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 Children's Hospital of Chicago, academic free-standing children's hospital. We included all children ≤ 18 years-old diagnosed with COVID-19 between October 15 ^th , 2020 and August 31 ^st , 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 ≥ 6). 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.

Figure 1:. SARS-CoV-2 Molecular and Clinical Epidemiology.

Frequencies (A) and proportions (B) of lineages of SARS-CoV-2 identified in pediatric patients during 10-month study period (October 2020 – August 2021). Variants of concern identified include alpha, beta, gamma, and delta. Corresponding data for adult patients at a partner hospital in Chicago are shown in Figure S1; the variant proportions and chronology in adults generally resembled what was observed in children during the same period.

Figure 2:. COVID-19 Incidence in Chicago Children and Adults.

Incidence of COVID-19 (weekly cases per 100K population) in children (age 0–17 years [y]) and adults (age >17y) in Chicago throughout the pandemic and during the study period (shaded) during which the sequencing data presented here were derived. Thresholds for community transmission levels as defined by the CDC are noted with colored vertical lines.