Introduction: Recently, Alex, a blogger with a million Chinese fans in the United States, said that he was infected with the BA.5 mutant strain and was still infected after receiving three shots of mRNA vaccines. At first, I felt uncomfortable in my throat, but I couldn't relieve it even if I tried to drink water. Then I lost my sense of taste and coughed up a few mouthfuls of bloody phlegm. The Chinese said that BA.5 is more toxic than the previous mutant strain! Is BA.5 really the worst version of virus mutated? See how medical scientists evaluate the virus.
in January 2022 Omicron swept the United States, but the increase in spring cases caused by the BA.2 sub-variant is small, and the new coronavirus seems to have been ignored for some time. After all, the Centers for Disease Control and Prevention predicted in December last year that almost all Americans have been vaccinated or have antibodies that have been infected with , the new crown . These "temporary" immunity has given people some breathing space.
However, between March and April this year, many patients who have been diagnosed with COVID-19 and recovered again. These patients with re-positive positive initially found that they were always exhausted and coughed continuously. The rapid antigen test obtained two red lines - re-positive results. Why does this happen again in the short term?
BA.5 - The worst virus variant version
This time the culprit is another branch of Omicron BA.5. Its spike protein has three key mutations, which enables it to better infect human cells and be better at bypassing the body's immune defenses . In just over two months, BA.5 defeated its "predecessor" and became the dominant factor in COVID-19 in the United States. According to the latest data from the CDC (Centers for Disease Control and Prevention), last week, 2 out of every 3 new confirmed cases of COVID-19 in the United States were caused by BA.5.
Extract antibodies from the blood of people who have been vaccinated or have recently confirmed Covid-19 has been recovered for experiments. Research has found that BA.5 can defeat existing antibodies. Therefore, people who have recently contracted Covid in the winter and even in the spring may be reinfected with the virus. "We do not know the clinical severity of BA.4 and BA.5 compared to other Omicron subvariants." Dr. Rochelle Walensky, director of the U.S. Centers for Disease Control and Prevention, said at a briefing on the White House Covid-19 response group. "But we do know that it is easier to spread and more immune. Even people who have been infected with BA.1 and BA.2 before will be at risk of reinfecting BA.4 or BA.5."
medical scientist Eric Topol said: The Omicron submutation BA.5 is the worst version of the virus variant he has ever seen. BA.5 takes the already extensive immune escape to the next level, with increased transmission and far beyond previous Omicrons (BA.1 and other Omicron family variants include BA.1.1, BA.1).
has many ways to understand how BA.5 differs from previous strains and Omicron series, including its genetic distance and how its sequence changes over time. The results show that BA.4 and BA.5 are derivatives of BA.2, which are in different branches from BA.1 (Figure 1).
Figure 1 Genetic distance of variants (Figure source: [1])
antigen Figure (Figure 2) shows the spike protein of the virus and how the human immune system "sees" it. BA.4 has very similar spike protein sequences to BA.5, with the antigen distance from BA.1 to BA.2 much larger than that of ancestral strains to Delta or Beta or Gamma. This is the basis of BA.5 immune escape—our relatively poor recognition and response to spike proteins.
Figure 2 Antigen map (Photo source: [1]) An important feature of
BA.5 is its fitness, which is a combination of lineage growth, basic reproduction number, degree of immune evasion and generation time. Analysis of 6.4 million SARS-CoV-2 sequences found that BA.2 is located in the upper right corner, while BA.5 will far exceed the chart of maximum fitness (Figure 3).
Figure 3 BA.5 fitness (Figure source: [2]) Is
BA.5 more toxic or pathogenic and can induce more serious diseases. So far, there is only one experimental study on this, and the results show that BA.4 and BA.5 induce more severe disease in Syrian hamster models and spread more efficiently in lung cell cultures.
BA.5 is currently in the world - it has become the mainstream variant of the United States
BA.5 first appeared in South Africa and soon appeared in Portugal, but has been detected around the world. It has resulted in a significant increase in hospitalizations in Portugal and quickly dominates, and now has varying degrees of impact on many European countries and Israel. It is often masked because in several countries the rise of BA.5 occurs simultaneously with the decline of BA.2, and the amplitude of BA.2 waves vary between countries. But not only these countries have experienced the development of BA.4 and BA.5, but have appeared all over the world, and the virus has developed very quickly (Figure 4).
