Omicron mutation: Ineffective in almost all monoclonal – The first studies

Omicron mutation: Ineffective in almost all monoclonal – The first studies

Almost all monoclonal antibodies that have been developed and used to prevent severe Covid-19 infection appear to be less effective against the new Omicron variant, according to early laboratory (non-clinical) studies. The scientists’ initial pre-publications cite evidence from their laboratory experiments that Omicron is fully or partially resistant to virtually all existing monoclonal antibody therapies, according to Nature.

If this is confirmed, then the already overburdened hospitals, which are preparing for the upcoming new epidemic wave of cases due to Omicron, may not be able to “bet” on monoclonal antibodies, at least to the extent that they have done so far. These antibodies are artificial imitations of natural antibodies and are usually intended for patients at high risk for severe Covid-19.

Some companies that make such antibodies, such as the American Regeneron, already admit that their products are less effective against Omicron than other variants. According to researchers, only two monoclonal antibodies appear to be effective against Omicron: sotrovimab from US biotechnology company Vir Biotechnology and British GSK, and DXP-604, which is currently undergoing clinical trials in China and has been developed. from the Chinese companies BeiGene and Singlomics.

The US health authorities have already stated that they will use sotrovimab more widely and distribute it in the US states depending on the number of infections and hospitalizations and the spread of Omicron in each state. But many countries are either unable to meet the expected demand for sotrovimab or may not have access to it at all.

Some treatments are based on a single monoclonal antibody, while others are based on a “cocktail” of several such antibodies. However, everything binds to the coronavirus protein, reducing by up to 85% the chance of causing serious disease. But Omicron has multiple mutations in this protein, which weakens or negates the effect of these therapies, to a greater extent than the initial fears of scientists. “We did not expect to see such a change in the effectiveness of the antibodies,” said virologist Olivier Schwartz of the Pasteur Institute in Paris.

Even sotrovimab, which is doing well, needs about three times the dosage compared to the other coronavirus variants, to halve the ability of Homicron to multiply in the patient’s body. The relative resistance of this monoclonal antibody, according to virologist Stuart Terville of the Kirby Institute in Sydney, is probably due to the fact that sotrovimab targets a portion of the spike protein that remains unchanged in many variants of the virus.

Some studies have found that both antibodies developed by AstraZeneca in Cambridge have some – albeit significantly reduced – antiviral activity. In any case, according to Dr. Schwartz of Pasteur, laboratory data must be confirmed by clinical, that is, real, data.

If the “arsenal” of monoclonal antibodies is found to be relatively weak against Omicron, doctors will lose a key tool in preventing serious disease. “If Omicron ‘bites’ so hard, it will be a recipe for disaster,” Terville said.

On the other hand, Pfizer (Paxlovid, a combination of nirmatrelvir and ritonavir) and Merck (molnupiravir) antiviral pills, which are much cheaper than monoclonal antibodies, are expected to be quite effective against Omicron, as they have a different mechanism of action. . Especially Paxlovid, according to the announcement of Pfizer on December 14, is 89% effective in preventing hospitalization and death in high-risk patients, as long as the treatment is given shortly after the onset of symptoms.

Another challenge, according to infectious disease specialist Dr. Rajs Gandhi of Massachusetts General Hospital, will be for doctors to determine in a timely manner whether a patient is infected with Delta or Omicron, as this will determine which treatments are most likely to be most effective. . Ideally, physicians should have access to a rapid test to detect variation. But without this tool, they will have to make their decisions more “blindly”, based on how widespread Omicron is in their area.

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