SARS-CoV-2 Omicron variant

SARS-CoV-2 Variant

Omicron
Scientifically accurate atomic model of the external structure of SARS-CoV-2. Each "ball" is an atom.
General details
WHO Designation	Omicron
Lineage	B1.1.529
First detected	South Africa
Date reported	24 November 2021 (2021-11-24)
Status	Variant of concern
Symptoms
Asymptomatic infection Body ache Cough Fainting Fatigue Fever Headache Loss of smell or taste — less common Nasal congestion or running nose Night sweats — unique Omicron symptom Upper respiratory tract infection Skin rash Sneezing Sore throat
Cases map
Cumulative confirmed Omicron variant cases by country and territory   100,000–999,999   10,000–99,999   1,000–9,999   100–999   10–99   1–9   0
Major variants
Alpha (B.1.1.7) Beta (B.1.351) Gamma (P.1) Delta (B.1.617.2) Omicron (B.1.1.529) BA.1 (B.1.1.529.1) BA.2 (B.1.1.529.2) BA.3 (B.1.1.529.3) BA.4 (B.1.1.529.4) BA.5 (B.1.1.529.5)

The Omicron variant (B.1.1.529) is a variant of SARS-CoV-2 (the virus that causes COVID-19) that was first reported to the World Health Organization (WHO) from South Africa on 24 November 2021.

Omicron multiplies around 70 times faster than the Delta variant in the bronchi (lung airways) but evidence suggests it is less severe than the previous strains, especially compared to the Delta variant. Omicron might be less able to penetrate deep lung tissue. Omicron infections are 91 percent less fatal than the delta variant, with 51 percent less risk of hospitalization. However, an estimated difference in intrinsic hospitalization risk largely decreases to 0–30 percent when reinfections are discounted. Overall, the extremely high rate of spread, combined with its ability to evade both double vaccination and the body's immune system, means the total number of patients requiring hospital care at any given time is still of great concern.

Vaccines continue to provide protection against severe disease and hospitalisation especially after a third dose of an mRNA vaccine is given. Early figures suggest that double vaccination offers 30 to 40 percent protection against infection and around 70 percent protection against hospitalization. A recent third vaccine dose boosts effectiveness against infection to around 75 percent, and 88 percent for severe disease.

Classification

Omicron variant and other major or previous variants of concern of SARS-CoV-2 depicted in a tree scaled radially by genetic distance, derived from Nextstrain on 1 December 2021

Nomenclature

On 26 November, the WHO's Technical Advisory Group on SARS-CoV-2 Virus Evolution declared PANGO lineage B.1.1.529 a variant of concern and designated it with the Greek letter omicron. Greek letters are used to identify variants of SARS-CoV-2. The WHO skipped the preceding letters nu and xi in the Greek alphabet to avoid confusion with the similarities of the English word "new" and the Chinese surname Xi. The previous designation was for the "variant of interest" Mu.

Possibly due to a lack of familiarity with the Greek alphabet among some English speakers and the relative frequency of the Latin prefix "omni" in other common speech, the name of the variant has also occasionally been mispronounced and misspelled as "Omnicron".

The GISAID project has assigned it the clade identifier GR/484A, and the Nextstrain project has assigned it the clade identifiers 21K and 21L, both belonging to a larger Omicron group 21M.

Mutations

• 
  The genomic sequence of the Omicron variant is pictured above.

Defining mutations in the
SARS-CoV-2 Omicron variant

Gene	Amino acid
ORF1ab	nsp3: K38R
	nsp3: V1069I
	nsp3: Δ1265
	nsp3: L1266I
	nsp3: A1892T
	nsp4: T492I
	nsp5: P132H
	nsp6: Δ105-107
	nsp6: A189V
	nsp12: P323L
	nsp14: I42V
Spike	A67V
	Δ69-70
	T95I
	G142D,
	Δ143-145
	Δ211
	L212I
	ins214EPE
	G339D
	S371L
	S373P
	S375F
	K417N
	N440K
	G446S
	S477N
	T478K
	E484A
	Q493R
	G496S
	Q498R
	N501Y
	Y505H
	T547K
	D614G
	H655Y
	N679K
	P681H
	N764K
	D796Y
	N856K
	Q954H
	N969K
	L981F
E	T9I
M	D3G
	Q19E
	A63T
N	P13L
	Δ31-33
	R203K
	G204R
Sources: UK Health Security Agency CoVariants

The variant has many mutations, some of which have concerned scientists. The Omicron variant has a total of 60 mutations compared to the reference / ancestral variant: 50 nonsynonymous mutations, 8 synonymous mutations, and 2 non-coding mutations. Thirty-two mutations affect the spike protein, the main antigenic target of antibodies generated by infections and of many vaccines widely administered. Many of those mutations had not been observed in other strains. The variant is characterised by 30 amino acid changes, three small deletions, and one small insertion in the spike protein compared with the original virus, of which 15 are located in the receptor-binding domain (residues 319–541). It also carries a number of changes and deletions in other genomic regions. Additionally, the variant has three mutations at the furin cleavage site. The furin cleavage site increases SARS-CoV-2 infectivity. The mutations by genomic region are the following:

Illustration of the locations of the Omicron mutations in the spike protein, top view (left) and side view (right), showing amino acid substitutions (yellow), deletions (red), and insertions (green). In this trimeric structure, two monomers (gray and light blue) have their receptor-binding domains in the "down" conformation while one (dark blue) is in the "up" or "open" conformation. Mutation data from WHO, structure from PDB: 6VYB​.

