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 two currently circulating variants of concern: Delta and Omicron.

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  DeltaOmicron
WHO label Delta Omicron
Scientific names

B.1.617.2

G/452.V3

21A/S:478K

Delta includes AY lineages (AY.1 and AY.2)

B.1.1.529

GR/484A

21K

WHO is monitoring BA.4, BA.5, BA.2.12.1, BA.2.9.1, BA.2.11 and BA.2.13.

First detected

India

October 2020

Multiple countries

November 2021
Mutations

~13

Includes spike mutation profiles L452R, E484Q and D614G and lacks mutations at amino acid positions 501 or 484 in its ACE2 receptor.

P681R change is a crucial feature of Delta*^

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

BA.4, BA.5 and BA.2.12.1 have acquired additional mutations that may impact their characteristics (BA.4 and BA.5 have the del69/70, L452R and F486V mutations; BA.2.12.1 has the L452Q and S704L mutations)

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.

Transmissibility

Reproduction number ranges from 3.2 to 8, with a  mean of 5.0.

Increased transmissibility and secondary attack rate compared with wild type*^ for household and non-household contacts.

Estimated 2.5-fold higher viral loads compared to other variants*^, and 15-fold higher saliva viral loads compared to wild type*^ Similar viral loads between vaccinated and unvaccinated individuals*^

Virological characteristics of vaccine breakthrough infections suggest  Ct-values decreased throughout the first three days of illness*^.  

Estimated mean of the latent period and the incubation period are 4.0 days and 5.8 days, respectively*^

Reports suggest full vaccination reduced infectious viral load for breakthrough cases and and rates of transmission compared to unvaccinated individuals.

Parental lineage:

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

Several reports suggest an overall growth advantage; Omicron is ~36.5% more transmissible than 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 25 in BA.2 infection*^

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; early reports that  B.5 has a larger growth advantage than BA.4*^

Virulence and severity

Increased risk of emergency care and hospitalisation, including higher odds of oxygen requirement, admission to an intensive care unit, and possible increased risk of mortality*^

Studies show hospitalisation rates for unvaccinated individuals are higher compared with vaccinated individuals*^

Some studies suggest symptoms can differ to wild type*^.

Estimated illness duration for children is 5 days, with symptoms including headache and fever*^.  Reports of low hospital presentation and the presence of long illness*^

Reports that asymptomatic cases clear more quickly, 11 days compared to 1 day, and had higher mean antibody levels than symptomatic cases *^

Parental lineage:

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 as well as lower risk of mortality in hospitalised patients with Omicron compared to Delta. Reports of less severe outcomes for paediatric age groups, adults and older adults.

Studies suggest an increase in reports of sore throat and in croup for pediatric 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; however studies suggest  BA.1/BA.1.1 and BA.2  is associated with reduced risk  of progression to severe outcomes compared to Delta*^

BA.2 is associated with reporting 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:

A preliminary comparative analysis and modelling study projected that BA.4 and BA.5 are about 36% more infectious than BA.2.  No indication of any change in severity for BA.4 and BA.5 compared to previous lineages. However, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2.*^

Vaccines

Comirnaty (Pfizer - BNT162b2), Vaxzevria (AstraZeneca -ChAdOx1) and Spikevac (Moderna -mRNA-1273): estimated vaccine effectiveness against symptomatic infection is ~92%, ~87% and ~95%, respectively. Estimated effectiveness against hospitalisation is up to ~90%.

Multiple studies suggest a strong effect of waning immunity and reduced effectiveness for Comirnaty, Spikevac and Vaxzevria *^ after the primary course. However, there is evidence for the maintenance of protection against severe disease*^ including hospitalisation and mortality*^

For Comirnaty and Vaxzevria the estimated vaccine effectiveness against symptomatic infection is ~87% and ~67%, respectively after the primary course; reducing to 66.3% and 44.3% respectively by 20 weeks. For Spikevac the estimated vaccine effective against infection is ~86.7%, reducing to ~80% 180+ days after the primary course.

Comirnaty (Pfizer - BNT162b2) and Vaxzevria (AstraZeneca -ChAdOx1): estimated vaccine effectiveness against symptomatic disease from 14 days after the booster was ~93.1% when the primary course was Vaxzevria and ~94% for Comirnaty*^

One study suggests a booster (third) dose increases neutralising antibodies and different immune phenotypes following heterologous (“mix-and-match”) compared with homologous boost strategies for COVID-19*^

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*^

Preliminary assessment of an Omicron-specific booster in nonhuman primates*^

Specific to BA.1 and BA.2 lineages:

Comirnaty (Pfizer - BNT162b2), Vaxzevria (AstraZeneca -ChAdOx1) and Spikevac (Moderna -mRNA-1273): estimated vaccine effectiveness against symptomatic disease with BA.1 is ~63.6%, and BA.2 is ~67.1% within the first two weeks of receiving the second dose; reducing to ~17.4% and ~24.3% after 25 or more weeks for BA.1 and BA.2, respectively. Estimated booster effectiveness (Comirnaty or Spikevac) is ~71.3% and 72.2% for BA.1 and BA.2 (irrespective of primary vaccination type). Similar rates of waning effectiveness for each sub-lineage*^

Comirnaty (Pfizer - BNT162b2) and Spikevac (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 Spikevac*^.  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 Spikevac*^

BA.2 did not evade the humoral immune response induced by the Comirnaty booster vaccine better than BA.1 did.

