SARS-CoV-2 Omicron variant BA.4 and BA.5 subvariants

SARS-CoV-2 Omicron variant BA.4 and BA.5 subvariants








Detection

Ordinary COVID-19 tests, both PCR and rapid, can detect all Omicron subvariants as COVID-19, but further tests are necessary to distinguish the subvariants from each other and from other COVID-19 variants.[54]




A notable difference between the 'standard' Omicron subvariant and BA.2 is that the latter lacks the characteristic S-gene target failure (SGTF)-causing deletion (Δ69-70) by which many qPCR tests are able to rapidly detect a case as an Omicron (or Alpha) variant, from the previously dominant Delta variant.[55][56] Thus, countries that primarily rely on SGTF for detection may overlook BA.2,[55] and British authorities consider SGTF alone as insufficient for monitoring the spread of Omicron.[57] This has resulted in it having been nicknamed 'Stealth Omicron'.[57] Because BA.2 still can be separated from other variants through normal full sequencing, or checks of certain other mutations, the nickname is however inaccurate.[48][54] Some countries, such as Denmark and Japan, use a variant qPCR that tests for several mutations, including L452R.[58][59] It can also distinguish Delta, which has L452R,[60] and all Omicron sublineages, which do not have L452R.[61][62] As Omicron became dominant and the Delta variant became rare, the SGTF mutation that had made Delta and BA.2 similar in qPCR tests could now be used for easily separating BA.1 and BA.2 from each other. As a consequence, BA.2 could now be regarded as decidedly un-stealthy.[63]




BA.2.12 subvariants

There were two new BA.2 subvariants detected in the US state of New York, which are BA.2.12 and BA.2.12.1,[64][65] both of which have a significant growth advantage of 23-27% over BA.2 and contributing to a rise in infections in central New York, centred on Syracuse and Lake Ontario, which later became dominant by May 24 in the US.[66][67][68]




BA.3 subvariant

The third Omicron sublineage, BA.3, is very rare. It has the same SGTF deletion (Δ69-70) as BA.1.[69][70]




BA.4 and BA.5 subvariants

In April 2022 the WHO announced it was tracking BA.4 and BA.5 subvariants with BA.4 having been detected in South Africa, Botswana, Denmark, Scotland and England.[71] Early indications from data collected in South Africa suggested BA.4 and BA.5 have a significant growth advantage over BA.2, which by May 12, earned the status Variant of Concern by the European Centre for Disease Prevention and Control and by May 20, by the UK Health Security Agency.[72][73][74][75] BA.5 soon after by May 25, was the dominant in Portugal, accounting for two-thirds of all new cases there.[76]




Affected countries and transmissibility

According to early research, BA.2 is roughly 30% to 60% more transmissible than BA.1.[77][78] As a consequence, it may prolong a COVID-19 wave when it overtakes BA.1,[79] although it is difficult to assess what part is caused by the higher transmissibility of BA.2 in countries that simultaneously reduce restrictions (allowing easier transmission than in earlier periods with more restrictions).[80] A new BA.1–BA.2 recombinant isolated from the UK in January 2022, dubbed the "XE" recombinant, was found by the WHO to be potentially 10% more transmissible than BA.2, making it about 43% to 76% to more transmissible than BA.1, and making the XE recombinant the most contagious variant identified.[81][82] On 7 April 2022 Brazilian authorities announced the first detected case of a person infected with Omicron XE.[83]




