At present, the virus has attracted global attention due to the rapid increase in the number of cases of the new coronavirus Omicron variant. The source of mutation, transmission characteristics, and vaccine resistance of Omicron mutants are still unclear, which brings great challenges to the prevention and control of the epidemic in various countries and regions.
Therefore, this paper reviews the research progress of the mutation source, transmission characteristics and risk assessment of Omicron mutant strains, epidemic status, vaccine protection effect, prevention and control measures, etc., in order to provide a reference for scientific prevention and control of the epidemic caused by Omicron mutant strains.
1. Source of variation in Omicron mutants
According to the SARS-CoV-2 database information currently shared by the GISAID platform, the number of mutation sites in the Omicron variant strain is significantly more than that of all SARS-CoV-2 variant strains circulating in the past two years, especially the virus spike protein has more mutations.
reasons may be:
(1) SARS-CoV-2 in patients with chronic COVID-19 infection has undergone a long period of evolution, accumulated a large number of mutations, and caused transmission by chance;
(2) A certain animal group is infected with SARS-CoV-2, and the virus undergoes adaptive evolution during the transmission of the animal group, the mutation rate is higher than that of humans, and then spills over to humans;
(3) Variants spread and evolve in populations lacking surveillance and gene sequencing. Due to insufficient surveillance capabilities, the evolutionary intermediate viruses have not been discovered in time.
Note: Please refer to the original part of the supporting literature for the above content.
2. Transmission characteristics of Omicron variant strains
The current study found that compared with wild strains or other VOCs, Omicron mutant strains have more mutations, which are likely to produce stronger infectivity and immune escape ability than Delta mutant strains, and the ability of Omicron mutant strains to cause repeated infection may be stronger.
(1) The Omicron variant may be more infectious than the Delta variant.
(2) The infectivity of the Omicron variant is roughly similar to or stronger than that of the Delta variant. The Delta variant has an R0 of 6, while the Omicron variant may have an R0 of 4-8.
(3) Metaculus, an online forecasting engine in the United States, predicts that the R0 of Omicron is 6.7 [95%CI (5.2, 8.4)].
(4) The infectivity of the Omicron variant was about 37.5% higher than that of the Delta variant.
(5) The infectivity of the Omicron variant is about 30% higher than that of the Delta.
(6) Omicron variants did not increase the risk of primary infection, but enhanced immune evasion. The hazard ratio of Omicron reinfection to primary infection was 2.39 [95%CI (1.88, 3.11)], which was 3 times higher than that of Beta and Delta variants, reflecting that Omicron variants may be more capable of causing superinfection.
Note: Please refer to the original part of the supporting literature for the above content.
3. Genomic characteristics and risk assessment of Omicron variant strains
Omicron variants carry multiple mutations that may be associated with increased viral infectivity, decreased neutralizing antibody binding, and increased viral RNA expression.
Some of the existing research results are as follows:
(1) The number of mutated amino acid residues in the Omicron variant is 43, which is much higher than the 18 in the Delta variant.
(2) The transmission characteristics of the Omicron variant are related to the obvious improvement of the virus conduction ability and membrane fusion ability caused by the mutation of multiple loci of the spike protein S, especially the multiple mutations of the S1 subunit.
(3) Genomic characteristics and risks of Omicron mutant strains. It is believed that the RBD region of Omicron mutant strains contains 15 amino acid mutation sites, which is more than 5 times that of other VOCs.
(4) K417N, Q493R, N501Y, Y505H mutations may enhance the binding ability of the virus to hACE2 and increase its infectivity.
(5) The binding affinity of the S protein with the N501Y mutation to the hACE2 receptor is 9 times that of the wild-type S protein.
(6) Mutations such as S477N, T478K, E484K enhance the affinity of the virus to the hACE2 receptor and are related to immune escape.
(7) The K417N mutation does not directly interact with hACE2, but it contributes to more efficient binding to hACE2. The N440K mutation found on the Delta variant makes it more evasive from antibodies, which may be why the Delta variant could cause a pandemic in March 2021.
(8) Cleavage of S1 and S2 enables the S protein to fuse with the host. SARS-CoV-2 has a unique S1/S2 Furin protease cleavage site (FCS) at its spike, which is associated with the infectivity and pathogenicity of SARS-CoV-2.
