SARS-CoV-2 Variants

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SARS-CoV-2 Variants

Last reviewed: February 22, 2022

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Overview

Viruses mutate over time, and as a result, new variants of viruses tend to emerge. Most mutations do not produce clinically relevant changes, but occasionally mutations occur that may be beneficial for the virus.

Multiple variants of SARS-CoV-2, the virus that causes COVID-19, have emerged or spread throughout different parts of the world, including the United States. Variant viruses may carry mutations that could be associated with differences in diagnostic test performance, changes in disease epidemiology, clinical outcomes and effectiveness of certain therapeutics or vaccines.


Clinical Data Summary

Selected CDC/World Health Organization Designees with Published Clinical Data 
Version 2/22/22

Variant
(WHO label/
Pango lineage)

Treatment efficacy (in vitro)** 

mRNA vaccine clinical effectiveness

Viral vector vaccine clinical effectiveness

Nanoparticle / subunit vaccine clinical effectiveness

 

Omicron 
B.1.1.529  

Southern Africa 
2021 

 

 

Bamlanivimab + etesevimab: No  neutralization efficacy (CDC; Gruell, December 2021 – preprint, not peer-reviewed) 

REGEN-COV (casirivimab + imdevimab): No neutralization efficacy (Wilhelm, December 2021 – preprint, not peer-reviewed) 

Sotrovimab: Retains neutralization efficacy (Takashita, January 2022)

Convalescent sera: Severely reduced neutralization efficacy (from patients recovering from Alpha and some Delta infections) (Ikemura, December 2021 – preprint, not peer-reviewed) 

Evusheld (tixagevimab co-packaged with cilgavimab): Retains neutralization efficacy (NIH OpenData, December 2021; Takashita, January 2022) 
 

 

Pfizer-BioNTech vaccine: 
Significantly reduced effectiveness of two doses of vaccine against infection in the US (Thompson, January 2022; Johnson, January 2022), UK (Andrews, December 2021 – preprint, not peer-reviewed), and South Africa (Collie, December 2021) and slightly reduced effectiveness against severe COVID-19 that is mitigated after a booster dose (Andrews, December 2021 – preprint, not peer-reviewed; Thompson, January 2022; Johnson, January 2022; Accorsi, January 2022; Ferdinands, February 2022)

Moderna vaccine:
Significantly reduced effectiveness of two doses of vaccine against infection in the US (Thompson, January 2022; Johnson, January 2022) and slightly reduced effectiveness against severe COVID-19 that is mitigated after a booster dose (Thompson, January 2022; Johnson, January 2022; Accorsi, January 2022; Ferdinands, February 2022) 

 

Oxford-AstraZeneca vaccine:
Significantly reduced effectiveness of two doses of vaccine against infection in the UK (Andrews, December 2021 – preprint, not peer-reviewed) 

Johnson & Johnson vaccine:
Significantly reduced effectiveness of one dose of vaccine against infection in South Africa (Goga, December 2021 – preprint, not peer-reviewed) that is mitigated after a booster dose (Gray, December 2021 – preprint, not peer-reviewed) 

 

No data 

Delta 
B.1.617.2 
 
India 
2020 

Bamlanivimab + 
etesevimab:  
Retains neutralization efficacy (FDA EUA)  
Bamlanivimab alone inefficacious 

REGEN-COV (casirivimab + imdevimab):  
Retains neutralization efficacy (FDA EUAPlanas, May 2021) 

Sotrovimab:  
Retains neutralization efficacy (FDA EUA) 

Convalescent sera:  
Potential moderately reduced neutralization (Planas, May 2021) 

Pfizer-BioNTech vaccine: 
Slightly reduced effectiveness against infection but preserved effectiveness*** against severe COVID-19 after 2 doses in the US (Tartof, October 2021), UK (Bernal, July 2021; Stowe, May 2021 - preprint, not peer-reviewed; Sheikh, June 2021; Sheikh, December 2021), Canada (Chung, August 2021), and Qatar (Tang, November 2021)  

Moderna vaccine: 
Slightly reduced effectiveness against infection but preserved effectiveness against severe COVID-19 in the US (Baden, November 2021; Chin, December 2021; Bruxvoort, December 2021), Canada (Chung, August 2021), and Qatar (Tang, November 2021) 

