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 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.
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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