Variants galore

Mutations, variants, and new waves of infection

Many variants of the SARS-CoV-2 have emerged throughout the pandemic.
Most disappeared quickly because they were unable to compete with other circulating variants. However, some have managed to displace previously circulating variants, because they are either more inherently transmissible, better at evading vaccine immunity, or capable of causing reinfections. This is why each new variant of concern has caused a new wave of infections at the regional or global level.

A viral glossary

with some helpful definitions

A random change in the genetic material (in this case, in the virus’s RNA) that may or may not result in a change in the protein it codes for, thereby potentially improving – or impairing- the protein’s function.

A viral variant is a virus isolated from a sample that has a number of differences in its genetic sequence compared to the virus of reference. The term variant does not necessarily imply changes in the behaviour of the virus.

This term is used only when a variant’s increase in transmissibility, pathogenicity or ability to evade immunity is suspected or confirmed.

Viral recombination occurs when two different variants of the same virus infect the same cell and exchange entire fragments of their genetic material. The likelihood of this happening increases when different variants circulate at the same time and in the same place.

A strain is a variant with unique and stable characteristics (i.e. distinct behaviour from the original virus). There is currently only one strain of SARS-CoV-2.

Five variants of concern have been identified since the start of the pandemic

First identified in Britain in late 2020 and spread worldwide. It has several mutations in its Spike protein which made it more infectious than the D614G variant which became dominant very early in the pandemic.

First identified in South Africa in late 2020, it did not spread worldwide. It displayed a higher immune escape from vaccine-induced antibodies than other circulating variants thanks to several mutations in Spike.

First identified in Brazil in late 2020, it became dominant in several South American countries. It shares several mutations with Beta.

First identified in India in early 2021, it rapidly became dominant worldwide, displacing the three variants mentioned above.

First identified in South Africa in November 2021, it quickly became dominant worldwide, displacing Delta. This variant represents a large jump in viral evolution – it has over 50 mutations, around 30 of them in the Spike protein, which have made it more transmissible and better at evading vaccine immunity and causing reinfections. All circulating variants reported today are subvariants of Omicron:

      • BA.1- this was the initial subvariant described, which became dominant worldwide between December and March 2022
      • BA.2 – this subvariant is considerably distinct from BA.1: it has 8 unique mutations not found in BA.1 and lacks 13 mutations BA.1 does have. It became dominant worldwide by April 2022
      • BA.2.12 – this subvariant, derived from BA.2, spread rapidly in the United States and became dominant by late May 2022.
      • BA.4 and BA.5 – these subvariants, also derived from BA.2, were linked to a surge of cases in South Africa on May 2o22. BA.5 has outcompeted BA.2 in many countries and became the dominant variant worldwide. Its increased growth advantage over the other Omicron subvariants is mainly due to a greater capacity to evade neutralising antibodies generated through vaccination or infections with previous variants, including Omicron BA.1 and BA.2.
      • XBB is a recombinant of BA.2.10.1 and BA.2.75 sublineages. Its prevalence has increased in some countries such as Singapore and there is some evidence it may pose an increased risk of reinfection, particularly in those infected with a pre-Omicron variant. To date, there is no evidence of increased disease severity.
      • BQ.1 is a sublineage of BA.5, with additional spike mutations, including K444T and N460K (and R346T in BQ1.1). It shows a growth advantage over other circulating Omicron subvariants, particularly in the US and Europe. Currently, there is no data to suggest an increase in disease severity. No major impact on vaccine protection against severe disease is expected.

Figure 1. SARS-CoV-2 VOC depicted in a tree scaled radially
by genetic distance nextstrain.org

Date:

Current situation

All circulating variants currently reported belong to the Omicron family. But the virus has continued evolving and accumulating mutations, particularly in the receptor binding domain of the Spike protein. The result is the simultaneous rise of multiple descendants of Omicron , sharing common mutations that allow the virus to better escape recognition by neutralizing antibodies (a process called convergent evolution).  These are the latest updates (in reverse chronological order):

May 2024: The FLiRT subvariants — including KP.2, KP.3 and KP.1. — are starting to overtake the dominant winter strain JN.1, and causing a rise in cases in several countries. They are all descendants of JN.1 and their name (FLiRT) refers to two additional mutations in the Spike protein which allow the virus to better evade neutralising antibodies. This gives them a growth advantage over JN.1, but there is no evidence that they cause more severe disease. The XBB1.5-updated vaccines are expected to provide some protection, particularly against severe disease and in people with hybrid immunity (infection plus vaccination). The WHO has recommended updating the vaccines to JN.1 for the next 2024/2025 season, which should provide strong protection against FLiRT variants.

Previous updates:

November 2023: The WHO reclassified the BA.2.86 variant (also known as Pirola) and its offshoots (including JN.1) as a variant of interest since it is becoming increasingly prevalent worldwide. Despite the many mutations in Spike, its capacity to evade immunity does not seem to be as dramatic as when Omicron emerged.  There is so far no indication that the disease is more severe.

August 2023: A new subvariant called BA.286 has been identified in a handful of unrelated cases in a few countries (7 cases in 4 countries as of August 23). This variant is notable due to a high number of mutations (33 mutations in Spike, relative to its putative ancestor BA.2). It is difficult to predict the impact of such a large number of mutations, but significant antibody escape can be expected. Its identification in individuals without travel history suggests there is established international transmission, but it is not yet clear whether this variant will be able to outcompete currently circulating XBB variants.

July 2023: The EG.5 subvariant, a descendant of the XBB lineage, now accounts for over 17% of cases in the US and has been rising in other countries also. The WHO has  classified it as a variant of interest but says that it does not seem to pose more of a threat than other variants. No change in disease severity has been observed.

March 2023: Another subvariant currently under observation is XBB1.16. It has been identified in many countries, where it is replacing the other subvariants in circulation. It has one additional mutation in the spike protein compared to XBB1.5, which in lab studies shows increased infectivity and “potential increased pathogenicity”.  It seems to be more immune evasive than XBB1.5 but there is no evidence for the moment that it causes more severe infections.

January 2023:   XBB1.5, derived from XBB1, is a recombinant between two Omicron BA.2 subvariants. It has mutations in Spike that allow it to better escape antibody recognition (as XBB1 and many other Omicron subvariants), but has one additional mutation (S486P) that helps it bind better to the human ACE2 receptor. This gives it a growth advantage over other currently circulating Omicron subvariants. There is no evidence for the moment that XBB1.5 causes more severe infections, and current vaccines remain effective.

 

References to other useful sources

From official assessments to news features

Additional information
Further readings: