SARS-CoV-2 Variants

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SARS-CoV-2 Variants

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This page undergoes regular review and was last comprehensively reviewed on February 24, 2023. Some sections may reflect more recent updates. 



Viruses including SARS-CoV-2 mutate over time, and as a result, new variants tend to emerge. Most mutations do not produce clinically relevant changes for individual infections, but occasionally mutations occur that may make the virus more infectious, cause more severe disease, evade the protection afforded by vaccines or therapeutics, or affect the sensitivity or specificity of diagnostic tools. 

Scientists have identified numerous SARS-CoV-2 variants. Some of these variants are more highly transmissible, cause more severe disease, or evade protection from therapeutics and/or vaccines; these have been designated “variants of concern” by the World Health Organization. Other variants could be more highly transmissible, cause more severe disease, or evade protection from therapeutics and/or vaccines, based on information about viral genomes or small-scale epidemiological studies, but these features may not be confirmed yet on a larger scale; WHO designates these “variants of interest.” Some variants are not associated with increased transmissibility or disease severity compared to the ancestral strain. 

Variant Terminology 

Here we define key terms to discuss SARS-CoV-2 variants: 

Variant: A specific viral genome that contains one or more changes from the ancestral strain. SARS-CoV-2 variants are numerous.  

Subvariant: A subgroup of variants categorized based on genomic changes that they have in common and the time frame in which those changes appeared in tandem. This term is sometimes used interchangeably with “sublineage.”  

Lineage: A group of closely related viruses with a common ancestor. 

Sublineage: A subgroup of lineages. For example, Omicron BA.2 is an Omicron sublineage. This term is sometimes used interchangeably with “subvariant.” 

Ancestral strain: The original form of SARS-CoV-2 identified in December 2019; often referred to elsewhere as the “original” or “Wuhan” strain.  

Recombinant virus: Viruses that occur when multiple variants infect the same individual at the same time and exchange genetic material with each other, changing their formulations. Recombination events occur more frequently when community transmission levels are high. Naming conventions for recombinant variants include an “X,” referring to the intersection of genetic material from two previously distinct lineages. 

U.S. Situation Report 

Some Omicron subvariants are more prevalent than others. Currently, the Omicron recombinant subvariant XBB is more prevalent in the U.S. compared to other Omicron subvariants; in late 2022, BQ.1 and BQ.1.1 were more highly prevalent. BQ.1 and BQ.1.1 are subvariants of BA.5, whereas XBB is a recombinant subvariant combining genetic information from Omicron BA.2.10.1 and BA.2.75 subvariants. 

XBB.1.5, a descendant of the subvariant XBB, is also recombinant and is sometimes called the Kraken variant. Limited existing evidence suggests that XBB.1.5 may be more transmissible than the XBB parent strain, due to both observed epidemiological characteristics and a higher ACE-2 binding affinity than other strains (U.K. Health Security Agency, January 2023 [PDF]Yue, February 2023). However, early and limited evidence from the U.S. indicates that vaccination with bivalent boosters is still effective against illness caused by XBB/XBB.1.5 at least for 3 months after vaccination (Link-Gelles, February 2023) and that XBB.1.5 does not cause severe disease more frequently than BQ.1 (Luoma, February 2023). 

CDC’s COVID Data Tracker illustrates the proportions of each of the lineages currently circulating in the U.S. 

Source: Screenshot of CDC Nowcast data accessed May 5, 2023. Data updates via CDC weekly on Fridays. 

The numerous mutations associated with Omicron variants can impact the performance of certain molecular tests targeting the spike protein gene, as well as viral transmissibility, and neutralization by monoclonal antibodies (see table) or antibodies elicited by COVID-19 vaccination or SARS-CoV-2 natural infection.


WHO designated the Omicron variant (B.1.1.529) a “variant of concern” in November 2021 based on the number and location of mutations present in the spike protein, many of which had 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.  

