SARS-CoV-2 variant rapid risk assessment report: XBB.1.5

Download in PDF format
(616 KB, 10 pages)

Organization: Public Health Agency of Canada

Date published: 2023-01-27

Assessment completed: January 20, 2023

On this page


Omicron variants have increased transmissibility and demonstrated immune evasion when compared to previously circulating variants. This rapid risk assessment compares the public health risk to Canadians posed by Omicron variant XBB.1.5 to those posed by BA.5 (excluding BF.7 and BQ). XBB.1.5 is a sub-lineage of XBB, which is a recombinant of two BA.2 sub-lineages (BA.2.10 and BA.2.75). XBB.1.5 was first detected in the United States in October 2022 and has been detected in 38 countries. According to the World Health Organization (WHO), over 80% of detections are from the US. As of January 16, 2023, the number of XBB.1.5 infections remains low in Canada but is growing at approximately 9% per day. Since November 2022, there have been 126 detections across 8 provinces. This assessment is based on available evidence as of January 17, 2023. This is an evolving situation with new evidence expected.

Risk statement

The potential public health risk posed by XBB.1.5 is driven by incremental increases in transmissibility and immune evasion compared to BA.5, however, disease severity and antiviral therapeutic effectiveness are comparable. The number of COVID-19 cases caused by XBB.1.5 will likely increase in Canada, however, it is not known whether XBB.1.5 will become the dominant strain and it is not known whether this will result in an increase in overall COVID-19 incidence. The level of uncertainty in this assessment is moderate to high.

Risk assessment summary

Table 1: Risk assessment for variant XBB.1.5 relative to BA.5 (excluding BF.7 and BQ)Table 1 Footnote a
Indicator RiskTable 1 Footnote b Uncertainty Assessment and rationaleTable 1 Footnote c
TransmissibilityTable 1 Footnote d Elevated Moderate XBB.1.5 has mutations that increase transmissibility through improved entry into cells and viral replication. Increases in the US, particularly in the Northeast regions, demonstrate growth advantage of this strain. In Canada, the overall growth advantage of this sub-lineage is approximately 9% per day. Growth estimates are changing quickly as information from other regions, including Canada, becomes available.
Disease severity Comparable High There is no indication that the disease severity of XBB.1.5 is different than that of currently circulating Omicron sub-lineages.
Immune evasionTable 1 Footnote e Elevated Moderate XBBTable 1 Footnote * is more immune evasive than earlier Omicron sub-lineages including BA.5, based on studies assessing neutralizing antibody responses.
Therapeutics Comparable High XBBTable 1 Footnote *, like BA.5, is not expected to be susceptible to currently available neutralizing monoclonal antibody therapies. Antiviral treatments are expected to remain effective against Omicron sub-lineages.
Table 1 - Footnote a

BA.5 was used as the reference as it has information available for all comparison attributes.

Return to Table 1 Footnote a referrer

Table 1 - Footnote b

See Appendix 2 for risk assessment framework and definitions.

Return to Table 1 Footnote b referrer

Table 1 - Footnote c

See Appendix 1 for evidence to support assessment.

Return to Table 1 Footnote c referrer

Table 1 - Footnote d

Selective advantages calculated relative to currently circulating lineages, particularly the most prevalent at the time. Increases of a growth rate over time may be due to decreases in the reference and not necessarily intrinsic jumps in growth by the lineage.

Return to Table 1 Footnote d referrer

Table 1 - Footnote e

Immune evasion is based on two indicators: immunity after infection and immunity after vaccination.

Return to Table 1 Footnote e referrer

Table 1 - Footnote *

Asterisk here is a technical symbol denoting inclusion of the sub-lineages in the overall lineage.

Return to Table 1 Footnote * referrer

Proposed actions for public health authorities

These actions are for consideration by jurisdictions according to their local epidemiology, policies, resources, and priorities. Due to the current level of uncertainty associated with XBB.1.5, it is important that the public health response be proportionate to the risk.

