Updates on COVID-19 Variants

SARS-CoV-2, which causes COVID-19, is a virus from the Coronavirus family. Coronaviruses are named after the Latin word, “corona”, meaning “crown” because they express spike proteins on their surface which resembles the ‘thrones of a crown’. The spike protein is comprised of three domains: a short cytoplasmic tail, a transmembrane domain, and an ectodomain. The ectodomain is arguably the most critical structure of the virus because of its role in facilitating the entry of SARS-CoV-2 into host cells. The ectodomain has two general subunits which can be denoted as S1 and S2. To infect host cells, SARS-CoV-2 uses its spike S1 unit to bind to the host entry receptor, angiotensin-converting enzyme 2 (ACE2). Once bound, SARS-CoV-2 then uses the spike S2 unit to fuse its viral envelope with the cellular outer membrane in order to enter the host cell.

Viruses including SARS-CoV-2 can undergo change by acquiring genetic mutations to generate new variants of the virus. As these new variants emerge, some will persist if their mutations improve their virulence and/or transmissibility. As a result, a major concern about the ongoing genetic evolution of SARS-CoV-2 is that the virus could acquire mutations to its spike protein that will improve the virus’ transmissibility and/or disguise its detection from the immune system.

On May 5, 2023,  the World Health Organization officially declared the end of the COVID-19 pandemic as a public health emergency, while emphasizing that it still remains a threat to global health (UN News, 2023). As such, the Public Health Agency of Canada will continue in its efforts to monitor emerging SARS-COV-2 variants and its associated infection and mortality rates (Public Health Agency of Canada, 2023a, 2023b).

Updated June 2, 2023

Authored by Toby Le

SARS-CoV-2 Variants of interest are characterized by genetic changes that alter the viral traits of SARS-CoV-2, thereby resulting in increased viral transmission, immune evasion, therapeutic/diagnostic evasion, and/or increased disease severity. VOC should are also linked with increased prevalence across both local and global communities (World Health Organization, 2021).    

XBB1.5 ; XBB.1.16

Variant of Concern:  XBB1.5 ; XBB.1.16

Sub-variants and Recombinants: BA.1, BA.2, BA.3, BA.4, BA.5, BA.2.12.1, BA.4/5, BF.7, BA.4.6, BA.2.75.2, BQ.1, BQ.1.1 , XBB.1, XBB1.5

Location of Origin: TBD

Initial Emergence: November 2021 (World Health Organization, 2021)

