Living Evidence - SARS-CoV-2 variants

Living evidence tables provide high level summaries of key studies and evidence on a particular topic, and links to sources. They are reviewed regularly and updated as new evidence and information is published.

Viruses constantly change through mutation and over time, new variants of a virus are expected to occur. Some variants have characteristics that have a significant impact on transmissibility, severity of disease and effectiveness of vaccines.  This table includes information on variants that are currently causing concern in the scientific community.

Currently, the World Health Organization  has identified one currently circulating variants of concern: Omicron.

Regular checks are conducted for new content and any updates that occur during the week are highlighted. All highlights are removed each Monday.

 Omicron
WHO labelOmicron
Scientific names

B.1.1.529

GR/484A

21K, 21L, 21M, 22A, 22B, 22C, 22D

WHO is monitoring BA.5, BA.2.75, BJ.1, BA.4.6, XBB and BA.2.3.20.

First detectedMultiple countries

November 2021
Mutations

~50 mutations, including 32 mutations on its spike protein and 15 on the receptor binding domain

BA.5 has additional mutations outside of the spike protein: N:G30-, N:S33F, N:E136D, ORF1a:Q556K, ORF1a:L3829F, ORF1b:Y264H, ORF1b:M1156I, ORF9b:P10F, ORF9b:D16G, ORF9b:M26-, ORF9b:A29I, ORF9b:V30L. BA.5 sublineages include BF.7, BF.14, BQ.1, BQ.1.1. BQ.1 has additional spike mutations K444T and N460K, while BQ.1.1 also has spike mutation R346T.

BA.2.75 has additional mutation outside the spike protein: ORF1a:S1221L, ORF1a:P1640S, ORF1a:N4060S; ORF1b:G662S; E:T11A. It is a BA.2 sublineage.

BJ.1 has additional mutations outside of the spike protein: Mutations: M:D3Y, N:T282I, ORF1a:K47R, ORF1b:G662S, ORF1b:S959P, ORF7a:I110T. It is a BA.2 sublineage.

BA.4.6 is a BA.4 sublineage and has a mutation in a known antigenically significant site (S: R346T).

XBB has additional mutations outside of the spike protein: E:T11A, ORF1a:K47R, ORF1b:G662S, ORF1b:S959P, ORF8:G8*. It is a recombinant of BA.2.10.1 and BA. 2.75.

BA.2.3.20 has additional mutations outside of the spike protein: ORF1a:T727I, ORF1a:I1714T, ORF1a:M2169V, ORF1a:T2174I, ORF1a:T2648I, ORF1a:A2909V, ORF1a:Q3922R, ORF1b:T1404M, ORF3a:L140F, ORF9b:D89E.

Reports that the ACE2 binding is increased for BA.2 receptor binding domain compared to BA.1. BA.2.12.1 exhibit increased ACE2-binding affinities compared to BA.1. BA.2.12.1, BA.4 and BA.5 exhibit similar ACE2-binding affinities to BA.2. BA.2.75 exhibits higher ACE2-binding affinity than BA.4/BA.5.*  The impact of the BQ.1 mutations on the affinity for ACE2 may be modest  compared to BA.5. ^

Transmissibility

Parental lineage:

Reproduction number ranges from 2.6 to 4.0, with an estimated doubling time of 1.5-3 days.

Omicron has growth advantage and increased transmissibility compared to Delta.

Increased risk of household transmission.* Household secondary attack rate estimates range from 15.8% to 39% for Omicron compared to 10.3% to 26% for Delta.

Specific to BA.1 and BA.2 lineages:

Estimated reproduction number of BA.2 is 1.4-fold higher than BA.1 and modelling suggests the reproduction number of BA.1 is 1.99 and BA.2 is 2.51.

Data suggests BA.2 may be 1.5 times more transmissible than BA.1 and there is a growth advantage for BA.2.12 over BA.2.

Preliminary analysis suggests a 13.4% secondary attack rate for BA.2.*^

Preliminary analysis suggests the mean serial interval of 3.27 days for BA.2 compared to 3.72 days for BA.1. Both are shorter than the mean serial interval for Delta of 4.09 days.

Reports of no significant differences for viral load and time to viral clearance between BA.1 and BA.2. Median Ct value of first positive sample was 29.4 in BA.1 and 24.5  in BA.2 breakthrough infection in triple vaccinated individuals.^

BA.2.75.X lineages (including BA.2.75.2) has a 18.78% larger growth advantage relative to BA.5.

