years or older appear to be at increased risk for progression to severe or critical COVID-19 compared with younger children.

Underlying conditions often influence the prognosis for children hospitalized with acute, severe COVID, Aronoff commented.

"Patients we see who classically have severe COVID are, interestingly enough, those children who are adolescents who are obese," he said, though he noted that "those children -- while they might require significant interventions -- tend to do relatively well."

However, "if the child has severe underlying immune defects, those children tend to have significant issues and may not do so well," he added.

How Has Treatment Evolved?

Supplemental oxygen, steroids, and antivirals continue to be the mainstays of treatment in hospitalized children with severe COVID, based on guidelines from and the .

However, treatment has become more refined, clinicians told 乌鸦传媒.

In the early days of the pandemic, "we used to give 10 days of steroids to everybody," Nash said. "Now it's more like, well, maybe you just need a few days. We'll see what the clinical trajectory is and adjust from there. So it's a little bit more nuanced."

Rellosa noted that "we now better understand the importance of supportive care and interventions while a patient is acutely ill and that many of our previous pharmacologic treatments may not provide as much benefit as we thought they would."

"Steroids for patients with severe pulmonary disease can be helpful, but antiviral medications may not provide as much benefit beyond the first days of infection once they are severely ill," he said. "Treatments like convalescent plasma or other immunomodulating therapies are no longer recommended, having limited effectiveness, especially with ever-changing virus variants."

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