Impact on Vaccine Efficacy

• May 18, 2023: The WHO Technical Advisory Group on COVID-19 Vaccine Composition released a statement recommending that COVID-19 immunization be switched to a monovalent vaccine against the XBB subvariants (World Health Organization, 2023d).
• January 25, 2023: Following 2-4 months after receiving the bivalent mRNA booster dose, individuals showed a 48% vaccine efficacy against symptomatic XBB/XBB.1.5 infection (Link-Gelles et al., 2023).
• January 23,2023: [Pre-print] Following the administration of the bivalent mRNA booster, the decline in neutralization titers against XBB.1.5. was much more rapid compared to the BA.2 and BA.5 subvariants (Lasrado et al., 2023).  
• January 18, 2023: Monovalent mRNA boosting (Pfizer/Moderna) produced lower neutralization titers against BQ.1.1 and XBB.1 than BA.5 by a factor of 7 and 17, respectively. Whereas for the bivalent mRNA booster, sera neutralization of BQ.1.1 and XBB.1 were lower than BA.5 by a factor 7, and 21, respectively (Miller et al. 2023).
• January 17, 2023: [Pre-print] The spike protein of XBB.1.5 showed a 2.2-fold increase in infectivity in HEK293T-ACE2 cells compared to the ancestral strain spike protein. Individuals who received three dose of the Pfizer/Moderna monovalent vaccines showed reduced sera neutralization against the XBB.1.5, CH.1.1, and CA.3.1 Omicron subvariants, with 3.3-, 24.6- and 21.9-times lower neutralizing titers than the BA.4/5 variant (Qu et al. 2023).
• January 12, 2023: Sera neutralization of BQ.1. and XBB were 22.2- and 25.8- fold lower than the ancestral strain in individuals who received the Moderna bivalent booster (Davis-Gardner et al. 2022).
• January 9, 2023: [Pre-print] XBB and XBB.1 Omicron subvariants were highly resistant to sera neutralization by triple vaccinated (Pfizer or Moderna) individuals, with 324- and 371-fold reductions in antibody titers, respectively, compared to the ancestral strain (Jiang et al. 2023). In the same pre-print, authors found participants who received the bivalent booster as their fourth dose, had a 12-fold increase in their titer neutralization of BQ.1 and BQ.1.1 (Jiang et al. 2023).
• January 5, 2023: Individuals who received three-doses of the CoroaVac vaccine prior to BA.5 breakthrough infection, had lower sera neutralization against XBB.1.5 than the ancestral strain by 40-fold (Yue et al. 2023).
• January 5, 2023: In a meta-analysis by Li et al., children and adolescents who received two-doses of the Pfizer vaccine showed 50.67% and 60.59% protection against Omicron infections, respectively (Y. Li et al. 2023). 
• January 5, 2023: Sera neutralization was ~60% lower against the XBB.1 spike protein than the ancestral spike in vaccinated individuals (4-dose) who received the bivalent booster (Arora et al. 2023).
• December 21, 2022: The rate of sera neutralization against Omicron was lower than the ancestral strain by 94.44%  in recipients who received two-doses of the Pfizer vaccine (Zapata-Cardona et al. 2022).
• December 16, 2022: In a pre-print systematic review, researchers found sera neutralization against XBB.1 was 72-fold lower than the ancestral strain in individuals who received 3-4 booster vaccinations (i.e. Mono/Bivalent Moderna, Pfizer, CoronaVac) (Sullivan et al. 2022).
• December 13, 2022: Compared to the 2020 ancestral strain, sera neutralization of BQ.1, BQ.1.1, XBB, and XBB.1 was lower by 37- to 155-fold in individuals with 3-doses and 4-doses of the monovalent mRNA vaccine. Whereas, for individuals who received the bivalent mRNA vaccine as their fourth dose, sera neutralization against BQ.1, BQ.1.1, XBB, and XBB.1 was 24- to 85-fold lower than the ancestral strain (Q. Wang et al. 2022).
• December 6, 2022: Antibody titers against XBB.1 and XBB.3 were lower than the ancestral strain by 16.8- and 22.5-fold, respectively, in recipients who received 3 or 4 doses of the Pfizer or CoronaVac vaccine (Zhang et al. 2022).
• November 8, 2022: Individuals with three doses of the Pfizer vaccine who previously acquired Omicron BA.1/BA.2 breakthrough infections showed improve neutralization of BA.5 (>8-folds) than individuals with three-dose vaccinations alone (Pedersen et al. 2022).
• November 3,2022: Vaccinated individuals with past Omicron breakthrough infections yielded higher neutralizing titers against Omicron subvariants than those with vaccinations alone (Atari et al. 2022).
• November 2, 2022: According to a pre-print study, recipients of the BA.5-bivalent booster vaccine showed higher neutralization against the spike protein of newly emerged Omicron subvariants:  BA.4/5, BF.7, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1. Although, when compared to the ancestral strain from 2020, the BA.5-bivalent booster showed reduced neutralization against BA.4/5 (-12.1 fold) BF.7 (-11.9 fold), BA.4.6 (-19.8 fold), BA.2.75.2 (-36.9 fold), BQ.1.1 (-49.6 fold), and XBB.1 (-103 fold)(Kurhade et al. 2022).
• October 30, 2022: According to a pre-print, recipients who received three doses of the CoronaVac vaccine showed 3.6-fold lower serum neutralization against XBB than the BA.4/5 Omicron subvariants (Cao, Jian, et al. 2022).
• October 22, 2022: In a pre-print study, researchers examined the neutralization capacity of triple-vaccinated individuals against new subvariants derived from BA.4/BA/5: BA.4.6, BF.7, BQ.1, and BQ.1.1. Compared to the ancestral strain (D614G), antibody titers from triple vaccinated individuals had reduced neutralization against BA.4.6, BF.7, and BQ.1 by  -10.6 fold, -11.0 fold, and -22.9 fold, respectively(Qu, Evans, et al. 2022).
• October 14, 2022: Vaccinated individuals with prior non-Omicron infections had increased levels of protection against Omicron-associated hospitalization in response to receiving boosters (86% at 1 dose, 94% at 2 doses, and 91% at 3 doses) (Carazo, Skowronski, Brisson, Sauvageau, et al. 2022a).
• October 13, 2022: Using serum from blood donated by populations in Stockholm, study found antibody neutralization against BA.2.75.5 to be 6.5-times lower than the BA.5 subvariant (Sheward et al. 2022).
• October 8, 2022: Triple-vaccinated individuals with Omicron infections were associated with having 92.7% protection against infection by BA.5. Further, past infection by Delta and Alpha variant showed weaker protection against BA.5 (73.4% and 61.2%, respectively)(Hansen et al. 2022).
• October 7, 2022: Patients with three doses of the Pfizer vaccine had 79% and 71% protection against hospitalization caused by BA.1 and BA.2 infections, respectively (Tartof et al. 2022).
• October 6, 2022:  Following two doses of the mRNA vaccines, the (average) monthly rate of decay in neutralizing titers against BA.1, B.2.12.1 and BA.4/5 were 19.50%, 18.44%, and 19.55%, respectively (Qu, Faraone, et al. 2022).
• September 29, 2022: Plasma from recipients who received two doses of the Sinovac vaccine showed significantly lower neutralization against the Delta and Omicron variants, compared to the wild-type(Xie et al. 2022).
• September 28, 2022: Adolescents, aged 12-17, with two doses of the Pfizer vaccine had 83% and 75% protection against hospitalization caused by the Delta and Omicron infection, respectively. Upon receiving a third booster of the Pfizer vaccine, the adolescents had 94% protection against Omicron-induced hospitalization (Chiew et al. 2022).
• September 21, 2022: Using regression modelling to predict variant infections, those who were previously infected with non-Omicron variants and were vaccinated showed over 80% protection against symptomatic reinfection by Omicron BA.2 (Carazo, Skowronski, Brisson, Barkati, et al. 2022).
• September 20, 2022: BA.2 breakthrough infections of vaccinated individuals generated higher neutralization titers  (~ 2-fold higher) against BA.4/BA.5 infection than BA.1 breakthrough infections (Muik, Lui, Bacher, et al. 2022).
• September 1, 2022: Experimental inoculation of domestic goats with the Beta variant showed low viral loads, thus indicating goats as unlikely reservoirs for SARS-COV-2 infections (Fernández-Bastit et al. 2022). 
• August 12, 2022: Research team identified 10.13% of dogs and cats within their study cohort to exhibit omicron infection, suggesting possible transmission between humans and domestic animals (Sánchez-Morales et al. 2022).
• July 1, 2022: Study found no evidence of reduced vaccine protection against symptomatic disease caused by BA.2 or BA.1 (Kirsebom et al. 2022).
• June 26, 2022: Paper found Omicron BA.1 infection of Syrian hamsters did not lead to weight loss and was associated with reduced viral shedding compared to Delta variant. Moreover, pulmonary lesions were found in 38% and 78% of hamsters that were infected with either Omicron BA.1 or Delta variants, respectively (Rissmann et al. 2022).
• November 8, 2022: Individuals with three doses of the Pfizer vaccine who previously acquired Omicron BA.1/BA.2 breakthrough infections showed improve neutralization of BA.5 (>8-folds) than individuals with three-dose vaccinations alone (Pedersen et al. 2022). 
• November 3, 2022: Vaccinated individuals with past Omicron breakthrough infections yielded higher neutralizing titers against Omicron subvariants than those with vaccinations alone (Atari et al. 2022). 
• November 2, 2022: According to a pre-print study, recipients of the BA.5-bivalent booster vaccine showed higher neutralization against the spike protein of newly emerged Omicron subvariants:  BA.4/5, BF.7, BA.4.6, BA.2.75.2, BQ.1.1, and XBB.1. Although, when compared to the ancestral strain from 2020, the BA.5-bivalent booster showed reduced neutralization against BA.4/5 (-12.1 fold) BF.7 (-11.9 fold), BA.4.6 (-19.8 fold), BA.2.75.2 (-36.9 fold), BQ.1.1 (-49.6 fold), and XBB.1 (-103 fold)(Kurhade et al. 2022). 
• October 22, 2022: In a pre-print study, researchers examined the neutralization capacity of triple-vaccinated individuals against new subvariants derived from BA.4/BA/5: BA.4.6, BF.7, BQ.1, and BQ.1.1. Compared to the ancestral strain (D614G), antibody titers from triple vaccinated individuals had reduced neutralization against BA.4.6, BF.7, and BQ.1 by  -10.6 fold, -11.0 fold, and -22.9 fold, respectively(Qu, Evans, et al. 2022). 
• October 14, 2022: Vaccinated individuals with prior non-Omicron infections had increased levels of protection against Omicron-associated hospitalization in response to receiving boosters (86% at 1 dose, 94% at 2 doses, and 91% at 3 doses) (Carazo, Skowronski, Brisson, Sauvageau, et al. 2022a) 
• October 13, 2022: Using serum from blood donated by populations in Stockholm, study found antibody neutralization against BA.2.75.5 to be 6.5-times lower than the BA.5 subvariant (Sheward et al. 2022) 
• October 8, 2022: Triple-vaccinated individuals with Omicron infections were associated with having 92.7% protection against infection by BA.5. Further, past infection by Delta and Alpha variant showed weaker protection against BA.5 (73.4% and 61.2%, respectively)(Hansen et al. 2022). 
• October 7, 2022: Patients with three doses of the Pfizer vaccine had 79% and 71% protection against hospitalization caused by BA.1 and BA.2 infections, respectively (Tartof et al. 2022). 
• October 6, 2022:  Following two doses of the mRNA vaccines, the (average) monthly rate of decay in neutralizing titers against BA.1, B.2.12.1 and BA.4/5 were 19.50%, 18.44%, and 19.55%, respectively (Qu, Faraone, et al. 2022). 
• September 29, 2022: Plasma from recipients who received two doses of the Sinovac vaccine showed significantly lower neutralization against the Delta and Omicron variants, compared to the wild-type(Xie et al. 2022). 
• September 28, 2022: Adolescents, aged 12-17, with two doses of the Pfizer vaccine had 83% and 75% protection against hospitalization caused by the Delta and Omicron infection, respectively. Upon receiving a third booster of the Pfizer vaccine, the adolescents had 94% protection against Omicron-induced hospitalization (Chiew et al. 2022). 
• September 21, 2022: Using regression modelling to predict variant infections, those who were previously infected with non-Omicron variants and were vaccinated showed over 80% protection against symptomatic reinfection by Omicron BA.2 (Carazo, Skowronski, Brisson, Barkati, et al. 2022) 
• September 20, 2022: BA.2 breakthrough infections of vaccinated individuals generated higher neutralization titers  (~ 2-fold higher) against BA.4/BA.5 infection than BA.1 breakthrough infections (Muik, Lui, Bacher, et al. 2022). 
