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SARS-CoV-2 Omicron variant

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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
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The Omicron variant is a variant of SARS-CoV-2, the virus that causes COVID-19. As of December 2021, it is the newest variant. It was first reported to the World Health Organization (WHO) from South Africa on 24 November 2021.[1] On 26 November 2021, the WHO designated it as a variant of concern and named it "Omicron", the fifteenth letter in the Greek alphabet.[2][3]

The variant has an unusually large number of mutations, several of which are novel[4][5] (see § Mutations) and a significant number of which affect the spike protein targeted by most COVID-19 vaccines at the time of the discovery of the Omicron variant. This level of variation has led to concerns regarding its transmissibility, immune system evasion, and vaccine resistance, despite initial reports indicating that the variant causes less serious disease than previous strains. The variant was quickly designated as being "of concern", and travel restrictions were introduced by several countries in an attempt to slow its international spread.

Compared to previous variants of concern, Omicron is believed to be far more contagious (spreading much quicker),[6] and spreads around 70 times faster than any previous variants in the bronchi (lung airways), but it is less able to penetrate deep lung tissue, and perhaps for this reason there is a considerable reduction in the risk of severe disease requiring hospitalisation.[7] However 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.[7]

The new variant was first detected on 22 November 2021 in laboratories in Botswana and South Africa based on samples collected 11–16 November.[8][9] The first known sample was collected in South Africa on 8 November.[10][11] In other continents, the first known cases were 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.[12][13] As of 16 December 2021, the variant has been confirmed in more than 80 countries.[14] The World Health Organization estimates that by mid-December, Omicron likely was in most countries, whether they had detected it or not.[15]

Classification

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.[1][2][3] 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.[2][3][16][17] The previous designation was for the "variant of interest" mu.[18][19][3]

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".[20]

The GISAID project has assigned it the clade identifier GR/484A,[21] and the Nextstrain project has assigned it the clade identifier 21K.[22]

Mutations

  • Genomic sequence
    Genomic sequence
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[23] CoVariants[22]

The variant has many mutations, some of which have concerned scientists.[24] The Omicron variant has a total of 60 mutations compared to the original Wuhan variant: 50 nonsynonymous mutations, 8 synonymous mutations, and 2 non-coding mutations.[5] 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.[25][26] 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.[27] The furin cleavage site increases SARS-CoV-2 infectivity.[28] The mutations by genomic region are the following:[29][30]

Spike protein with mutations highlighted, looking down onto the receptor-binding domain
Spike protein with mutations highlighted, looking at the side of the protein
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,[1] structure from PDB: 6VYB​.[31]
  • 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.[32][citation needed] 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.[33] This is the case in HIV patients in South Africa, who represent more than 20% of the population.[34] 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 that uncontrolled HIV is driving the emergence of Covid variants.[35]

In addition, it is believed that one of these many mutations, comprising a 9-nucleotide sequence, may have been acquired from another type of virus (known as HCoV-229E), responsible for the common cold.[36] 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.[36]

Sublineages and stealth variant

Researchers have established the existence of three sublineages of Omicron. The 'standard' sublineage is now referred to as BA.1​/B.1.1.529.1, and the two other sublineages are known as BA.2​/B.1.1.529.2 and BA.3​/B.1.1.529.3.[37]

All three can be detected by full sequencing, but BA.2 has been nicknamed 'Stealth Omicron' because it differs from the 'standard' variety by not having the characteristic S gene target failure (SGTF)-causing deletion (Δ69-70) by which many PCR tests are able to detect a case as an Omicron, or Alpha, variant. Thus, countries that primarily rely on SGTF for detection may overlook BA.2.[38] Some countries, including Denmark, use a variant qPCR that tests for several mutations, including Δ69-70, E484K, L452R and N501Y.[39] It can also distinguish Delta (the heavily dominant variant worldwide, prior to the spread of Omicron), which has L452R but not N501Y,[40] and all Omicron sublineages, which have N501Y but not L452R.[41][42] As of 19 December 2021, BA.2 appears to be very rare with about twenty known cases from half a dozen countries.[37][42] The third sublineage, BA.3, is also very rare and it does not represent the same potential problem in detection since it has the SGTF deletion (Δ69-70), similar to BA.1.[37][43]

Possible consequences

The WHO is concerned that a large number of mutations 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.[44]

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."[45]

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."[46]

On 15 December, 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 the exponential growth in cases caused by increased transmissibility.[47]

Signs and symptoms

Main article: Symptoms of COVID-19

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".[48]

A study performed between the first of December to the 7th of December by the Center for Disease Control found that "The most commonly reported symptoms [were] cough, fatigue, and congestion or runny nose".[49]

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."[50]

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.[26] 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.[30]

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.[51]

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.[52]

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 majority of the population being vaccinated. 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".[53]

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.[48]

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.[54] 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.[55] 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.[56]

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.[57] 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.[58]

Diagnosis

See also: COVID-19 testing

The FDA has published guidelines on how PCR tests will be affected by Omicron.[59] 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 may be identified by sequencing and genotyping.[60] The BA.1 lineage, but not the BA.2 lineage, can be identified by S gene target failure (SGTF) of the TaqPath assay, a trait shared with subsets of SARS-CoV-2 Alpha variant.[38] Several other commercial assays can also be used, though they test for different amino acid substitutions.[a]

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.[1][61]

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.[62] 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.[63][64] 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.[65] 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.[66] 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.[67] On December 2, the Finlay Institute was already developing a version of Soberana Plus against the variant.[68]

On 29 November 2021, the WHO said cases and infections are expected among those vaccinated, albeit in a small and predictable proportion.[69]

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.[70][71][72] 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.[73]

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),[74] vaccine effectiveness against symptomatic disease was at 70%–75%, and the effectiveness against severe disease was expected to be higher.[75]

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.[76]

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.[77][78]

On 29 November 2021, Pfizer CEO Albert Bourla said that Pfizer had submitted an Emergency Use Authorization application to the FDA for development of the RNA virus antiviral drug Paxlovid, and the company was confident that it could treat the Omicron variant.[79][medical citation needed] Merck and Ridgeback were evaluating the anti–RNA virus drug molnupiravir for omicron treatment at the time.[80]

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.[81] Current data suggest Omicron would cause significant humoral immune evasion, while neutralizing antibodies targeting the sarbecovirus conserved region remain most effective.[82] Indeed, most receptor-binding motif (RBM)-directed monoclonal antibodies lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs 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.[83]

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).[84] 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.[85][86] 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.[87] Omicron is frequently able to infect previously Covid-positive people.[88][89]

It has been estimated the Omicron variant diverged in late September or early October 2021, based on Omicron genome comparisons.[90] 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.[91][10] "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."[92]

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).[93] 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.[94]

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 0.41 per day,[b] which is exceptionally high.[95] Furthermore, by 14 December it appears to have become the most dominant strain.[c][96] 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.[d][60] In Denmark, the growth rate has been roughly similar with a doubling time of about 2–3 days (with some geographical differences), it having reached about 39% of all COVID-19 cases on 14 December.[97][98] Switzerland is not far behind and neither is Germany.[99][100] In Scotland, Omicron apparently became the most prevalent variant on 17 December.[101][102] In Ontario it became the most prevalent strain on 13 December.[103] In the US, the variant appears to have become the most prevalent strain on December 13, growing at 0.42 per day.[104] This was one day before the CDC published the strain showed up in the variant surveillance.[105] In Belgium, the strain may become the most prevalent around 25 December,[106] and, the Netherlands appears to be on a similar path.[107][108] Other countries may not have enough timely information, as they may not use Thermo Fisher TaqPath Assay or equivalent for their PCR tests to indicate Omicron. Researchers recommend sampling at least 5% of COVID-19 patient samples in order to detect Omicron or other emerging variants.[109]

Data on the SGTF status of sampled cases in South Africa indicates a similar growth of 21% per day relative to Delta, generating an increased reproduction number by a factor of 2.4.[e] Omicron became the majority strain in South Africa around 10 November.[110][111] Another analysis showed 32% growth per day in Gauteng, South Africa, having become dominant there around 6 November.[112]

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.[113][114] 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.[115] Denmark and Norway regard cases found by their variant qPCR test, which is relatively fast and checks several genes,[39] as sufficient for counting it as an Omicron, also before full sequencing.[116][117]

