The original author | Ewen Callaway & Heidi Ledford
COVID researchers are working around the clock to study the spread, severity, and ability of Omicron to escape the vaccine.
About a week ago, scientists in Botswana and South Africa reported the emergence of a new fast-spreading variant of the coronavirus (SARS-CoV-2), Omicron, sounding the global alarm. Right now, researchers around the world are constantly assessing the power of the strain — Omicron has been discovered in more than 20 countries and territories (see: Omicron strain that alarms scientists). Still, it may take scientists a few weeks to fully understand Omicron, including its spread and severity, as well as its ability to escape vaccines and cause re-infection.
With the advent of the highly variable strain of Omicron, there has been a sharp increase in COVID-19 infections in South Africa. Source: wikimedia commons
"Everywhere I go, someone asks me to talk about Omicron," said Senjuti Saha, a molecular microbiologist and director of the Bangladesh Children's Health Research Foundation, "and frankly, we know too little about the current situation, even scientists." ”
Here, Nature combs through the information scientists have about the Omicron variant.
How fast does Omicron spread?
The rapid spread of Omicron in South Africa is the most worrying place for researchers, as it means that Omicron will also trigger an explosive increase in infections elsewhere. On 1 December, South Africa had 8,561 confirmed cases – 3,402 on 26 November and only a few hundred in mid-November, with these new cases mainly occurring in Gauteng, where Johannesburg is located.
Epidemiologists usually use R-values to assess the development of outbreaks, which is the average number of people infected per infected person. South Africa's National Institute of Infectious Diseases (NICD) said in late November that Gauteng's R value had exceeded 2. The last time there was such rapid growth was early in the outbreak, Richard Lessels, an infectious disease physician at KwaZulu Natal University in South Africa, said at a recent news conference.
Gauteng's R value had fallen below 1 in September, when the main epidemic strain was Delta, and the number of cases declined, suggesting that Omicron is likely to spread much faster than Delta and increase the number of infections, says Tom Wenseleers, an evolutionary biologist at the University of Leuven in Belgium. Judging from the increase in the number of infections and sequencing data, Wenseleers estimates that Omicron will be 3-6 times more infected than Delta in the same period. "It's good for COVID-19, but it's bad for us," he said. ”
Researchers will continue to watch Omicron spread in other parts of South Africa as well as around the world to determine how strong its transmission capacity really is, said Christian Althaus, a computational epidemiologist at the University of Bern in Switzerland. Increased surveillance in South Africa may have led researchers to overestimate the speed at which Omicron spreads. But if this trend is also emerging in other countries, we have strong evidence that Omicron has a spread advantage, Althaus said. "If this doesn't happen, say in European countries, it's complicated and depends a lot on the immunity profile of the population." So we'll have to look at it again. ”
While genome sequencing is required to confirm that it is Omicron who is infected, some PCR nucleic acid tests can reveal a key feature that sets Omicron apart from Delta. According to this signal, initial indications are that Omicron cases, while not much now, have a tendency to increase in the UK. "It's certainly not what we want to see now, and it might mean that Omicron also has a spread advantage in the UK." Althaus said.
Omicron can escape from vaccines
Or infection of immunity?
The speed of Omicron's spread in South Africa suggests that it has some immune escape ability. About a quarter of South Africa's population has been fully vaccinated; the rising mortality rate since the outbreak shows that a large proportion of the population may have been infected with the new crown virus, Wenseleers said.
The reason why Omicron can still "camp" in such South Africa may be mainly because it can re-infect people who have recovered from infection with variants such as Delta and those who have been vaccinated. A team from the South African Institute of Infectious Diseases found in a preprint paper published on 2 December[1] that as The spread of Omicron, the number of reinfections in South Africa is also increasing. Althaus said: "Unfortunately, this is the best environment for the emergence of immune escape strains. ”
As for the spread of Omicron elsewhere, it may also depend on local vaccination rates and previous infection rates, said Aris Katzourakis, an expert on virus evolution at oxford university in the United Kingdom. "If you put it in a population that lifts the lockdown because of high vaccination rates, Omicron might have an advantage."
