This article was written by z_popeye
What kind of virus is Omicron that is sweeping the world today? On May 16, 2022, Nature published a research paper on the virulence of the new coronavirus Omicron BA.2 (a type of new coronavirus mutant virus Omicron), which was confirmed in the in vivo model for the first time The virulence of BA.2 was indeed lower than the previous original strain. This also seems to be in line with what has been observed: the new coronavirus mutants have been developing in an increasingly milder direction.
So, will this be the last new coronavirus mutant?
New study: BA.2 is less virulent than original strain span>
Nature This latest study comes from renowned virologists from the University of Tokyo and the University of Wisconsin, Yoshihiro Kawaoka, Academician of the National Academy of Sciences, This is also the most comprehensive study to date to evaluate the effectiveness of antiviral therapy (including small molecule drugs and antibodies) on BA.2 in vivo span>.
Researchers selected live BA.2 virus isolated in Japan to infect humanized k18-hACE2 mice and hamsters. After infection with the same dose of virus, the infectious virus titers in the lungs and nose of mice infected with BA.2 and BA.1 were significantly lower than those infected with the original strain of SARS-CoV-2 (p<0.0001).
This gold standard result confirms that Omicron is indeed less virulent than the original wild type. No significant differences were observed in the viral titers produced in the lung and nose following infection with BA.2 and BA.1.
Source: Reference 1
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PCR viral load detection showed that the viral loads in the lungs and noses of mice infected with BA.2 and BA.1 were lower than the original strains of the new coronavirus, especially in the lungs were significantly lower in the original strain of the new crown (p<0.0001).
Virus detected in the nose and lungs of hamsters infected with BA.2 and BA.1 after being “vaccinated” with the same dose of virus The titers of the hamsters were lower than the original strains, especially in the lungs. The virus titers detected in the nose of hamsters infected with BA.2 were slightly lower than those of BA.1——Actually , Half of BA.2-infected hamsters did not develop lung infection.
The study further found that the original strains, BA.2 and BA.1 sera after infection lacked cross-neutralization—— This is consistent with what was observed when real-world humans were infected with different SARS-CoV-2 mutants.
Source: Reference 1
The study also assessed the live virus neutralizing activity (FRNT) of vaccine recipient sera against the original strain, Delta, and three Omicron mutant viruses BA.1, BA.1.1, BA.2, and the results It was found that 14 days after inoculation of 3 doses of Pfizer/BioNTech new crown vaccine BNT162b2, the neutralizing activity of BA.1 and BA.2 was significantly lower than that of the original strain. However, the neutralizing titer FRNT50 against BA.2 rose from 631 to 2029 1 month after vaccination.
Source: Reference 1
In addition, the researchers administered antibody treatment to virus-infected hamsters and found that REGN10987/REGN10933 (Regeneron REGEN-COV), COV2-2196/COV2-2130 (AstraZeneca AZD7442) and S309 ( A SARS recovered antibody) has a certain therapeutic effect on BA.2 infection.
In terms of antiviral drugs, Merck’s Molnupiravir, the main component of Pfizer’s Paxlovid, Nirmatrelvir, and the new protease inhibitor S-217622 can all be effective in the lungs. The virus was completely inhibited in the nasal cavity, and S-217622 could significantly inhibit the virus replication in the nose.
Will the new crown mutant become weaker and weaker?
Validated by multiple laboratory studies and real-world conditions, compared to the original strain and multiple previous mutants , Omicron is a more transmissible and less virulent mutant.
Does this mean that the new coronavirusWill the mutation become milder?
Some view that as the new crown continues to mutate, the new variant is more and more like the flu, or becomes a Seasonal, endemic diseases. However, a review article published in Nature Reviews Microbiology raised the opposite point.
Source: Reference 2
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Three scientists from the University of Oxford and the European Union Joint Research Centre believe that Omicron’s lower severity is a coincidence, Continued rapid antigenic evolution may lead to new variants that may escape immune evasion and cause severe disease.
