Pediatric COVID-19 and PIMS-TS: hospitalization, severe disease and mortality risk

Since its emergence in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over five million documented deaths, among well over 200 million infections. While children appear to be spared severe disease compared to adults, measuring the absolute risk requires a knowledge of the number of cases in this age group.

Study: Risk of Hospitalization, severe disease, and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany. Image Credit: visivastudio/ShutterstockStudy: Risk of Hospitalization, severe disease, 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 severe coronavirus 2019 (COVID-19) and those who died of the disease. The investigators used cases reported by the statutory notification 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 the statutory notification system in Germany for COVID-19 hospitalization and deaths, and a national registry on children hospitalized with COVID-19 and Pediatric Inflammatory Multisystem Syndrome - Temporarily-Associated with SARS-CoV-2 (PIMS-TS).

PIMS-TS is a hyperinflammatory syndrome that usually occurs 4-6 weeks after a mild or asymptomatic SARS-CoV-2 infection. The aim of the study, which appears on the medRxiv* preprint server, was to assess the risk for these outcomes among children of various ages.

What did the study show?

The SARS-CoV-2 KIDS study showed that almost 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 over 1.4 million children had been exposed to the virus and were thus at risk for hospital admission, treatments, admission to the intensive care unit (ICU), and death as a result of either severe COVID-19 or PIMS-TS, or both.

The number of cases required to be treated for SARS-CoV-2 infection in the 5-11-year age group was 89, but 352 among those aged 12-17 years. If only those children who required ICU admission were considered, the numbers would be sharply reduced.

In May 2021, the cumulative hospitalization rate for COVID-19 was ~36 per 10,000 children, but 5.5 times less, at 6.5 per 10,000, if only those patients required to be treated were considered. Thirdly, if including only ICU pediatric admissions, the number went down 20 times, to 1.7 per 10,000.

The hospitalization and intervention rates were consistently highest in the youngest children, below five years of age, and then in those aged 12-17 years. The rate of ICU admission was highest in the latter. Children between 5-11 years were found to be at very low risk, with less than one death per million – there were just 14 deaths among children due to COVID-19. Moreover, about 40% of these deaths were in pediatric palliative care patients who had serious underlying illnesses already.  

When only previously healthy children were considered, 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. Under the age of five, no deaths were reported from COVID-19.

PIMS-TS and ICU admission

The risk for developing PIMS-TS was less than 3 per 10,000 overall, but fewer cases were reported among 12-17-year-olds than other age groups. Conversely, the overall risk of requiring ICU admission because of PIMS-TS was just over 1 per 10,000, without any obvious 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.

Moreover, PIMS-TS seems to affect healthy children for the most part, with a somewhat higher overall risk of developing the condition and of 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. Secondly, most hospitalizations occurred in healthy children infected with the virus, but almost half the active treatments for the disease occurred in children who had prior underlying disorders.

In addition, these already sick children made up two of every three pediatric ICU admissions for COVID-19. This is despite the fact that they make up only a fraction of the total pediatric population, indicating their heightened risk for severe disease following SARS-CoV-2 infection.

In contrast, less than 2 in 100,000 healthy children aged 5-11 years needed ICU admission following SARS-CoV-2 infection, with no recorded deaths.

What are the implications?

The measures used in this study helped achieve a reliable projection of both the acute SARS-CoV-2 disease burden and of PIMS-TS, combining the results from clinical registries and statutory notification system data with a national seroprevalence study. The findings unmistakably indicate a very low risk for severe disease in children following SARS-CoV-2 infection, as has been the case since the pandemic began, irrespective of geographical location.

This study has pioneered an accurate estimate of the incidence of PIMS-TS following SARS-CoV-2 infection, at 1 in 4,000 cases, a definite improvement from the earlier rough estimates based on the number of infections. About half of these cases will be admitted to the ICU.

Healthy children had a higher risk of PIMS-TS overall and ICU admissions for this reason. Thus, PIMS-TS is a significant contributor to the overall disease burden following pediatric SARS-CoV-2 infection, making up a quarter of all hospital admissions that need active treatment in this age group and 40% of ICU admissions. The toll is higher among previously healthy children, who make up 40% of all hospitalizations that need active treatment, and two-thirds of ICU admissions, due to PIMS-TS.

The researchers point out that internationally, despite these numbers, few patients have been reported to suffer residual illness following recovery from PIMS-TS, showing the effectiveness of current treatments for this condition. Moreover, with the rise to dominance of the Delta SARS-CoV-2 variant, the incidence of this hyper-inflammatory sequel has fallen.

Further research will be required to validate these findings, but they offer reassurance about the role played by PIMS-TS in children’s health following SARS-CoV-2 infection.

*Important notice

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

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.

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