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 surges in coronavirus 2019 disease (COVID-19) is attributed to the emergence of more transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs). However, the relative severity of SARS-CoV-2 VOCs in children is unknown. Methods: This retrospective single-center cohort study was performed at the Ann & Robert H. Lurie Childrens Hospital of Chicago, academic free-standing childrens hospital. We included all children 0-18 years-old diagnosed with COVID-19 between October 15th, 2020 and August 31st, 2021 and whose SARS-CoV-2 isolate was sequenced using the Illumina platform. For each patient sample, we identified the SARS-CoV-2 lineage, which was assigned to one of the following groups: Non-VOC, alpha VOC, beta VOC, gamma VOC, or delta VOC. We measured frequency of 5 markers of COVID-19 severity: hospitalization; COVID-19 pharmacologic treatment; respiratory support; intensive care unit admission; and severe disease as classified by the COVID-19 World Health Organization (WHO) Clinical Progression Scale (severe disease; score of 6 or higher). A series of logistic regression models were fitted to estimate odds of each severity marker with each VOC (in comparison to non-VOCs), adjusting for COVID-19 community incidence and demographic and clinical co-variates. Results: During the study period, 2,025 patients tested positive for SARS-CoV-2; 1,422 (70.2%) had sufficient viral load to permit sequencing. Among the 499 (35.1%) patients whose isolate was sequenced, median (inter-quartile range) age was 7 (1,12) years; 256 (51.3%) isolates were a VOC: 96 (37.5%) alpha, 38 (14.8%) gamma, and 119 (46.5%) delta. After adjusting for age, Black race, Hispanic ethnicity, high-risk medical conditions, and COVID-19 community incidence, neither alpha nor delta was associated with severe COVID-19. Gamma was independently associated with hospitalization (OR 5.9, 95% CI 1.6-21.5, p=0.007), respiratory support (OR 8.3, 95% CI 1.5-56.3, p=0.02), and severe disease as classified by the WHO Clinical Progression Scale (OR 7.7, 95% CI 1.0-78.1, p=0.05). Conclusions: Compared to non-VOC COVID-19 infections, the gamma VOC, but not the alpha or delta VOCs, was associated with increased severity. These data suggest that recent increased in pediatric COVID-19 hospitalizations are related to increased delta COVID-19 incidence rather than increased delta virulence in children.

The role of SARS-CoV-2 variants of concern in children and adolescents with COVID-19: a systematic review

“…17-21 In two studies reporting on paediatric inpatients and outpatients one from Brazil and one from the USA, the overall hospitalisation rate as well as the ICU admission rate of children infected with the gamma variant was higher than for non-VOCs (Gamma vs. non-VOC: 28.3% vs. 24.9%. 47 , Gamma vs. non-VOC: 5.2% vs. 1.2% 48 ). 47,48 Severity of delta variant infection was compared with the pre-delta period (including periods where previous VOCs where predominant) in eight studies but the reported data were inconsistent, and differences in disease severity could not be assessed.…”

“…A detailed comparison between studies was not possible owing to differences in study populations (community or health care setting), symptoms recorded and age groups reported. 14-18,20,22-24,27,31-33,35,36,38-40…”

“…47,48 Severity of delta variant infection was compared with the pre-delta period (including periods where previous VOCs where predominant) in eight studies but the reported data were inconsistent, and differences in disease severity could not be assessed. 26,28-30,32-35 Studies of omicron variant infection described less severe disease than infection with the delta variant in children and adolescents <18 years old, based on data from nine studies from South Africa, Qatar and the USA. 36,39-46…”

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.…”