Omicron lineages share 39 mutations from the ancestral strain of SARS-CoV-2, and BA.1 and BA.2 also differ by 28 mutations (Colson, March 2022; Yu, April 2022) — approximately twice as many amino acid differences as those that exist between the ancestral strain of SARS-CoV-2 and the first four WHO-designated variants of concern (Alpha, Beta, Gamma and Delta). It is likely that Omicron variants will continue to emerge and develop as the pandemic continues. Currently, there are several subvariants designated “Omicron,” including B.1.1.529, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5 and BF.7 as well as BQ.1 and XBB. The subvariant B.1.1.529 includes BA.1 and BA.3; BA.1.1 and BA.2 are categorized separately. BQ.1 is a subvariant of BA.5 and has several constituent subvariants itself. XBB is a recombinant subvariant of BA.2.10.1 and BA.2.75. 

As new subvariants of Omicron continue to emerge, the possibility increases that immunological protection from a previous Omicron infection may not protect against a new variant. Preliminary evidence from in vitro studies suggests that immunological protection from BA.1 infection may not protect against BA.4 or BA.5 infection (Khan, May 2022 – preprint, not peer-reviewed; Cao, June 2022). 


Variants and subvariants may account for an increased proportion of new cases for several reasons. Two primary reasons are: 

  • The variant or subvariant is able to replicate more quickly in respiratory tracts, reducing the time interval and increasing the capacity for onward transmission as well as potentially increasing viral load; and/or 
  • The variant or subvariant grows at a pace that is similar to other variants or subvariants but has genetic changes that allow it to evade immune system detection more easily. 

There are several recombinant forms of SARS-CoV-2 that involve Omicron genetic material, including XD (Delta-Omicron), XE (BA.1-BA.2) and XBB (BA.2.10.1 and BA.2.75). Current evidence suggests that XD is not associated with higher transmissibility or more severe outcomes than its parent strains. However, early evidence suggests that XBB may have a higher reinfection risk compared to other circulating Omicron subvariants (WHO's Technical Advisory Group on SARS-CoV-2 Virus Evolution, October 2022).  

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) have illustrated the epidemic importance of this variant. Certain Omicron subvariants, including BA.2.75 and BA.Q*, seem to have an increased growth advantage over the original Omicron strain (WHO's Technical Advisory Group on SARS-CoV-2 Virus Evolution, October 2022). Early evidence suggests that the heightened transmissibility of the Omicron variant is not attributable to higher viral loads compared to previous variants (Puhach, April 2022; Hay, January 2022 – preprint, not peer-reviewed) but instead greater immune evasion. However, this information is still being collected, especially for newer Omicron subvariants. 


Limited evidence suggests that the comparative increase in cases of BA.5 (including subvariant BQ.1) is due to an increased ability to evade immune system detection compared with other variants and subvariants (European Center for Disease Prevention and Control, May 2022). The subvariants BQ.1 and BQ.1.1 contain additional mutations in the spike protein that appear to increase viral ability to evade immune detection beyond the original BA.5 strains (Miller, November 2022 – preprint, not peer-reviewed); this may also result in subsequent reinfection with the recombinant XBB subvariant after breakthrough BA.5 infection (Cao, October 2022 – preprint, not peer-reviewed). Epidemiological information about new Omicron subvariants is limited and continues to emerge; evidence about the severity, diagnostic performance, vaccine effectiveness and reinfection risk specifically regarding BQ.1 and BQ.1.1 is limited and is still being investigated. 

Multiple other 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, February 2022; 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. Importantly, booster doses of vaccine appear to restore in vitro neutralization titers in the short term (Nemet, December 2021; Garcia-Beltran, December 2021; Pajon, January 2022; Lyke, January 2022 – preprint, not peer-reviewed) as well as clinical effectiveness (Andrews, April 2022; Thompson, January 2022; Johnson, January 2022; Accorsi, January 2022; Gray, December 2021 – preprint, not peer-reviewed; Ferdinands, February 2022; Danza, February 2022). In an observational analysis using COVID-19 surveillance data from 25 jurisdictions, comparing case and mortality rates among unvaccinated individuals versus individuals vaccinated pre-Delta, Delta emergence, Delta predominance and Omicron emergence, the relative reduction in COVID-19 incidence was lowest during the period of Omicron emergence, consistent with significant immune escape (Johnson, January 2022).

For additional information, please refer to our Immunity FAQ.

