Is Omicron really so bad? So far, scientists have discovered

Researchers at COVID are working furiously to discover more about the variant's transmissibility, severity, and capacity to elude immunizations.

It's been less than a week since scientists in Botswana and South Africa warned the world about Omicron, a fast-spreading new SARS-CoV-2 mutation. Researchers from all around the world are scrambling to comprehend the harm that the variation poses to the world, which has already been confirmed in more than 20 countries. However, it could take weeks for scientists to get a better picture of Omicron, including its transmissibility and severity, as well as its ability to escape immunizations and cause reinfections.

What is the rate of Omicron's spread?

The quick rise of Omicron in South Africa is what researchers are most concerned about, as it shows the mutation could induce a surge in COVID-19 cases elsewhere. South Africa reported 8,561 cases on December 1, up from 3,402 on November 26 and several hundred per day in mid-November, with majority of the surge taking place in Gauteng Province, which includes Johannesburg.

R, the average number of new cases spread by each infection, is used by epidemiologists to track the spread of an epidemic. The National Institute for Communicable Disease (NICD) in Johannesburg, South Africa, determined that R was above 2 in Gauteng in late November. According to Richard Lessels, an infectious-disease physician at KwaZulu-Natal University in Durban, South Africa, that degree of increase was last seen in the early days of the pandemic.

According to Tom Wenseleers, an evolutionary biologist at KU-Leuven in Belgium, Gauteng's R value was considerably below 1 in September, when Delta was the main form and cases were dropping, indicating that Omicron has the potential to spread more faster and infect far more individuals than Delta. Wenseleers believes that Omicron can infect 3 to 6 times as many people as Delta during the same time frame, based on the growth in COVID-19 cases and sequencing data. "For the virus, that's a big benefit — but not for us," he adds.

According to Christian Althaus, a computational epidemiologist at the University of Bern in Switzerland, researchers will be studying how Omicron spreads in other parts of South Africa and around the world to gain a better understanding of its transmissibility. Researchers may overstate Omicron's rapid expansion due to increased surveillance in South Africa. However, if this trend is replicated in other nations, Althaus believes it is very strong proof that Omicron has a transmission advantage. "If it doesn't happen in European countries, for example, it suggests things are a little more complicated and heavily reliant on the immunological landscape." As a result, we'll have to wait."

Although genome sequencing is required to identify Omicron cases, some PCR tests can detect a distinguishing feature of the variant that sets it apart from Delta. On the basis of this signal, there are preliminary indications that, despite their rarity, cases are increasing in the United Kingdom. "That's certainly not what we want to see right now," Althaus continues, "and it shows that Omicron may have a transmission advantage in the UK as well."

Is Omicron capable of overcoming vaccination or infection-induced immunity?

The rapid spread of the variation in South Africa suggests that it has the potential to bypass immunity. According to Wenseleers, just around a quarter of South Africans are fully vaccinated, and it's possible that a considerable proportion of the population was infected with SARS-CoV-2 in earlier waves, based on higher death rates since the pandemic began.

Omicron's success in southern Africa may be attributable in part to its ability to infect persons who have recovered from COVID-19 cases caused by Delta and other variations, as well as those who have been vaccinated. According to a preprint1 published on December 2 by researchers at the NICD, as Omicron has spread, reinfections in South Africa have increased. "Unfortunately," says Althaus, "this is the ideal habitat for immunological escape variations to evolve."

According to Aris Katzourakis, a viral evolution researcher at the University of Oxford in the United Kingdom, how successfully the variation spreads depends on factors including vaccination and prior infection rates. "It might have the edge there if you throw it into the mix in a heavily vaccinated population that has given up on other control strategies."

Researchers want to see how well Omicron can dodge immune reactions and how well it protects itself. In a laboratory test, for example, a team led by Penny Moore, a virologist at the NICD and the University of Witwatersrand in Johannesburg, is assessing the efficacy of neutralizing, or virus-blocking, antibodies triggered by past infection and vaccination to prevent Omicron from infecting cells. Her team is developing 'pseudovirus' particles — an engineered version of HIV that infects cells using SARS-spike CoV-2's protein — to match Omicron, which has up to 32 alterations to the spike protein.

Similar tests on virus-neutralizing antibodies are being conducted by a South African team led by virologist Alex Sigal at the African Health Research Institute in Durban utilizing infectious SARS-CoV-2 particles. A team lead by Pei-Yong Shi, a virologist at the University of Texas Medical Branch in Galveston, is working with Pfizer–BioNtech to see how well its vaccination stands up to Omicron. "When I observed the constellation of mutations in the spike, I was pretty concerned," he says. "All we have to do now is wait for the results."

Previous research on Omicron's spike mutations has suggested that the variant will reduce the efficacy of neutralizing antibodies, particularly in the region that targets receptors on human cells. For example, a team led by Paul Bieniasz, a virologist at Rockefeller University in New York City, created a severely mutated version of spike — in a virus incapable of generating COVID-19 — that shares several mutations with Omicron in a September 2021 Nature paper2. Most of the persons they studied who had either gotten two doses of an RNA vaccine or recovered from COVID-19 found the 'polymutant spike' totally resistant to neutralizing antibodies. "We predict a major hit" with Omicron, according to Bieniasz.

How effective are vaccinations against Omicron?

Even though Omicron is impervious to neutralizing antibodies, immunological responses triggered by immunization and earlier infection may provide some protection against the variation. According to Miles Davenport, an immunologist at the University of New South Wales in Sydney, Australia, "immunity studies suggest that relatively low levels of neutralizing antibodies may protect persons from severe forms of COVID-19."