Oxford-AstraZeneca vaccine:  
Slightly reduced effectiveness against infection but preserved effectiveness*** against severe COVID-19 after 2 doses in the U.K. (Bernal, July 2021; Stowe, May 2021 - preprint, not peer-reviewed; Sheikh, June 2021; Sheikh, December 2021) and Canada (Chung, August 2021) 

No data 

Gamma 
P.1 
 
Brazil 
2020 

Bamlanivimab + 
etesevimab:  
Markedly reduced neutralization (FDA EUA) 

REGEN-COV (casirivimab + imdevimab):  
Retains neutralization efficacy (FDA EUA) 

Sotrovimab:  
Retains neutralization efficacy (FDA EUA) 

Convalescent sera:  
Moderately reduced neutralization (Wang, June 2021) 
 

Moderna vaccine:
Preserved effectiveness against COVID-19 in the US (Bruxvoort, December 2021) 

Oxford-AstraZeneca vaccine:  
Preserved effectiveness against COVID-19 after 2 doses in Brazil (Hitchings, October 2021)

No data 

(Presumed to be similar to Beta variant based on relevant mutations) 

Beta 
B.1.351 
 
South Africa 

2020 

Bamlanivimab + 
etesevimab: 
 
Markedly reduced efficacy (FDA EUAChen, June 2021) 

REGEN-COV (casirivimab + imdevimab):  
Retains neutralization efficacy (FDA EUAWang, March 2021)     
Markedly reduced neutralization with casirivimab alone 

Sotrovimab:  
Retains neutralization efficacy (FDA EUA) 

Convalescent sera:  
Moderately reduced neutralization (Planas, May 2021) 

Pfizer-BioNTech vaccine: 
Slightly reduced effectiveness against infection but preserved effectiveness against severe COVID-19 in Qatar (Abu-Raddad, May 2021) 

Moderna vaccine: 
Slightly reduced effectiveness against infection but preserved effectiveness against severe COVID-19 in Canada (Chung, August 2021and Qatar (Chemaitelly, July 2021)

Oxford-AstraZeneca vaccine: 
No effectiveness against infection in South Africa (Madhi, May 2021); reduced effectiveness against infection but preserved effectiveness against severe COVID-19 in Canada (Chung, August 2021) 

Johnson & Johnson vaccine: 
Reduced effectiveness against infection but preserved effectiveness against severe COVID-19 in South Africa (Sadoff, May 2021) 

Novavax vaccine: 
Reduced effectiveness against infection (Shinde, May 2021) 

Alpha 
B.1.1.7 
 
U.K. 
2020 

 

Bamlanivimab + etesevimab:
Retains neutralization efficacy (FDA EUA) 

REGEN-COV (casirivimab + imdevimab):  
Retains neutralization efficacy (FDA EUA) 

Sotrovimab:  
Retains neutralization efficacy (FDA EUA) 

Convalescent sera: Retains neutralization efficacy (Planas, May 2021) 

 Pfizer-BioNTech vaccine: 
Preserved effectiveness against infection and severe COVID-19 in the U.K. (Hall, May 2021), Israel (Haas, May 2021), Qatar (Abu-Raddad, May 2021) and Canada (Chung, August 2021) 

Moderna vaccine: 
Preserved effectiveness against infection and severe COVID-19 in the US (Bruxvoort, December 2021), Canada (Chung, August 2021), and Qatar (Chemaitelly, July 2021) 

Oxford-AstraZeneca vaccine: 
Slightly reduced effectiveness against infection but preserved effectiveness against severe COVID-19 in the U.K. (Emary, April 2021) and Canada (Chung, August 2021) 

Novavax vaccine: 
Preserved effectiveness against infection and severe COVID-19 in the U.K. (Heath, June 2021) 

*As compared with vaccine efficacy/effectiveness against wildtype or D614G variant SARS-CoV-2.
**The susceptibility results refer, as a default, to in vitro testing of sotrovimab against both pseudotyped virus-like particles and authentic SARS-CoV-2 virus. Where results are discordant, both pseudotyped and authentic virus susceptibility is presented. Where only one type of virus was tested, it was in all cases pseudotyped virus. In the case of the Delta variant, binding of the monoclonal antibodies to variant strain was tested with the S-Fuse binding assay. The extent of correlation of neutralizing activity in in vitro cell culture experiments with clinical outcomes is as yet unknown.
*** As compared with vaccine efficacy/effectiveness against Alpha/B.1.1.7 variant.