For a long time, many people believed that the virus would reduce pathogenicity/lethality for the purpose of continuous transmission, and evolve more mild. And this review article proposes that, unlike immune evasion and transmission under strong evolutionary pressure, virus virulence is usually just a “by-product” of evolution strong>.
Viruses evolved to maximize their ability to spread, which may also lead to increased virulence. For example, by increasing the viral load to promote transmission, it can still cause more serious disease.
Not only that, if the symptoms caused by the virus mainly appear in the later stage of infection, then the harm caused by virulence in the process of virus transmission will also be Very limited – such as influenza viruses, HIV and hepatitis C viruses, etc., they have ample time to spread before causing serious consequences.
Under such circumstances,it is difficult to predict COVID-19 from the lower virulence of Omicron Based on the development trend of mutant strains, it is entirely possible that new coronavirus mutant strains with increased transmissibility and increased virulence will appear in the future.
Source: Reference 2
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So, is it possible for us to build herd immunity through widespread vaccination to slow the spread of Covid-19 in the future?
Nature sub-journal review articles disagree.
Looking back at several major variants since the COVID-19 pandemic, early on, they increased their effective reproduction number Rt by increasing their transmissibility, thereby Predominantly popular – both Alpha and Delta have a 50% higher spread than the previous variant.
However, nowadays, the promotion of the new crown vaccine and previous infections have made the population quite immune, In this regard, the virus may not only improve the transmission ability, but also continuously improve the immune escape ability to bypass the established immune barrier and re-infect more people.
This is also known as a breakthrough infection.
The popularity of Omicron confirms this, the new crown can evolve a strong immune escape ability in a relatively short period of time, and quickly Spread among people who have been vaccinated against the new crown virus, replacing Delta as the mainstream strain.
Therefore, with the improvement of the immunity level of the population, the evolutionary strategy of the new coronavirus may be more inclined To enhance immune evasion, increase the risk of reinfection, and possibly increase the severity of disease in reinfection.
The next mutation, can it be predicted?
Omicron will not be the last mutant of the new crown, so where will the next mutant come from? ? When will it come again?
In the popular process from Alpha, Delta to Omicron, we often overlook a very crucial message – The variation of these mainstream mutants is not actually “linear”.
Epidemiologist Adam Kucharski mentioned in his personal Twitter that in the past, the evolution of seasonal coronaviruses and influenza viruses In the process, we observed a clear “linear” evolutionary trend, as new variants always escaped the body’s immunity to previous variants.
The “linear” evolution trend is as shown above
span>Source: Reference 3
This has been reported in seasonal coronavirus 229E, seasonal influenza virus A/H3N2, and in 2009 The phylogenetic tree of the pandemic-causing influenza A (H1N1p) virusreflect.
Influenza A H1N1p>
Evolutionary tree Source: Reference 4
However, as of Omicorn’s popularity, we have not observed The new coronavirus shows this “linear” evolutionary trend.
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Delta did not evolve from Alpha, nor did Omicron evolve from Delta. We need to go back a long time to find the common ancestor of these mutant strains, which also means that the mutations of the new coronavirus are more random and unpredictable.
On May 10, the Science homepage published a news report titled “Omicron The new subtype is the master of immune escape”, in this report, Wang Linfa, an expert on emerging infectious diseases, proposed that according to the immunological characteristics of the Omicron strain, it is recommended to define it as SARS-CoV -3, a completely different virus from SARS-CoV-2.
And now, a series of sub-variants of Omicron are attracting more and more attention.
BA.2 has occupied a major popular position in at least 68 countries around the world, and at the same time, BA.4 and BA.5 have become The main South African variant.
As of May 8, 2022, BA.5 has accounted for positive cases, according to the Portuguese National Institute of Health At this rate of growth,by May 22, 2022, BA.5 will be the main variant in Portugal.