Specific to BA.4 and BA.5 lineages:

Estimated growth advantages for BA.4 and BA.5 of 0.08 and 0.10 per day respectively over BA.2 in South Africa.  Early reports suggest the growth advantage for BA.4 and BA.5 is likely due to the ability to evade immune protection induced by prior infection and/or vaccination; reports that  B.5 has a larger growth advantage than BA.4.*

BA.4.6 has a 5.66% larger growth advantage relative to BA.5.*

BQ.1.1 has an estimated weekly growth rate of 63.14% relative to BA.5.2.* BQ.1 + BQ.1.X has an estimated weekly growth rate of 53.26% relative to BA.5.2.*

BA.2.75 + BA.2.75.X has an estimated relative growth rate of 24.18% relative to BA.5.2.*

Specific to BA.2.75 lineage:

Relative effective reproduction number (Re) of BA.2.75 is 1.34-fold higher than that of BA.2, and 1.13-fold higher than that of BA.5.

BA.2.75 + BA.2.75.X has an estimated weekly growth rate of 24.18% relative to BA.5.2.*

Virulence and severity

Parental lineage:

A large analysis of South African data by WHO showed evidence of reduced severity and lower mortality for the Omicron variant as compared with the Delta variant after adjusting for the confounding effects of age, sex, ethnicity, prior infection, vaccination status, comorbidities, effect of province and effect of public/private sector.

Estimates of disease severity suggest that the adjusted hazard ratios for any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation, and death comparing cases with Omicron versus Delta variant infection were 0.59, 0.59, 0.50, 0.36, and 0.21 respectively.

Studies suggest milder disease trajectory and lower risk of developing severe disease (including among high-risk older populations); as well as lower risk of mortality with Omicron compared to Delta. Reports of less severe outcomes for paediatric age groups, adults and older adults compared to Delta.^

SARS-CoV-2 infection in pregnancy during Omicron-dominant period is associated with a lower risk of short-term maternal and perinatal complications compared to infections during the Delta-dominant period.

Studies suggest an increase in reports of sore throat and in croup for paediatric patients.  There are also reports of increased frequency of fever and respiratory symptoms in hospitalised paediatric patients. The loss or change of sense of smell and taste are less predictive of swab positivity for Omicron than for other variants.*^

Specific to BA.1 and BA.2 lineages:

One study assessed the severity of BA.2 infections compared to BA.1. Findings suggest that while BA.2 may have a competitive advantage over BA.1 in some settings, the clinical profile of illness remains similar. Reports of no differences in risk of hospitalisation and other severe outcomes between BA.1 and BA.2 infections. Compared to Omicron B.1.1.529, BA.2 is found to be intrinsically less severe.

BA.2 is associated with the reporting of more symptoms and  greater disruption to daily activities than BA.1. Studies suggest  an increase in reports of chest pain, severe fatigue, runny nose, muscle aches, sneezing, fever, chills, tiredness, block nose and headache for BA.2.*^

Specific to BA.4 and BA.5 lineages:

Earlier reports suggested no clear indication of change in severity for BA.4 and BA.5 compared to BA.2. A population-based study from Denmark however suggested that BA.5 infections were associated with increased risk of hospitalisation compared with BA.2 infections. Data from South Africa suggested that disease severity was similar amongst diagnosed COVID-19 cases during the BA.4/BA.5 and BA.1 periods,^ with prior infection and vaccination having protective effects.

No difference in risk between BA.4/BA.5 and BA.2 in terms of inpatient hospital admission following presentation to emergency care.

Vaccines

Parental lineage:

Estimated vaccine effectiveness against  infection compared to no vaccination ranges between 30-62% after full primary doses, and between 34-66% after a booster dose.

Estimated vaccine effectiveness against symptomatic disease ranges between 6-76% after primary doses, and between 19-73.9% after booster dose, compared to no vaccination.

Estimated vaccine effectiveness against severe disease compared to no vaccination ranges between 3-84% after full primary doses, and between 12-100% after a booster dose.

Reports suggest a decline in vaccine effectiveness within three to six months for infections and symptomatic disease. Against severe disease protection is maintained for at least six months. Data suggests waning immunity is more profound after primary than booster vaccination.

During Omicron predominant period and in children aged five to 11, Comirnaty vaccine effectiveness against PCR-confirmed infection and hospitalisation was 65.3% and 82.7%, respectively.

Vaccination, prior COVID infection, and both the vaccination and prior infection reduced the risk of transmitting Omicron to close contacts by 22%, 23% and 40%, respectively.^

A systematic review and meta-regression estimates that prior infection and hybrid immunity provide greater and more sustained protection against Omicron than vaccination alone.*^ Hybrid immunity conferred higher levels of neutralising capacity against Omicron (96.4%)  compared to both vaccine-induced (79.5%) and infection-induced immunity (47.5%).^

The Spikevax (Moderna, BA.1-adapted) bivalent booster vaccine is found to induce stronger neutralising antibody activities against the Omicron variant than the original booster version; and have similar safety and reactogenicity profile to the original versions.