The first known sequence of BA.2 was in a sample from 15 November 2021.[84] In mid-December 2021, BA.2 still appeared to be rare with relatively few sequences from half a dozen countries having been uploaded to GISAID, but subsequently numbers rapidly increased. As of 17 January 2022, BA.2 had been detected in at least 40 countries and in all continents except Antarctica.[62][85] By 31 January, it had been detected in at least 57 countries.[86] In global samples collected from 4 February to 5 March and uploaded to GISAID, BA.2 accounted for c. 34%, compared to 41% for BA.1.1, 25% for BA.1 and less than 1% for BA.3.[87] In a review two weeks later, covering 16 February to 17 March, BA.2 had become the most frequent.[88] However, the data is geographically skewed due to sequencing rate and speed; for example, among the c. 205,000 COVID-19 sequences from March that had been uploaded to GISAID as of 22 March, United Kingdom and Denmark accounted for more than 3⁄4, and most of the remaining were from other European countries, Australia, Canada and the United States (altogether, c. 6,000 were from Africa, Asia and Latin America).[89] Based on GISAID uploads, BA.1 peaked in early January 2022, after which it was overtaken by both BA.1.1 and BA.2.[90] In North America, parts of Europe and parts of Asia, BA.1 was first outcompeted by BA.1.1. For example, in the United States, France and Japan, BA.1.1 became the dominant subvariant in January 2022.[91][92][93]




By late December 2021/early January 2022, BA.2 appears to have become dominant in at least parts of India (already making up almost 80 percent in Kolkata in late December 2021[94]) and the Philippines, had become frequent in Scandinavia, South Africa and Singapore, and was showing signs of growth in Germany and the United Kingdom.[95][96][97][98] In Japan, which has quarantine and detailed screening of all international travellers, as of 24 January, the vast majority of BA.2 had been detected in people that had arrived from India or the Philippines with cases going back at least to 1 December 2021 (far fewer BA.1 or other variants were detected among arrivals from the two countries in that period), but small numbers had also been detected in people arriving from other countries.[59][99][100]




In Denmark, the first BA.2 was in a sample collected on 5 December 2021 and extremely few were found in the directly following period.[101] By week fifty (13–19 December) it had started to increase, with BA.2 being at around 2 percent of sequenced cases compared to 46 percent BA.1 (remaining Delta). The frequency of both Omicron subvariants continued to increase throughout the last half of December; in week fifty-two (27 December–2 January), BA.2 had reached 20 percent and BA.1 peaked at 72 percent. In January 2022, BA.1 began decreasing, whereas BA.2 continued its increase. By the second week (10–16 January) of 2022, the frequency of the two was almost equal, both being near 50 percent (around one percent was the rapidly disappearing Delta).[101] In the following week, BA.2 became clearly dominant in Denmark with 65 percent of new cases being the BA.2 subvariant.[102] Trends from the other Scandinavian countries, India, South Africa and the United Kingdom also showed that BA.2 was increasing in proportion to the original BA.1.[103][104] In early February 2022, it had become the dominant subvariant in South Africa, in late February it had become dominant in Germany and in early March it had become dominant in the United Kingdom.[105][106][107] In early March, BA.1.1 was still heavily dominant in the United States (having overtaken BA.1 in January), but BA.2 was increasing in frequency, later becoming dominant in the US by March 29.[91][108]




Severity and immunity

The risk of hospitalization is the same in BA.1 and BA.2 based on reviews from Denmark, India, South Africa and the United Kingdom.[57][87][102][109] Norwegian studies show that the amount of virus in the upper airways is similar in those infected with BA.1 and BA.2.[104] In general, Omicron (all subvariants) have a higher reinfection rate than other COVID-19 variants. Studies from Denmark and Qatar found that after an infection with BA.1, the vast majority of people were well-protected against a BA.2 infection, although it is unknown how long this protection lasts.[87][110][111] Laboratory studies also show that antibodies for BA.1 generally protect against BA.2.[111] In Denmark, preliminary data found breakthrough rates in people that had been vaccinated that were similar to the breakthrough rates seen for BA.1.[102] An initial study by the UK Health Security Agency found that vaccines afford similar levels of protection against symptomatic disease by BA.1 and BA.2, and in both it is considerably higher after two doses and a booster than two doses without booster.[112][113] Because of the gradually waning effect of vaccines, further booster vaccination may later be nec










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