Age-Specific SARS-CoV-2 Infection Fatality and Case Identification Fraction in Ontario, Canada

  1. David N. Fisman
  2. Steven J. Drews
  3. Ashleigh R. Tuite
  4. Sheila F. O’Brien

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Abstract

Background

SARS-CoV-2 is a novel pandemic pathogen that displays great variability in virulence across cases. Due to limitations in diagnostic testing only a subset of infections are identified. Underestimation of true infections makes calculation of infection fatality ratios (IFR) challenging.

Seroepidemiology allows estimation of true cumulative incidence of infection in populations, for estimation of IFR.

Methods

Seroprevalence estimates were derived using retention samples stored by Canadian Blood Services in May 2020. These were compared to non-long-term care-linked case and fatality data from the same period. Estimates were combined to generate IFR and case identification fraction estimates.

Results

Overall IFR was estimated to be 0.80% (0.75 to 0.85%), consistent with estimates from other jurisdictions. IFR increased exponentially with age from 0.01% (0.002 to 0.04%) in those aged 20-29 years, to 12.71% (4.43 to 36.50%) in those aged 70 and over. We estimated that 5.88 infections (3.70 to 9.21) occurred for every case identified, with a higher fraction of cases identified in those aged 70 and older (42.0%) than those aged 20-29 (9.4%). IFR estimates in those aged 60 and older were identical to pooled estimates from other countries.

Conclusions

To our knowledge these are the first Canadian estimates SARS-CoV-2 IFR and case identification fraction. Notwithstanding biases associated with donor sera they are similar to estimates from other countries, and approximately 80-fold higher than estimates for influenza A (H1N1) during the 2009 epidemic. Ontario’s first COVID-19 pandemic wave is likely to have been accurately characterized due to a high case identification fraction.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.09.20223396: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics Statement: The study received ethics approval from the Research Ethics Boards at the University of Toronto and Canadian Blood Services.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All plasma samples were tested using the Abbott Architect SARS-CoV-2 IgG assay (chemiluminescent microparticle immunoassay (CMIA)).
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Global Comparison: We extracted observed and modeled (via meta-regression techniques) estimates for log-transformed IFR by age from the recent meta-analysis of Levin et al. using WebPlotDigitizer (24).
    WebPlotDigitizer
    suggested: (WebPlotDigitizer, RRID:SCR_013996)

    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:
    While blood donor-derived seroprevalence estimates are known to have limitations (3, 26, 27), we find the overall IFR estimate in this population to be similar to estimates from a number of other countries. The relatively high quality of Ontario’s case data resources allowed us to avoid overestimation of IFR via exclusion of individuals in long-term care settings, who are likely to experience extreme risk of mortality conditional on COVID-19, and who have experienced outbreak epidemiology in Ontario that is distinct from that seen in the community-dwelling populations from which blood donors are drawn (18, 28). Even after sensitivity analyses that resulted in exclusion of individuals from the numerator who would have been unable to donate blood due to medical or age contraindications, our resultant lower bound IFR estimate remained similar in order of magnitude to those obtained elsewhere, and also approximately two orders of magnitude higher than IFR estimates published for influenza (29). While adjusting seroprevalence to account for the possibility that it is higher in blood donors than the general population resulted in a predictable increase in IFR, even these upper bound estimates were of similar order of magnitude to estimates published previously (3, 4). Not unexpectedly, we saw marked increases in estimated IFR by age. Perhaps more surprisingly, although our IFR estimates in older adults were similar to those seen elsewhere, we found that our IFR estimates in younger...

    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.

    About SciScore

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  2. Version published to 10.1101/2020.11.09.20223396 on medRxiv