• Spike protein: A67V, Δ69-70, T95I, G142D, Δ143-145, Δ211, L212I, ins214EPE, G339D, S371L, S373P, S375F, K417N, N440K, G446S, S477N, T478K, E484A, Q493R, G496S, Q498R, N501Y, Y505H, T547K, D614G, H655Y, N679K, P681H, N764K, D796Y, N856K, Q954H, N969K, L981F
  • Half (15) of these 30 changes are located in the receptor binding domain-RBD (residues 319–541)
• ORF1ab
  • nsp3: K38R, V1069I, Δ1265, L1266I, A1892T
  • nsp4: T492I
  • nsp5: P132H
  • nsp6: Δ105-107, A189V
  • nsp12: P323L
  • nsp14: I42V
• Envelope protein: T9I
• Membrane protein: D3G, Q19E, A63T
• Nucleocapsid protein: P13L, Δ31-33, R203K, G204R

A link with HIV infection may explain a large number of mutations in the sequence of the Omicron variant. Indeed, in order to be affected by such a high number of mutations, the virus must have been able to evolve a long time without killing its host, nor being eliminated. One such situation occurs in people with a weakened immune system but receiving enough medical care to survive. This is the case in HIV patients in South Africa, who represent more than 20% of the population. Due to lack of access to clinics, fear of stigmatisation and disrupted healthcare, millions living with HIV in the region are not on effective HIV therapy. HIV prevention could be key to reducing the risk of uncontrolled HIV driving the emergence of Covid variants.

In addition, it is believed that one of these many mutations, comprising a 9-nucleotide sequence, may have been acquired from another coronavirus (known as HCoV-229E), responsible for the common cold. This is not entirely unexpected — at times, viruses within the body acquire and swap segments of genetic material from each other, and this is one common means of mutation.

One hypothesis to explain the novel mutations is that SARS-CoV-2 was transmitted from humans to mice and mutated in a population of mice sometime between mid-2020 and late 2021 before reinfecting humans.

Sublineages and BA.2 subvariant

Researchers have established the existence of three sublineages of Omicron. The 'standard' sublineage is now referred to as BA.1 (or B.1.1.529.1), and the two other sublineages are known as BA.2 (or B.1.1.529.2) and BA.3 (or B.1.1.529.3). They share many mutations, but also significantly differ. In general, BA.1 and BA.2 share 32 mutations, but differ by 28. This makes them as different as some other major variants, and it has been suggested that BA.2 should receive its own name based on the Greek alphabet. BA.1 has itself been divided in two, the original BA.1 and BA.1.1, where the main difference is that the latter has a R346K mutation.

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.

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. Thus, countries that primarily rely on SGTF for detection may overlook BA.2, and British authorities consider SGTF alone as insufficient for monitoring the spread of Omicron. This has resulted in it having been nicknamed 'Stealth Omicron'. 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. Some countries, such as Denmark and Japan, use a variant qPCR that tests for several mutations, including L452R. It can also distinguish Delta, which has L452R, and all Omicron sublineages, which do not have L452R. 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.

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

Affected countries and transmissibility

According to early research, BA.2 is roughly 30% more transmissible than BA.1. As a consequence, it may prolong a COVID-19 wave when it overtakes BA.1.

The first known sequence of BA.2 was in a sample from 15 November 2021. 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. By 31 January, it had been detected in at least 57 countries. 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. Based on GISAID uploads, BA.1 peaked in early January 2022, after which it was overtaken by both BA.1.1 and BA.2. 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.

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) and the Philippines, had become frequent in Scandinavia, South Africa and Singapore, and was showing signs of growth in Germany and the United Kingdom. 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.

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. 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). In the following week, BA.2 became clearly dominant in Denmark with 65 percent of new cases being the BA.2 subvariant. 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. 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. 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.

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. Norwegian studies show that the amount of virus in the upper airways is similar in those infected with BA.1 and BA.2. 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-proteced against a BA.2 infection, although it is unknown how long this protection lasts. Laboratory studies also show that antibodies for BA.1 generally protect against BA.2. In Denmark, preliminary data found breakthrough rates in people that had been vaccinated that were similar to the breakthrough rates seen for BA.1. 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. Because of the gradually waning effect of vaccines, further, booster vaccination may later be necessary.

Possible consequences

The WHO is concerned that the large number of mutations in Omicron compared to earlier variants may reduce immunity in people who were previously infected and in vaccinated people. It is also possible the Omicron variant might be more infective in this regard than prior variants. The effects of the mutations, if any, are unknown as of late November 2021. The WHO warns that health services could be overwhelmed especially in nations with low vaccination rates where mortality and morbidity rates are likely to be much higher, and urges all nations to increase COVID-19 vaccinations.

Professor Paul Morgan, immunologist at Cardiff University, also recommends vaccination. Morgan said, "I think a blunting rather than a complete loss [of immunity] is the most likely outcome. The virus can't possibly lose every single epitope on its surface, because if it did that spike protein couldn't work any more. So, while some of the antibodies and T cell clones made against earlier versions of the virus, or against the vaccines may not be effective, there will be others, which will remain effective. (...) If half, or two-thirds, or whatever it is, of the immune response is not going to be effective, and you're left with the residual half, then the more boosted that is the better."

Professor Francois Balloux of the Genetics Institute at University College London said, "From what we have learned so far, we can be fairly confident that – compared with other variants – Omicron tends to be better able to reinfect people who have been previously infected and received some protection against COVID-19. That is pretty clear and was anticipated from the mutational changes we have pinpointed in its protein structure. These make it more difficult for antibodies to neutralise the virus."

On 15 December 2021, the European Centre for Disease Prevention and Control assessed that, even if the variant turns out to be milder than Delta, its spread will very likely increase hospitalizations and fatalities due to the exponential growth in cases caused by increased transmissibility.

On 23 December 2021, Nature indicates that, though Omicron likely weakens vaccine protection, reasonable effectiveness against Omicron may be maintained with currently available vaccination and boosting approaches.

Zoonotic

Omicron is a zoonotic disease. In February 2022, the first confirmed case infecting a wild animal was confirmed by researchers at Pennsylvania State University in white-tailed deer in Staten Island, N.Y.