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.^

Fourth dose of vaccination:

Comirnaty (Pfizer - BNT162b2) and Spikevac (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*^

Hybrid immunity:

Previous infection and vaccination with Comirnaty, Vaxzevria or Johnson & Johnson): estimated protection against severe outcomes after a previous infection is ~85.6% and increasing with vaccination (effectiveness ranging from ~88.0 to 100%). Compared to those unvaccinated 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.

Reinfection

Estimated reinfection risk of ~46% *^. Prior infections result in less severe disease against subsequent infections*^

Studies suggest vaccine-induced immunity provides greater protection than infection-induced immunity against laboratory-confirmed COVID-19*^

Parental lineage:

Estimated reinfection risk is 5.4 times higher than Delta. Reports that prior infection prevents symptomatic reinfection with Omicron (~60%) to a much lesser extent than other variants (Alpha, Beta and Delta ~ 90%). One study suggests non-Omicron infection reduced the Omicron re-infection risk by 44%, decreasing from 66% at 3-5 months to 35% at 9-11 months post-infection and <30% thereafter*^

Specific to BA.1 and BA.2 lineages:

Evidence that Omicron BA.2 reinfections do occur shortly after BA.1 infections but are rare.  Early studies suggest the effectiveness of BA.1 infection against reinfection with BA.2 is ~94.9%*^. Reports of co-infections

Specific to BA.4 and B.5 lineages:

Early reports suggest the observed escape of BA.4 and BA.5 from BA.1 elicited immunity is more moderate than of BA.1 against previous immunity.  Data suggests that BA.2.12.1 and BA.4/BA.5 substantially escape neutralising antibodies induced by both vaccination and infection; BA.4/BA.5 and to a lesser extent BA.2.12.1 titers were lower than BA.1 and BA.2*^

One study found a 23-fold drop in relative neutralising titres against BA.4 and BA.5, and 7.6-fold reduction against BA.2 using sera from unvaccinated individuals with a single known exposure to BA.1*^

Neutralisation experiments also suggest immunity induced by BA.1 and BA.2 infections is less effective against BA.4 and BA.5^*

Treatment

review study found that monoclonal antibodies had reduced efficiency in neutralising variants^.  One study suggests Delta is resistant to bamlanivimab*^

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, partly inhibited by imdevimab and resistant to adintrevimab and sotrovimab.  Reports suggest sotrovimab retained neutralising activity against BA.1.

Antiviral drugs: studies suggest molnupiravir and nirmatrelvir/ritonavir is associated with lower risks of disease progression and all-cause mortality, in addition to achieving low viral load faster for individuals hospitalised with BA.2 and not requiring oxygen therapy; and, nirmatrelvir/ritonavir is associated with lower risks of morality, hospitalisation and in-hospital outcomes (use of invasive mechanical ventilation and admission to the intensive care unit)*^

Specific to BA.4 and BA.5 lineages:

Monoclonal antibodies: preliminary studies suggest the sensitivity of BA.4 and BA.5 to neutralisation by therapeutic monoclonal antibodies is similar BA.2; recognised less well by sotrovimab than BA.1, and with marginally better recognition by imbedvimab than BA.1. One study found that while cilgavimab is antiviral against BA.2; BA.4 and BA.5 exhibits higher resistance to this antibody compared to BA.2*^

Antiviral drugs: preliminary studies (non-human primates) suggests molnupiravir or nirmatrelvir  reduced the infectious virus titers in the lungs*^

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

Early data suggests the prevalence of long COVID after an Omicron infection is less than that of the other strains. Data suggests long COVID symptoms four to eight weeks after infection were 49.7% lower for BA.1 compared to Delta among adults who were double-vaccinated when infected and 21.8% higher after an infection compatible with  BA.2 than BA.1*^

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

No reported impacts on diagnostics*^

Lateral flow devices effective in detecting*^

Estimated lower PCR Ct values and significantly longer duration of Ct value ≤30. One study suggests higher loads do not translate into different testing  scenarios*^.  Another study suggests no significant differences in the duration of RT-PCR positivity among fully vaccinated individuals versus not fully vaccinated individuals, or in duration of culture positivity*^

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 ~160 countries

Detected in ~178 countries (BA.1), ~146 (BA.2), ~58 (BA.4), and 62 (BA.5).

Dominant variant globally and BA.2 has become the dominant lineage; however BA.4 and BA.5 continue to rise in prevalence in many countries. Reports suggest that the rate of replacement of BA.4 and BA.5 over BA.2 is higher than the rate at which BA.2 replaced BA.1.

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).

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 24 Jun 2022

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