IMAGE_LINK1R
A very long intermission: The variant is spreading so rapidly in global cities such as New York that one Broadway show — Moulin Rouge — was canceled mid-show Thursday night after cast members tested positive. Your author’s Christmas lunch booking was canceled when restaurant staff tested positive: Shutdowns scenes like this are being repeated across the city at a speed that reminds residents of March 2020. Let’s hope there is no return of morgue trucks parked in the street.
Across Europe, many countries are instituting restrictions that are summarized as canceling Christmas, again. Even Queen Elizabeth canceled her family Christmas lunch.
OMICRON VARIANT
BBBB
The Omicron variant is a variant of SARS-CoV-2, the virus that causes COVID-19. It was first reported to the World Health Organization from South Africa on 24 November 2021. On 26 November 2021, the WHO designated it as a variant of concern and named it 'Omicron', the fifteenth letter in the Greek alphabet.
The variant has an unusually large number of mutations, several of which are novel 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, 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. As of 15 December 2021, the variant has spread to over 80 countries.
The new variant was detected on 22 November 2021 in laboratories in Botswana and South Africa. The global patient zero was a man arriving in Hong Kong from South Africa via Qatar on 11 November. Another early case on 19 November was later identified in the Netherlands.
The variant has many mutations, some of which have concerned scientists. 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. 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 characterized 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. It also carries a number of changes and deletions in other genomic regions. Additionally, the variant has three mutations at the furin cleavage site. The furin cleavage site increases SARS-CoV-2 infectivity. The mutations by genomic region are the following:
Stealth variant Researchers have established the existence of two variants of Omicron. The 'standard' one is now referred to as BA.1?/B.1.1.529.1, and a second variant of Omicron is known as BA.2?/B.1.1.529.2. BA.2 has been nicknamed 'Stealth Omicron' because it differs from the 'standard' variety by not having the characteristic SGTF-causing deletion by which many PCR tests were able to detect it as an Omicron, or Alpha, variant. Some countries, including Denmark, use a variant qPCR that tests for several mutations, including ?69-70, E484K, L452R and N501Y. It can also distinguish Delta, which has L452R but not N501Y, and both Omicron sublineages, which have N501Y but not L452R.
2222R
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 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, 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.
Signs and symptoms Main article: Symptoms of COVID-19 No unusual symptoms had been associated with the variant as of 26 November 2021, and, as with other variants, some individuals are asymptomatic. 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.
British epidemiologist Tim Spector said in mid-December 2021 that the majority of symptoms of the Omicron variant were the same as a common cold, including headaches, sore throat, runny nose, fatigue and sneezing, so that people with cold symptoms should take a test. 'Things like fever, cough and loss of smell are now in the minority of symptoms we are seeing. Most people don’t have classic symptoms.' People with cold symptoms in London are 'far more likel'y to have Covid than a cold.
1111L
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 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'.
Work made available online by researchers at the University of Hong Kong on 15 December 2021 before peer review reports that Omicron grew seventy times faster than Delta in bronchial tissue, which could help explain the variant's rapid transmission. Omicron also grew ten times slower in lung tissue, which the authors suggest could indicate lower disease severity. The researchers said that the result needed to be interpreted with caution; in particular, even a less virulent variant could cause more cases of severe disease and death by infecting more people, concluding that 'the overall threat from the Omicron variant is likely to be very significant'.
Virulence Fergus Walsh wrote in November 2021 '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.' 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', even if it has not been determined that this is attributed to this specific 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. 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. As of 15 December 2021, 20 days after the first significant uptick in South Africa cases, there was still no significant uptick in COVID deaths. This contrasted with the previous two waves, in both of which a substantial increase in deaths occurred starting 12 days after the first uptick in cases.
3333L
Diagnosis See also: COVID-19 testing The FDA has published guidelines on how PCR tests will be affected by Omicron.'SARS-CoV-2 Viral Mutations: Impact on COVID-19 Tests'. Retrieved 16 December 2021. 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. The BA.1 lineage, but not the BA.2 lineage, can be identified by S gene target failure of the TaqPath assay, a trait shared with subsets of SARS-CoV-2 Alpha variant. Several other commercial assays can also be used, though they test for different amino acid substitutions.
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.
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 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. A preprint from Germany also suggests that many of the people who receive three doses of an mRNA vaccine can form antibodies to omicron.
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, 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. On December 14, Davide Corti et al. released a preprint suggesting that previous infection with COVID-19 with no vaccine or two doses of the Johnson & Johnson, Sinopharm or Sputnik vaccines were not generating significant antibodies to a virus with an Omicron spike, but many of the health care workers who had had two doses of the Pfizer or Moderna vaccines and had also previously recovered from COVID-19 did generate antibodies.
Treatment See also: Treatment and management of COVID-19 Corticosteroids such as dexamethasone and IL6 receptor blockers such as tocilizumab 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 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.
A preprint of early December 2021 suggests that casirivimab/imdevimab may no longer be effective at inhibiting Omicron. According to another preprint, the monoclonal antibody sotrovimab may be effective against viruses similar to Omicron. A third preprint suggests that sotrovimab and DXP-604 may function at reduced efficacy against Omicron, and that the variant may escape tixagevimab/cilgavimab, casirivimab/imdevimab, bamlanivimab/etesevimab and amubarvimab. Davide Corti et al. released a preprint suggesting that casirivimab/imdevimab and bamlanivimab/etesevimab were generating fewer neutralizing antibodies, but sotrovimab and Vir-7832 seem to be holding up.
Epidemiology On 26 November 2021, the South African National Institute for Communicable Diseases announced that 30,904 COVID-tests detected 2,828 new COVID infections. One week later, on 3 December 2021, the NICD announced that 65,990 COVID tests had found 16,055 new infections 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.
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.'
Detectable changes in levels of COVID-19 in wastewater samples from South Africa's Gauteng province were seen as early as 17–23 October. The National Institute for Communicable Diseases reports that children under the age of 2 make up 10% of total hospital admissions in the Omicron epicentre Tshwane in South Africa.
A study suggests that Omicron has picked up one of its mutations, ins214EPE, from HCoV-229E, a 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.
In the UK, the logarithmic growth rate of Omicron-associated S gene target failure cases over S gene target positive cases was estimated at 0.41 per day, which is exceptionally high. Furthermore, by 13 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. Denmark, in which the logistic growth is similar, appears to be ahead in Europe, and the Omicron variant there may become the most prevalent strain around 14 December. Switzerland is not far behind and neither is Germany. In Scotland, Omicron apparently became the most prevalent variant around 11 December, or otherwise may occur early in the week afterwards. In Ontario it appears to have become the most prevalent strain around 13 December. 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.
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. 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.