Signs and symptoms

Main article: Symptoms of COVID-19

A unique reported symptom of the Omicron variant is night sweats. Also, loss of taste and smell seem to be uncommon compared to other strains.

A study performed between 1 and 7 December by the Center for Disease Control found that: "The most commonly reported symptoms [were] cough, fatigue, and congestion or runny nose" making it difficult to distinguish from a less damaging variant or other virus.

Research published in London on 25 December 2021 suggested the most frequent symptoms stated by users of the Zoe Covid app were "a running nose, headaches, fatigue, sneezing and sore throats."

Characteristics

Many of the mutations to the spike protein are present in other variants of concern and are related to increased infectivity and antibody evasion. Computational modeling suggests that the variant may also escape cell-mediated immunity. On 26 November, the ECDC wrote that an evaluation of the neutralizing capacity of convalescent sera and of vaccines is urgently needed to assess possible immune escape, saying these data are expected within two to three weeks.

Although transmission via fomites is rare, preliminary data indicate that the variant lasts for 194 hours on plastic surfaces and 21 hours on skin, compared with just 56 and 7 hours, respectively, for the ancestral Wuhan strain.

Contagiousness

It was not known in November 2021 how the variant would spread in populations with high levels of immunity. It was also not known if the Omicron variant causes a milder or more severe COVID-19 infection. According to pharmaceutical companies, vaccines could be updated to combat the variant "in around 100 days" if necessary.

Relating to naturally acquired immunity, Anne von Gottberg, an expert at the National Institute for Communicable Diseases, believed at the beginning of December 2021 that immunity granted by previous variants would not protect against Omicron.

On 15 December 2021 Jenny Harries, head of the UK Health Security Agency, told a parliamentary committee that the doubling time of COVID-19 in most regions of the UK was now less than two days despite the country's high vaccination rate. She said that the Omicron variant of COVID-19 is "probably the most significant threat since the start of the pandemic", and that the number of cases in the next few days would be "quite staggering compared to the rate of growth that we've seen in cases for previous variants".

In January 2022, William Schaffner, professor of infectious diseases at Vanderbilt University Medical Center, compared the contagiousness of the Omicron variant to the contagiousness of the measles.

Immune evasion

Further information: Viral strategies for immune response evasion

A study suggests that mutations that promote breakthrough infections or antibody-resistance "like those in Omicron" could be a new mechanism for viral evolution success of SARS-CoV-2 and that such may become a dominating mechanism of its evolution. A preprint supports such an explanation of Omicron's spread, suggesting that it "primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility". Studies showed the variant to escape the majority of existing SARS-CoV-2 neutralizing antibodies, including of sera from vaccinated and convalescent individuals. Nevertheless, current vaccines are expected to protect against severe illness, hospitalizations, and deaths due to Omicron and, on an individual level, the Omicron variant is milder than earlier variants that evolved when the antibody/vaccination share was lower than it was when Omicron emerged.

Virulence

Further information: Virulence

As of 28 November 2021 the World Health Organization's update states "There is currently no information to suggest that symptoms associated with Omicron are different from ... other variants". Increased rates of hospitalization in South Africa may be due to a higher number of cases, rather than any specific feature of the Omicron variant.

On 4 December 2021, the South African Medical Research Council reported that from 14 to 29 November 2021 at a hospital complex in Tshwane, inpatients were younger than in previous waves and the ICU and oxygen therapy rates were lower than in earlier waves. These observations are not definitive and the clinical profile could change over the following two weeks, allowing for more accurate conclusions about disease severity. Excess deaths nearly doubled in the week of 28 November, suggesting under-reporting, but the level was still much lower than that seen in the second wave in mid-January 2021. On 12 December, director-general of the World Health Organization Tedros Adhanom asserted that it was wrong for people to consider Omicron as mild. This is because high exposure to previous infections in South Africa likely affects the clinical course of the new infections.

On 20 December, a report by the Imperial College COVID-19 Response Team, based on data from England, found that hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta. On 22 December, the team reported an approximately 41% (95% CI, 37–45%) lower risk of a hospitalization requiring a stay of at least 1 night compared to the Delta variant, and that the data suggest that recipients of 2 doses of the Pfizer–BioNTech, the Moderna or the Oxford–AstraZeneca vaccine remain substantially protected from hospitalization.

In January, the CDC confirmed that the variant causes less severe disease than previously dominant variants. The novel Omicron subtype 'BA.2' did not initially show an increase over this lower virulence, albeit one preprint found that "infection experiments using hamsters show that BA.2 is more pathogenic than BA.1". Nevertheless, in the U.S., the daily new COVID-19 deaths were higher during Omicron dominance than during Delta's during fall and high volumes of hospitalizations due to the variant's other characteristics can cause indirect harm via local health care system strains, beyond less severe but often non-mild disease effects.

Diagnosis

See also: COVID-19 testing

PCR testing

The FDA has published guidelines on how PCR tests will be affected by Omicron. Tests that detect multiple gene targets will continue to identify the testee as positive for COVID-19. S-gene dropout or target failure has been proposed as a shorthand way of differentiating Omicron from Delta. The variant can also be identified by sequencing and genotyping.

Rapid antigen testing

See also: COVID-19 rapid antigen test § Omicron

In January 2022 the medicine and therapeutic regulatory agency Therapeutic Goods Administration (TGA) of the Australian Government states that only one of their 23 approved COVID-19 rapid antigen tests (RAT) detected Omicron in their review.

Prevention

See also: COVID-19 § Prevention

As with other variants, the WHO recommended that people continue to keep enclosed spaces well ventilated, avoid crowding and close contact, wear well-fitting masks, clean hands frequently, and get vaccinated.