Preliminary evidence shows that Omicron BA.4/BA.5-adapted bivalent vaccine (Pfizer) is well tolerated with a safety profile similar to that of the original vaccine.  A fourth dose of mRNA bivalent vaccine adapted for BA.4/BA.5 however did not induce a superior neutralising antibody response against all variants tested (including Omicron BA.4/BA.5) compared to a fourth dose of the original monovalent mRNA vaccine.^

Specific to BA.1 and BA.2 lineages:

mRNA vaccines appear to provide moderate and short-lived protection against symptomatic BA.1 and BA.2 Omicron infections, but strong and durable protection against COVID-19 hospitalisation and death.  In immunocompetent people, vaccine effectiveness during the BA.2/BA.2.12.2 period was lower than that during the BA.1 period.

Comirnaty (Pfizer - BNT162b2), Vaxzevria (AstraZeneca -ChAdOx1) and Spikevax (Moderna -mRNA-1273): estimated vaccine effectiveness against symptomatic disease with BA.1 was ~63.1%, and BA.2 was ~64.3% within the first two weeks of receiving the second dose; reducing to ~14.8% and ~27.8% after 25 or more weeks for BA.1 and BA.2, respectively. Estimated booster effectiveness (Comirnaty or Spikevax) after a week was ~70.6% and 74.0% for BA.1 and BA.2 (irrespective of primary vaccination type). Similar rates of waning effectiveness for each sub-lineage.

Comirnaty (Pfizer - BNT162b2) and Spikevax (Moderna -mRNA-1273): estimated vaccine effectiveness in preventing symptomatic BA.1 infection is ~46.6% in the first three months and then declines to ~10% below, increases to ~59.9% in the first month after a booster, and then declines to ~40.5% in the second month and thereafter for Comirnaty and with a similar pattern for Spikevax.  For BA.2, vaccine effectiveness was ~51.7% in the first three months after the second dose and declined to ~10% or below, and increased to 43.7% in the first month after the booster, and then declined to ~40.2% in the second month and thereafter for Comirnaty and with a similar pattern for Spikevax.

Despite immunity waning over time, booster vaccines can elicit broad neutralising antibodies against a large number of SARS-CoV-2 variants, including BA.1 and BA.2, especially in older adults. Observational studies suggest booster vaccination can significantly increase vaccine effectiveness against severe disease and death.

Vaccination enhanced protection against symptomatic BA.1 and BA.2 infection among persons who have had a previous infection. Hybrid immunity resulting from previous infection and recent booster vaccination conferred the strongest protection.

Prior Omicron BA.1 primary infection plus two or three doses of mRNA vaccine provided the highest-level protection against BA.2 infection and lasted for five months post-infection.^

Preliminary evidence shows that XBB.1 recombinant variant is more resistant to the neutralisation antibodies induced by prior booster vaccination (fourth dose, either monovalent or bivalent) than BA.4/5, BQ.1.1 and BA.2.75.2.^ BA.5-adapted bivalent booster elicited better neutralising response against XBB.1 than original monovalent booster vaccine, although the response was not robust. The neutralising response elicited by the bivalent vaccine against XBB.1 was further enhanced in individuals with a prior infection history.^

Specific to BA.4 and BA.5 lineages:

Comirnaty (Pfizer - BNT162b2) and Vaxzevria (AstraZeneca -ChAdOx1):  estimated reduction in neutralisation of BA.4 and BA.4 compared to BA.1 (3.2- fold for Pfizer and 2.1-fold for Vaxzeveria)  and BA.2 (3.2-fold for Pfizer and 1.8-fold for Vaxzeveria). Three doses of Comirnaty, and two doses of Vaxzevria plus one dose of Comirnaty as a booser increased BA.4 neutralising titres by 10-fold, similar to that 74 observed for BA.1 and BA.2.

BA.4/5 had the highest propensity to evade vaccine neutralisation compared to the original Omicron variant BA.1. Administration of a homologous or heterologous booster markedly enhanced neutralising antibody titers and breadth in vaccinated as well as convalescent individuals.

Preliminary evidence shows that titres for BA.4.6 are reduced two-fold compared to neutralisation of BA.4/BA.5 using sera from triple dosed recipients of the Comirnaty  vaccine.