• September 1, 2022: Experimental inoculation of domestic goats with the Beta variant showed low viral loads, thus indicating goats as unlikely reservoirs for SARS-COV-2 infections (Fernández-Bastit et al. 2022).   
• August 12, 2022: Research team identified 10.13% of dogs and cats within their study cohort to exhibit omicron infection, suggesting possible transmission between humans and domestic animals (Sánchez-Morales et al. 2022). 
• July 1, 2022: Study found no evidence of reduced vaccine protection against symptomatic disease caused by BA.2 or BA.1 (Kirsebom et al. 2022) 
• June 26, 2022: Paper found Omicron BA.1 infection of Syrian hamsters did not lead to weight loss and was associated with reduced viral shedding compared to Delta variant. Moreover, pulmonary lesions were found in 38% and 78% of hamsters that were infected with either Omicron BA.1 or Delta variants, respectively (Rissmann et al. 2022). 
• May 16, 2022: During the Omicron outbreak in Brazil, prior infection conferred 85.6% against severe outcomes. Whereas, hybrid immunity, composed prior infection and three doses of vaccination (Pfizer), increased protection against severe outcomes up to 96% (Cerqueira-Silva et al. 2022).
• May 2, 2022: [Pre-print] Children aged 0-17, who received 2-doses of either the BBIBP-CorV or CoronaVac vaccine were found to be 35% less susceptible to symptomatic infection during the Omicron outbreak in Shanghai (Wang et al. 2022).  
• April 21, 2022: At 20-25 weeks after receiving two doses of either the AstraZeneca, Pfizer, or Moderna vaccine, the protective efficacy against Omicron dropped to below 0%, 8.8% and 14.9%, respectively. Boosting with either the Pfizer or Moderna vaccine was able to recover the protective efficacy to high levels against Omicron (Andrews et al. 2022).
• February 17, 2022: In vitro neutralization against Omicron was found to be substantiality higher in serum from patients who received 3 doses of the Pfizer vaccine than only two-doses (Xia et al. 2022). 
• February 10, 2022: A study on COVID-19 infection susceptibility was conducted on individuals of <18 years old that were previously double-vaccinated (Pfizer) or had recovered from COVID-19. Results showed that 100% of vaccine recipients and previously infected patients were able to produce neutralizing antibodies against the wild-type strain. Conversely, only 38.2% and 26.7% of vaccine recipients and infected patients, respectively, were able to generate detectable neutralizing antibodies against Omicron (Chen et al. 2022).
• January 21, 2022: Recipients who received 3 doses of the mRNA COVID-19 vaccines (Pfizer or Moderna) were at less risk for symptomatic infection caused by Omicron and Delta, compared to both unvaccinated individuals and recipients of 2 doses (Accorsi et al. 2022).
• January 25, 2022: Pfizer and BioNTech started their clinical trial to evaluate the efficacy of an Omicron-based vaccine candidate in individuals aged 18-55 (Pfizer 2022a).
• January 18, 2022: Neutralization titers in double vaccinated (Pfizer) recipients were 22.8-folds lower against Omicron than the wild-type strain. However, following a third booster, neutralizing titers against Omicron increased (23.4-folds) to levels comparable to that of the wild-type strain (Muik et al. 2022).
• December 26, 2021: According to a pre-print study, a booster dose of the BBIBP-CorV vaccine can produce significantly higher neutralizing titers against the Omicron variant compared to its twodose regimen. FYI: BBIBP-CorV is an inactivated virus vaccine produced by Sinopharm, a state-owned company in China, Beijing (Yu et al. 2021).
• December 16, 2021: Individuals who were vaccinated with the CoronaVac (2-dose regimen) were unable to produce detectable neutralizing titers against the Omicron variant. FYI: CoronaVac is a live inactivated whole virion vaccine produced by a Beijing-based company called Sinovac (Lu et al. 2021).
• November 29, 2021: Moderna announces three vaccine strategies under investigation for addressing Omicron variants: [a] Higher dose booster of mRNA-1273/Moderna vaccine. Development of [b] multi-valent boosters and [b] Omicron-specific boosters (mRNA-1273.529)(Moderna, 2021c).
• November 30, 2021: Chief executive of Moderna, Stéphane Bancel, predicts the existing vaccines will be less effective against Omicron compared to past SARS-CoV-2 variants (Smyth, 2021).
• December 7, 2021: According to preliminary data collected from researchers in South Africa, the ability of the Pfizer vaccine to induce antibody neutralization against the Omicron variant is reduced by 41-folds compared to the wild type SARS-CoV-2 (Joseph & Branswell, 2021; Sigallab, 2021).
• December 8, 2021: Data released by Pfizer showed a 25-fold increase in vaccine-induced antibody neutralization of the Omicron variant in patients who received a booster dose of the Pfizer vaccine (Pfizer, 2021a; Pfizer & BionTech, 2021).
• December 14, 2021: A pre-print study from Israel found a booster shot of the Pfizer vaccine to be associated with increased protection against Omicron. In comparison, individuals who received only two vaccine doses were found to be less protected against Omicron (Peer-reviewed & Published: December 29, 2021) (Nemet et al. 2021a, 2021b) – December 14, 2021: According to a study by South Africa’s largest health insurance company, Discovery Ltd., individuals with two vaccine doses had 33% protection against Omicron compared to 80% in the pre-Omicron period. Protection against hospitalisation by Omicron infection also reduced from 93% to 70% post-Omicron period (Discovery Ltd. 2021).
• December 15, 2021: A study by researchers from The University of Hong Kong showed the Omicron variant can infect and replicate 70-times faster than SARS-CoV-2 wild type and Delta variant in isolated human bronchial tissue(HKUMed 2021). – December 20, 2021: Moderna Inc. released data showing high antibody neutralization of Omicron using two different booster doses of Moderna. Further, a booster vaccination of Moderna at either 50 μg or 100 μg were able to increase antibody neutralization against Omicron by ~37- and ~83-folds, compared to pre-boost, respectively (Moderna 2021b).
• December 22, 2021: A study by Oxford University found a third-dose of the AstraZeneca vaccine to increase antibody neutralization against the Omicron variant (AstraZeneca 2021; Dejnirattisai et al. 2021).

Impact on Transmission

• January 17, 2023: [Pre-print] An epidemic dynamic analysis of COVID-19 cases in the USA showed recent Omicron subvariant, BQ.1.1, to be outcompeted by the new Omicron subvariant, XBB.1.5, since December of 2022  (Uriu et al. 2023).
• November 21, 2022: In the week ending on November 19th 2022, the CDC found 24.2% and 25.5% of reported SARS-COV-2 cases to be attributed to BQ.1.1 and BQ.1, respectively (Mandowara 2022).
• April 19, 2022: [Pre-print] Regardless of vaccination status, patients infected with BA.1 and BA.2 were found with similar viral loads in their nasopharyngeal swaps(Hirotsu et al. 2022).
• April 9, 2022: In a WHO video, starring COVID-19 Technical Lead Dr Maria Van Kerkhove, she shared that XE is speculated to be more transmissible than BA.2 by ~10%  (WHO 2022).
• April 8, 2022: UK Public Health confirmed 1,125 cases of XE as of April 5th, 2022. According to their analyses, the weekly growth rate of XE was 12.6% higher than BA.2 (UK Health Security Agency 2022b).
• February 15, 2022: According to the database Outbreak.info, the BA.2 sub-variant has been identified in at least 74 countries globally (Outbreak.info 2022).
• February 15, 2022: According to the database Outbreak.info, the BA.2 sub-variant has been identified in at least 74 countries globally (Outbreak.info 2022).
• February 15, 2022: According to a pre-print study, the effective reproduction number of the BA.2 Omicron sub-variant was found 1.4-folds higher than the Omicron BA.1 sub-variant (Yamasoba et al. 2022).
• February 10, 2022: According to the director of the Centre for Epidemic Response & innovation, Dr. Tulio de Oliveira, about 100% of cases detected in South Africa are caused by the BA.2 sub-variant (Sguazzin 2022).
• January 30, 2022: Following initial household infections, the BA.2 sub-variant was found to infect more household members than the BA.1 sub-variant (Lyngse et al. 2022).
• January 14, 2022: Using an artificial model system, such as the BHK21-ACE2 cell lines, researchers showed the Omicron variant were more infectious than both the Delta and wild type strain (Ma et al. 2022).
• December 1, 2021: South Africa reported 8,561 cases of the Omicron variant; about 2.5-fold increase from its total cases on November 26, 2021 (3,402) (Callaway & Ledford, 2021).
• December 2, 2021: A pre-print study found an increase in Omicron cases among individuals previously infected with SAR-CoV-2, suggesting that the variant might be able to evade natural immunity (Pulliam et al., 2021).
• December 3, 2021: World Health Organization’s chief scientist, Soumya Swaminathan, speculated that the Omicron variant might be able to displace the Delta variant in community/global transmissions (Guarascio & Nebehay, 2021).

Arrival to Canada

• April 25, 2023: The XBB.1.5 and XBB.1.16 subvariant were found to account for 61% and 7% of cases in Alberta, respectively (J. Lee, 2023).
• March 31, 2023: Alberta Public Health confirmed its first case of the XBB.1.16 subvariant (J. Lee, 2023).
• January 10, 2023: New Brunswick reported its first 2 cases of the XBB.1.5 Omicron subvariant (MacKinnon 2023).
• January 7, 2023: First case of the XBB.1.5 subvariant was detected in Saskatchewan following winter holidays (Benson 2023; Quon 2023)
• January 5, 2023: Two cases of the XBB.1.5 Omicron subvariant were confirmed in Nova Scotia (Patil 2023; Tutton 2023).
• January 5, 2023: Department of Health in Newfoundland and Labrador declared first provincial case of XBB.1.5 Omicron subvariant (CBC News 2023; Tutton 2023)
• January 5, 2023: Public Health in Quebec reported 8 cases of the XBB.1.5 Omicron subvariant (Sherwin 2023).
• January 4, 2023: Alberta confirmed its first four cases of the XBB.1.5 Omicron subvariant (Kaufmann 2023).
• January 4, 2023: Twenty-one cases of the XBB.1.5 Omicron subvariant detected in Canada to date (Lee 2023).
• July 12, 2022: Cases of BA.2.75 have been detected by the Public Health Agency of Canada (Otis 2022).
• July 12, 2022: Cases of BA.2.75 have been detected by the Public Health Agency of Canada (Otis 2022).
• April 6, 2022: The Public Health Agency of Canada (PHAC) confirmed that they have detected 6 cases of XE in Canada  (A. Khan 2022).
• January 28, 2022: Chief Public Health Officer of Canada, Dr. Theresa Tam, shared that more than 100 cases of the BA.2 sub-variant have been identified in Canada (Pelley 2022).
• November 28, 2021: Ontario detected its first two cases of the Omicron variant in Ottawa. Both individuals had recently travelled to Nigeria (Aguilar 2021a; Government of Ontario 2021; Paas-Lang 2021).
• November 29, 2021: Quebec confirmed first case of the Omicron variant who had recent travels from Nigeria (Lofaro 2021; Marchand 2021).
• November 30, 2021: British Columbia confirmed its first case of the Omicron variant in Fraser health who traveled to Nigeria (Dickson 2021; Martins 2021; Zussman 2021).
• November 30, 2021: Alberta confirmed first case of the Omicron variant from an individual travelling from Nigeria and the Netherlands(Gervais 2021).
• December 7, 2021: Manitoba confirmed its first case of the Omicron variant from an individual with recent international travel (Bergen 2021a).
• December 8, 2021: Yukon confirmed its first two cases of the Omicron variant (Ritchie 2021) – December 8, 2021: Saskatchewan detected its first four cases of the Omicron variant from one household with recent international travels (Giles 2021).
• December 13, 2021: Nova Scotia detected its first cases of the Omicron variant from an outbreak at St. Francis Xavier University in Antigonish. A total of 40 cases from the outbreak were linked to the Omicron variant. (Doucette 2021; Munro 2021).
• December 13, 2021: New Brunswick confirmed its three first cases of the Omicron variant: two in the Miramichi region and one in the Moncton region. All of these cases were linked to a past outbreak at St. Francis Xavier University in Antigonish, Nova Scotia (L. Brown 2021; Perry 2021).
• December 14, 2021: Prince Edward Island linked its first case of the Omicron variant to the outbreak at St. Francis Xavier University in Antigonish, Nova Scotia (Government of Prince Edward Island 2021; Price 2021) – December 15, 2021: Newfoundland and Labrador reported its first case of the Omicron variant from the province’s Eastern Health region (CBC News 2021d; Whiffen 2021).
• December 19, 2021: Northwest Territories confirmed first case of the Omicron variant with direct links to interprovincial travel (Down 2021; Government of Northwest Territories 2021; Williams 2021).

