Do the New Omicron Sub-variants Pose a Risk? Here is a look on how Scientists are Keeping Track

A network of scientists in South Africa are currently investigating whether the new COVID-19 lineages BA.4 and BA.5 can elude immunity induced by previous infections and COVID-19 vaccination. A group of researchers discovered the new Omicron sub-variants at the Stellenbosch

University in South Africa. Tulio De Olivera, the team's head biologist, who also leads one of the world's most robust genomic surveillance programs for SARS-CoV-2, indicated increasing numbers of new infections with the sub-variants in South Africa. The World Health Organization (WHO) monitors the viruses because laboratory tests show that their changes may enable them to circumvent immunity induced by COVID-19 vaccinations or prior infections more effectively than existing sub-variants of Omicron. On the other hand, De Oliveira believes there is no need to panic yet. Although the BA.4 and BA.5 Omicron sub-variants have gained a significant foothold in South Africa over the last month, the country's rates of COVID-19 infections and hospitalizations remain steady. He explained that it is not the first time his researchers have dealt with similar situations throughout the pandemic. He encouraged the global science community to be calm, work attentively and diligently to unravel the mysteries of the new omicron sub-variants.

Scientists are now analyzing these new sub-variants globally. They aim to assess whether the effects of these viruses are significant enough to justify action. Wendy Barclay, a leading virologist at Imperial College London, reiterated that the Covid-19 virus will keep changing. Still, not all of these alterations will be significant. In addition, she said the science community was concerned about a difference in illness severity and about variants that circumvent immunity generated by vaccinations as it can lead to an increase in cases and significantly impact the fight against that pandemic. At the same time, researchers globally struggle with how to openly communicate their concerns and uncertainty about variants without inciting unwarranted government regulations and alarms among the public. When de Oliveira's team discovered the original Omicron late last year, several countries imposed travel prohibitions on South Africa, notably the United States and the United Kingdom. The bans were ineffective in preventing the variant's spread but badly harmed South Africa's already-fragile economy. If that occurs again, de Oliveira adds, "I would cease real-time data sharing with the rest of the world but continue sharing with my government to direct our own response.

What To Know About The New Variants

Tulio De Olivera's team of researchers discovered numerous aberrant SARS-CoV-2 genomic sequences on April 1. The genetic sequences contained several significant mutations in the region of the virus that encodes the spike protein. Because the spike protein is required for the virus to infect cells, the team saw an urgent need to search for these mutations in all genomes sequenced in the country during the last six months to determine if they had gone unnoticed. Preliminary data revealed that the BA.4 and BA.5 sequences comprised about 5% of the 500 genomes sequenced in South Africa. By the first week of April, the portion had risen to 50%. The same week, an international virus classification group determined that BA.4 and BA.5 were their own separate lineages on the Omicron variant and assigned their names. In addition to the sequences from South Africa, there have been a few BA.4 and BA.5 sequences from Botswana, Belgium, Denmark, and the United Kingdom in the last two weeks, and BA.5 has been found in China, France, Germany, and Portugal.

One feature that distinguishes BA.4 and BA.5 from other viruses is a common amino acid mutation called F486V. It is positioned on the virus's spike protein near the point where the protein binds to the ACE2 receptor on cells – a binding site that initiates infection. Significant antibodies developed in response to COVID-19 vaccines and earlier SARS-CoV-2 disease neutralize the virus by sticking to this location. Since last year, researchers have noticed this spot's vulnerability in laboratory experiments. For instance, Benhur Lee and his team of virologists at the Icahn School of Medicine at Mount Sinai in New York City tested a promising monoclonal antibody treatment by exposing it to artificial virus-containing multiple variants of the SARS-CoV-2 spike protein. The antibodies were circumvented by only one variant of the spike protein. The spike protein possessed an almost identical mutation to F486V. Lee was relieved at the moment to learn that the alteration was highly unusual in real life, implying that it hampered the virus in some way. Because the mutation was found in just approximately 50 of the almost 10 million SARS-CoV-2 sequences in GISAID, Lee was confident that the antibody treatment would still be effective. However, Lee says that given the fast spread of BA.4 and BA.5 in South Africa, it appears that the coronavirus has developed to the point where the mutation no longer holds it back.

How dangerous are the new sub-variants?

Virologists at the World Health Organization (WHO) presently monitor the sub-variants. However, most researchers think that conclusions should not be drawn about whether they offer more significant harm than other Omicron sub-lineages. Further information from epidemiological studies of humans is needed to make an inference. Immunologists are also examining immune evasion by exposing BA.4 and BA.5 samples to blood from persons who have previously been infected with SARS-CoV-2 and those who have received the Covid-19 vaccines.

"This is why we immediately distributed samples to researchers worldwide," de Oliveira explains. Scientists from South Africa, the United Kingdom, the US National Institutes of Health, and the Chinese Center for Disease Control and Prevention were included. De Oliveira and his team met with the South African government and a consortium of roughly 200 researchers shortly after recognizing BA.4 and BA.5 to plot subsequent actions. With no increase in hospitalizations and only approximately 1,200 instances per day in South Africa, he counselled the government against enacting harsher guidelines than the country already has. The administration has not amended its policies so far. 

De Oliveira and his colleagues were very cautious in communicating news of sub-lineages to health officials in other countries, encouraging them to keep an eye on things while avoiding regulations that are usually ineffective, such as travel bans, and can cause more harm than good. "We're under a lot of stress," de Oliviera explains. "When we reported on the new Omicron sub-variants, my colleagues and I received death threats." Security had to be placed in front of the lab."

South Africa's monitoring efforts and transparency were applauded by the scientific community worldwide for their conscientious efforts in the face of great difficulty. 

Data indicates that this year's SARS-CoV-2 variants cause less severe symptoms than previous versions of the virus. Still, researchers warn that this does not mean the Covid-19 virus will continue to deteriorate in strength. Apart from gaining common mutations, SARS-CoV-2 can evolve fast by recombination, the process by which one segment of a sequence from one lineage is inserted into the genome. Suppose an Omicron sub-variant recombines with another SARS-CoV-2 lineage. In that case, it might result in a virus that evades immunity and makes patients sicker. The researchers are hopeful that the new sub-variants will be part of a more significant trend of the virus getting milder.

Still, outside of hope though, there's no scientific reason to expect this will always be the case.