COVID-19: Variant risk assessment methods

Published: Updated January 16, 2025

Variant risk assessment framework

The framework below has been adapted from the Public Health England Risk Assessment Framework (PDF) for SARS-CoV-2 variants of concern and variants under investigation to determine the level of risk posed by the variant.^{Footnote a} It serves as a guidance when determining the comparative risk level to the reference variant(s).

Table 1. Risk comparison relative to reference variant(s)^{Footnote a} (e.g., Omicron BA.2)
Indicator	Reduced risk	Comparable risk	Elevated risk
Transmissibility	Less transmissible than reference variant(s)	Similar transmissibility to reference variant(s)	Substantially more transmissible than reference variant(s)
Disease severity	Less severe clinical picture^{Table 1 Footnote 1} compared with reference variant(s)	Similar clinical picture^{Table 1 Footnote 1} compared with reference variant(s)	More severe clinical picture^{Table 1 Footnote 1} compared with reference variant(s)
Immune evasion^{Table 1 Footnote 2}	Evidence of no infection in humans with known prior infection or vaccination (e.g. very limited reinfection/breakthrough cases found in humans previously infected with or vaccinated against any variant), or Structural data suggesting no antigenic differences or differences in vaccine target epitopes	Evidence of limited infection in humans with known prior infection or vaccination (e.g., limited reinfection or breakthrough infections), or Evidence of limited functional evasion of natural or vaccine derived immunity, or Structural data suggesting some antigenic differences or differences in vaccine target epitopes	Evidence of frequent infection in humans with known prior infection or vaccination (e.g., reinfection, breakthrough infections), or Evidence of substantial functional evasion of natural or vaccine derived immunity, or Structural data suggesting significant antigenic differences or differences in vaccine target epitopes
Therapeutics	Evidence of increased clinical effectiveness of therapeutics^{Table 1 Footnote 3} or Increase in the number of effective therapeutics^{Table 1 Footnote 3} or Evidence of increased in vitro activity^{Table 1 Footnote 4} of a therapeutic	Evidence of comparable clinical effectiveness of therapeutics^{Table 1 Footnote 3} or No change in the number of effective therapeutics^{Table 1 Footnote 3} or Evidence of retained in vitro activity or slight variations in in vitro activity^{Table 1 Footnote 4} of therapeutics	Evidence of decreased clinical effectiveness of therapeutics^{Table 1 Footnote 3} or Decrease in the number of effective therapeutics^{Table 1 Footnote 3} or Evidence of reduced in vitro activity or loss of in vitro activity^{Table 1 Footnote 4} of therapeutics
Table 1 - Footnote 1 Where clinical picture includes new or intensified disease presentation, sequalae, hospitalization rates, case fatality rates, and other indicators. Return to Table 1 Footnote 1 referrer Table 1 - Footnote 2 Immune evasion is based on immunity after infection and/or immunity after vaccination. Return to Table 1 Footnote 2 referrer Table 1 - Footnote 3 Therapeutic: Refers to a therapeutic procured and available in Canada. Return to Table 1 Footnote 3 referrer Table 1 - Footnote 4 Activity: Refers to a variant's in vitro fold change in activity for therapeutics. It is not known how in vitro data correlate with clinical outcomes. Return to Table 1 Footnote 4 referrer

Criteria for estimating the level of uncertainty

Very high uncertainty: Criteria is lack of data or reliable information; results are based on crude speculation only.

High uncertainty: Criteria is limited data or reliable information available; results are based on educated guess.

Moderate uncertainty: Criteria is some gaps in availability or reliability of data and information, or conflicting data; results based on limited consensus.

Low uncertainty: Criteria is reliable data and information available but may be limited in quantity, or be variable; results based on expert consensus.

Very low uncertainty: Criteria is reliable data and information are available in sufficient quantity; results strongly anchored in empiric data or concrete information.

Footnotes

Footnote a

The reference variant(s) is used as a comparator to the emerging variant of interest in order to obtain a comparative risk level i.e., does the new variant have reduced, comparable, or elevated risk compared to the given reference variant(s). The evidence used to inform the growth advantage (Transmissibility) usually uses a single referent variant to measure this indicator. For the other indicators in the risk assessment (Disease severity, Immune evasion, and Therapeutics), a single referent variant is used when there is a clear dominant circulating variant and evidence is available, but multiple referent variants may be used if evidence suggests no clear single variant exists; or it is not possible to disentangle the variants reported in the available evidence. The same reference variant(s) may not be possible across all risk assessment indicators due to limited whole genome sequencing data and limited evidence in the literature.

Return to footnote a referrer

Page details

Date modified:: 2025-02-21

Language selection

Search

COVID-19: Variant risk assessment methods

On this page

Variant risk assessment framework

Criteria for estimating the level of uncertainty

Footnotes

Page details