Surveillance and reporting

Risk communication

Public health interventions

Appendix 1: Supporting information

Table 2: Indicators and evidence to support risk assessment as of January 17, 2023 (unless otherwise stated)
Indicator Evidence


  • XBB.1.5 is a sub-lineage of the SARS-CoV-2 lineage XBB.1, a recombinant of Omicron variants BA.2.10Table 2 Footnote * and BA.2.75Table 2 Footnote *. XBB.1.5 has acquired an additional mutation in the spike protein (Receptor Binding Domain mutation 486P). Thus, XBB.1.5 likely is more transmissible than XBB.1 because of the increased ACE2 affinityFootnote 1.


  • As of January 11, 2023, 5,288 sequences have been reported across 38 different countries. Most of these submissions are from the United States, but there are also increasing numbers of detections in EuropeFootnote 2.
  • As of January 16, 2023, XBB.1.5 is estimated to have a growth advantage (~10% per day) over currently circulating lineages in North America and Europe. However, local growth estimates vary from ~10–20% per day relative to lineages circulating in those US states or EU countriesFootnote 3.
  • From data posted on January 13, 2023, the US CDC estimates the current proportion of XBB.1.5 to be 11.5% for the week ending December 24, 2022. Projections for the week ending January 14, 2023, suggest XBB.1.5 will comprise 43.0% of sequences in the US. There is large geographic variation noted, with 2 regions in the northeastern US projecting that XBB.1.5 will comprise over 80% of sequences and 5 other regions projected at between 8-16% of sequences for the week ending January 14, 2023Footnote 4.


  • As of January 16, 2023, there are 126 detections of XBB.1.5 in Canada reported to the Public Health Agency of Canada dating back to November 20, 2022. Most of them are reported from Ontario.
  • Ontario has reported that the proportion of XBB.1.5 is increasing and that projected prevalence will be 22.2% by January 18, 2023. XBB.1.5 has been detected in multiple health regionsFootnote 5.
  • By January 16, 2023, XBB.1.5 is projected to be 7% of sequences reported to the Public Health Agency of Canada.
  • The overall growth advantage of this sub-lineage relative to all other currently circulating strains in Canada is ~ 9% per day (6-10%, 95% CI).

Disease severity


  • The ECDC assessment of the XBB.1.5 sub-lineage stated that there is no indication that infections from XBB.1.5 differ in severity from currently circulating Omicron lineagesFootnote 6.
  • The WHO reports that severity data is unavailable and assessments are ongoing. However, XBB.1.5 does not carry any mutation known to be associated with potential change in severity (such as S:P681R)Footnote 2.
  • According to the WHO TAG-VE, the early evidence as of October 27, 2022, does not suggest substantial differences in disease severity for XBB (and XBB sub-lineages) infections compared to other Omicron sub-lineagesFootnote 7.


  • As of January 12, 2023, there are 18 COVID-19 cases associated with XBB.1.5 in the national case surveillance database, with 4 hospitalizations, no ICU admissions, and no deaths.

Immune evasionTable 2 Footnote a

Neutralizing antibody responses

  • Currently, most studies evaluating immunity from a prior SARS-CoV-2 infection include individuals with hybrid immunity (immunity obtained from vaccination and SARS-CoV-2 infection), as a result there are fewer studies conducted on those who have only infection-acquired immunity.
  • Preliminary in-vitro evidence suggests that XBBTable 2 Footnote * sub-lineages are the most antibody-evasive SARS-CoV-2 sub-lineages identified to date and XBB.1.5 is shown to be similarly immune evasive as XBB.1 in 3 pre-prints. Two studies show that XBB.1.5 resists neutralizing immune responses from individuals with hybrid immunity (including prior BA.5 or BA.2 infection after 2-4 doses of monovalent mRNA vaccines)Footnote 1Footnote 8. Additional data demonstrates XBB.1.5 resists neutralizing immune responses from individuals infected with BA.4/5 (most of whom were unvaccinated), vaccinated with 3 doses of the monovalent vaccine, and vaccinated with a bivalent booster after 2 to 4 monovalent doses (most received 3 monovalent doses)Footnote 9.
  • Nine additional studies have evaluated neutralization of XBBTable 2 Footnote * variants by sera from individuals with 3 different immune backgrounds (vaccination and/or infection): (1) vaccinated with 3-4 doses of the original monovalent mRNA vaccine, (2) vaccinated with a bivalent booster, or (3) breakthrough infection with BA.2 or BA.4/5.