Response by vaccine producers

On 26 November 2021, BioNTech said it would know in two weeks whether the current vaccine is effective against the variant and that an updated vaccine could be shipped in 100 days if necessary. AstraZeneca, Moderna and Johnson & Johnson were also studying the variant's impact on the effectiveness of their vaccines. On the same day, Novavax stated that it was developing an updated vaccine requiring two doses for the Omicron variant, which the company expected to be ready for testing and manufacturing within a few weeks. On 29 November 2021, The Gamaleya Institute said that Sputnik Light should be effective against the variant, that it would begin adapting Sputnik V, and that a modified version could be ready for mass production in 45 days. Sinovac said it could quickly mass-produce an inactivated vaccine against the variant and that it was monitoring studies and collecting samples of the variant to determine if a new vaccine is needed. On 7 December 2021, at a symposium in Brazil with its partner Instituto Butantan, Sinovac said it would update its vaccine to the new variant and make it available in three months. On December 2, the Finlay Institute was already developing a version of Soberana Plus against the variant. Pfizer hopes to have a vaccine targeted to immunize against Omicron ready by March 2022.

WHO

On 29 November 2021, the WHO said cases and infections are expected among those vaccinated, albeit in a small and predictable proportion.

Vaccine efficacy

In December, studies, some of which using large nationwide datasets from either Israel and Denmark, found that vaccine effectiveness of multiple common two-dosed COVID-19 vaccines is substantially lower against the Omicron variant than for other common variants including the Delta variant, and that a new (often a third) dose – a booster dose – is needed and effective, with it i.a. substantially reducing deaths from the disease compared to cohorts who received no booster but two doses.

On 7 December 2021, preliminary results from a laboratory test conducted at the Africa Health Research Institute in Durban with 12 people who received the Pfizer-BioNTech vaccine found a 41-fold reduction in neutralizing antibody activity against the variant in some of the samples. This is a big reduction, but it does not mean that the variant can escape vaccines completely, so vaccination with current vaccines is still recommended. Neutralizing antibody activity against the variant was greater in those fully vaccinated after being infected about a year earlier. Effectiveness estimates will likely change as more data is collected, as antibodies generated by vaccination vary widely between individuals and the sample was small. On 8 December 2021, Pfizer and BioNTech reported that preliminary data indicated that a third dose of the vaccine would provide a similar level of neutralizing antibodies against the variant as seen against other variants after two doses.

On 10 December 2021, the UK Health Security Agency reported that early data indicated a 20- to 40-fold reduction in neutralizing activity for Omicron by sera from Pfizer 2-dose vaccinees relative to earlier strains and a 20-fold reduction relative to Delta. The reduction was greater in sera from AstraZeneca 2-dose vaccinees, falling below the detectable threshold. An mRNA booster dose produced a similar increase in neutralising activity regardless of the vaccine used for primary vaccination. After a booster dose (usually with an mRNA vaccine), vaccine effectiveness against symptomatic disease was at 70%–75%, and the effectiveness against severe disease was expected to be higher.

WHO recommendations for epidemiology

On 26 November 2021, the WHO asked nations to do the following:

• Enhance surveillance and sequencing efforts to better understand circulating SARS-CoV-2 variants.
• Submit complete genome sequences and associated metadata to a publicly available database, such as GISAID.
• Report initial cases/clusters associated with virus-of-concern infection to WHO through the IHR mechanism.
• Where capacity exists and in coordination with the international community, perform field investigations and laboratory assessments to improve understanding of the potential impacts of the virus of concern on COVID-19 epidemiology, severity, and the effectiveness of public health and social measures, diagnostic methods, immune responses, antibody neutralization, or other relevant characteristics.

Treatment

See also: Treatment and management of COVID-19

Corticosteroids such as dexamethasone and IL6 receptor blockers such as tocilizumab (Actemra) are known to be effective for managing patients with the earlier strains of severe COVID-19. The impact on the effectiveness of other treatments was being assessed in 2021.

Relating to monoclonal antibodies (mAbs) treatments, similar testing and research is ongoing. Preclinical data on in vitro pseudotyped virus data demonstrate that some mAbs designed to use highly conserved epitopes retain neutralizing activity against key mutations of Omicron substitutions. Similar results are confirmed by cryo-electron microscopy and X-ray data, also providing the structural approach and molecular basis for the evasion of humoral immunity exhibited by Omicron antigenic shift as well as the importance of targeting conserved epitopes for vaccine and therapeutics design. While 7 clinical mAbs or mAb cocktails experienced loss of neutralizing activity of 1-2 orders of magnitude or greater relative to the prototypic virus, the S309 mAb, the parent mAb of sotrovimab, neutralized Omicron with only 2-3-fold reduced potency. Further data suggest Omicron would cause significant humoral immune evasion, while neutralizing antibodies targeting the sarbecovirus conserved region remain most effective. Indeed, most receptor-binding motif (RBM)-directed monoclonal antibodies lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs examined in another study retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab (VIR-7831), S2X259 and S2H97.

Epidemiology

On 26 November 2021, the South African National Institute for Communicable Diseases announced that 30,904 COVID-tests (in one day) detected 2,828 new COVID infections (a 9.2% positivity rate). One week later, on 3 December 2021, the NICD announced that 65,990 COVID tests had found 16,055 new infections (5.7 times as many as seven days before; positive rate 24.3%) and that 72 percent of them were found in Gauteng. This province of South Africa is densely populated at about 850 inhabitants per km². Gauteng's capital Johannesburg is a megacity (about 5.5 million inhabitants in the city itself plus 9.5 million in the urban region).

In November 2021 the transmissibility of the Omicron variant, as compared to the Delta variant or other variants of the COVID-19 virus, was still uncertain. Omicron is frequently able to infect previously Covid-positive people.

