The isolated effect of age on the risk of COVID-19 severe outcomes: a systematic review with meta-analysis

  1. Karla Romero Starke
  2. David Reissig
  3. Gabriela Petereit-Haack
  4. Stefanie Schmauder
  5. Albert Nienhaus
  6. Andreas Seidler

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Abstract

Increased age has been reported to be a factor for COVID-19 severe outcomes. However, many studies do not consider the age dependency of comorbidities, which influence the course of disease. Protection strategies often target individuals after a certain age, which may not necessarily be evidence based. The aim of this review was to quantify the isolated effect of age on hospitalisation, admission to intensive care unit (ICU), mechanical ventilation and death.

Methods

This review was based on an umbrella review, in which Pubmed, Embase and preprint databases were searched on 10 December 2020, for relevant reviews on COVID-19 disease severity. Two independent reviewers evaluated the primary studies using predefined inclusion and exclusion criteria. The results were extracted, and each study was assessed for risk of bias. The isolated effect of age was estimated by meta-analysis, and the quality of evidence was assessed using Grades of Recommendations, Assessment, Development, and Evaluation framework.

Results

Seventy studies met our inclusion criteria (case mortality: n=14, in-hospital mortality: n=44, hospitalisation: n=16, admission to ICU: n=12, mechanical ventilation: n=7). The risk of in-hospital and case mortality increased per age year by 5.7% and 7.4%, respectively (effect size (ES) in-hospital mortality=1.057, 95% CI 1.038 to 1.054; ES case mortality=1.074, 95% CI 1.061 to 1.087), while the risk of hospitalisation increased by 3.4% per age year (ES=1.034, 95% CI 1.021 to 1.048). No increased risk was observed for ICU admission and intubation by age year. There was no evidence of a specific age threshold at which the risk accelerates considerably. The confidence of evidence was high for mortality and hospitalisation.

Conclusions

Our results show a best-possible quantification of the increase in COVID-19 disease severity due to age. Rather than implementing age thresholds, prevention programmes should consider the continuous increase in risk. There is a need for continuous, high-quality research and ‘living’ reviews to evaluate the evidence throughout the pandemic, as results may change due to varying circumstances.

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  1. Version published to 10.1136/bmjgh-2021-006434
  2. ScreenIT

    SciScore for 10.1101/2021.05.27.21257909: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    To summarize, on December 11, 2020 a systematic search for systematic reviews was done in PubMed and Embase, with hand searches on preprint servers (search string in supplement).
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Embase
    suggested: (EMBASE, RRID:SCR_001650)

    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:
    Strengths and limitations To our knowledge, since our rapid review published (13), this is the first systematic review primarily focused on estimating the isolated effect of age on the risk of COVID-19 disease severity, including case and in-hospital mortality, hospitalization, ICU admission, and intubation. It encompasses 70 primary studies with data from more than 400,000 participants and includes only studies adjusting for important age-related factors associated with COVID-19 disease severity (14). Adjusting for comorbidities allows to explicitly “factor out” the mediating effect of comorbidities in order to get the isolated effect of age, or the risk presented by a person of a given age who has no preexisting conditions. The results in this review should be considered in light of its limitations. For studies reporting age as a categorical value, since the age categories used in the studies could not be compared because of their heterogeneity, the median of the age category represented the age for the reported effect size. This procedure could have led to inaccuracies of the effect size. This was evident in that effect sizes increased when using finer age categories, indicating that the use of wide age categories most likely leads to an underestimation of the age effect. We reported the pooled effect sizes for studies using age as a continuous variable for the outcome in-hospital mortality. For the other outcomes we reported the pooled effect size for studies using catego...

    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

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  3. Version published to 10.1101/2021.05.27.21257909v1 on medRxiv