Cellular responses

  • No studies assessing T-cell immunity are available for XBB.1.5 specifically. However, recent in-vitro studies suggest that CD8+ and CD4+ T-cell responses against XBB are largely conservedFootnote 19.
  • A pre-print retrospective study from Singapore evaluated the protective effectiveness (PE) of a previous SARS-CoV-2 infection among those who received monovalent mRNA vaccination (2-3 doses) against a BA.4/5 and XBB reinfection (specific sub-lineage not reported)Footnote 20. PE against an XBB reinfection was lower than PE against BA.4/5 reinfection regardless of the prior infecting variant (PE from a prior BA.2 infection among those with 3 mRNA doses was 78% against a BA.4/5 infection versus 51% against XBB infection).

There is no data on vaccine effectiveness against XBB.1.5 infection or severe outcomes as well as no data on protective effectiveness from a prior infection against XBB-related severe outcomes.


  • Paxlovid (nirmatrelvir/ritonavir) and Remdesivir seem to retain their activity against SARS-CoV-2 OmicronFootnote 21. It is unknown currently if the same holds true for the recombinant XBB.1.5.
  • Limited in-vitro data on the activity of COVID-19 mAbs is available against XBB.1.5.
  • A preprint listed on the Stanford University coronavirus antiviral and resistance database suggests that tixagevimab/cilgavimab (Evusheld) and sotrovimab have reduced or no activity against XBB.1.5Footnote 1. They also demonstrate that XBB.1 and XBB.1.5 show comparable mAb evasion.
    • Sub-lineage group: XBB.1.5; mAbs tested: sotrovimab; viral type: pseudovirus; fold-changeTable 2 Footnote b: 1; reference strain: XBB.1; source: Yue et al.Footnote 1
    • Sub-lineage group: XBB.1.5; mAbs tested: Tixagevimab/ cilgavimab: viral type: pseudovirus; fold-changeTable 2 Footnote b: 0.9; reference strain: XBB.1; source; Yue et al.Footnote 1
  • In an in-vitro study, Evusheld and Sotrovimab had decreased in activity against XBB compared to BA.5Footnote 22. Evusheld and Sotrovimab may not be effective against XBB.1 and XBB when compared to the ancestral (original) SARS-CoV-2 strainFootnote 11.
  • The product monograph for Evusheld reports a reduction in susceptibility to XBB compared to BA.5.
  • No Canadian in-vitro data is available on the activity of COVID-19 antivirals against XBB.1.5.
  • No Canadian data on the clinical effectiveness of COVID-19 therapeutics (antivirals or monoclonal antibodies [mAbs]) is available for XBB.1.5.


  • The U.S. Food and Drug Administration (PDF) defines 'no change' in in-vitro activity for mAbs in its authorized fact sheet guidance documents as <5-fold reduction in susceptibility
  • Since in-vitro assays are often conducted under controlled conditions, they do not reflect the in-vivo pharmacokinetic properties of the therapeutic under investigation. Therefore, in-vitro studies do not correlate with therapeutic effectiveness or treatment failure.
Table 2 - Footnote a

Immune evasion is based on two indicators: immunity after infection and immunity after vaccination.

Return to Table 2 Footnote a referrer

Table 2 - Footnote b

Fold-change values provided from the Stanford University coronavirus antiviral and resistance database (>1 indicates decreased activity).

Return to Table 2 Footnote b referrer

Table 2 - Footnote *

Asterisk here is a technical symbol denoting inclusion of the sub-lineages in the overall lineage.

Return to Table 2 Footnote * referrer

Table 3: Contextual information to support risk assessment and proposed actions
Criteria Considerations

Health systems impact, including hospital capacity and infection prevention and control measures
(Capacity: beds, health care workers)

  • Hospital and health care capacity in Canada remains strained due to circulating influenza, RSV, and SARS-CoV-2 and other pressures. Infection, prevention and control practices are in place to limit transmission of COVID-19.