Preliminary evidence shows that BQ.1 and BQ.1.1 are more resistant to the neutralisation antibodies induced by prior infection and vaccination than BA.5.^ There are reports of BA.5-adapted bivalent booster vaccine eliciting better neutralising response against BQ.1.1 than the original monovalent booster vaccine. Previous infection enhanced the magnitude and breadth of BA.5-bivalent-booster-elicited neutralisation.

Specific to BA.2.75 lineage:

BA.2.75 is more neutralisation resistant to sera from vaccinated/boosted individuals than BA.2 (1.8-fold), similar to BA.2.12.1 (1.1-fold), but less neutralisation resistant than BA.4/5 (0.6-fold).*^

Fourth dose of vaccination:

Comirnaty (Pfizer - BNT162b2) and Spikevax (Moderna -mRNA-1273): estimated vaccine effectiveness in preventing mild or asymptomatic infections is ~30% and 11%  respectively, following a fourth dose of vaccine*^  Another study suggests the vaccine effectiveness is 64% at three weeks after the fourth dose of Comirnaty; reducing to ~29% at 10 weeks.  Estimated relative effectiveness against severe disease is ~73%, following a fourth dose of vaccine of Comirnaty.*^  Reports that the fourth dose of Comirnaty reduces breakthrough infections among healthcare workers.

Elderly persons (80 years or older) who receive fourth dose of mRNA vaccine have lower risk of symptomatic infection, COVID-19–related hospitalisation, and severe disease, with vaccine effectiveness estimates at 22.2%, 55.0%, and 63.0%, respectively.

In individuals aged 18 and over, effectiveness of a fourth-dose Spikevax vaccine against hospitalisation with BA.2 and  BA.4/BA.5 infections were 96.4% and 88.5%, respectively.^

There are reports of BA.5-adapted bivalent booster vaccine eliciting better neutralising response against BA.2.75.2 than the original monovalent booster vaccine.^

Hybrid immunity:

Hybrid immunity (prior infection and vaccination) conferred a relative gain in the magnitude and duration of protection compared to prior infection alone or vaccination alone.

Previous infection and vaccination with Comirnaty, Vaxzevria or Johnson & Johnson: estimated protection against severe outcomes after a previous infection is ~85.6% and increases with vaccination (effectiveness ranging from ~88.0 to 100%). Compared to those unvaccinated but with a previous infection, hybrid immunity showed a modest increase in protection against symptomatic infection, once again waning over time, and substantial protection against severe outcomes after the booster.

Both Comirnaty vaccine and prior infection presented considerable protection against hospitalization and death in children aged five to 11 years.

Interval from infection to vaccination inversely correlates with booster vaccination response.

Reinfection

Parental lineage:

Previous natural SARS-CoV-2 infection was associated with lower risk of reinfection, regardless of the variant, than mRNA primary-series vaccination.

Protection against Omicron reinfection three months after prior infection with a pre-Omicron variant: 63.7% for any infection, 57.0% for symptomatic infection, 82.5% for severe disease. Protection against any infection and symptomatic infection waned by nearly 50% after 15 months, however, protection against severe disease waned more slowly by 11%.

Specific to BA.1 and BA.2 lineages:

Evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.  Effectiveness of BA.1 infection against reinfection with BA.2 is estimated at ~94.2%; effectiveness of BA.2 infection against reinfection with BA.1 is estimated at ~80.9%.

Specific to BA.4 and B.5 lineages:

Reports suggest considerable escape of BA.4 and BA.5 from BA.1 elicited immunity.  Data suggests that BA.2.12.1 and BA.4/BA.5 substantially escape neutralising antibodies induced by both vaccination and infection; BA.5 is associated with higher odds of reinfection compared with BA.2, regardless of the vaccination status.^

Observational studies suggest immunity induced by prior infection with BA.1 and BA.2 confers stronger protection against BA.4/BA.5 infection than immunity induced by infection with previous non-Omicron variants.

The effectiveness of pre-Omicron infections against symptomatic BA.4 or BA.5 reinfection is 35.5% and 27.7% against any BA.4 or BA.5 reinfection regardless of symptoms; whereas the effectiveness of post-Omicron infection against symptomatic BA.4 or BA.5 reinfection is 76.2% and 78% against any BA.4 or BA.5 reinfection.

Treatment

Specific to BA.1 and BA.2 lineages:

Monoclonal antibodies: studies suggest substantial differences in the neutralisation profiles of BA.1 and BA.2. BA.1 demonstrates considerable escape from neutralisation by monoclonal antibodies. In contrast to BA.1, one study showed BA.2 was sensitive to cilgavimab and tixagevimab, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab.  Reports suggest sotrovimab retained moderate neutralising activity against BA.1 and weak neutralising activity against BA.2.