 

Omicron

In late November 2021, the World Health Organization, the United States Department of Health and Human Services’ SARS-CoV-2 Interagency Group, and the European Center for Disease Prevention and Control designated the Omicron variant (B.1.1.529) as a “variant of concern.” This VOC designation was determined based on the number and location of mutations present in the spike protein – many of which have been previously associated with increased transmissibility and immune evasion – as well as epidemiological data from southern Africa suggestive of high rates of reinfection and replacement of Delta by Omicron as the dominant circulating variant.

Omicron was first reported from South Africa and neighboring countries in November 2021 but has since become the dominant variant around the world. The Omicron variant differs from previous variants of SARS-CoV-2 in the increased number of mutations present in the spike protein (at least 30, including 15 in the receptor binding domain [RBD] region), relative to previous variants such as Beta (10) and Delta (9), many of which are unique. These mutations impact the performance of certain molecular tests targeting the spike protein gene, as well as viral transmissibility, and neutralization by monoclonal antibodies or antibodies elicited by COVID-19 vaccination or SARS-CoV-2 natural infection. 

As information continues to emerge, we collect key timely resources here and provide key literature reviews on Omicron transmissibility, immunityseverity and impact on testing:

Transmissibility

The Omicron variant emerged in late November 2021 in southern Africa and within weeks became the dominant variant in multiple countries around the world. A number of notable transmission events and outbreaks (Gu, December 2021; Jansen, December 2021; Brandal, December 2021) and the rapid expansion of Omicron in South Africa (Viana, January 2022) and the U.S. (Lambrou, February 2022) highlighted the epidemic potential of this variant. Early evidence suggests that the heightened transmissibility of the Omicron variant is not attributable to higher viral loads compared to previous variants (Puhach, January 2022 – preprint, not peer-reviewed; Hay, January 2022 – preprint, not peer-reviewed), but instead greater immune evasion. 

 

Immunity

Multiple studies have demonstrated reduced neutralization of Omicron by antibodies from vaccinated or convalescent individuals compared with previous SARS-CoV-2 variants. This includes recipients of the Pfizer-BioNTech (Cele, December 2021; Edara, December 2021 – preprint, not peer-reviewed; Dejnirattisai, January 2022; Muik, January 2022; Rossler, January 2022), Moderna (Rossler, January 2022), Johnson & Johnson/Janssen (Lyke, January 2022 – preprint, not peer reviewed), and Oxford-AstraZeneca (Dejnirattisai, January 2022; Rossler, January 2022) COVID-19 vaccines. These observations also translate to reduced effectiveness of prior infection (Altarawneh, February 2022) as well as mRNA and viral vector vaccines against both infection and severe disease due to the Omicron variant (see Emerging Variants Table above). Importantly, booster doses of vaccine appear to restore in vitro neutralization titers (Nemet, December 2021; Garcia-Beltran, December 2021; Pajon, January 2022; Lyke, January 2022 – preprint, not peer-reviewed) as well as clinical effectiveness (Andrews, December 2021 – preprint, not peer-reviewed; Thompson, January 2022; Johnson, January 2022; Accorsi, January 2022; Gray, December 2021 – preprint, not peer-reviewed; Ferdinands, February 2022; Danza, February 2022). 

COVID-19 Incidence and Death Rates Among Unvaccinated and Fully Vaccinated Adults with and Without Booster Doses During Periods of Delta and Omicron Variant Emergence — 25 U.S. Jurisdictions, April 4–December 25, 2021 (Johnson, January 2021). 

In this analysis, CDC investigators used COVID-19 surveillance data from 25 jurisdictions to determine COVID-19 case and death rates among unvaccinated individuals compared with individuals who had received two or three doses of a COVID-19 vaccine across 4 time periods – pre-Delta (April–May 2021), Delta emergence (June 2021), Delta predominance (July–November 2021), and Omicron emergence (December 2021). Vaccinated individuals had lower rates of infection and death in all time periods, but the relative reduction in incidence was lowest during the period of Omicron emergence, consistent with significant immune escape. Fully vaccinated individuals who had received a booster dose of vaccine had the lowest case and death rates, compared with both unvaccinated individuals and those who had received two doses of vaccine. The effect of a booster dose was most significant among individuals aged >50 years of age. 