Confirmed and suspected cases by country and territory
Country/Territory Confirmed cases (PANGOLIN)[118]
as of 5 May 2022 		Confirmed cases (GISAID)[119]
as of July 29, 2022 		Confirmed cases (other sources)
As of 24 June 2022 		Suspected cases
 United States 999,565 1,431,772 62,480[120]As of January 8, 2022 –
 United Kingdom 999,565 1,253,700 246,780[121] 600,041[121]
 Germany 207,407 365,837 268,661[122] –
 Austria 6,809 57,379 290,378[123][124] –
 Denmark 196,746 264,998 66,563[125] –
 France 83,564 184,880 5,591[126] –
 Canada 73,584 147,223 174,248[127] –
 Japan 67,203 153,110 12,453[128] –
 India 37,542 81 017 8,209[129][130] –
 Australia 33,905 80,013 11,071[131] –
 Norway 14,729 24,529 45,296[116] –
 Thailand 6,778 12,811 5,397[132] –
 Indonesia 9,761 12,028 3,779[133] –
 Singapore 4,543 7,300 4,322[134][135][136][137] –
 Estonia 1,982 3,778 3,857[138][139][140] –
 Israel 22,164 60,435 1,741[141][142] 861[141]
 South Africa 9,631 16,451 1,095[143] 19,070[144]
 South Korea 7,731 27,705 1,318[145] –
 Spain 24,607 31,992 51[122][146] –
 Belgium 26,448 30,865 121[123][146] –
 Sweden 38,397 42,525 53.760[147] –
  Switzerland 30,034 32,635 19,269[123][148] –
 Argentina 2,228 2,583 455[149][150] 80[151]
 Botswana 931 1,594 23[152] –
 Netherlands 24,381 26,601 123[153][146] –
 Ireland 24,654 29,518 29,576[154] –
 Gibraltar 112 122 24[155] –
 Iceland – – 84[156] –
 Italy 23,707 27,292 84[157] –
 Chile 4,097 4,572 684[158][159][160] –
 Portugal 7,683 8,870 69[161][146] 6[162][123]
 Morocco 128 138 76[163] 246[163]
 Zimbabwe 185 219 50[164] –
 Ghana 441 605 33[152] –
 Brazil 27,787 32,224 203[165] –
 Finland 4,029 5,239 523[166][167] –
 Cyprus – – 31[168][169] –
 Kenya 1,653 2,329 27[170] –
 Russia 1,273 1,738 8,239[171] –
 Cayman Islands – – 44[172] 59[172]
 Uganda 12 38 25[173][174] –
 Mexico 12,736 13,678 1[175] –
 New Zealand 3,169 3,739 116[176] –
 Namibia 125 213 18[177] –
 Hong Kong 1,432 3,526 102[178][179] –
 Senegal 14 229 3[180] –
 Mozambique 133 176 2[181] 2[120]
 Greece 3,268 3,276 17[123][182] –
 Bermuda – 24 144[183][184] –
 Latvia 407 407 644[185][146][186] –
 Romania 4,034 4,282 25[187][188][189] –
 Malaysia 5,330 7,353 245[190] –
 Zambia 141 365 11[191] –
 Nigeria 827 1,638 6[192] –
 Czech Republic 13,264 15,147 10[123][193][146] –
 Kosovo 245 262 9[194] –
 Slovenia 15,684 17,106 1,418[195][146][196][197] –
 Lebanon 85 107 433[198][199] 16[198]
 Reunion 2,014 2,402 2[200] –
 Mauritius – 763 7[120] –
 Poland 31,766 33,327 1[201] –
 Rwanda 70 178 6[201] –
 Turkey 9,135 10,239 6[202] –
 Montenegro 142 211 5[203] –
 Cambodia 950 974 31[204] –
 Peru 5,653 5,960 10,032[205] –
 Jordan 83 83 832[206] –
 China 96 96 4[207][208][209] –
 Cuba – – 92[210][211][212] –
 Croatia 10,379 11,742 3[123] –
 Egypt 15 40 3[201] –
 Malawi 133 166 3[213] –
 Palestinian Territory 5 9 126[214][215] –
 Taiwan 34 34 89[216] –
 Lithuania 7,063 9,136 2[217] –
 Colombia 1,629 3,816 3[218]
 Slovakia 13,501 15,625 3[219] –
 Trinidad and Tobago 291 499 1[220] –
 Puerto Rico 3,166 3,558 1[221] –
 Fiji – – 2[222] –
   Nepal 255 349 2[223] –
 Myanmar 25 28 4[224] –
 Philippines 1,281 1,549 535[225][226][227][228][229][230] –
 Northern Cyprus – – 9[231] –
 Bangladesh 690 998 10[232] –
 Liechtenstein 246 736 1[233] 3[120]
 Hungary 28 28 61[234][146][235] –
 Oman 71 85 2[236] –
 Pakistan 359 463 75[237][238] –
 Sri Lanka 626 927 1[239] –
 Georgia (country) 718 822 600[240] –
 Algeria 61 73 1[201] –
 Bahrain – – 1[241] –
 Ecuador 1,177 1,561 1[242] –
 Kuwait 54 72 1[243] –
 Luxembourg 4,031 11,149 1[123] –
 Maldives – 281 5[244][245] –
 Sierra Leone – 1 1[246] –
 Saudi Arabia 28 30 1[247] –
 Tunisia 51 52 1[248] –
 United Arab Emirates – 1 1[249] –
 Iran 595 682 467[250] –
 Ukraine 73 99 1[251] –
 Panama 821 822 1[252] –
 Costa Rica 1,430 1,529 1[253] –
 Aruba 61 61 1[254] –
 North Macedonia 46 47 9[255][256] –
 Vietnam 1,085 1,790 108[257] –
 Brunei 1,163 1,253 8[258] –
 Malta 138 162 2[259] –
 Venezuela 60 62 7[260] –
 French Guiana – 366 20[261] –
 Republic of the Congo 50 78 1[262] –
 Qatar 267 290 4[263] –
 Paraguay 122 139 3[264] –
 Burkina Faso – 17 2[265] –
 Curacao 482 487 1[266] –
 Saint Kitts and Nevis – 16 2[267] –
 Libya – – 2[268] –
 Albania 1 1 1[269] –
 Barbados 1 7 1[270] –
 Saint Vincent and the Grenadines – 62 1[271] –
 Dominican Republic 69 73 1[272] –
 Jamaica 443 622 1[273] –
 Serbia 81 81 1[274] –
 Tanzania 2 3 1[275] –
 Togo – – 5[276] –
 Belarus – 71 4[277] –
 Bosnia and Herzegovina 118 122 10[278] –
 Angola 25 37 16[279] –
 Democratic Republic of the Congo 34 204 1[280] –
 Bulgaria 2,516 2,520 12[281] –
 Mayotte 123 130 1[282] –
 Martinique – 593 1[283] –
 Gambia 30 155 26[284] –
 Seychelles – 235 464[60] –
 Saint Martin 224 240 2[285] –
 Laos – – 1[286] –
 Iraq 36 103 5[287] –
 Mauritania – – 14[288] –
 South Sudan 28 28 41[289] –
 Ivory Coast 41 60 78[290] –
 Cape Verde – 152 175[291] –
 Antigua and Barbuda – 36 1[292] –
 Gabon – – 1[293] –
 Bolivia 2 7 1[294] –
 Moldova 287 314 29[295] –
 Kazakhstan 8 8 8[296] –
 Guadeloupe 264 300 1[297] –
 Azerbaijan 12 12 12[298] –
 Suriname 81 96 146[60] –
 Sint Maarten – 479 753[60] –
 British Virgin Islands 20 26 39[60] –
 Mali 1 2 – –
 Anguilla 20 24 30[60] –
 Bonaire – 400 692[60] –
 Bhutan – – 14[299] –
 Papua New Guinea 379 565 1[300] –
 Mongolia 133 133 12[301] –
 Antarctica – – 24[302] –
 Uzbekistan – – 1[303] –
 Saint Lucia 1 9 54[60] –
 Burundi – 1 28[60] –
 American Samoa – 35 84[60] –
 Armenia 4 16 17[60] –
 Guinea 48 167 159[60] –
 Guam 168 274 348[60] –
 Belize 223 240 441[60] –
 Eswatini 124 133 – –
 Djibouti 306 308 337[60] –
 World total (170 countries and territories) 2,986,573 3,517,102 1,168,383 620,384


History

A December 2021 article in Science[304] 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,[1] based on samples that had been collected from 14 to 16 November.[305] 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.[306][307] The first confirmed specimens of Omicron were collected on 8 November 2021 in South Africa,[10][11] and on 9 November in Botswana.[26] Likely Omicron (SGTF) samples had occurred on 4 November 2021 in Pretoria, South Africa.[308]

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.[307][309][310]

On 25 November, one confirmed case was identified in Israel from a traveler returning from Malawi,[311] along with two who returned from South Africa and one from Madagascar.[312] All four initial cases reported from Botswana occurred among fully vaccinated individuals.[313]

On 26 November, Belgium confirmed its first case; an unvaccinated person who had travelled from Egypt via Turkey on 11 November.[12][314][315] All three initial confirmed and suspected cases reported from Israel occurred among fully vaccinated individuals,[311] as did a single suspected case in Germany.[316]

On 27 November, two cases were detected in the United Kingdom, another two in Munich, Germany and one in Milan, Italy.[317]

On 28 November, 13 cases were confirmed in the Netherlands among the 624 airline passengers who arrived from South Africa on 26 November.[318] Confirmation of a further 5 cases among these passengers followed later.[319] 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.[320] 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.[321] 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.[322][323] On the same day, Austria also confirmed its first Omicron case.[324] A detected Omicron case was reported in the Czech Republic, from a traveler who spent time in Namibia.[325] 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.[326]

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.[327] Two more people who travelled to Sydney from southern Africa via Singapore tested positive.[328] Portugal reported 13 Omicron cases, all of them members of a soccer club.[329] Sweden also confirmed their first case on 29 November,[163] as did Spain, when a traveler came from South Africa.[330]

On 30 November, the Netherlands reported that Omicron cases had been detected in two samples dating back as early as 19 November.[331] 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.[332] Japan also confirmed its first case.[333] 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.[334] In Brazil, three cases of the Omicron variant were confirmed in São Paulo.[335] Another five are under suspicion.[336][337] A person in Leipzig, Germany with no travel history nor contact with travellers tested positive for Omicron.[338]

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.[339][340] 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[341] and was confirmed to have a mild case of COVID-19 on 29 November.[342] Ireland and South Korea also reported their first cases.[343] South Korea reported its cases from five travelers arriving in South Korea from Nigeria.[344]

On 2 December, Dutch health authorities confirmed that all 14 passengers with confirmed Omicron infection on 26 November had been previously vaccinated.[345] 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.[346] France has confirmed only 25 cases of the new Omicron variant but officials say the number could jump significantly in the coming weeks.[347]

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.[348] 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.[349] Fiji also confirmed two positive cases of the variant. They travelled from Nigeria arriving in Fiji on November 25.[350]

On 8 December, WHO announced the variant had been detected in 57 countries.[351]

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.[352]

On 13 December, the first death of a person with Omicron was reported in the UK.[353]

On 16 December, New Zealand confirmed its first case of the Omicron variant, an individual who had traveled from Germany via Dubai.[354]

The first death of a person with Omicron was reported in Germany on 23 December[355] and in Australia on 27 December.[356]

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.[357] Cryptocurrency markets were also routed.[358][359][360] 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.[361][362][363]

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."[364]

International response

On 26 November, WHO advised countries not to impose new restrictions on travel, instead recommending a "risk-based and scientific" approach to travel measures.[365] 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.[30]

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,[366] 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.[367][368]

The Brazilian Health Regulatory Agency recommended flight restrictions regarding the new variant.[369] 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.[370] 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.[371]

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.[372]

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.[373] At the same time, inoculation has slowed in South Africa due to vaccine hesitancy and apathy, with only 35% of the population being fully vaccinated as of November 2021.[374]

On 29 November 2021, 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.[69]

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."[375]

In mid-December 2021, 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",[376][377][378] 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.[379]

On the 18th of December, the Dutch government announced a hard lockdown for the entire country.

See also

Notes

  1. ^ ECDC rapid risk assessment of Omicron,[47] annex 1.
  2. ^ Logarithmic growth rate of 0.41/day means that the log odds loge(SGTF/SGTP) is increasing by 0.41 in a day. So SGTF/SGTP was increasing by a multiplicative factor of exp(0.41) ~ 1.51. This is substantially higher than a naive increase to 100%+41%. The difference is mathematically due to compound growth within the day, which does not imply that epidemically people are already infectious within a day. Rather, simplified (non-delay) differential equations are used for convenience for the modeling. This also indicates a doubling time of log_e(2)/(0.41/day) ~ 1.69 days for the Omicron to Delta prevalence ratio.
  3. ^ Referring to ref 6 in the reference, where the x-axis is crossed at 14 December
  4. ^ A doubling time of 2.5 days corresponds to an exponential growth rate of ln(2)/(2.5 days) ~ 28%/day. Direct comparison to the logistic growth rate needs to take the growth/decline of Delta into account
  5. ^ With a presumed an identical person-to-person serial interval of log_e(2.4)/0.21 ~ 4.2 days, or a distribution thereof to the same effect.

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Further reading

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