The researchers also wanted to measure Omicron's ability to escape immune responses and their corresponding protective powers. For example, Penny Moore, a virologist at the Institute of Infectious Diseases in South Africa and the University of Witwatersland, is leading a team to conduct laboratory studies to test infections and vaccine-induced neutral antibodies that block the virus to prevent Omicron from infecting cells. Her team is preparing "pseudoviral" particles — an HIV that was engineered to infect cells using the coronavirus spike protein — to match Omicron, who found 32 mutations in the spike protein.
Alex Sigal, a virologist at the African Health Institute in Durban, leads another South African team that is conducting similar tests with neutralizing antibodies to infectious coronavirus particles. Peiyong Shi's team at the University of Texas at Galveston School of Medicine is also working with Pfizer-BioNTech to test whether its vaccine works for Omicron. "I was really worried when I saw so many mutations in the spike protein," he said, "and we just have to wait for the results." ”
For mutations in the Omicron spike protein, especially in areas that recognize receptors on human cells, previous studies suggested that Omicron should be able to greatly reduce the potency of neutralizing antibodies. In a Nature paper published in September 2021[2], a team co-led by Paul Bieniasz, a virologist at Rockefeller University in New York City, engineered a highly variable spike protein in a virus that causes COVID-19, with many mutation sites identical to Omicron. This "multi-mutant spike protein" has been shown to resist neutralizing antibodies in most subjects, some of whom received two doses of RNA vaccine and some of whom have recovered from previous COVID-19 infections. For its part, Omicron, "We expect it to be a hit hard. Bieniasz said.
Early analysis suggested that the vaccine's efficacy against Omicron may be reduced. Source: wikimedia commons
How effective is the vaccine on Omicron?
Even if Omicron is not afraid of neutralizing antibodies, it does not mean that the immune response established by the vaccine and previous infections is completely ineffective against it. Immunization studies have shown that neutralizing antibody levels are relatively low or can prevent severe illness from COVID-19, says Miles Davenport, an immunologist at the University of New South Wales in Australia.
Other parts of the immune system, especially T cells, may not be as greatly affected by the Omicron mutation as the antibody response. Researchers in South Africa intend to analyze the activity of T cells and natural killer cells, an immune member, which could be extremely important in preventing severe covid-19, said Shabir Madhi, a vaccine scientist at the University of Witwatersrand.
Madhi has led the COVID-19 vaccine trial in South Africa and is also conducting epidemiological studies on the effectiveness of vaccines on Omicron. The Johnson & Johnson vaccine, Pfizer-BioNTech vaccine, and Oxford-AstraZeneca vaccine used in South Africa are rumored to have had breakthrough infections. But Madhi said the researchers wanted to first quantify how much protection the vaccine and pre-existing infections could provide to Omicron.
He speculates that the final result may be similar to the protection of the AstraZeneca-Oxford vaccine against the Beta variant. Beta is an immune-escaping strain discovered in South Africa in late 2020. Madhi's team has found that the AstraZeneca-Oxford vaccine does not prevent mild and moderate infections in relatively young people, but real-world research in Canada has found that its effectiveness in preventing hospitalization is more than 80%.
If Omicron is similar to that, Madhi said, "we're going to see a spike in the number of cases, see a lot of breakthrough infections, a lot of reinfections." But there will be a large gap between community infection rates and hospitalization rates. Early reports showed that the vast majority of breakthrough infections caused by Omicron were mild, Madhi said, "and in my opinion, that's a good sign." ”
The current reinforcement needle can be strengthened
Preventive effect on Omicron?
In the face of the Omicron threat, some rich countries, including the United Kingdom, have accelerated the vaccination of booster needles, but it is unclear how effective these boosters will be.