It has been estimated the Omicron variant diverged in late September or early October 2021, based on Omicron genome comparisons. Sequencing data suggests that Omicron had become the dominant variant in South Africa by November 2021, the same month where it had been first identified in the country.

Phylogeny suggests a recent emergence. Data from South Africa suggests that Omicron has a pronounced growth advantage there. However, this may be due to transmissibility or immune escape related, or both." Also the serial interval plays a role in the growth.

Detectable changes in levels of COVID-19 in wastewater samples from South Africa's Gauteng province were seen as early as 17–23 October (week 42). The National Institute for Communicable Diseases reports that children under the age of 2 make up 10% of total hospital admissions in the Omicron point of discovery Tshwane in South Africa. Data on the S gene target failure (SGTF) of sampled cases in South Africa indicates a growth of 21% per day relative to Delta, generating an increased reproduction number by a factor of 2.4. Omicron became the majority strain in South Africa around 10 November. Another analysis showed 32% growth per day in Gauteng, South Africa, having become dominant there around 6 November.

In the UK, the logarithmic growth rate of Omicron-associated S gene target failure (SGTF) cases over S gene target positive (SGTP) cases was estimated at 0.37 per day, which is exceptionally high. Furthermore, by 14 December it appears to have become the most dominant strain. Without presuming behavior change in response to the variant, a million infections per day by December 24 are projected for a 2.5 days doubling time. In Denmark, the growth rate has been roughly similar with a doubling time of about 2–3 days, it having become the most prevalent strain on 17 December. Switzerland is not far behind. In Germany Omicron became the most prevalent variant on January 1. In Scotland, Omicron apparently became the most prevalent variant on 17 December. In the Canadian province of Ontario it became the most prevalent strain on 13 December. In the US, the variant appears to have become the most prevalent strain on December 18, growing at 0.24 per day. In Portugal, Omicron had reached 61.5% of cases on 22 December. In Belgium, the strain has become the most prevalent on 25 December, and in the Netherlands on 28 December. In Italy, it had reached 28% of cases on 20 December and was doubling every two days, while it became the dominant variant in Norway on 25 December. In France, it made up about 15% of COVID-19 cases in mid-December, but around 27 December it had increased to more than 60%. Researchers recommend sampling at least 5% of COVID-19 patient samples in order to detect Omicron or other emerging variants.

During January 2022, in Denmark the BA.2 variant grew at ~0.10 per day (+11% per day) as a ratio to BA.1 (the legacy Omicron variant), and became the dominant strain in week 2, 2022. In the United Kingdom, the BA.2 variant was growing at ~0.18 per day (+20% per day) as a ratio to BA.1.

On 13 January 2022, the BBC reported that the hospitalization rate was higher in the US and Canada than in Europe and South Africa. This was attributed to a combination of a greater number of elderly people than in South Africa, greater prevalence of comorbidities such as hypertension and obesity than in Europe, higher indoor transmission due to the winter, lower vaccination rate in the US than in Europe and Canada, and a possible still high prevalence of the Delta variant, which more often leads to hospitalization.

Statistics

Cumulative confirmed Omicron variant cases by country and territory

•   100,000–999,999
•   10,000–99,999
•   1,000–9,999
•   100–999
•   10–99
•   1–9
•   0

The chance of detecting a case particularly depends on a country's sequencing rate. For example, South Africa sequences far more samples than any other country in Africa, but at a considerably lower rate than most Western nations. Furthermore, it can take up to two weeks to return a viral sequence in places with the technical capability, hence solid statistics on confirmed cases lag the actual situation. Denmark and Norway regard cases found by their variant qPCR test, which is relatively fast and checks several genes, as sufficient for counting it as an Omicron, also before full sequencing.