Risk to Canadians

• April 17, 2023: Omicron subvariant, XBB.1.16, was designated a variant of interest due to its detection across 33 countries (World Health Organization, 2023c).
• March 16, 2023: The World health Organization classified new Omicron subvariant, XBB.1.5, as a variant of interest (World Health Organization, 2023b).
• January 27, 2023: The XBB.1.5 subvariant was linked to 61.3% of COVID-19 cases reported in United States of America (Reuters, 2023).
• January 26, 2023: FDA discontinued the prevention medication against COVID-19, Evusheld, due to observations that the drug may not be effective against newly emerging SARS-COV-2 variants (U.S. Food & Drug Administration, 2023).
• January 25, 2023: Omicron subvariant, XBB.1.5, has been detected in 54 countries, including Canada and the United States of America (World Health Organization, 2023a).
• January 23, 2023: Sera from individuals who were vaccinated with a third dose of the mRNA vaccine showed a 21.6-fold decrease in neutralization titers against the XBB variant than the ancestral strain (Uraki et al., 2023).
• January 20, 2023: Former head of the Ontario Science Table, Dr. Fahad Razak, encourages Canadians to get up to date with their COVID-19 vaccinations in order to establish protection against the spread of the XBB.1.5 Omicron subvariant (Mangione 2023; Taylor 2023).
• January 20, 2023: In Canada, the XBB.1.5 Omicron subvariant accounted for 2.5% of all new COVID-19 cases during the week of December 25, 2022 to January 2, 2023. Its rate of transmission has since increased to 7% of all new infections (Dubois 2023; Wright 2023).
• January 5, 2023: Upon screening the sensitivity of the XBB.1 spike protein to 16 different antibody therapies, only two monoclonal antibodies (sotrovimab and S2H9) were able to neutralize the subvariant, albeit their efficacy was reduced by more than 10 times compared to the ancestral spike (Arora et al. 2023).
• January 4, 2023: During a press conference,  Dr Van Kerkhove, the technical lead on COVID-19 at WHO, shared that XBB.1.5 is the most transmissible subvariant to date due to mutations that enable the virus for better cell adhesion and replication (WHO 2023).
• December 13, 2022: Clinically authorized monoclonal antibody treatments, bebtelovimab and  Evusheld, were found ineffective in neutralizing XBB and BQ.1 Omicron subvariants (Q. Wang et al. 2022).
• October 27, 2022: The WHO’s Technical Advisory Group on SARS-CoV-2 Virus Evolution released a statement confirming XBB and BQ.1 as sublineages of Omicron that required close monitoring (WHO 2022b).
• October 4, 2022: Risk of hospitalization and severe outcome were similar in BA.4/BA.5- and BA.1- infected individuals (Wolter et al. 2022).
• October 4, 2022: Risk of hospitalization and severe outcome were similar in BA.4/BA.5- and BA.1- infected individuals (Wolter et al. 2022).
• May 3, 2022: [Pre-print] Prior infection by non-omicron variants was associated with 81% protection against hospitalization by Omicron infection; this protection increased to 97% in patients who also received three doses of the mRNA vaccine (Pfizer/Moderna)(Carazo et al. 2022).  
• May 2, 2022: [Pre-print] BA.4 and BA.5 were found to evade antibody neutralization more effectively than BA.2 in sera collected from patients who previously received three dose of the CoronaVac vaccine (Cao et al. 2022).
• February 9, 2022: Patients who were previously infected with non-Omicron variants had poor neutralization titers against the Omicron spike protein (Zou, Xia, et al. 2022).
• May 1, 2022: Prior infection by BA.1 generated low serum neutralization against BA.4 (3.2-folds lower) and BA.5 (2.6-folds lower) Omicron subvariants(K. Khan et al. 2022).
• May 26, 2022: Using serum from patients that were previously infected with BA.1, researchers found limited cross-neutralization of the other variant strains: BA.2 (4.2-folds lower), BA.3 (4.4-folds lower) and wild-type (28.4-folds lower) (Zou, Kurhade, et al. 2022).
• March 25, 2022: UK Public Health identified 3 recombinants related to Omicron: XF, XE, and XD. Both XD and XF are recombinants of the Delta and Omicron BA.1 variant. Whereas XE is a recombinant of Omicron BA.1 and BA.2, which has been linked to 637 cases in the UK (UK Health Security Agency 2022a).
• March 4, 2022: Using RT-qPCR to study patient samples, researchers found the Omicron BA.2 subvariant to be more infectious than BA.1 based on its higher genomic load (i.e. lower Ct values) in infected patients (Qassim et al. 2022).
• February 22, 2022: According to a pre-print study by the Statens Serum Institut, researchers found that re-infection with BA.2 shortly after BA.1 to be a rare occurrence that affected mostly young unvaccinated individuals. Further, among those who were re-infected with BA.2, the clinical consequences were mild and did not lead to hospitalization or death (Stegger et al. 2022). 
• February 07, 2022: In a pre-print study, both vaccinated and previously infected patients were found to produce similar levels of neutralizing antibodies against Omicron BA.1 and BA.2  (J. Yu et al. 2022).
• January 24, 2022: The UK Health Security Agency identified a sub-lineage of the Omicron variant, denoted as BA.2 (UK Health Security Agency 2021b).
• January 14, 2022: The Public Health of Agency Canada (PHAC) released data showing an intense surge in COVID-19 cases due to the Omicron variant, which has quickly replaced Delta as the dominant variant in Canada. The high infection rates are speculated to stress healthcare capacity within the near future (Public Health Agency of Canada 2022).
• December 27, 2021: A pre-print study showed booster-vaccinated individuals were more protected against household secondary transmission of the Omicron variant than those who were unvaccinated or fully vaccinated (2-dose) (Lyngse et al. 2021).
• December 14, 2021: According to a study by South Africa’s largest health insurance company, Discovery Ltd., the relative risk for re-infection with Omicron was 40% and 60% for individuals that were previously infected with either Delta or Beta, respectively. (Discovery Ltd. 2021).
• December 22, 2021: A report from the Imperial College London found the risk of hospitalization by Omicron infections to be lower than Delta by at least 20-25% (Imperial College London 2021).
• December 28, 2021: According to the US Food and Drug Administration, rapid antigen tests might be less sensitive for detecting Omicron infections (i.e. more false negatives) (U.S Food & Drug Administration 2021).