(9) There are 3 mutations (H655Y, N679K, P681H) near the cleavage site of S1/S2 Furin protease. The H655Y and N679K mutations can improve the immune evasion ability of Omicron variants, play an important role in increasing resistance to monoclonal antibodies, and may regulate mammalian S protein fusion and host cell entry.
(10) The P681H mutation enhances the binding affinity of Furin protease to the S protein, which may facilitate virus entry into host cells.
(11) R203K and G204R mutations on nucleocapsid proteins are associated with enhanced expression of viral RNA and increased viral load.
(12) The R203K/G204R mutation is highly adaptive and helps to increase the transmissibility and virulence of specific SARS-CoV-2 mutant strains.
4. Prevalence of Omicron variants
As of December 8, 2021, a total of 57 countries and regions around the world have reported Omicron variant cases. However, it is currently difficult to judge the impact of the Omicron variant on the global COVID-19 epidemic, given that the Delta variant is predominant in many countries, especially in Europe and North America. At present, there are few studies on the clinical symptoms of Omicron variant strains, and the results of the studies are as follows:
Clinical symptoms
(1) According to the report of the European Center for Disease and Prevention and Control, the confirmed cases of Omicron variant strain infection in EU countries are all asymptomatic or mild, and no death case of Omicron variant strain has been found.
(2) Botswana reported that 85% of new Omicron variant infections were asymptomatic infections, and the other 15% of infected people had relatively mild symptoms.
(3) Dr. Angelique Kotze of the South African Medical Association believes that Omicron variant infection presents with mild symptoms, mainly including fatigue, muscle aches, headache and dry cough, but no patients reported obvious symptoms such as loss of smell or taste, and difficulty breathing.
(4) On December 4, Fareed Abdullah of the South African Medical Research Council and others analyzed the COVID-19 cases in a hospital in Gauteng two weeks before the current round of Omicron variant infection (November 29 to December 3, 2021). In the case finding, 29 of the 42 admissions were not on oxygen and no respiratory symptoms were found. Of the 38 adult patients in the COVID-19 ward, 6 were vaccinated, 24 were unvaccinated, and 8 were unvaccinated. Patients infected with the Omicron variant tend to be younger, with 80% of patients under the age of 50, possibly because Gauteng has a higher vaccination rate for those over 50 than for those aged 18-49 (57% vs. 34%) .
(5) The Omicron variant did not lead to an increase in local mortality, although the number of new cases did increase rapidly.
5. The protective effect of the vaccine on Omicron variant strains
The relevant research results are as follows:
(1) The spread of the Omicron variant was associated with a decrease in the risk factor of primary infection and an increase in the risk factor of reinfection. The mutant strains have the ability to evade the natural immune defenses triggered by the initial infection.
(2) The 4 cases of early Botswana Omicron variant infection have been fully vaccinated, indicating that the Omicron variant may have vaccine escape.
(3) This mutation reduces the efficacy of neutralizing antibodies.
(4) Neutralizing antibodies in patients who received two doses of mRNA vaccine or recovered from COVID-19 were fully resistant. The high-precision "gold standard"-live virus neutralization test (FRNT) was used to evaluate the serum neutralization activity of Pfizer's vaccine (BNT162b2), and the results showed that the neutralization activity of these sera against the original strain of SARCoV-2 (D614G) (FRNT50) was 1 321, while the FRNT50 for the Omicron variant was 32, a 41.4-fold decrease. The Omicron variant can evade the antibody immunity induced by the Pfizer vaccine, but retain comparable immunity in vaccinated and infected people.
(5) China and some developed countries have begun to promote the vaccination of COVID-19 vaccine boosters. Both Pfizer and BioNTech claim that the vaccine booster can provide a high level of protection against Omicron variant infection.
(6) Compared with the two-dose vaccine, the booster shot of the vaccine can increase the antibody protection by 25 times, and the antiviral ability after the booster shot is equivalent to the 95% protection provided by the two-dose vaccine against the original virus strain.
6. Suggestions on my country's prevention and control strategies
(1) Accelerate the whole process of vaccination;
(2) Accelerate the development of vaccines against new variants;
(3) Strengthen the management and control of overseas import risks;
(4) Adhere to normalized epidemic prevention and control measures