Confirmed and suspected cases by country and territory

Country/Territory	Confirmed cases (PANGOLIN) as of 5 May 2022	Confirmed cases (GISAID) as of July 29, 2022	Confirmed cases (other sources) As of 24 June 2022	Suspected cases
United States	999,565	1,431,772	62,480As of January 8, 2022	–
United Kingdom	999,565	1,253,700	246,780	600,041
Germany	207,407	365,837	268,661	–
Austria	6,809	57,379	290,378	–
Denmark	196,746	264,998	66,563	–
France	83,564	184,880	5,591	–
Canada	73,584	147,223	174,248	–
Japan	67,203	153,110	12,453	–
India	37,542	81 017	8,209	–
Australia	33,905	80,013	11,071	–
Norway	14,729	24,529	45,296	–
Thailand	6,778	12,811	5,397	–
Indonesia	9,761	12,028	3,779	–
Singapore	4,543	7,300	4,322	–
Estonia	1,982	3,778	3,857	–
Israel	22,164	60,435	1,741	861
South Africa	9,631	16,451	1,095	19,070
South Korea	7,731	27,705	1,318	–
Spain	24,607	31,992	51	–
Belgium	26,448	30,865	121	–
Sweden	38,397	42,525	53.760	–
Switzerland	30,034	32,635	19,269	–
Argentina	2,228	2,583	455	80
Botswana	931	1,594	23	–
Netherlands	24,381	26,601	123	–
Ireland	24,654	29,518	29,576	–
Gibraltar	112	122	24	–
Iceland	–	–	84	–
Italy	23,707	27,292	84	–
Chile	4,097	4,572	684	–
Portugal	7,683	8,870	69	6
Morocco	128	138	76	246
Zimbabwe	185	219	50	–
Ghana	441	605	33	–
Brazil	27,787	32,224	203	–
Finland	4,029	5,239	523	–
Cyprus	–	–	31	–
Kenya	1,653	2,329	27	–
Russia	1,273	1,738	8,239	–
Cayman Islands	–	–	44	59
Uganda	12	38	25	–
Mexico	12,736	13,678	1	–
New Zealand	3,169	3,739	116	–
Namibia	125	213	18	–
Hong Kong	1,432	3,526	102	–
Senegal	14	229	3	–
Mozambique	133	176	2	2
Greece	3,268	3,276	17	–
Bermuda	–	24	144	–
Latvia	407	407	644	–
Romania	4,034	4,282	25	–
Malaysia	5,330	7,353	245	–
Zambia	141	365	11	–
Nigeria	827	1,638	6	–
Czech Republic	13,264	15,147	10	–
Kosovo	245	262	9	–
Slovenia	15,684	17,106	1,418	–
Lebanon	85	107	433	16
Reunion	2,014	2,402	2	–
Mauritius	–	763	7	–
Poland	31,766	33,327	1	–
Rwanda	70	178	6	–
Turkey	9,135	10,239	6	–
Montenegro	142	211	5	–
Cambodia	950	974	31	–
Peru	5,653	5,960	10,032	–
Jordan	83	83	832	–
China	96	96	4	–
Cuba	–	–	92	–
Croatia	10,379	11,742	3	–
Egypt	15	40	3	–
Malawi	133	166	3	–
Palestinian Territory	5	9	126	–
Taiwan	34	34	89	–
Lithuania	7,063	9,136	2	–
Colombia	1,629	3,816	3
Slovakia	13,501	15,625	3	–
Trinidad and Tobago	291	499	1	–
Puerto Rico	3,166	3,558	1	–
Fiji	–	–	2	–
Nepal	255	349	2	–
Myanmar	25	28	4	–
Philippines	1,281	1,549	535	–
Northern Cyprus	–	–	9	–
Bangladesh	690	998	10	–
Liechtenstein	246	736	1	3
Hungary	28	28	61	–
Oman	71	85	2	–
Pakistan	359	463	75	–
Sri Lanka	626	927	1	–
Georgia (country)	718	822	600	–
Algeria	61	73	1	–
Bahrain	–	–	1	–
Ecuador	1,177	1,561	1	–
Kuwait	54	72	1	–
Luxembourg	4,031	11,149	1	–
Maldives	–	281	5	–
Sierra Leone	–	1	1	–
Saudi Arabia	28	30	1	–
Tunisia	51	52	1	–
United Arab Emirates	–	1	1	–
Iran	595	682	467	–
Ukraine	73	99	1	–
Panama	821	822	1	–
Costa Rica	1,430	1,529	1	–
Aruba	61	61	1	–
North Macedonia	46	47	9	–
Vietnam	1,085	1,790	108	–
Brunei	1,163	1,253	8	–
Malta	138	162	2	–
Venezuela	60	62	7	–
French Guiana	–	366	20	–
Republic of the Congo	50	78	1	–
Qatar	267	290	4	–
Paraguay	122	139	3	–
Burkina Faso	–	17	2	–
Curacao	482	487	1	–
Saint Kitts and Nevis	–	16	2	–
Libya	–	–	2	–
Albania	1	1	1	–
Barbados	1	7	1	–
Saint Vincent and the Grenadines	–	62	1	–
Dominican Republic	69	73	1	–
Jamaica	443	622	1	–
Serbia	81	81	1	–
Tanzania	2	3	1	–
Togo	–	–	5	–
Belarus	–	71	4	–
Bosnia and Herzegovina	118	122	10	–
Angola	25	37	16	–
Democratic Republic of the Congo	34	204	1	–
Bulgaria	2,516	2,520	12	–
Mayotte	123	130	1	–
Martinique	–	593	1	–
Gambia	30	155	26	–
Seychelles	–	235	464	–
Saint Martin	224	240	2	–
Laos	–	–	1	–
Iraq	36	103	5	–
Mauritania	–	–	14	–
South Sudan	28	28	41	–
Ivory Coast	41	60	78	–
Cape Verde	–	152	175	–
Antigua and Barbuda	–	36	1	–
Gabon	–	–	1	–
Bolivia	2	7	1	–
Moldova	287	314	29	–
Kazakhstan	8	8	8	–
Guadeloupe	264	300	1	–
Azerbaijan	12	12	12	–
Suriname	81	96	146	–
Sint Maarten	–	479	753	–
British Virgin Islands	20	26	39	–
Mali	1	2	–	–
Anguilla	20	24	30	–
Bonaire	–	400	692	–
Bhutan	–	–	14	–
Papua New Guinea	379	565	1	–
Mongolia	133	133	12	–
Antarctica	–	–	24	–
Uzbekistan	–	–	1	–
Saint Lucia	1	9	54	–
Burundi	–	1	28	–
American Samoa	–	35	84	–
Armenia	4	16	17	–
Guinea	48	167	159	–
Guam	168	274	348	–
Belize	223	240	441	–
Eswatini	124	133	–	–
Djibouti	306	308	337	–
World total (170 countries and territories)	2,986,573	3,517,102	1,168,383	620,384

History

On 26 November 2021, WHO designated it as a variant of concern and named it "Omicron" after the fifteenth letter in the Greek alphabet. Omicron was first detected on 22 November 2021 in laboratories in Botswana and South Africa based on samples collected on 11–16 November. The first known sample was collected in South Africa on 8 November. The first known case, outside of South Africa, was a person arriving in Hong Kong from South Africa via Qatar on 11 November, and another person who arrived in Belgium from Egypt via Turkey on the same date. As of 7 January 2022, the variant has been confirmed in 135 countries. Omicron has an unusually large number of mutations compared to previous variants. Several of the mutations are novel and involve changes to the spike protein reducing the ability for COVID-19 vaccines to prevent symptomatic disease.

A December 2021 article in Science observes Omicron did not evolve from any other variant of note, but instead on a distinct track diverging in perhaps mid-2020. The article expounds on three theories that might explain this surprising genetic lineage:

1. The virus could have circulated and evolved in a population with little surveillance and sequencing.
2. It could have gestated in a chronically infected COVID-19 patient.
3. It might have evolved in a nonhuman species, from which it recently spilled back into people.