Border measures
(Vaccination, quarantine and testing)

  • Border measures are designed to slow the importation of new variants, while XBB.1.5 has been detected in Canada since November 2022.

Surveillance capacity

  • Wastewater assays in Canada can detect XBB.1.5.
  • Confirmatory testing volumes have remained relatively stable, but outpatient testing is generally restricted to specific populations and symptomatic patients. Asymptomatic testing is primarily for at-risk populations, including individuals at risk of severe outcomes, and their contacts. As such, surveillance data are not representative of all COVID-19 infections in Canada.
  • Testing and sequencing strategies may differ across the country.

Public health measures

  • The current Public Health Agency of Canada guidance on public health measures includes the layered use of individual public health measures such as staying home when ill, properly wearing a well-constructed and well-fitting mask in public indoor settings, improving indoor ventilation, performing frequent hand hygiene and proper respiratory etiquette, and cleaning and disinfecting high-touch surfaces and objects, to reduce the risk of infection and spread.
  • Public health measures recommendations in Canada continue to vary across jurisdictions as provinces and territories experience differing epidemiology and risks as well as transition to the longer-term management of COVID-19.
  • Most community-based measures such as lockdowns, widespread case and contact management activities, including quarantine and isolation requirements as well as universal masking have ended. Individual risk-based measures are being promoted (e.g., staying home when ill, wearing a mask in certain circumstances, etc.).


  • As of January 1, 2023 (most recent available data), 80.6% of the total population has completed a primary series of COVID-19 vaccine.
  • As of January 1, 2023 (most recent available data), 25.0% of the total population have completed their primary series or received a booster dose of COVID-19 vaccine in the last six monthsFootnote 23.

Appendix 2: Methods

For the variant risk assessment framework and criteria for estimating the level of uncertainty, consult:


Footnote 1

Yue C, Song W, Wang L, et al. Enhanced transmissibility of XBB.1.5 is contributed by both strong ACE2 binding and antibody evasion. bioRxiv. 2023:2023.01.03.522427. doi:10.1101/2023.01.03.522427 Available at:

Return to footnote 1 referrer

Footnote 2

World Health Organization (WHO). XBB.1.5 Rapid risk assessment, 11 January 2023. Geneva: WHO; 2023.

Return to footnote 2 referrer

Footnote 3

covSPECTRUM. Detect and analyze variants of SARS-CoV-2.

Return to footnote 3 referrer

Footnote 4

Centers for Disease Control and Prevention (CDC). COVID Data Tracker Weekly Review. Atlanta, GA: CDC.

Return to footnote 4 referrer

Footnote 5

Public Health Ontario. SARS-CoV-2 Genomic Surveillance in Ontario, January 13, 2023.

Return to footnote 5 referrer

Footnote 6

European Centre for Disease Prevention and Control. Implications for the EU/EEA of the spread of the SARS-CoV-2 Omicron XBB.1.5 sub-lineage for the EU/EEA – 13 January 2023. ECDC: Stockholm; 2023.

Return to footnote 6 referrer

Footnote 7

World Health Organization (WHO). TAG-VE statement on Omicron sublineages BQ.1 and XBB. Geneva: WHO.

Return to footnote 7 referrer

Footnote 8

Uriu K, Ito J, Zahradnik J, et al. Enhanced transmissibility, infectivity and immune resistance of the SARS-CoV-2 Omicron XBB.1.5 variant. bioRxiv. 2023:2023.01.16.524178. doi:10.1101/2023.01.16.524178. Available at:

Return to footnote 8 referrer

Footnote 9

Qu P, Faraone JN, Evans JP, et al. Extraordinary Evasion of Neutralizing Antibody Response by Omicron XBB.1.5, CH.1.1 and CA.3.1 Variants. bioRxiv. 2023:2023.01.16.524244. doi:10.1101/2023.01.16.524244. Available at:

