Q and A

Question

What are the main COVID-19 variants? How can they affect vaccine responses?

Answer

NOTE: This page is updated as new variants are reported. Last update 18 December 2023.

Simon Collins, HIV i-Base

Although all viruses change and evolve the new coronavirus variants are especially important because we now have effective vaccines.

By November 2021, several well-publicised variants had been described with brief characteristics listed in Table 1. These have continued to evolve since, often quickly becoming the dominant strain.

Variants are generally first reported in countries where changes in the virus are being studied. Once identified they are usually quickly found in many other regions. Some variants (including D614G and N501Y) are associated with increased replication and are transmitted more easily. Others (including E484K, L452R and K417N/T) are associated with immune invasion with increased risk of reinfection or reducing vaccine efficacy.

The clinical impact of new variants also takes time to understand – at least weeks, but often longer. This includes the implications of whether they evade current vaccines.

However, all manufacturers are already testing updated versions of their vaccines against these new variants.

Variants are also categorised as variants of interest (VOI) when first identified. The become variants of concern (VOC) if they have characteristics that are associated with faster transmission or more serious clinical outcomes.

Table 1: Key variants and predicted impact on current vaccines

Date reported Original region Name Mutation Impact Comment
April 2020 Western Europe (Italy, Germany) – but quickly global. B.1 or D614G.1 (“Doug”) D614G in the
S-protein
Quickly became main global strain. Increased the replication efficiency and transmissibility. NAbs still recognised
June 2020 Denmark By November reported in more than 200 mink farms and in humans. >1.4 million animals culled. 7 unique variants in S protein. Mink-related outbreaks also reported in the Netherlands, Spain, Sweden, Italy and the US. These are small and largely contained reports. No information on impact on vaccines.
August 2020. UK (Kent) WHO: Alpha.

B.1.1.7
(also 20I/501Y.V1 and VUI 202012/01 – variant under investigation)

23 mutations including N501Y and others in S-protein. Expanded in UK Nov to Jan. >600 cases reported in 33 US states. Increased transmission.
NAbs still recognised by Oxford, Pfizer and Moderna vaccines. Reduces sensitivity to neutralising Abs.
October 2020. South Africa WHO: Beta.

B.1.351

(also 20H/501Y.V2)

17 unique mutations in both S and N terminal including K417N, E484K and N501Y). Already reported in 50 countries including the US. E484K might cause some reduction in NAb but impact is not fully known. Reduced efficacy has been reported to Pfizer, Moderna, Oxford and Novavax vaccines.
Reduces sensitivity to neutralising Abs.
November 2020. New York B.1.526. Includes E484K. Increased from 3% in Jan to ~40% of cases in NYC by April 2021. So far: “does not lead to more severe disease” (MMWR report).
January 2021. Brazil (but detected in travelers to Japan). WHO: Gamma.

P.1

(also as 20J/501Y.V3)
B.1.1.248
(variants of B.1.1.28).

P.2 is WHO: Zeta

P.3 (Philippines) is WHO: Theta

More sequence changes in both S and N terminal including K417N, E484K and N501Y). Already reported in many countries including Japan, Brazil, Germany and the US. Not yet known.
January 2021 (designated VOC in March). California or Colorado. CAL.20C
B.1.427/
B.1.429
ORF1a: I4205V, ORF1b:D1183Y, S: S13I, W152C, L452R. Increasing in California, 20% in Colorado by March, but so far limited to the US. Modest” increase in risk of transmission. Also MMWR report.
March 2021 Tanzania NK Multiple new mutations reported. Tanzania, few details. Impact not yet known.
April 2021 India WHO: Delta.

VOC-21APR-02

B.1.617.2 and two others B.1.617.1 and B.1.617.3.

B.1.617 = WHO Kappa

13 mutations, 7 in S-protein, including L452R and E484Q. Detected in London, the US and 18 other countries (not currently in Africa). “At least as transmittable as UK B.1.1.1.7”. Limited clinical data or impact on vaccines.

More transmittable and possible reduced vaccine protection.

June 2021 Peru WHO lambda

variant or interest (not concern) – also called C.37.

Similar deletions in ORF1a gene to Beta and Gamma; spike mutations include: G75V, T76I, L452Q, F490S, T859N. Identified in Peru in Dec 2020, now in 29 countries including UK. Limited data suggest similar properties to Delta. Includes more infectious and resistant.
October 2021 UK “Delta plus”

aka AY.4.2

Variation of Delta with Y145H and A222V. UK Still only variant of interest (not of concern).
November 2021.