Other components of the immune system, particularly T cells, may be less affected than antibody responses by Omicron's mutations. According to Shabir Madhi, a vaccinologist at the University of Witwatersrand, researchers in South Africa want to examine the activity of T cells and another immunological component known as natural killer cells, which may be especially crucial for protection against severe COVID-19.

Madhi, who conducted the COVID-19 vaccination trials in South Africa, is also working on epidemiological studies to determine the efficiency of vaccines against Omicron. Breakthrough infections have been reported in all three vaccinations provided in South Africa — Johnson & Johnson, Pfizer–BioNtech, and Oxford–AstraZeneca. Researchers, however, would want to quantify the level of protection offered by vaccines, as well as prior infection with Omicron, according to Madhi.

He expects the outcomes to be similar to how the AstraZeneca–Oxford vaccine fared against the Beta variation, an immune-evading mutation discovered in late 2020 in South Africa. In a study led by Madhi, it was discovered that the vaccination provided minimal protection against mild and moderate cases in relatively young persons, but a real-world analysis in Canada revealed that the vaccine provided better than 80% protection against hospitalization.

"We're going to witness a rise of instances," Madhi predicts if Omicron behaves similarly. There will be numerous breakthrough infections and reinfections. However, there will be an unhinging of the community case rate relative to the hospitalization rate." According to early studies, most Omicron breakthrough infections have been moderate, according to Madhi. "That's a positive indicator for me."

Will the present boosters help with Omicron protection?

Omicron's threat has encouraged some wealthy countries, like as the United Kingdom, to speed up and expand the distribution of COVID vaccination booster doses. However, it's unclear how effective these extra doses will be.

The third dose boosts neutralizing antibody levels, which Bieniasz believes will act as a bulwark against Omicron's capacity to evade these antibodies. His research discovered that persons who had recovered from COVID-19 months before getting their vaccines still had antibodies capable of preventing the mutant spike. According to Bieniasz, those who have been exposed to SARS-spike CoV-2's protein multiple times, whether through infection or a booster dosage, are "very likely to have neutralizing activity against Omicron."

Is Omicron associated with a milder or more severe illness than other variants?

Early reports linked Omicron to modest disease, prompting optimism that the variant will be milder than its forerunners. However, according to Müge evik, an infectious disease specialist at the University of St Andrews in the United Kingdom, these reports — which are sometimes based on anecdotes or sparse data — can be deceptive. "Everyone is looking for data that will help us," she explains. "However, it's quite difficult right now."

Controlling for the many confounding circumstances that might impact the course of disease, especially when outbreaks are geographically limited, is a key difficulty when determining the severity of a variation. In South Africa, for example, reports of moderate sickness from Omicron infection likely reflect the country's young population, many of whom have already been exposed to SARS-CoV-2.

There were reports in the early days of the Delta outbreak that the variant was causing more significant sickness in children than other variants – a relationship that was disproved as additional data was gathered, according to evik.

Data on Omicron infections in other nations will be sought by researchers. Researchers will have a better understanding of how generalizable the early tales are as the number of instances grows, thanks to the geographic distribution and greater sample size. Researchers will eventually wish to undertake case-controlled trials in which the demographics of Omicron-infected patients are closely matched to the demographics of a control group. Scientists will be able to better control for critical aspects including age, immunization status, and health issues as a result of this. Because the number of hospitalizations might be influenced by general hospital capacity in a region, data from both groups will need to be collected in real time.

Researchers will also need to account for the extent of economic deprivation. According to evik, a rapidly spreading novel variety may reach vulnerable groups more quickly due to their employment or housing conditions. And people in these groups are more likely to get sick.

This will all take time. "I believe the severity question will be one of the final things we can figure out," she says. "It was the same way with Delta."

What is the status of Omicron and how are scientists tracking it?

Omicron has been found in over 20 nations so far, a number that is continuously increasing as attempts to track the variant grow around the world.

However, because the ability to sequence viruses from positive COVID testing quickly is concentrated in wealthier countries, early data on Omicron's spread will be distorted.

According to virologist Renato Santana of the Federal University of Minas Gerais in Brazil, surveillance efforts in Brazil and several other countries are taking use of a characteristic result on specific COVID PCR tests that could allow them to pinpoint possible Omicron cases for sequencing. The test looks for portions of three viral genes, one of which is the spike protein-encoding gene. Omicron's spike gene has mutations that prevent it from being detected in the test, hence samples carrying the variant will only test positive for two of the genes.

Nonetheless, not everyone utilizes that equipment, and mapping Omicron's spread may take some time. Despite some guidelines asking countries to sequence 5% of samples that test positive for SARS-CoV-2, computational virologist Anderson Brito of the All for Health Institute in So Paulo, Brazil, says few countries can afford to do so. Brito is also concerned that the travel prohibitions imposed by certain countries on South Africa and other southern African countries in the aftermath of the Omicron finding may dissuade governments from sharing surveillance data. "Those who performed a decent job are being punished," he says.

According to Senjuti Saha, a molecular microbiologist and director of the Child Health Research Foundation in Dhaka, researchers would be eager to ramp up genomic surveillance to monitor for Omicron and other emerging variants in Bangladesh, which sequences about 0.2 percent of positive coronavirus samples. However, funds are scarce. She also mentions that Bangladesh is recovering from a huge dengue outbreak. "We are all concerned about COVID in the Global South, but let us not forget about our endemic diseases," Saha says. "There's only so much we can do."