Variants of SARS-CoV-2

Variants of severe acute respiratory syndrome coronavirus 2 are viruses that, while similar to the original, have genetic changes that are of enough significance to lead virologists to label them separately. SARS-CoV-2 is the virus that causes coronavirus disease 2019. Some have been stated to be of particular importance, due to their potential for increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. These variants contribute to the continued circulation of SARS-CoV-2.
, the variants of interest as specified by the World Health Organization are JN.1, and the variants under monitoring are KP.3, KP.3.1.1, JN.1.18, LP.8.1, NB.1.8.1, XEC and XFG.

Overview

The origin of SARS-CoV-2 has not been identified. However, the emergence of SARS-CoV-2 may have resulted from recombination events between a bat SARS-like coronavirus and a pangolin coronavirus through cross-species transmission. The earliest available SARS-CoV-2 viral genomes were collected from patients in December 2019, and Chinese researchers compared these early genomes with bat and pangolin coronavirus strains to estimate the ancestral human coronavirus type; the identified ancestral genome type was labeled "S", and its dominant derived type was labeled "L" to reflect the mutant amino acid changes. Independently, Western researchers carried out similar analyses but labeled the ancestral type "A" and the derived type "B". The B-type mutated into further types including B.1, which is the ancestor of the major global variants of concern, labeled in 2021 by the WHO as alpha, beta, gamma, delta and omicron variants.
Early in the pandemic, the relatively low number of infections resulted in fewer opportunities for mutation of the viral genome and, therefore, fewer opportunities for the occurrence of differentiated variants. Since the occurrence of variants was rarer, the observation of S-protein mutations in the receptor-binding domain region interacting with ACE2 was also not frequent.
As time went on, the evolution of SARS-CoV-2's genome led to mutant specimens of the virus, observed to be more transmissible, to be naturally selected. Notably, both the Alpha and the Delta variants were observed to be more transmissible than previously identified viral strains.
Some SARS-CoV-2 variants are considered to be of concern as they maintain their replication fitness in the face of rising population immunity, either by infection recovery or via vaccination. Some of the variants of concern show mutations in the RBD of the S-protein.

Definitions

The term variant of concern for SARS-CoV-2, which causes COVID-19, is a category used for variants of the virus where mutations in their spike protein receptor binding domain substantially increase binding affinity in RBD-hACE2 complex, while also being linked to rapid spread in human populations.
Before being allocated to this category, an emerging variant may have been labeled a variant of interest, or in some countries a variant under investigation. During or after fuller assessment as a variant of concern the variant is typically assigned to a lineage in the Pango nomenclature system and to clades in the Nextstrain and GISAID systems.
Historically, the WHO regularly listed updates on variants of concern, which are variants with an increased rate of transmission, virulence, or resistance against mitigations, like vaccines. The variant submissions from member states are then submitted to GISAID, followed by field investigations of the variant. Updated definitions, published on 4 October 2023, add variants of interest and variants under monitoring to the World Health Organization's working definitions for SARS-CoV-2 variants. The updated definition of VUMs includes having a suspected epidemiological growth advantage or community transmission in at least two countries over a 2–4 week period; while the definition of VOIs requires known genetic changes related to greater epidemiological risk and a known growth advantage in at least two WHO regions and increasing prevalence, or other epidemiological evidence "suggest an emerging risk to global public health". A VOC, under the October 2023 definition, must satisfy the definition of VOIs and satisfy other criteria defining a risk to global health. Greek letter names for the variants are restricted to VOCs since March 2023.
Other organisations such as the CDC in the United States typically define their variants of concern slightly differently; for example, the CDC de-escalated the Delta variant on 14 April 2022, while the WHO did so on 7 June 2022.
, The WHO defines a VOI as a variant "with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, virulence, antibody evasion, susceptibility to therapeutics and detectability" and that is circulating more than other variants in over one WHO region to such an extent that a global public health risk can be suggested. Furthermore, the update stated that "VOIs will be referred to using established scientific nomenclature systems such as those used by Nextstrain and Pango".

Notability criteria

Viruses generally acquire mutations over time, giving rise to new variants. When a new variant appears to be growing in a population, it can be labelled as an "emerging variant". In the case of SARS-CoV-2, new lineages often differ from one another by just a few nucleotides.
Some of the potential consequences of emerging variants are the following:

Increased transmissibility
Increased morbidity
Increased mortality
Ability to evade detection by diagnostic tests
Decreased susceptibility to antiviral drugs
Decreased susceptibility to neutralising antibodies, either therapeutic or in laboratory experiments
Ability to evade natural immunity
Ability to infect vaccinated individuals
Increased risk of particular conditions such as multisystem inflammatory syndrome or long COVID.
Increased affinity for particular demographic or clinical groups, such as children or immunocompromised individuals.

Variants that appear to meet one or more of these criteria may be labelled "variants under investigation" or "variants of interest" pending verification and validation of these properties. The primary characteristic of a variant of interest is that it shows evidence that demonstrates it is the cause of an increased proportion of cases or unique outbreak clusters; however, it must also have limited prevalence or expansion at national levels, or the classification would be elevated to a "variant of concern". If there is clear evidence that the effectiveness of prevention or intervention measures for a particular variant is substantially reduced, that variant is termed a "variant of high consequence".

Nomenclature

PANGO lineages	Notes to PANGO lineages	Nextstrain clades, 2021	GISAID clades	Notable variants
		19B	S	Contains "reference sequence" WIV04/2019
,,,			L
,,,
			V
		20A	G	Lineage B.1 in the PANGO Lineages nomenclature system; includes Delta/B.1.617
	,,,,	20A	GH
		20C	GH	Includes Epsilon/B.1.427/B.1.429/CAL.20C and Eta/B.1.525
		20G	GH	Predominant in US generally, Feb '21
		20H	GH	Includes Beta/B.1.351 aka 20H/501Y.V2 or 501.V2 lineage
		20B	GR	Includes B.1.1.207 and Lambda
		20D	GR
		20J	GR	Includes Gamma/P.1 and Zeta/P.2
		20F	GR
		20I	GR	Includes Alpha/B.1.1.7 aka VOC-202012/01, VOC-20DEC-01 or 20I/501Y.V1
	B.1.177	20E	GV	Derived from 20A

SARS-CoV-2 variants are grouped according to their lineage and component mutations. Many organisations, including governments and news outlets, referred colloquially to concerning variants by the country in which they were first identified. After months of discussions, the World Health Organization announced Greek-letter names for important strains on 31 May 2021, so they could be easily referred to in a simple, easy to say, and non-stigmatising fashion. This decision may have partially been taken because of criticism from governments on using country names to refer to variants of the virus; the WHO mentioned the potential for mentioning country names to cause stigma. After using all the letters from Alpha to Mu, in November 2021 the WHO skipped the next two letters of the Greek alphabet, Nu and Xi, and used Omicron, prompting speculation that Xi was skipped to avoid offending Chinese leader Xi Jinping. The WHO gave as their explanation that Nu is too easily confounded with "new" and to avoid "causing offense" as "Xi is a common last name". In the event that the WHO uses the entirety of the Greek alphabet, the agency considered naming future variants after constellations.

Lineages and clades

While there are many thousands of variants of SARS-CoV-2, subtypes of the virus can be put into larger groupings such as lineages or clades. Three main, generally used nomenclatures have been proposed:

, GISAID—referring to SARS-CoV-2 as hCoV-19—had identified eight global clades.
In 2017, Hadfield et al. announced Nextstrain, intended "for real-time tracking of pathogen evolution". Nextstrain has later been used for tracking SARS-CoV-2, identifying 13 major clades .
In 2020, Rambaut et al. of the Phylogenetic Assignment of Named Global Outbreak Lineages software team proposed in an article "a dynamic nomenclature for SARS-CoV-2 lineages that focuses on actively circulating virus lineages and those that spread to new locations";, 1340 lineages had been designated.

National public health institutes may also create their own nomenclature system for the purposes of tracking specific variants. For example, Public Health England designated each tracked variant by year, month and number in the format /, prefixing 'VUI' or 'VOC' for variant under investigation or variant of concern respectively. This system has been modified and now uses the format -, where the month is written out using a three-letter code.