Reported cases

See also: Timeline of the SARS-CoV-2 Omicron variant

On 24 November 2021, the variant was first reported to the WHO from South Africa, based on samples that had been collected from 14 to 16 November. South African scientists were first alerted by samples from the very beginning of November where the PCR tests had S gene target failure (occurs in a few variants, but not in Delta which dominated in the country in October) and by a sudden increase of COVID-19 cases in Gauteng; sequencing revealed that more than 70 percent of samples collected in the province between 14 and 23 November were a new variant. The first confirmed specimens of Omicron were collected on 8 November 2021 in South Africa, and on 9 November in Botswana. Likely Omicron (SGTF) samples had occurred on 4 November 2021 in Pretoria, South Africa.

When WHO was alerted on 24 November, Hong Kong was the only place outside Africa that had confirmed a case of Omicron; one person who traveled from South Africa on 11 November, and another traveler who was cross-infected by this case while staying in the same quarantine hotel.

On 25 November, one confirmed case was identified in Israel from a traveler returning from Malawi, along with two who returned from South Africa and one from Madagascar. All four initial cases reported from Botswana occurred among fully vaccinated individuals.

On 26 November, Belgium confirmed its first case; an unvaccinated person who had travelled from Egypt via Turkey on 11 November. All three initial confirmed and suspected cases reported from Israel occurred among fully vaccinated individuals, as did a single suspected case in Germany.

On 27 November, two cases were detected in the United Kingdom, another two in Munich, Germany and one in Milan, Italy.

On 28 November, 13 cases were confirmed in the Netherlands among the 624 airline passengers who arrived from South Africa on 26 November. Confirmation of a further 5 cases among these passengers followed later. Entry into the Netherlands generally required having been vaccinated or PCR-tested, or having recovered. The passengers of these two flights had been tested upon arrival because of the newly imposed restrictions (which were set in place during their flight), after which 61 tested positive for SARS-CoV-2. A further two cases were detected in Australia. Both people landed in Sydney the previous day, and travelled from southern Africa to Sydney Airport via Doha Airport. The two people, who were fully vaccinated, entered isolation; 12 other travellers from southern Africa also entered quarantine for fourteen days, while about 260 other passengers and crew on the flight have been directed to isolate. Two travellers from South Africa who landed in Denmark tested positive for COVID-19; it was confirmed on 28 November that both carried the Omicron variant. On the same day, Austria also confirmed its first Omicron case. A detected Omicron case was reported in the Czech Republic, from a traveler who spent time in Namibia. Canada also reported its first Omicron cases, with two from travelers from Nigeria, therefore becoming the first North American country to report an Omicron case.

On 29 November, a positive case was recorded in Darwin, Australia. The person arrived in Darwin on a repatriation flight from Johannesburg, South Africa on 25 November, and was taken to a quarantine facility, where the positive test was recorded. Two more people who travelled to Sydney from southern Africa via Singapore tested positive. Portugal reported 13 Omicron cases, all of them members of a soccer club. Sweden also confirmed their first case on 29 November, as did Spain, when a traveler came from South Africa.

On 30 November, the Netherlands reported that Omicron cases had been detected in two samples dating back as early as 19 November. A positive case was recorded in Sydney from a traveller who had visited southern Africa before travel restrictions were imposed, and was subsequently active in the community. Japan also confirmed its first case. Two Israeli doctors have tested positive and have entered isolation. Both of them had received three shots of the Pfizer vaccine prior to testing positive. In Brazil, three cases of the Omicron variant were confirmed in São Paulo. Another five are under suspicion. A person in Leipzig, Germany with no travel history nor contact with travellers tested positive for Omicron.

On 1 December, the Omicron variant was detected in three samples in Nigeria that had been collected from travelers from South Africa within the last week. On the same day, public health authorities in the United States announced the country's first confirmed Omicron case. A resident of San Francisco who had been vaccinated returned from South Africa on 22 November, began showing mild symptoms on 25 November and was confirmed to have a mild case of COVID-19 on 29 November. Ireland and South Korea also reported their first cases. South Korea reported its cases from five travelers arriving in South Korea from Nigeria.

On 2 December, Dutch health authorities confirmed that all 14 passengers with confirmed Omicron infection on 26 November had been previously vaccinated. The same day, the Norwegian Institute of Public Health confirmed that 50 attendees of a company Christmas party held at a restaurant in Norway's capital, Oslo, were infected with the Omicron variant. France has confirmed only 25 cases of the new Omicron variant but officials say the number could jump significantly in the coming weeks.

By 6 December, Malaysia confirmed its first case of the variant. The case was a South African student entering to study at a private university. In Namibia, 18 cases out of 19 positive COVID-19 samples that had been collected between 11 and 26 November were found to be Omicron, indicating a high level of prevalence in the country. Fiji also confirmed two positive cases of the variant. They travelled from Nigeria arriving in Fiji on November 25.

On 8 December, WHO announced the variant had been detected in 57 countries.

On 9 December, Richard Mihigo, coordinator of the World Health Organisation's Immunisation and Vaccine Development Programme for Africa, announced that Africa accounted for 46% of reported cases of the Omicron variant globally.

On 13 December, the first death of a person with Omicron was reported in the UK.

On 16 December, New Zealand confirmed its first case of the Omicron variant, an individual who had traveled from Germany via Dubai.

The first death of a person with Omicron was reported in Germany on 23 December and in Australia on 27 December.

On 3 January 2022, South Korea reported the first two deaths of people who tested positive post mortem for Omicron.