Return to footnote 9 referrer

Footnote 10

Uraki R, Ito M, Furusawa Y, et al. Humoral immune evasion of the omicron subvariants BQ.1.1 and XBB. Lancet Infect Dis. Jan 2023;23(1):30-32. doi:10.1016/S1473-3099(22)00816-7. Available at:

Return to footnote 10 referrer

Footnote 11

Akerman A, Milogiannakis V, Jean T, et al. Emergence and antibody evasion of BQ and BA.2.75 SARS-CoV-2 sublineages in the face of maturing antibody breadth at the population level. medRxiv. 2022:2022.12.06.22283000. doi:10.1101/2022.12.06.22283000. Available at:

Return to footnote 11 referrer

Footnote 12

Wang Q, Iketani S, Li Z, et al. Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants. bioRxiv. 2022:2022.11.23.517532. doi:10.1101/2022.11.23.517532. Available at:

Return to footnote 12 referrer

Footnote 13

Tamura T, Ito J, Uriu K, et al. Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants. bioRxiv. 2022:2022.12.27.521986. doi:10.1101/2022.12.27.521986. Available at:

Return to footnote 13 referrer

Footnote 14

Vikse EL, Fossum E, Erdal MS, Hungnes O, Bragstad K. Poor neutralizing antibody responses against SARS-CoV-2 Omicron BQ.1.1 and XBB in Norway in October 2022. bioRxiv. 2023:2023.01.05.522845. doi:10.1101/2023.01.05.522845. Available at:

Return to footnote 14 referrer

Footnote 15

Chalkias S, Whatley J, Eder F, et al. Safety and Immunogenicity of Omicron BA.4/BA.5 Bivalent Vaccine Against Covid-19. medRxiv. 2022:2022.12.11.22283166. doi:10.1101/2022.12.11.22283166. Available at:

Return to footnote 15 referrer

Footnote 16

Zou J, Kurhade C, Patel S, et al. Improved Neutralization of Omicron BA.4/5, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1 with Bivalent BA.4/5 Vaccine. bioRxiv. 2022:2022.11.17.516898. doi:10.1101/2022.11.17.516898. Available at:

Return to footnote 16 referrer

Footnote 17

Kurhade C, Zou J, Xia H, et al. Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1, and XBB.1 by 4 doses of parental mRNA vaccine or a BA.5-bivalent booster. bioRxiv. 2022:2022.10.31.514580. doi:10.1101/2022.10.31.514580. Available at:

Return to footnote 17 referrer

Footnote 18

Davis-Gardner ME, Lai L, Wali B, et al. Neutralization against BA.2.75.2, BQ.1.1, and XBB from mRNA Bivalent Booster. N Engl J Med. Jan 12 2023;388(2):183-185. doi:10.1056/NEJMc2214293 Available at:

Return to footnote 18 referrer

Footnote 19

Muik A, Lui BG, Diao H, et al. Progressive loss of conserved spike protein neutralizing antibody sites in Omicron sublineages is balanced by preserved T-cell recognition epitopes. bioRxiv. 2022:2022.12.15.520569. doi:10.1101/2022.12.15.520569. Available at:

Return to footnote 19 referrer

Footnote 20

Tan CY, Chiew CJ, Pang D, et al. Protective Effectiveness of Natural SARS-CoV-2 Infection and Vaccines against Omicron BA. 4/BA. 5 and XBB Reinfection in Singapore: A National Cohort Study. Available at SSRN 4308740. 2022. Available at:

Return to footnote 20 referrer

Footnote 21

Vangeel L, Chiu W, De Jonghe S, et al. Remdesivir, Molnupiravir and Nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. bioRxiv. 2022:2021.12.27.474275. doi:10.1101/2021.12.27.474275. Available at:

Return to footnote 21 referrer

Footnote 22

Imai M, Ito M, Kiso M, et al. Efficacy of Antiviral Agents against Omicron Subvariants BQ.1.1 and XBB. N Engl J Med. Jan 5 2023;388(1):89-91. doi:10.1056/NEJMc2214302. Available at:

Return to footnote 22 referrer

Footnote 23

Government of Canada. COVID-19 vaccination in Canada.

Return to footnote 23 referrer

Page details

Date modified: