Risk factors associated with severe outcomes of COVID-19: A systematic rapid review to inform national guidance on vaccine prioritization in Canada

Abstract

Background

To inform vaccine prioritization guidance in Canada, we systematically reviewed evidence on the magnitude of association between risk factors and severe outcomes of COVID-19. The urgent nature of this review necessitated an adapted methodology, which may serve as an exemplar for reviews undertaken under strict timelines.

Methods

We updated our existing review by searching online databases and websites for cohort studies providing multivariate adjusted associations. After piloting, one author screened studies and extracted data. Two authors estimated the magnitude of association between exposures and outcomes as little-to-no (odds, risk, or hazard ratio <2.0, or >0.50 for reduction), large (2.0-3.9, or 0.50-0.26 for reduction), or very large (≥4.0, or ≤0.25 for reduction), and rated the evidence certainty using GRADE.

Results

Of 11,734 unique records we included 134 reports. There is probably (moderate certainty) at least a large increase in mortality from COVID-19 among people aged 60-69 vs. <60 years (11 studies, n=517,217), with ≥2 vs. no comorbidities (4 studies, n=189,608), and for people with (vs. without): Down syndrome (1 study, n>8 million), type 1 and 2 diabetes (1 study, n>8 million), end-stage kidney disease (1 study, n>8 million), motor neuron disease, multiple sclerosis, myasthenia gravis, or Huntington’s disease (as a grouping; 1 study, n>8 million). The magnitude of association with mortality is probably very large for Down syndrome and may (low certainty) be very large for age 60-69 years, and diabetes. There is probably little-to-no increase in severe outcomes with several cardiovascular and respiratory conditions, and for adult males vs. females.

Conclusion

There is strong evidence to support at least a large increase in mortality from COVID-19 among older adults aged 60 to 69 years versus <60 years; people having two or more versus no comorbidities; and for people affected by several pre-existing conditions. The methodology employed in this review may provide an important exemplar for future syntheses undertaken under urgent timelines.

Systematic review registration

PROSPERO #CRD42021230185.

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SciScore for 10.1101/2021.04.23.21256014: (What is this?)

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

Table 1: Rigor

Ethics	Field Sample Permit: Studies needed to take place in Organization for Economic Cooperation and Development (OECD) countries and include ≥1,000 participants (i.e., sufficiently powered for multivariate adjustment). IRB: Ethics approval: Ethics approval was not required.
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

No key resources detected.

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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

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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