Disease Severity

Studies from multiple countries — including the U.S. (Iuliano, January 2022; Lewnard, May 2022 – preprint, not peer-reviewed; Christensen, April 2022; Wang, January 2022 – preprint, not peer-reviewed; Wang, January 2022 – preprint, not peer-reviewed; Modes, February 2022; Lauring, March 2022), U.K. (Sheikh, April 2022) and South Africa (Abdullah, December 2021; Maslo, December 2021; Wolter, January 2022; Davies, April 2022) — 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). In an observational analysis, CDC investigators characterized indicators of COVID-19 disease severity from three surveillance systems and a large health care database and found that overall COVID-19 cases, ED visits and hospital admissions were higher during the Omicron period, but hospital length of stay was shorter, a lower proportion of hospitalized individuals required ICU admission or mechanical ventilation, and fewer died during the Omicron period (Iuliano, January 2022). However, rates of ED visits and hospitalizations were higher for those less than 18 years old, presumably related to lower vaccination coverage in this group. It is important to note that many investigations of Omicron disease severity are occurring among populations with substantial vaccination coverage, which could affect interpretation of overall disease severity.  

Impact on Testing & Diagnostics 

The lineages BA.1 and BA.1.1, as well as BA.4 and BA.5 (including BQ.1 subvariants), experience S-gene target failure. While these viruses are identifiable by PCR, some PCR tests specifically look for an S-gene component that fails to be recognized for BA.1 and BA.1.1. This led to these lineages being colloquially termed “stealth” variants; however, S-gene target failure is now used as a tool to identify the presence of these subvariants specifically. 

Omicron cases of all lineages can be detected using a molecular method such as RT-PCR in two ways. The first is to assess for spike gene target failure in PCR assays that assess for presence of the spike gene. The BA.2 lineage lacks the mutation that results in spike gene target failure and therefore would not be detected using this method. The second way to identify these cases is to use a PCR designed to look for the major mutations specific to the Omicron variant. This method would be able to detect all lineages. In December 2022, FDA recognized a specific molecular test (DxTerity SARS-CoV-2 RT PCR CE Test) that may have reduced diagnostic capability to identify Omicron SARS-CoV-2. However, no other molecular tests were identified to have reduced diagnostic capability for identifying Omicron. 

With respect to rapid antigen tests, 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 was 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 nine other rapid antigen tests available in Australia and found no attenuation in sensitivity. A second study used 32 Omicron and 30 Delta samples collected as part of a university screening program and showed no difference in analytic sensitivity for the BinaxNOW test by variant. The authors also found that the limit of detection 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 and showed that the BinaxNOW test had a sensitivity of 95% for detecting virus below a cycle threshold value of 30 (Schrom, March 2022). The study did not provide an estimate of the viral copy number associated with a cycle threshold value <30. However, an additional independent laboratory-based study found reduced ability to detect cases caused by Omicron compared to Delta using nine rapid antigen tests available in Germany (Osterman, February 2022). 

An analysis of several other rapid antigen tests in the Netherlands found low test sensitivities compared to PCR results in the Omicron era (Venekamp, November 2022). These findings included an estimated test sensitivity of 25.6% (95% CI: 19.1%-33.1%) for CLINITEST, a rapid antigen assay produced by Siemens-Healthineers that is also in use in the United States. However, another U.S.-based analysis of rapid antigen testing found little difference in test sensitivity/specificity across three different variants (Omicron, Delta and a wild-type strain representative of the ancestral SARS-CoV-2 strain) (Drain, August 2022). That analysis investigated the BinaxNOW test as well as the SCoV-2 Ag Detect Rapid Self-Test.  

Finally, in December 2022, the FDA provided an assessment of COVID-19 test diagnostic capabilities against Omicron. In that report, the only rapid antigen test identified to have reduced diagnostic capability to detect Omicron was the Luminostics, Inc. Clip COVID Rapid Antigen Test. 

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's suggestion. Conversely, individuals testing positive for SARS-CoV-2 on PCR may be more likely to simultaneously have a negative rapid antigen test if the PCR cycle threshold value is high (a proxy measure for low viral load) (Landaverde, October 2022; Cocherie, October 2022; Drain, August 2022). Conversely, performing a throat swab, which is off-label use, later in the course of illness may also be falsely negative. 

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, such as throat specimens. This includes the Abbott BinaxNOW COVID-19 Antigen Self-Test, the Quidel QuickVue SARS Antigen Test, the ACON FlowFlex COVID-19 Antigen Home Test and the iHealth COVID-19 Antigen Rapid Test. 




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