A third shot raises neutralizing antibody levels, which may weaken Omicron's ability to escape these antibodies like a golden bell hood, Bieniasz said. His team's previous study of multimutant spike proteins has found that people who are vaccinated months after recovering from COVID-19 have antibodies that block the multi-mutant spike protein. For Bieniasz, these results suggest that people who have been exposed multiple times to the coronavirus spike protein, either through infection or through a booster needle, are likely to have antibodies that neutralize the activity of Omicron.
Omicron causes more infections than that
Is the previous strain lighter or heavier?
Early reports found that Omicron was associated with mild illness, giving people the good news that Omicron may be a little weaker than several of its predecessors. But the reports are often from anecdotal or fragmented data, sometimes misleading, as Müge evik, an infectious disease expert at the University of St Andrews in the UK, cautions, "Everyone wants to search for some data as a guide, but at this stage it's very difficult." ”
A major difficulty in judging the severity of a variant is how to control for the various confounding variables that affect the course of the disease, especially when the variant only erupts in local areas. For example, the Report of Micron mild infections in South Africa may reflect the relatively young age of the South African population, many of whom have already been exposed to covid-19.
At the time of the Delta epidemic, there were reports that Delta was more likely to cause severe illness in children than other variants, and this link slowly faded as more data became available, evik said.
The researchers also wanted to analyze Omicron infections in other countries and regions. This geographic spread, combined with the larger sample size that cases have accumulated, will help researchers better judge whether some of the early rumors can be generalized. The researchers' ultimate goal was to conduct a case-control study that closely matched the demographics of the infectiond Omicron with those of the control group. This allows researchers to better control important factors such as age, vaccination status, health status, and more. Data from both groups need to be collected simultaneously, as the number of hospitalizations may be affected by the overall capacity of a regional hospital.
Researchers must also control levels of economic poverty. Evik said a new strain that spreads rapidly may spread more quickly among vulnerable populations, both because of the nature of the work and living conditions of those people. And these vulnerable groups are also more susceptible to severe illness.
All of this takes time. "I think severity is a question we're going to have to answer very later," she said, "delta was like that at the time." ”
Where has Omicron affected?
How do scientists track it?
So far, Omicron has appeared in more than 20 countries – a range that is gradually expanding as testing efforts increase around the world.
However, the ability to perform rapid viral sequencing of COVID-19-positive samples is mostly in wealthy countries, suggesting that our early data on the spread of Omicron are incomplete.
Virus surveillance efforts in countries such as Brazil have utilized a specialized COVID-19 PCR test that can show suspected cases of Omicron that need to be sequenced, said Renato Santana, a virologist at the Federal University of Minas Gerais in Brazil. The test examines fragments of three viral genes, one of which is a gene encoding spike proteins. Genetic mutations in the Omicron spike protein prevented it from being detected in the test, so only two other genes tested positive for the sample with Omicron.
However, not everyone has this test, and it may take some time to fully grasp the spread of Omicron. While some guidelines urge countries to sequence 5 percent of COVID-19-positive samples, not many are able to do so, said Anderson Brito, a computational virologist at Brazil's All for Health Institute. Brito also worries that some countries that have enacted travel bans on southern African countries such as South Africa as a result of Omicron's findings could discourage governments from making monitoring data public. "This is punishing countries that are actively open." He said.
Researchers there are eager to increase genetic surveillance to monitor the emergence of Omicron and other variants in Bangladesh, where 0.2 percent of COVID-19-positive samples are sequenced, Saha said. But that's all there is to it. Bangladesh, who has just recovered from a dengue outbreak, said, "In the countries of the global South, we are all worried about COVID-19, but we must not forget that we still have endemic epidemics," Saha said. ”
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[1] Schmidt, F. et al. Nature
Originally written as How bad is Omicron? What scientists know so far was published as a headline in the News section of Nature on December 2, 2021
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