The combination of tixagevimab and cilgavimab, and sotrovimab had substantially reduced neutralising potency against BA.2.75. Bebtelovimab efficiently neutralised BA.2.75.

Antiviral drugs: Studies suggest molnupiravir and nirmatrelvir/ritonavir are associated with lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster, in individuals hospitalised with BA.2 and not requiring oxygen therapy.

One in-vitro study suggested that remdesivir, molnupiravir, and nirmatrelvir retained neutralising activities against BA.2.75.

Specific to BA.4 and BA.5 lineages:

Monoclonal antibodies:  Studies suggest that the sensitivity of BA.4 and BA.5 to neutralisation by bamlanivimab, casirivimab, etesevimab, imdevimab, and tixagevimab was similar to that of BA.2. BA.4/5 is more sensitive to sotrovimab than BA.2. BA.4/5 exhibited about 20-fold more resistance to cilgavimab and Evusheld (cilgavimab and tixagevimab) than BA.2. For BA.4.6, BA.4.7, BA.5.9, and BA.5.2.6 descendent lineages,  Evusheld lost its neutralising potency;  casirivimab with imdevimab and sotrovimab had reduced potency; and bebtelovimab remained highly potent.  BQ.1.1 was found to be resistant to all tested monoclonal antibodies in one study, although in another it was sensitive to neutralisation by sotrovimab.

Antiviral drugs: One in-vitro study suggests that molnupiravir and remdesivir and nirmatrelvir remained susceptible to Omicron subvariants BA.2.12.1, BA.4 and  BA.5 at a similar level to that of the ancestral strain.

Specific to XBB recombinant lineage:

XBB exhibited strong resistance to neutralisation by tixagevimab and cilgavimab, and bebtelovimab.

Post-acute sequelae of COVID-19 (Long COVID)

Studies suggest lower prevalence of long COVID following infection with Omicron (4.5%) than with Delta (10.8%), especially among double vaccinated individuals and irrespective of time elapsed between infection and most recent vaccination. In triple vaccinated individuals, the prevalence was similar for Delta (5.0%), Omicron BA.1 (4.5%) and Omicron BA.2 (4.2%) infections.

Reports of a reduction in odds of long COVID with the Omicron variant versus the Delta variant, with an odd ratio ranging from 0·24 to 0·50.

Testing and detection

Omicron (parental lineage, BA.1, BA.4 and BA.5) can be identified through S-gene target failure. N-gene target failure can detect BA.2.

PCR and antigen-based rapid diagnostic test (Ag-RDT assays detect Omicron. However, results are mixed as to whether or not there may be decreased sensitivity. Reports of impaired detection of Omicron and rapid-antigen tests*^ and another study suggests non-significant differences in the analytical limit of detection or clinical diagnostic accuracy of rapid antigen testing across variants*^

Countries reporting detection

Detected in ~146 (BA.5).

Dominant variant globally and BA.5 and its descendent lineages have become the dominant lineage.

The World Health Organization (WHO) announced the Variant naming system on 1 June 2021.

Details are tabulated when Variants meet the World Health Organization (WHO) definition of Variant of Concern (VOC).

  • Previously circulating VOC listed by WHO: Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2)
  • Variant of Concern lineages under monitoring (VOC-LUM) by WHO: BA.5, BA.2.75, BJ.1, BA.4.6, XBB, and BA.2.3.20
  • Previously circulating Variants of Interest by WHO: Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu
  • Recombinant lineages: XD and XF (combination of Delta AY.4 and BA.1, XD has the Omicron S gene incorporated into a Delta genome), XE (combination of BA.1 and BA.2, with the majority of the genome including the S gene belonging to BA.2), and XBB (combination of BA.2.10.1 and BA.2.75 sublineages, i.e. BJ1 and BM.1.1.1, with a breakpoint in S1). The XD recombinant is now classified as a formally monitored variant (FMV) by WHO and XE is being tracked as part of the Omicron variant
Notes

*Preliminary data, not fully established, in some cases small numbers or short follow up; interpret with caution

^ Commentary grey literature, pre-peer review or news

The "last updated" date refers to the date when the evidence was last reviewed.

Background

Evidence check - SARS-CoV-2 variants (PDF)

Living evidence tables include some links to low quality sources and an assessment of the original source has not been undertaken. Sources are monitored regularly but due to rapidly emerging information, tables may not always reflect the most current evidence. The tables are not peer reviewed, and inclusion does not imply official recommendation nor endorsement of NSW Health.

Last updated on 25 Nov 2022

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