Market reactions

Main article: Financial market impact of the COVID-19 pandemic

Worry about the potential economic impact of the Omicron variant led to a drop in global markets on 26 November, including the worst drop of the Dow Jones Industrial Average in 2021, led by travel-related stocks. The price of Brent Crude and West Texas Intermediate oil fell 10% and 11.7%, respectively. Cryptocurrency markets were also routed. The South African rand has also hit an all-time low for 2021, trading at over 16 rand to the dollar, losing 6% of its value in November.

In early December 2021, the chairman of the Federal Reserve, Jerome Powell, testified before the U.S. Senate Committee on Banking that "The recent rise in COVID-19 cases and the emergence of the Omicron variant pose downside risks to employment and economic activity and increased uncertainty for inflation."

International response

On 26 November 2021, WHO advised countries not to impose new restrictions on travel, instead recommending a "risk-based and scientific" approach to travel measures. On the same day, the European Centre for Disease Prevention and Control (ECDC) reported modeling indicating that strict travel restrictions would delay the variant's impact on European countries by two weeks, possibly allowing countries to prepare for it.

After the WHO announcement, on the same day, several countries announced travel bans from southern Africa in response to the identification of the variant, including the United States, which banned travel from eight African countries, although it notably did not ban travel from any European countries, Israel, Canada, or Australia where cases were also detected at the time the bans were announced. Other countries that also implemented travel bans include Japan, Canada, the European Union, Israel, Australia, the United Kingdom, Singapore, Malaysia, Indonesia, Morocco, and New Zealand.

The Brazilian Health Regulatory Agency recommended flight restrictions regarding the new variant. The state of New York declared a state of emergency ahead of a potential Omicron spike, although no cases had yet been detected in the state or the rest of the United States. On 27 November, Switzerland introduced obligatory tests and quarantine for all visitors arriving from countries where the variant was detected, which originally included Belgium and Israel.

In response to the various travel bans, South African Minister of Health Joe Phaahla defended his country's handling of the pandemic and said that travel bans went against the "norms and standards" of the World Health Organization.

Some speculate that travel bans could have a significant impact on South Africa's economy by limiting tourism and could lead to other countries with economies that are reliant on tourism to hide the discovery of new variants of concern. Low vaccine coverage in less-developed nations could create opportunities for the emergence of new variants, and these nations also struggle to gain intellectual property to develop and produce vaccines locally. At the same time, inoculation has slowed in South Africa due to vaccine hesitancy and apathy, with a nationwide vaccination rate of only 35% as of November 2021.

On 29 November, the WHO warned countries that the variant poses a very high global risk with severe consequences and that they should prepare by accelerating vaccination of high-priority groups and strengthening health systems. WHO director-general Tedros Adhanom described the global situation as dangerous and precarious and called for a new agreement on the handling of pandemics, as the current system disincentivizes countries from alerting others to threats that will inevitably land on their shores. CEPI CEO Richard Hatchett said that the variant fulfilled predictions that transmission of the virus in low-vaccination areas would accelerate its evolution.

In preparation for the Omicron variant arriving in the United States, President Joe Biden has stated that the variant is "cause for concern, not panic" and reiterated that the government is prepared for the variant and will have it under control. He also stated that large-scale lockdowns, similar to the ones in 2020 near the beginning of the pandemic, are "off the table for now."

In mid-December, multiple Canadian provinces reinstated restrictions on gatherings and events such as sports tournaments, and tightened enforcement of proof of vaccination orders. British Columbia expressly prohibited any non-seated "organized New Year's Eve event", while Quebec announced a partial lockdown on 20 December, ordering the closure of all bars, casinos, gyms, schools, and theatres, as well as imposing restrictions on the capacity and operating hours of restaurants, and the prohibition of spectators at professional sporting events.

On 18 December, the Netherlands government announced a lockdown intended to prevent spread of the variant during the holiday period.

In late December, some countries shortened the typical six-month interval for a booster dose of the vaccine to prepare for a wave of Omicron, as two doses are not enough to stop the infection. UK, South Korea and Thailand reduced to three months; Belgium, four months; France, Singapore, Taiwan, Italy and Australia, five months. Finland reduced it to three months for risk groups. Other countries continued with a six-month booster schedule. While antibody levels begin to drop at four months, a longer interval usually allows time for the immune system's response to mature.

See also

• Timeline of the SARS-CoV-2 Omicron variant
• COVID-19 pandemic in Africa
  • COVID-19 vaccination in Africa
  • COVID-19 vaccination in Botswana
  • COVID-19 vaccination in South Africa
• Variants of SARS-CoV-2
  • Other variants of either interest or concern: Alpha, Beta, Gamma, Delta, Epsilon, Zeta, Eta, Theta, Iota, Kappa, Lambda, Mu

Further reading

• WHO: Update on Omicron
• Live Omicron Variant Location Map
• Omicron variant: What have COVID vaccine makers said and are they working on new doses?
• Callaway E, Ledford H (December 2021). "How bad is Omicron? What scientists know so far". Nature. 600 (7888): 197–199. Bibcode:2021Natur.600..197C. doi:10.1038/d41586-021-03614-z. PMID 34857948. S2CID 244840636.

External links

• Corum J, Zimmer C (9 February 2021). "Coronavirus Variant Tracker". The New York Times. Archived from the original on 30 November 2021. Retrieved 1 December 2021. Constantly Updated
• Archived video:
  • Mohale F, Phaahla J, Oliveira T, Lessels R, Gottberg A, Moore P, Crisp N (25 November 2021). Health Department briefs media about a new so-called super-variant (Internet video live stream). South Africa: eNCA. Retrieved 27 November 2021. Archived at the Wayback Machine and Ghostarchive.
  • Oliveira T, Kamwendo S (26 November 2021). Professor Tulio de Oliviera on the new COVID-19 variant (Internet video live stream). South Africa: SABC News. Archived from the original on 29 November 2021. Retrieved 27 November 2021. Archived at the Wayback Machine and Ghostarchive