Disease Severity

• October 28, 2022: According to a statement by the Indian SARS-CoV-2 Genomics Consortium (INSACOG), the disease severity caused by XBB is similar to other Omicron subvariants (INSACOG 2022).
• September 13, 2022: A higher frequency of individuals infected with BA.2 self-reported symptoms of ‘chills or sweating’, ‘freeze’ and ‘runny nose’ than those infected with BA.5 (Goller et al. 2022).
• September 13, 2022: A higher frequency of individuals infected with BA.2 self-reported symptoms of ‘chills or sweating’, ‘freeze’ and ‘runny nose’ than those infected with BA.5 (Goller et al. 2022).
• January 27, 2022: Compared to past variants (Wild-type, Alpha, Beta, and Delta), the Omicron variant had the lowest replication efficiency in lung parenchyma samples. Authors speculated that the decreased replication capacity of Omicron could explain its reduced disease severity (Hui et al. 2022).
• February 15, 2022: Using hamsters as model systems, the BA.2 sub-variant was found more pathogenic than the BA.1 sub-variant (Yamasoba et al. 2022).
• December 14, 2021: A study by South Africa’s largest health insurance company, Discovery Ltd., described a 29% decrease in hospital admissions for adults in South Africa, compared to its first COVID-19 wave in 2020 (Discovery Ltd. 2021).
• December 21, 2021: A pre-print study by researchers in South Africa found the risk for severe disease by Omicron infection to be lower than Delta infection by 70% (Wolter et al. 2021).

Critical Mutations

• November 23, 2021: The global science initiative, GISAID, confirmed 32 spike mutations on Omicron (UK Health Security Agency, 2021).
• November 25, 2021: There are speculations that these 32 spike mutations might contribute to increased immune evasion and transmission (Callaway, 2021).

Information and Resources

Updates about Vaccine Development

• April 3, 2023: A live-attenuated virus vaccine against SARS-CoV-2 (sCPD9) developed by researchers from Germany was found to be more protective than the Pfizer mRNA vaccine in Syrian hamsters (Nouailles et al., 2023).
• February 15, 2023: Neutralization against Omicron subvariants was lower in participants who received homologous CoronaVac booster compared with the heterologous Pfizer or AstraZeneca boost regimen.
• January 18, 2023: The Novavax Vaccine showed similar vaccine efficacy as the mRNA bivalent vaccine in boosting immunity against Omicron subvariants (Novavax Inc., 2023).
• January 25, 2022: Pfizer and BioNTech started their clinical trial to evaluate the efficacy of an Omicron-based vaccine candidate in individuals aged 18-55 (Pfizer 2022a).
• November 29, 2021: Moderna announces three vaccine strategies under investigation for addressing Omicron variants: [a] Higher dose booster of mRNA-1273/Moderna vaccine. Development of [b] multi-valent boosters and [b] Omicron-specific boosters (mRNA-1273.529)(Moderna 2021d).
• November 30, 2021: Chief executive of Moderna, Stéphane Bancel, predicts the existing vaccines will be less effective against Omicron compared to past SARS-CoV-2 variants (Smyth 2021).
• July 28, 2021: Findings released by Pfizer suggested that a third dose of the Pfizer/BioNTech COVID-19 vaccine could increase neutralizing antibody titers by >5-folds against the Delta variant (Stevo, 2021).
• February 24, 2021: Moderna announced its shipment of the B.1.351 variant-specific vaccine candidate to NIH for Phase 1 clinical trials (Moderna, 2021a).
• February 27, 2020: FDA approves Johnson & Johnson vaccine for emergency use (FDA NEWS RELEASE, 2021).
• February 19, 2021: Pfizer submits vaccine stability data to the Food and Drug Administration (FDA) revealing that their vaccine, BNT162b2, can be stored at higher temperatures between -25 to -15 °C. This current label requires that the vaccine be stored between -80 to -60 °C. New storage conditions is currently pending approval from the FDA (Pfizer, 2021; Reuters Staff, 2021).
• February 10, 2021: South Africa replaced its original vaccine candidate, AstraZeneca, with the Johnson & Johnson vaccine, which has not yet been approved by the U.S. Food and Drug Administration and the South Africa’s regulatory authority. The South African government intends to provide this vaccine to its front-line health workers in the following week (Meldrum, 2021; Meyer, 2021).
• February 7, 2021: South Africa halted their rollout of the AstraZeneca vaccines due to its reduced efficacy against the B.1.351 variant (Mueller, Robbins, & Chutel, 2021).
• February 7, 2021: AstraZeneca is developing a 2nd generation vaccine that is effective against the B.1.351 variant. This is a response to its recent clinical trials in South Africa where researchers deemed the AstraZeneca to be ineffective against the B.1.351 variant (Wits University, 2021).
• February 4, 2021: Johnson & Johnson is pursuing Emergency Use Authorization (EUA) from the U.S. Food and Drug Administration (FDA) for its single-dose vaccine, Janssen (Johnson & Johnson, 2021b).
• January 25, 2021: Moderna Inc. is looking to study how an additional booster of its vaccine can impact the level of neutralizing titers against the B.1.351 variant. Additionally, the company is also seeking to develop a booster vaccine, mRNA- 1273.351, against the B.1.351 variant (Moderna, 2021b; Wu et al., 2021).

