Since its emergence in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than five million documented deaths, among more than 200 million infections. Although children appear to save from serious illness compared to adults, measuring absolute risk requires knowledge of the number of cases in this age group.
Study: Risk of hospitalization, serious illness and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany. Image credit: visivastudio/Shutterstock
A new preprint from Germany projects estimates of the number of children affected by SARS-CoV-2 infection, along with those who developed the severe coronavirus 2019 (COVID-19) and those who died from the disease. The researchers used cases reported by the regulatory reporting systems and seroprevalence monitoring data to correct for undetected cases.
Background
The scientists used information from the SARS-CoV-2 KIDS study, a seroprevalence study in children, along with public domain data from Germany’s legal reporting system for hospitalizations and deaths from COVID-19, and a national registry of children living in hospitalized with COVID-19 and pediatric inflammatory multisystem syndrome – temporally associated with SARS-CoV-2 (PIMS-TS).
PIMS-TS is a hyperinflammatory syndrome that usually occurs 4-6 weeks after mild or asymptomatic SARS-CoV-2 infection. The aim of the study, which appears on the medRxiv* preprint server, was to assess the risk of these outcomes in children of different ages.
What did the investigation reveal?
The SARS-CoV-2 KIDS study found that nearly 11% of children had SARS-CoV-2 immunoglobulin G (IgG) antibodies between March and May 2021. All age groups showed similar seroprevalence. Overall, using all three sources, the scientists concluded that more than 1.4 million children had been exposed to the virus and were thus at risk of hospitalization, treatment, admission to the intensive care unit (ICU) and death from either severe COVID-19 or PIMS-TS, or both.
The number of cases requiring treatment for SARS-CoV-2 infection in the age group 5-11 years was 89, but 352 under 12-17 years. If only those children who needed ICU admission were taken into account, the number would be greatly reduced.
In May 2021, the cumulative hospitalization rate for COVID-19 was ~36 per 10,000 children, but 5.5 times less, i.e. 6.5 per 10,000, if only the patients requiring treatment were taken into account. Third, if only children’s ICU admissions were included, the number dropped 20 times, to 1.7 per 10,000.
The number of hospital admissions and interventions was consistently highest in the youngest children, younger than five years, and then in the children aged 12-17 years. The latter had the highest number of IC admissions. Children aged 5-11 were found to be at very low risk, with less than one death per million – there were only 14 child deaths from COVID-19. In addition, approximately 40% of these deaths were in pediatric palliative care patients who already had serious underlying diseases.
When considering only previously healthy children, the hospitalization risk from COVID-19 remained unchanged. However, the need for active treatment and/or ICU admission was still lower, at five and >1 per 10,000 children, respectively, with 0.3 deaths per 1 million cases. No deaths from COVID-19 have been reported under the age of five.
PIMS-TS and IC recording
The overall risk of developing PIMS-TS was less than 3 per 10,000, but fewer cases were reported in 12-17 year olds than in other age groups. Conversely, the overall risk of IC admission due to PIMS-TS was slightly more than 1 per 10,000, with no apparent variation with age. Thus, older children were less likely to develop this inflammatory complication of SARS-CoV-2, but the severity profile was similar at all ages.
In addition, PIMS-TS appears to primarily affect healthy children, with a slightly higher overall risk of developing the condition and requiring ICU admission in this subgroup.
The lowest risk in this study was found in children 5-11 years old, with slightly higher risks in the younger and older children in the study. Second, most hospitalizations occurred in healthy children infected with the virus, but nearly half of active treatments for the disease were in children with previous underlying conditions.
In addition, these already sick children accounted for two out of three pediatric ICU admissions for COVID-19. This is despite the fact that they represent only a fraction of the total pediatric population, suggesting an increased risk of serious disease following SARS-CoV-2 infection.
In contrast, fewer than 2 in 100,000 healthy children aged 5-11 years required ICU admission after SARS-CoV-2 infection, with no recorded deaths.
What are the implications?
The measures used in this study helped to obtain a reliable projection of both acute SARS-CoV-2 disease burden and PIMS-TS, combining results from clinical registries and regulatory reporting system data with a national seroprevalence survey. The findings unequivocally point to a very low risk of serious illness in children following SARS-CoV-2 infection, as has been the case since the start of the pandemic, regardless of geographic location.
This study has resulted in an accurate estimate of the incidence of PIMS-TS after SARS-CoV-2 infection, in 1 in 4,000 cases, a marked improvement over the previous rough estimates based on the number of infections. About half of these cases are admitted to the ICU.
Healthy children had a higher risk of PIMS-TS in general and ICU admission for this reason. Thus, PIMS-TS is an important contributor to the overall burden of disease after pediatric SARS-CoV-2 infection, accounting for a quarter of all hospital admissions requiring active treatment in this age group and 40% of ICU admissions. The toll is higher in previously healthy children, who account for 40% of all hospital admissions requiring active treatment, and in two-thirds of ICU admissions due to PIMS-TS.
The researchers point out that internationally, despite these numbers, few patients have been reported with residual disease after recovery from PIMS-TS, demonstrating the effectiveness of current treatments for this condition. In addition, with the emergence of the dominance of the Delta SARS-CoV-2 variant, the incidence of this hyperinflammatory sequela has decreased.
Further research will be needed to validate these findings, but they provide reassurance about the role PIMS-TS plays in the health of children after SARS-CoV-2 infection.
*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.
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