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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 (for other names, see § Nomenclature) is a variant of SARS-CoV-2, the virus that causes COVID-19. 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 after 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 discovering the Omicron variant. This level of variation has led to concerns regarding its transmissibility, immune system evasion, and vaccine resistance. As a result, 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.

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] 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][6][7] The World Health Organization reserves a Greek-letter designation for "variants of concern".[8][3]

Possibly due to a lack of familiarity with the Greek alphabet among some English speakers, the name of the variant has also occasionally been mispronounced as "Omnicron".[9][10][11][12]

The GISAID project has assigned it the clade identifier GR/484A[13] and the Nextstrain project has assigned it the clade identifier 21K.[14]

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: EDCD Threat Assessment Brief[15] CoVariants[14]

The variant has a large number of mutations, some of which have concerned scientists.[16] 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.[17][18] 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.[19] The furin cleavage site increases SARS-CoV-2 infectivity.[20] The mutations by genomic region are the following:[21][15]

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​.[22]
  • 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

At least one new mutation may have been acquired from one of the coronaviruses that causes the common cold (HCoV-229E) or the human immunodeficiency virus (HIV), since that particular genetic sequence is known to exist in both of these viruses; South Africa likewise has the world's highest incidence of HIV infection, creating a high likelihood of concurrent infection.[23]

Possible consequences

The WHO is concerned that the 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.[24]

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."[25]

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,.”[26]

Signs and symptoms

Main article: Symptoms of COVID-19

No unusual symptoms have yet been associated with the variant and, as with other variants, some individuals are asymptomatic.[27] Angelique Coetzee, chair of the South African Medical Association, said she had first encountered the variant in patients who had fatigue, aches and pains, but no cough or change in sense of smell or taste.[28]

Fergus Walsh wrote, "South Africa has a young population and it is encouraging that doctors there are reporting that Omicron is causing mild symptoms with no increase in hospital admissions. But we need to see what happens when the variant moves into older age groups who are the most vulnerable to Covid."[29] However, in an update on the variant, the World Health Organization stated "Preliminary data suggests that there are increasing rates of hospitalization in South Africa",[30] even if it has not been determined that this is attributed to this specific variant.

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.[18] 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.[15]

As of November 2021, it is unknown how the variant will spread in populations with high levels of immunity, it is also unknown 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.[31]

Relating to monoclonal antibodies (moAb) treatments, similar testing and research is undergoing. Preclinical data on in vitro pseudotyped virus data demonstrate that some moAbs designed to use highly conserved epitopes retain neutralizing activity against key mutations of Omicron substitutions.[32] Anne von Gottberg, an expert at the National Institute for Communicable Diseases, believes that immunity granted by previous variants will not protect against Omicron.[33]

Diagnosis

See also: COVID-19 testing

Current PCR tests can detect the variant. Some laboratories have indicated that a widely used PCR test does not detect one of the three target genes. Just as with the Alpha variant, this partial detection ("S gene target failure") can serve as a marker for the variant, however.[1] Rapid antigen tests are most likely not affected.[27]

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][34]

On 26 November, BioNTech said it would know in two weeks whether the current vaccine is effective against the variant and that an updated vaccine can 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.[35] On the same day, Novavax stated that it was developing an updated vaccine for the Omicron variant, which the company expected to be ready for testing and manufacturing within a few weeks requiring two doses.[36][37] On 29 November, Sinovac said it can quickly mass-produce an inactivated vaccine against the variant and that it is monitoring studies and collecting samples of the variant to determine if a new vaccine is needed.[38] 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.[39]

On 29 November, the WHO said cases and infections are expected among those vaccinated, albeit in a small and predictable proportion.[40]

On 29 November, Pfizer CEO Albert Bourla said that Pfizer 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.[41][medical citation needed] Also, Merc and Ridgeback are evaluating the anti–RNA virus drug molnupiravir for omicron treatment.[42]

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, effectiveness of public health and social measures, diagnostic methods, immune responses, antibody neutralization, or other relevant characteristics.[43]

Treatment

See also: Treatment and management of COVID-19

Corticosteroids and IL6 receptor blockers are known to be effective for managing patients with severe COVID-19. The impact on the effectiveness of other treatments is currently being assessed.[44][45]

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 (positive rate 9.2%).[46] 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.[47][48] This province of South Africa is densely populated at about 850 inhabitants per km². Gautengs 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.[49] The virus appears to be strongly dependent on reinfections.[50][51]

It has been estimated the Omicron variant diverged in late September or early October 2021, based on Omicron genome comparisons.[52] 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.[53][54] "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."[55]

In the UK, the logistic growth rate of Omicron-associated S-gene target failure (SGTF) cases over S-gene target positive (SGTP) cases was estimated at 141% per week during the week of 24 to 30 November 2021. That the "natural" logarithm of the ratio ("log odds") increased with 141% (= 1.41) during this week implies that SGTF was growing exponentially with respect to SGTP by a multiplicative factor of on a weekly basis. The quality of the data is hampered by background SGTF cases from the waning B.1.617.1 Delta subvariant, so this strong growth was only seen for 1 week yet, before which the background cases had to become relatively small and stable.[56]

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 (for a days presumed identical typical generational interval). This also implies a doubling time of days with respect to Delta, and a weekly multiplicative growth factor with respect to Delta of Omicron became the majority strain in South Africa around 10 November.[57][58]

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).[59] The National Institute for Communicable Diseases reports that kids under the age of 2 make up 10% of total hospital admissions in the Omicron epicentre Tshwane in South Africa.[60]

A study suggests that Omicron has picked up one of its mutations, ins214EPE, from the HCoV-229E common cold coronavirus strain, a genetic sequence also present in the human genome. This appears to aid the virus in circumventing the human immune system.[61][62][63]

In Denmark[64][65] and the UK[56], the Omicron indicating SGTF proportion is approaching 1% of cases.[66] The ratio between Omicron and the legacy strains is then at 1/99 = 0.0101. The log odds of 0.0101 (= exp(-4.60 )) is , so the log odds has to grow by 460% for Omicron to become the majority strain when the log odds become 0 for a ratio of 1 (=exp(0)) between Omicron and the legacy strains. Currently, the log odds appears to grow at the 21%/day and 141%/week logistic growth rates as mentioned above.

