Age-Specific Changes in Virulence Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern

  1. David N Fisman
  2. Ashleigh R Tuite

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs are similar across the age spectrum or are limited to some age groups is unknown.

Methods

We created a retrospective cohort of people in Ontario, Canada, who tested positive for SARS-CoV-2 and were screened for VOCs (n = 259 984) between 7 February 2021 and 31 October 2021. Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate associations between N501Y-postive or Delta VOC infections and infection severity using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, comorbidity, vaccination status, and temporal trends.

Results

Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death across age groups compared with infections where a VOC was not detected. The Delta VOC increased hospitalization risk in children aged <10 years by a factor of 2.5 (adjusted odds ratio; 95% confidence interval, 1.3 to 5.0) compared with non-VOCs. There was a significant inverse relationship between age and relative increase in risk of death with the Delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals.

Conclusions

SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.

Article activity feed

  1. Version published to 10.1093/cid/ciac174
  2. ScreenIT

    SciScore for 10.1101/2021.09.25.21264097: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsField Sample Permit: The study was conducted in accordance with the STROBE guidelines for observational research (27), and received ethics approval from the Research Ethics Board at the University of Toronto.
    IRB: The study was conducted in accordance with the STROBE guidelines for observational research (27), and received ethics approval from the Research Ethics Board at the University of Toronto.
    Sex as a biological variableModels were adjusted for male sex, time (modeled as a week-on-week linear trend), vaccination status (in age groups 10 years and older), documented major comorbidity (including asthma, COPD, hematological disease, liver disease, cardiac disease, diabetes, renal disease, neurological disease, malignancy, or obesity), and immune compromise.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    As of June 2021, routine WGS was discontinued on N501Y-POSITIVE/E484-specimens, which were presumed to be alpha lineage.
    WGS
    suggested: None

    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:
    Our analysis is subject to important limitations: first, the relative rarity of severe outcomes in younger age groups means that our estimates for these groups are imprecise. Furthermore, our failure to identify heterogeneity in severity by age, when evaluating effects in children and teens, may simply be related to the imprecision of estimates in these age groups, rather than true lack of heterogeneity. A second limitation is the degree to which frequency of testing, particularly in younger age groups, has been dynamic in Ontario during the COVID-19 pandemic (21). Increasing frequency of testing in under-tested younger age groups over time, as VOC emerged in the population, could increase the fraction of mild cases identified, and may have served to mask increases in severity. In summary, however, we find no evidence to suggest that the apparent increase in virulence of SARS-CoV-2 VOC is limited to a particular age group; indeed, we present evidence that the relative virulence of Delta VOC, as represented by mortality risk, may be inversely related to age. The relative rarity of severe outcomes in children and teens means that more study is needed to assess the robustness and generalizability of these findings.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.09.25.21264097v1 on medRxiv