The European Center for Disease Control and Prevention officially released BA.4 and BA.5 on May 13 from the Variants of Interest “Upgraded to “Variants of Interest”, although BA.4 and BA.5 have not been observed to change from BA.2 in terms of pathogenicity, some in vitro studies have shown that both variants can escape by Immune protection by BA.1.
On May 16, 2022, the Chinese Center for Disease Control and Prevention reported the first case of Omicron BA.2.12.1 in mainland my country, which was imported from abroad. . Meanwhile, BA.2.12.1 is spreading at an alarming rate, according to data detected by the U.S. Centers for Disease Control and Prevention. For the week of May 8 to May 14, BA.2.12.1 accounted for 47.5% of reported cases in the United States.
Source: US CDC
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It is worth noting that BA.4, BA.5, BA.2.12.1 three new Asia Both types carry the same mutation site as BA.2: L452 mutation.
L452 protein is part of the SARS-CoV-2 S protein receptor binding domain, which is also a protective antibody. Importantly, this mutation may help increase its immune evasion ability.
The subsequent neutralizing antibody test conducted by immunologist Cao Yunlong of Peking University and others found that the serum of subjects who had been infected with BA.1 had no significant effect on BA. 4. The neutralizing ability of the three new subtypes BA.5 and BA.2.12.1 is very weak, and the neutralization ability of the sera of the subjects who have been infected with SARS and who have completed the new crown vaccination is even worse for the new subtypes.
These rapid changes have brought many challenges to vaccine development and epidemic prevention policy formulation. Although vaccine research and development manufacturers continue to announce that they are developing new mutant strains, it is still difficult to produce results faster than the speed of iterative updates of the new coronavirus.
In this regard, Wang Linfa said, a broad range of monoclonal antibody drugs against different strains may be the follow-up better coping direction.
Wang Linfa said that this method can provide protection for vulnerable groups, such as those with low immunity. Populations that respond to vaccines. Protecting this group is critical, he suggested, because many researchers suspect that patients with deficient immune systems, unable to clear the virus, may develop more new mutations during prolonged infection.
The Natrue sub-issue review article also mentions this. The article argues that, in addition to exploring the relationship between antigen escape and disease severity,We also need to carefully study the mechanisms by which highly antigenically differential variants arise and the context in which they arise.
These settings may be individuals with chronic diseases or immunodeficiencies, or specific areas with immune deficits, It may even be an animal group that is more closely related to human society. Only by understanding these factors can we more accurately assess the risks we may face in the future, and plan and prepare for them. (Planning: z_popeye | Producer: gyouza)
Thanks:< span>This article has been reviewed by Zhou Panpan, PhD, Tsinghua University School of Medicine, postdoctoral researcher at the Scripps Institute, and PhD in Immunology @ Pasteur Institute, Shanghai, Chinese Academy of Sciences @ Last Sugar Specialty. Thanks to Wang Yuge, a research scholar at the National Institutes of Health and a PhD in Immunology Contributions to this article
Source of caption: Screenshot of reference 1
References:
[1]Kawaoka Y, Uraki R, Kiso M, et al. Characterization and antiviral susceptibility of SARS-CoV-2 Omicron/ BA. 2[J]. Research Square, 2022.
[2]Markov P V, Katzourakis A, Stilianakis N I. Antigenic evolution will lead to new SARS-CoV-2 variants with unpredictable severity[J]. Nature Reviews Microbiology, 2022: 1-2.
[3]https://journals.plos.org/ploscompbiol/article?id =10.1371/journal.pcbi.1002947
[4]Jones S, Nelson-Sathi S, Wang Y, et al. Evolutionary, genetic, structural characterization and its functional implications for the influenza A (H1N1) infection outbreak in India from 2009 to 2017[J]. Scientific reports, 2019, 9(1): 1-10.< /p>
[5]https://www.science.org/content/article/new-versions-omicron-are-masters-immune-evasion
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