 

Severity

Studies from multiple countries – including the U.S. (Iuliano, January 2022; Lewnard, January 2022 – preprint, not peer-reviewed; Christensen, January 2022 – preprint, not peer-reviewed; Wang, January 2022 – preprint, not peer-reviewed; Wang, January 2022 – preprint, not peer-reviewed; Modes, February 2022; Lauring, February 2022 – preprint, not peer-reviewed), U.K. (Sheikh, December 2021 – preprint, not peer-reviewed), and South Africa (Abdullah, December, 2021; Maslo, December 2021; Wolter, January 2022; Davies, January 2022 – preprint, not peer-reviewed) – indicate that infection due to the Omicron variant is associated with less severe disease (decreased risk of hospitalization and death, reduced length of stay, etc.) compared with previous variants of concern, including Delta. This may be attributable to relatively less lower respiratory tract replication (Diamond, December 2021 – preprint, not peer-reviewed; Hui, February 2022; Meng, February 2022; Suzuki, February 2022) as well as greater population-level immunity (due to prior natural infection and/or vaccination). 

Trends in Disease Severity and Health Care Utilization During the Early Omicron Variant Period Compared with Previous SARS-CoV-2 High Transmission Periods — United States, December 2020–January 2022 (Iuliano, January 2022). 

In this analysis, CDC investigators used data from three surveillance systems and a large health care database to characterize indicators of COVID-19 disease severity – including rates of hospitalization, ICU admission, and death as well as markers of healthcare utilization such as need for mechanical ventilation and hospital length of stay – across three high-COVID-19 transmission periods, spanning winter 2020-21, July 15-October 31, 2021 (Delta surge), and December 19, 2021-January 15, 2022 (Omicron surge). They found that overall COVID-19 cases, ED visits, and admissions were significantly higher during the Omicron period than during previous high-COVID-19 transmission periods, but deaths were significantly lower – additionally, hospitalized COVID-19 patients had a shorter length of stay, and a smaller proportion required ICU admission or mechanical ventilation, and fewer died during the Omicron period. Notably, rates of ED visits and hospitalization were higher for those aged under 18 years, presumably related to their lower rates of vaccination. 

Impact on Testing

Three independent studies have shown no change in the analytic sensitivity of one of the most widely-used rapid antigen tests in the U.S., the Abbott BinaxNOW COVID-19 Antigen test. The first study is from Australia and showed no attenuation in sensitivity relative to detection of the Delta variant using samples obtained from viral culture (Deerain, December 2021). The study also evaluated 9 other rapid antigen tests available in Australia and found no attenuation in sensitivity. A second study used 32 Omicron and 30 Delta samples previously collected as part of a university screening program, also showing no difference in analytic sensitivity for the BinaxNOW by variant. The authors also found that the limit of detection (LoD) of the assay was in the range of prior estimates made during earlier pandemic waves (Kanjilal, January 2022 – preprint, not peer-reviewed). A third study at a community testing center in San Francisco compared nasal swabs to nasal RT-PCR, showing the BinaxNOW had a sensitivity of 95% for detecting virus below a cycle threshold (Ct) value of 30 (Schrom, January 2022 – preprint, not peer-reviewed). The study did not provide an estimate of the viral copy number associated with a Ct <30.   

In December 2021, FDA announced that studies from independent laboratories have shown that rapid antigen tests can still detect the Omicron variant but that the analytic sensitivity may be decreased by an unspecified amount. The data supporting this announcement has not yet been published. 

The clinical sensitivity of rapid antigen tests varies depending on when the test is performed in the illness course. Tests performed too early may be falsely negative because the amount of virus at the time of sampling is below the limit of detection for the assay. Thus, if people infected with the Omicron variant are developing symptoms earlier, or in the throat before the nasopharynx, then sampling from the nose at the time when symptoms begin may lead to a false negative result (Adamson, January 2022 - preprint, not peer-reviewed). Testing may be repeated within 24 to 48 hours per CDC suggestion.  

Most rapid antigen tests in current use in the United States are not validated - and are therefore not interpretable - for specimen types OTHER than the anterior nares (e.g., the throat). This includes the Abbott BinaxNOW COVID-19 Antigen Self-Test, the Quidel Quickvue SARS Antigen Test and the iHealth COVID-19 Antigen Rapid Test. 


Resources

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