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SITAATTI
SARS-CoV-2 Omicron variant
Abas Khan, Senior Resident, hospital adminstration, SKIMS
Mohd Sarwar Mir,Resident Medical Officer,SKIMS
Ruksana Hamid,Medical officer and anesthesiologist, JK health
Rayees Ul Hamid Wani, Senior Resident, Emergency medicine, SKIMS
Corresponding author
Ruksana Hamid, Medical officer and Anesthesiologist, JK health
https://www.researchgate.net/publication/357574328_SARS-CoV-2_Omicron_variant
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. 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.
[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".
The GISAID project has assigned it the clade identifier GR/484A, and
the Nextstrain project has assigned it the clade identifier 21K.
Mutations
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 1are 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.
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
o Half (15) of these 30 changes are located in the receptor binding
domain-RBD (residues 319–541)
ORF1ab
o nsp3: K38R, V1069I, Δ1265, L1266I, A1892T
o nsp4: T492I
o nsp5: P132H
o nsp6: Δ105-107, A189V
o nsp12: P323L
o 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 type of virus
(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.
Sublineages and stealth variant (Alalinjat ja häivevariantti; suomeksi)
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.
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. Some countries, including Denmark, use a variant qPCR that tests for
several mutations, including Δ69-70, E484K, L452R and N501Y. It can also
distinguish Delta (the heavily dominant variant worldwide, prior to the spread
of Omicron), which has L452R but not N501Y, and all Omicron sublineages,
which have N501Y but not L452R. As of 19 December 2021, BA.2 appears to
be very rare with about twenty known cases from half a dozen countries. 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.
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.
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 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.
Signs and symptoms
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".
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".
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."
A unique reported symptom of the omicron variant is night sweats.
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.
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".
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.[60] 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.[61]
Diagnosis
See also: COVID-19 testing
The FDA has published guidelines on how PCR tests will be affected by
Omicron.[62] 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.[63] 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
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.
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.
On 29 November 2021, the WHO said cases and infections are expected among
those vaccinated, albeit in a small and predictable proportion.
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.
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
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.
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. Merck and Ridgeback were
evaluating the anti–RNA virus drug molnupiravir for omicron treatment at the
time.
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
0.41 per day,[c] 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 and
neither is Germany. 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 21, growing at
0.23 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, the Netherlands appears to be on a similar path. 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%. Many 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.
History
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.
.
Market reactions
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, 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 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.
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 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", 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 2021, the Netherlands government announced a lockdown
intended to prevent spread of the variant during the holiday period.
References
1. ^ "Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of
Concern". World Health Organization. 26 November
2021. Archived from the original on 26 November 2021. Retrieved 26
November 2021.
2. ^ Parekh, Marcus; Platt, Poppie; Team, Global Health Security;
Barnes, Joe (26 November 2021). "Coronavirus latest news: EU
suspends all flights to southern Africa over omicron Covid variant
fears". The Telegraph. ISSN 0307-1235. Archived from the original on
26 November 2021. Retrieved 26 November 2021.
3. Meyer, David (26 November 2021). "What's Omicron? Here's what
we know and don't know about the new COVID variant that's roiling
markets and air travel". Fortune. Archived from the original on 26
November 2021. Retrieved 26 November 2021.
4. ^ Torjesen, Ingrid (29 November 2021). "Covid-19: Omicron may be
more transmissible than other variants and partly resistant to existing
vaccines, scientists fear". BMJ. 375:
n2943. doi:10.1136/bmj.n2943. ISSN 1756-1833. PMID 34845008. S2CI
D 244715303. Archived from the original on 2 December 2021.
Retrieved 2 December 2021
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