Figure 4 The current status of BA.5 worldwide (Photo source: [2])
can see the losses caused by the increase in cases around the world. As of July 13, the US CDC reported that the Omicron sub-variants BA.5 and BA.4 are the main strains of SARS-CoV-2 in the United States, accounting for more than 80% of the cases. The risk of reinfection of BA.5 has increased significantly.
The current vaccine is effective for BA.5? The new UKHSA report begins to address vaccine-related issues, focusing on symptomatic infections and serious illnesses, but the conclusions are not clear. The researchers expressed great surprise as the degree of immune evasion of BA.5 and the recent trend of reduced vaccine effectiveness with severe disease (Table 1), vaccine protection for hospitalization and death has further declined.
Table 1 Vaccine effectiveness decreases with severe disease trends
Table Source: [3]
BA.5 is more than 4 times more resistant to mRNA vaccines
A recent new study titled "Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, BA.5" was published on Nature (Figure 5). The researchers conducted experiments to understand how antibodies from vaccinated individuals can well neutralize new subvariants. The results of the study show that BA.4 and BA.5 are at least 4 times more resistant to antibodies in individuals receiving mRNA vaccines than BA.2.
Figure 5 Research results (Photo source: Nature)
study shows that:
■ Although the immunity of the vaccine against the Omicron subvariant seems to be weakening, it is important to note that the mRNA vaccine continues to provide long-lasting protection based on B and T cells to prevent serious consequences of COVID-19, including hospitalization and death;
■ The protective effect of natural infection on reinfection is weakened and may be weakened within a few years. Viral immune evasion accelerates this attenuation. has a very strong protection against very serious reinfection . Within 14 months of the initial infection, no matter the primary infection or reinfection variant, and there is no evidence of attenuation;
■ still has a 97% protective effect on the current Omicron sub-variant for more than 14 months after the initial infection. Generally, T-cell immunity from mRNA vaccines is protective against all COVID-19 variants.
In this study, the researchers collected blood samples from people who received three doses of mRNA COVID-19 vaccine. They also collected samples from individuals who had received two mRNA COVID-19 vaccines and had previously been infected with non-Omicron SARS-CoV-2 variants. The researchers tested antibodies from these people to fight various " pseudovirus " of the Omicron subvariant.
Researchers found that
■ Omicron BA.2.12.1—the SARS-CoV-2 variant that dominated the United States between May and June—is 1.8 times more resistant to antibodies from vaccinated and boosted individuals than the BA.2 subvariant;
■ However, BA.4 and BA.5 are 4.2 times more resistant to antibodies from vaccinated and boosted individuals.
Researchers also tested pseudoviruses for 21 monoclonal antibody treatments, which are made in the laboratory and are usually used to help the immune system fight infections through infusions. Of the 21 monoclonal antibody treatments, only one remains efficient against BA.2.12.1, BA.4 and BA.5. According to the study authors, as the Omicron lineage of SARS-CoV-2 continues to evolve, it is more transmissible and avoidable to antibodies.
Vanderbilt University Public Health Dr. Clarence Buddha Creech said: "BA.4 and BA.5 may lead to an increase in hospitalizations, especially in unvaccinated, immunosuppressed and elderly people.That's why vaccination is so important; while we're seeing an increase in cases, we're seeing fewer hospitalizations due to immunity than other times during the pandemic. ”
title picture source: Forum-leczeniaran, only for academic exchanges.
Written by | Qiao Weijun
Typeset | Luna
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Reference materials:
[1]https://erictopol.substack.com/p/the-ba5-story
[2]Obermeyer F, Jankowiak M, Barkas N, et al. Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness. Science. 2022 Jun 17;376(6599):1327-1332. doi: 10.1126/science.abm1208. Epub 2022 May 24. PMID: 35608456; PMCID: PMC9161372.
[3]https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1086494/Technical-Briefing-43-28.06.22.pdf
[4]Wang Q, Guo Y, Iketani S, et al. Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4, BA.5. Nature. 2022 Jul 5. doi: 10.1038/s41586-022-05053-w. Epub ahead of print. PMID: 35790190.
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