Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study

Abstract

Background Recent COVID-19 surges are attributed to emergence of more transmissible SARS-CoV-2 variants of concern (VOCs). The relative severity of VOCs in children is unknown. Methods We performed a single-center retrospective cohort study of children ≤18 years old diagnosed with COVID-19 from October 2020–February 2022 and whose SARS-CoV-2 isolate underwent Illumina sequencing. We measured the frequency of five markers of COVID-19 severity. Logistic regression models were fitted to estimate the odds of each severity marker with each VOC. Results Among 714 children, 471 (66.0%) were infected with a VOC: 96 (13.4%) alpha, 38 (5.3%) gamma, 119 (16.7%) delta, and 215 (30.1%) omicron. High-risk medical conditions and increasing age were independently associated with COVID-19 severity. After adjusting for age, race, ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha, delta, nor omicron was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 6.7, 95% CI 2.0–22.1); pharmacologic treatment (OR 5.7, 95% CI 1.2–26.8); respiratory support (OR 11.9, 95% CI 2.7–62.4); and severe disease per the WHO Clinical Progression Scale (OR 11.7, 95% CI 2.1–90.5). Upon subgroup analyses, omicron was independently associated with ICU admission and severe disease per the WHO Clinical Progression Scale in children without SARS-CoV-2 immunization or prior COVID-19 infection. Conclusions Compared to non-VOC COVID-19, the gamma VOC was independently associated with increased COVID-19 severity, as was omicron in children without SARS-CoV-2 immunization or prior COVID-19 infection. SARS-CoV-2 vaccination and prior COVID-19 prevented severe outcomes during the omicron surge.

The Impact of Alpha Variant (B.1.1.7), Viral Load, and Age on the Clinical Course of Pediatric COVID-19 Patients

“…35 Edward et al reported that the Alpha variant (B.1.1.7) was not associated with severe COVID-19 in the pediatric population. 5 Brookman et al also suggested that the Alpha variant (B.1.1.7) did not cause a different clinical course than the original strain. 37 This study has some limitations.…”

“…During the pandemic, variants of concerns (VOC) have emerged, among which may be variants that are associated with increased transmission, immune evasion, and worse clinical outcome. 5 One of these VOCs, Alpha variant/VOC 202012/01 (Pango lineage B.1.1.7), outcompeted other SARS-CoV-2 lineages in the United Kingdom after its appearance at the end of 2020 and has spread promptly throughout the world. 6 It began circulating in Turkey in early 2021.…”

COVID-19 in children: epidemic issues and candidate vaccines

“…An important consideration for the necessity of accelerating pediatric vaccination is the potential increased transferability and higher susceptibility, which might be brought by SARS-CoV-2 variants [59–62] . A retrospective cohort study on severity of COVID-19 caused by SARS-CoV-2 variants of concern (VOC) in children demonstrated there was an increased Delta COVID-19 incidence in children and Gamma (P.1 and sublineages) rather than Alpha (B.1.1.7 and sublineages) or Delta (B.1.617.2 and sublineages) increased severity of the disease [63] . In Israel, a doubled transmission rate of SARS-CoV-2 from children aged 0 to 9 years was found during the circulation of Alpha (B.1.1.7) variant [64] .…”

“…[ 59 – 62 ] A retrospective cohort study on severity of COVID-19 caused by SARS-CoV-2 variants of concern (VOC) in children demonstrated there was an increased Delta COVID-19 incidence in children and Gamma (P.1 and sublineages) rather than Alpha (B.1.1.7 and sublineages) or Delta (B.1.617.2 and sublineages) increased severity of the disease. [ 63 ] In Israel, a doubled transmission rate of SARS-CoV-2 from children aged 0 to 9 years was found during the circulation of Alpha (B.1.1.7) variant. [ 64 ] These findings suggest that problems brought by SARS-CoV-2 variants deserve our attention and the importance of vaccination for children under 12 years old after a rigorous risk assessment and approval procedures.…”

Editorial Commentary on “Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study”

“…In this edition of Journal of the Pediatric Infectious Diseases Society , Edwards et al compare clinical outcomes in 714 children diagnosed (October 2020 to February 2022) with COVID-19, by VOC [ 3 ]. Illumina sequencing was undertaken on randomly selected samples from SARS-CoV-2-positive children.…”