Statistics

Cumulative confirmed Omicron variant cases by country and territory
  •   100–999
  •   10–99
  •   1–9
  •   0

The chance of detecting a case varies significantly, especially depending on a country's sequencing rate. For example, South Africa sequences far more samples than any other country in their continent, but at a considerably lower rate than most Western nations.[67][68]

Confirmed infections as of 5 December 2021:

Confirmed cases by country and territory
Country/Territory Confirmed cases Suspected cases
 United Kingdom 246[69][70][71][72] –
 South Africa 228[69] 55,755[70]
 Zimbabwe 50[70][73] –
 United States 39[74][70] –
 Portugal 38[75] 6[70]
 Ghana 33[69] –
 Denmark 32[76] 151[70]
 Australia 28[77][78] –
 Botswana 23[69][79] –
 India 21[80][81] –
 Netherlands 20[82][83] –
 Norway 19[84] 47[70]
 Canada 18[85] –
 France 16[86] –
 Germany 15[69][70] –
 South Korea 12[87][88] –
 Austria 11[69] –
 Hong Kong 9[69] –
 Italy 9[89][90][91] –
 Finland 7[92] –
 Spain 7[69][93][94][95] –
 Sweden 7[96] –
  Switzerland 7[69][97] –
 Belgium 6[69][98] –
 Brazil 6[99][100][101][102] –
 Israel 4[103][104][105] 24[70]
 Iceland 3[106] 4[70]
 Nigeria 3[107][108] –
 Zambia 3[109] –
 Japan 2[110] –
 Romania 2[111] –
 Singapore 2[69][112] 1[70]
 Chile 1[113][114] –
 Czech Republic 1[115][116] –
 Greece 1[117] –
 Ireland 1[118] –
 Luxembourg 1[69] –
 Malaysia 1[119] –
 Maldives 1[69] –
 Mexico 1[120] –
 Saudi Arabia 1[121] –
 Sri Lanka 1[122] –
 Tunisia 1[123] –
 United Arab Emirates 1[124] –
 Senegal 1[125] –
 Mozambique – 2[70]
 Estonia – 2[70]
World (46 countries and territories) Total: 939 Total: 48,856

History

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.[126] 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.[127][128] The first confirmed specimens of Omicron were collected on 8 November 2021 in South Africa,[54][129] and on 9 November in Botswana.[18]

When WHO was alerted on 24 November, Hong Kong was the only place outside of 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.[128][130][131] On 25 November, one confirmed case was identified in Israel from a traveler returning from Malawi,[132] along with two who returned from South Africa and one from Madagascar.[133] Belgium confirmed its first case; an unvaccinated person who had travelled from Egypt via Turkey on 11 November.[134][135][136] All four initial cases reported from Botswana occurred among fully vaccinated individuals.[137] All three initial confirmed and suspected cases reported from Israel occurred among fully vaccinated individuals,[132] as did a single suspected case in Germany.[138]

On 27 November, two cases were detected in the United Kingdom, another two in Munich, Germany and one in Milan, Italy.[89]

On 28 November, 13 cases were confirmed in the Netherlands among the 624 airline passengers who arrived from South Africa on 26 November.[139] Confirmation of a further 5 cases among these passengers followed later.[140] 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.[141] 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.[142] 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.[143][144] On the same day, Austria also confirmed its first Omicron case.[145] A detected Omicron case was reported in the Czech Republic, from a traveler who spent time in Namibia.[116] 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.[146]

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.[147] Two more people who travelled to Sydney from southern Africa via Singapore tested positive.[148] Portugal reported 13 Omicron cases, all of them members of a soccer club.[149] Sweden also confirmed their first case on 29 November,[150] as did Spain, when a traveler came from South Africa.[151]

On 30 November, the Netherlands reported that Omicron cases had been detected in two samples dating back as early as 19 November.[152] 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.[153] Japan also confirmed its first case.[154] 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.[105] In Brazil, three cases of the Omicron variant were confirmed in São Paulo.[155] Another five are under suspicion.[156][157] A person in Leipzig, Germany with no travel history nor contact with travellers tested positive for Omicron.[158]

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.[107][108] 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[159] and was confirmed to have a mild case of COVID-19 on 29 November.[160] South Korea also reported its first cases, from five travelers arriving in South Korea from Nigeria.[161]

On 2 December, Dutch health authorities confirmed that all 14 passengers with confirmed Omicron infection on 26 November had been previously vaccinated.[162] 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.[84]

Recent travelers[who?] have been subject to more testing.[163]

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.[164] Cryptocurrency markets were also routed.[165][166][167] 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.[168][169][170]

In 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."[171]

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.[172] 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.[15]

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,[173] 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.[174][175]

The Brazilian Health Regulatory Agency recommended flight restrictions regarding the new variant.[176] 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.[177] 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.[178]

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.[179]

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.[180] 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.[181]

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.[40]

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."[182]

See also

References

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Further reading

External links

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