Key Events

• January 18, 2022: Pfizer presents pre-print data from three independent laboratory studies showing high in vitro efficacy of its new COVID-19 oral drug, PaxlovidTM, against the Omicron variant (Pfizer 2022).
• January 11, 2022: BioNTech and InstaDeep Ltd announces their newly developed computational method to sequence and predict SARS-CoV-2 variants of concern (BioNTech 2022).
• August 6, 2021: Among those who were infected with SARS-COV-2 in 2020, researchers found that risk of re-infection was 2.34-times higher among those who were unvaccinated than vaccinated (Cavanaugh, Spicer, Thoroughman, Glick, & Winter, 2021).
• March 24, 2021: Data released by the Public Health Agency of Canada (PHAC) showed increased COVID-19 cases among young adults aged 20-39. Daily cases of COVID-19 are predicted to spike to new record levels (Public Health Agency of Canada, 2021).
• February 27, 2020: FDA approves Johnson & Johnson vaccine for emergency use (FDA NEWS RELEASE, 2021).
• February 19, 2021: The Public Health Agency of Canada (PHAC) released modeling predicting a high resurgence in COVID-19 cases if stringent public health measures are not implemented as vaccine programs expand (Public Health Agency of Canada, 2020).
• February 10, 2021: South Africa replaced its original vaccine candidate, AstraZeneca, with the Johnson & Johnson vaccine, which has not yet been approved by the U.S. Food and Drug Administration and the South Africa’s regulatory authority. The South African government intends to provide this vaccine to its front-line health workers in the following week (Meldrum, 2021; Meyer, 2021).
• February 8, 2021: Ontario confirmed Canada’s first case of the P.1 variant in Toronto, Ontario. The case was linked to international travel to Brazil (Favaro et al., 2021).
• February 7, 2021: AstraZeneca is developing a 2nd generation vaccine that is effective against the B.1.351 variant. This is a response to its recent clinical trials in South Africa where researchers deemed the AstraZeneca to be ineffective against the B.1.351 variant (Wits University, 2021).
• February 7, 2021: South Africa halted their rollout of the AstraZeneca vaccines due to its reduced efficacy against the B.1.351 variant (Mueller et al., 2021).
• January 27, 2021: Researchers declared the P.1 variant as the dominant SARS-CoV-2 strain in Manaus Brazil (France24, 2021; Medical Xpress, 2021).
• January 25, 2021: Moderna Inc. is looking to study how an additional booster of its vaccine can impact the level of neutralizing titers against the B.1.351 variant. Additionally, the company is also seeking to develop a booster vaccine, mRNA- 1273.351, against the B.1.351 variant (Moderna, 2021b; Wu et al., 2021).
• January 8, 2021: Alberta confirmed Canada’s first case of the B.1.351 variant (Heidenreich & Ramsay, 2021).
• December 26, 2020: Ontario confirmed Canada’s first cases of the B.1.1.7 variant in two individuals from Toronto (Aziz, 2020; Jabakhanji, 2020; Rocca, 2020).
• December 2020: Emergence of P.1 variant in Brazil.
• October, 2020: Emergence of B.1.351 variant in South Africa.
• September, 2020: Emergence of B.1.1.7 variant in the United Kingdom.

Global COVID-19 Variant Trackers

NextStrain

This phylogeny shows evolutionary relationships of SARS-CoV-2 viruses from the ongoing COVID-19 pandemic. Although the genetic relationships among sampled viruses are quite clear, there is considerable uncertainty surrounding estimates of specific transmission dates and in reconstruction of geographic spread. Please be aware that specific inferred geographic transmission patterns and temporal estimates are only a hypothesis.

GSAID

GSAID obtained COVID-19 virus sequence data from several sources in Saudi Arabia (CDC, Hospitals) and worldwide. They process genome isolates to first obtain a fingerprint of mutations appearing in sampled populations across different locations, which helps to understand COVID-19 virus variants and their infection track.

Additional GSAID COVID-19 variant tracker featuring relative variant genome frequency per region.

More Information on Variants

https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm?s_cid=mm7003e2_e

https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-brief-emerging-variants.html

https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/variant-surveillance/variant-info.html

https://cov-lineages.org/global_report.html

https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html

https://covariants.org/

References

Other

Additional information was facilitated by Zeeshan Qadar.

Past Variants