A recent study posted to Preprints with The Lancet* investigated the disease severity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron BA.2 infection among Hong Kong children.

Study: Intrinsic Severity of SARS-CoV-2 Omicron BA.2 in Uninfected, Unvaccinated Children: A Population-Based, Case-Control Study on Hospital Complications. Image Credit: Beenicebeelove/Shutterstock
Study: Intrinsic Severity of SARS-CoV-2 Omicron BA.2 in Uninfected, Unvaccinated Children: A Population-Based, Case-Control Study on Hospital Complications. Image Credit: Beenicebeelove/Shutterstock


Before the coronavirus disease 2019 (COVID-19) vaccination program commenced in the United Kingdom (UK), more than 469,900 children under 18 years had been diagnosed with COVID-19, with five fatalities per 100,000 children. COVID-19 has killed more than six million people, and pediatric deaths constitute about 0.4%. SARS-CoV-2 Omicron, the recently emerged variant of concern (VOC), has caused the latest surge in COVID-19 cases worldwide.

Although the disease severity with Omicron infections is reportedly milder in those protected from previous infection or immunization or both, it may not hold true for those (children) who are yet to be vaccinated.

Hong Kong, which has enforced stringent COVID-19-related measures since the onset of the COVID-19 pandemic, has been witnessing an alarming surge of infections lately. Hong Kong had recorded just over 14,000 cases before the emergence of the Omicron variant. Still, infections soared to record highs, and more than 0.9 new million cases were reported between December 31st, 2021, and March 15th, 2022. Many studies suggest that SARS-CoV-2 Omicron might not just cause milder infections as previously speculated.

The study

The researchers of the present population-based, case-control study evaluated the disease outcomes in Hong Kong children hospitalized with COVID-19. Children aged 11 years or below hospitalized between February 5 and 28, 2022 (an Omicron BA.2-dominant period) were studied, who lacked prior immunity as Hong Kong began vaccination of 5 to 11-year-olds in mid-January 2022.

Electronic medical records obtained from the clinical data analysis and reporting system (CDARS) in the specified period were reviewed. Additionally, hospitalization data of SARS-CoV-2-infected children were extracted between January 1st, 2021, and November 1st, 2021 (pre-Omicron period). Lastly, influenza and parainfluenza-associated child hospitalization data between 2015 and 2019 were also retrieved. Those coinfected with two or more respiratory viruses were excluded from the study.

The extracted data were categorized into the following classes– 1) fatality and severe, 2) neurological, and 3) respiratory complications. Fatality and severe complications were classified based on the case fatality rate (CFR), pediatric intensive care (PICU) admissions, mechanical ventilation, and oxygen use. Those with neurological complications were stratified into seizures and encephalitis or encephalopathy sub-classes. Children were further grouped based on respiratory complications like croup or pneumonia. Odds ratios (OR) for the specified outcomes were calculated using binary logistic regression analysis.


In the period between February 5th and 28th, 2022, about 1147 children were hospitalized due to Omicron infections, of which 80.21% were aged under five years. Before November 1st, 2021, 737 children were hospitalized with SARS-CoV-2 infection. During the period between 2015 and 2019, around 32,212 and 16,423 child hospitalizations were due to influenza and parainfluenza infections, respectively. In the Omicron-dominant wave, four children died due to COVID-19.

Two deaths were attributed to their neurological complications – one of them had encephalopathy, and the other had fulminant cerebral edema, a recently recognized encephalitis phenotype. However, COVID-19-related deaths were not observed in the pre-Omicron period. CFR of COVID-19 during Omicron surge (0.35%) was higher than that of influenza (0.05%) and parainfluenza (0.04%) infections. PICU admissions were higher during the Omicron surge (1.83%) than in pre-Omicron waves (0.14%) and the five years (2015 to 2019) due to influenza (0.79%) and parainfluenza (1.64%). The odds of PICU admissions were higher in the Omicron period than previous COVID-19 waves and influenza but similar to parainfluenza cases.

During the Omicron-dominant period, 171 hospitalized children had neurological complications, the most common being febrile seizure with 11.6% incidence. Before the Omicron period, there were no seizure cases in COVID-19-hospitalized children. Moreover, the odds of all types of seizures among children with Omicron infections were higher than those with influenza and parainfluenza. Sixty-one (5.32%) children infected with the SARS-CoV-2 Omicron variant developed croup compared to two (0.27%) infected with previous SARS-CoV-2 variants, 601 (1.87) with influenza, and 889 (5.41%) with parainfluenza. The incidence of pneumonia in children due to SARS-CoV-2 Omicron was similar to those infected with previous variants but lower in influenza and parainfluenza cases.


The study findings showed that SARS-CoV-2 Omicron BA.2 infections resulted in more child hospitalizations in the 23 days of the study than 22 months before. This indicated that the BA.2 variant of SARS-CoV-2 Omicron was more pathogenic than prior SARS-CoV-2 variants and influenza virus and suggested that children be vaccinated to prevent severe outcomes.

One notable limitation of the study was the lack of viral genome sequencing data verifying that all infections in February 2022 were caused only by the SARS-CoV-2 Omicron BA.2 variant. Nonetheless, epidemiological data indicate the preponderance of the Omicron variant right from the start of the latest surge.

*Important notice

Preprints with The Lancet publish 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.


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