Sub-variants reported since January 2022.

Botswana, South Africa. WHO: Omicron (VOC)

B.1.1.529.

Three lineages: BA.1 (original), BA.2 and BA.3.

Also recombinant XE variant and subvariants BA.2.12 and BA.2.12.1.

See also BA.5 and BA.5 below.

32 mutations in spike protein site. More than 20 countries identified within two weeks. Omicron now dominant in most countries. Clinical implications unclear, but much more transmittable than Delta. More transmissible but maybe lower risk of severe outcomes.

BA.2 is more transmissible. Nature paper comparing BA.1 and BA.2.

March 2022. South Africa. WHO omicron variants BA.4 and BA.5. BA.4 and BA.5 mutations include L452R and F486V (in addition to many more seen with BA.2. BA.4 and BA.5 started mainly in S. Africa. By early June they were 20% of US cases. Report on BA.4 and BA.5. Neither are increasing infections of more serious COVID-19.

Vaccine responses against BA.4/5 are significantly lower.

May 2022 India WHO omicron subvariant.

BA 2.75.

(Centaurus).

BA.2 + other spike mutations (W152R, F157L, I210V, G257S, D339H, G446S, N460K, Q493 reversion). Also additional mutations outside spike (ORF1a:S1221L, ORF1a:P1640S, ORF1a:N4060S; ORF1b:G662S; E:T11A). India, UK, US, Australia, Germany and Canada by mid July 2022. Defined by ECDC as “variant under monitoring” (July 2022).

Clinical implications currently unclear.

October 2022 WHO omicron sub-variants.

XBB* and BQ.1*

XBB* is a recombinant of BA.2.10.1 and BA.2.75 sublineages.

BQ.1* is a sublineage of BA.5, which carries spike mutations in some key antigenic sites, including K444T and N460K.

Widespread including EU and US.   BQ.1 may be fitter than other Omicron variant but need further monitoring data. See: WHO statement that  these are still sub-variants.
July 2023 Asia EG.5.1 (Eris) Descendant of omicron. Widespread inc Asia, the US and the UK, Symption include similar to common cold.
August 2023 Multiple countries BA.2.86

(Pirola)

highly mutated inc. >30 amino acid changes vs XBB.1.5 First cases were in Denmark (3); South Africa (2); Israel (1); US (2) and (1).

By Sept 28/34 UK cases were from one care home. Also reported in 9 US states.

Too few cases to know significance (Aug 23)

New cases are being tracked and recently doubled.

More fit than XBB and highly able to evade immune responses.

Nov 2023 US JN.1 Subvariant of Omicron  BA.2.86 Likely low impact with full vaccination, but population vaccine uptake is now low.. Further information is needed.

References and further reading

WHO: Tracking variants of interest and concern – with new names.
https://www.who.int/en/activities/tracking-SARS-CoV-2-variants

PANGO. Comprehensive updated list of lineages.
cov-lineages.org/lineage_list.html

UK website tracking variants in the UK.
https://www.gov.uk/government/publications/covid-19-variants-genomically-confirmed-case-numbers

Karim A et al. New SARS-CoV-2 Variants — Clinical, Public Health, and Vaccine Implications. N Engl J Med 2021; 384:1866-1868. DOI: 10.1056/NEJMc2100362. (13 May 2021).
https://www.nejm.org/doi/full/10.1056/NEJMc2100362

Wang Z et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. bioRxiv preprint. DOI:10.1101/2021.01.15.426911. (30 January 2021).
https://www.biorxiv.org/content/10.1101/2021.01.15.426911v2

A guide to emerging SARS-CoV-2 variants. The Scientist. (26 January 2021).
https://www.the-scientist.com/news-opinion/a-guide-to-emerging-sars-cov-2-variants-68387

NYT variant tracker
https://www.nytimes.com/interactive/2021/health/coronavirus-variant-tracker.html

Multitude of coronavirus variants found in the US — but the threat is unclear. Nature. (5 March 2021).
https://www.nature.com/articles/d41586-021-00564-4

WHO website on variants
https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en/

The following websites include sophisticated databases including details genome sequencing. They also epidemiological maps of variant distribution and spread by country and more detail on naming and categorising variants.
https://covariants.org/variants
https://nextstrain.org/sars-cov-2
https://www.gisaid.org

This article was first posted on 10 February 2021. It has been updated several times as new information becomes available (last on 19 September 2023).

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