Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study
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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.
Article activity feed
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Alfredo Tagarro
Review 2: "Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study"
This preprint offers a retrospective analysis evaluating correlations between SARS-CoV-2 Variants of Concern and disease severity in children. The study finds that neither alpha or delta variants were associated with severe COVID-19 symptoms. Reviewers deemed the study reliable.
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Francisco José Sanz-Santaeufemia
Review 1: "Severity of Illness Caused by Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern in Children: A Single-Center Retrospective Cohort Study"
This preprint offers a retrospective analysis evaluating correlations between SARS-CoV-2 Variants of Concern and disease severity in children. The study finds that neither alpha or delta variants were associated with severe COVID-19 symptoms. Reviewers deemed the study reliable.
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Strength of evidence
Reviewers: Francisco José Sanz-Santaeufemia( Hospital Infantil Universitario Niño Jesús) | 📗📗📗📗◻️
Alfredo Tagarro (Fundacion para la Investigacion Biomedica del Hospital Universitario 12 de Octubre) | 📗📗📗📗◻️ -
SciScore for 10.1101/2021.10.23.21265402: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The Lurie Children’s Institutional Review Board approved this study (IRB 2020-3792). Sex as a biological variable not detected. Randomization Twice monthly, approximately 25-50% of samples meeting these criteria are randomly selected for WGS. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Using residual diagnostic samples from pediatric inpatients and outpatients who tested positive by SARS-CoV-2 polymerase chain reaction (PCR) in our clinical microbiology laboratory, we perform surveillance for SARS-CoV-2 variants using whole genome sequencing (WGS) with the Center for Pathogen Genomics and Microbial Evolution at Northwestern … SciScore for 10.1101/2021.10.23.21265402: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: The Lurie Children’s Institutional Review Board approved this study (IRB 2020-3792). Sex as a biological variable not detected. Randomization Twice monthly, approximately 25-50% of samples meeting these criteria are randomly selected for WGS. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources Using residual diagnostic samples from pediatric inpatients and outpatients who tested positive by SARS-CoV-2 polymerase chain reaction (PCR) in our clinical microbiology laboratory, we perform surveillance for SARS-CoV-2 variants using whole genome sequencing (WGS) with the Center for Pathogen Genomics and Microbial Evolution at Northwestern University. WGSsuggested: NoneStatistical analyses were performed using Stata/IC 16.0 (StataCorp, College Station, TX) and R version 4.1.0. StataCorpsuggested: (Stata, RRID:SCR_012763)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:This study has several limitations. As a single-center study, our findings may not be generalizable to other geographic locations and patient populations. However, the referral area for our hospital in Chicago extends throughout the city and suburban areas and includes a diverse patient base in terms of demographics and medical complexity. These findings should be confirmed in other pediatric and adult populations. Further, the relatively small sample size and rarity of severe outcomes in children contributed to wide CIs, reducing the precision of the effect estimates for the association between the gamma VOC and severe COVID-19 outcomes. This study was limited to those infections for which SARS-CoV-2 was able to be sequenced, biasing the study to inclusion of infections associated with relatively low cycle thresholds (i.e., high viral loads). Although we performed multivariable analyses, it is possible that unmeasured confounding has contributed to our findings. Although we limited our definition of high risk for COVID-19 complications to those for which there are high-quality and reproducible data (i.e., meta-analysis, systematic review, or observational study; not small studies, case reports/series, or conflicting evidence) per CDC classification. (Table S2),8 these data are predominantly from adult populations and may not all apply to children. Nonetheless, based on our observations of COVID-19 severity being strongly associated with, and sometimes mutually inclusive with...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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