On May 20 local time, the US Centers for Disease Control and Prevention (CDC) released the weekly report of COVID-19, a new variant of Omicron ba 2.12.1 it has accounted for 47.5% of new cases in the United States. Two months ago, BA The proportion of 2.12.1 was 1.5%, which increased 30 times within 60 days.
The United States just experienced the Omicron epidemic tsunami from last winter to this spring, and the first half was ba 1. The second half is ba 2。 However, the infection of a large population and the high immune level of the population brought by vaccination can not stop ba 2.12.1 make waves again. Because ba 12.2 the mutant spike protein has strong immune escape ability.
BA. 2.12.1 the mutation of spike protein l452 is Omicron ba 1、BA. The mutation site of spike protein that is not found in the 2 mutant but owned by the delta mutant. This means that the Omicron mutant has a convergent evolution with the delta strain in the spike protein gene under the strong positive selection pressure. The variation of spike protein deserves special attention because spike protein plays a key role in the entry of novel coronavirus into human cells: spike protein can bind to ACE2 receptor of human cells and invade across cell membrane. It is the "key" to open the door of cells and the main target of mRNA vaccine and antibody drug design.
BA. 2.12.1 it has strong immune escape ability. The latest research from Ohio University shows that ba 1、BA. The neutralizing antibody in the serum of the convalescent population after infection and the serum of the population vaccinated with 2 or 3 doses of mRNA vaccine was tested, and it was found that the most widely transmitted sub variant BA was compared with Omicron 1、BA. 2， BA. 2.12.1 stronger resistance. In addition to immune escape ability, studies have shown that ba The spike protein of 2.12.1 also has stronger infectivity, processing ability and cell fusion.
In Ba Driven by 2.12.1, the number of new coronavirus cases in the United States is soaring. According to the CDC's weekly report, the number of new cases in the United States increased by 18.8% compared with a week ago, the nucleic acid positive detection rate increased by 23.2%, and the number of new hospital admissions increased by 24.2%.
Specifically, as of May 18, 2022, the current 7-day moving average of new cases per day was 101100, while the previous 7-day moving average was 85100. As of May 18, 2022, a total of 82820565 new coronal cases had been reported in the United States. The positive rate of nucleic acid was 10.6%, compared with 8.6% a week ago. The 7-day moving average of newly admitted patients per day was 3250, compared with 2629 a week ago.
According to the latest monitoring data of CDC, BA 2.12.1 the mutant has accounted for 73.1% of New York and New Jersey. In the United States, BA 2.12.1 mutants have also accounted for the proportion of, up 11.5% from 42.6% a week ago. There is no evidence that ba 2.12.1 can cause more severe symptoms than the seed variants of the original Omicron strain.
Previously, it was generally believed that the virulence of Omicron was weak. However, recent studies from two teams of HKU and Harvard University showed that without vaccination, the infection of Omicron strain faced a similar risk of death to the original strain of Xinguan in the early stage of infection.
Extended reading: BA 2.12.1 l452q mutation on spike protein
According to evolutionary tree analysis, BA 2.12.1 should appear from the end of 2021 to the beginning of 2022, probably in the United States. As of April, Ba uploaded globally 2.12.1 97% of the sequences are from the United States.
To understand ba 2.12.1 to understand what l452q means, we must first understand the spike protein.
Spike protein is an important structure for novel coronavirus to bind to human cell receptors and enter host cells. Because spike proteins are also targeted by neutralizing antibodies and T cells, spike proteins are subjected to extra pressure of positive selection and frequent variation.
The spike protein has 1273 amino acid sites, which can be divided into S1 and S2 subunits by the relative middle 681 point. S1 subunit is composed of N-terminal domain and receptor binding domain (RBD). S2 subunit is composed of fusion peptide (FP), internal fusion peptide (IFP) and two seven peptide repeats.
Novel coronavirus particles are anchored to human cells by binding to ACE2 receptor through RBD domain of S1 subunit of spike protein. Transmembrane protease serine 2 (TMPRSS2) can activate novel coronavirus to invade cells. Under the action of TMPRSS2, S1 subunit is cleaved, FP in S2 subunit is exposed, membrane fusion is initiated and the virus is further released into host cells. Then the virus ssRNA attaches to the ribosome for replication and protein translation, and further processed and packaged into a new virus, which causes the spread of infection and the damage of host cells and activates the immune system after release.
Considering that the receptor domain (RBD, between 319 and 537) is the region where spike protein binds to ACE2 receptor, this part of the mutation may affect immune escape ability and receptor affinity, so this part of the mutation has attracted special attention of virologists. 452 site is located in the receptor domain (RBD).
If 452 refers to the location of spike protein, the two letters L and Q refer to the corresponding amino acids. Protein consists of 20 amino acids, of which l refers to the amino acid before mutation, leucine, and R represents the amino acid type after mutation, glutamine. The complete meaning of l452q is that leucine at spike protein site 452 is mutated to glutamine.
The global wave of Omicron mat roll can be divided into two parts: BA 1. Lead the early stage, and then ba 2 quickly replace the former. The study of virologist stegger et al found that ba 2 can re infect newly from Ba 1 patients recovering from infection because of Ba 2 has several key mutations that distinguish it from Ba 1 lineage, including T191, l24s, a25 / 27, v213g, t376a and r408s. These key mutations have led to a surge in new coronavirus infections worldwide.
Recently, BA 2. Ba under pedigree 2.12.1 Ba is being continued 2 replaces ba 1. BA. 2.12.1 is the name under Pango nomenclature. Pango is named after the English letters in front of it represent belonging to a certain branch, and the points and numbers in the back represent the branches of the first generation from the previous branch. BA. 2.12.1 means that it is the first grandbranch under the 12th sub branch under the second branch of Omicron pedigree.
BA. 2.12.1 compared with its ancestor ba The biggest difference of 2 is the l452q mutation. It is worth noting that the mutation at l452 site is owned by the delta mutant previously defined by who as "VOC", while Omicron ba 1、BA. 2 not available.
According to the research of Xie Xiaoliang's team of Peking University, BA 2.12.1 relative to ba 1 has stronger receptor affinity. With BA 2 compared with BA 2.12.1 the sera of subjects who have received three doses of vaccine show stronger neutralizing antibody escape ability.
Xie Xiaoliang's team also screened a total of 1640 receptor domain neutralizing antibodies, of which 614 were from Ba 1 antibodies isolated from the serum of rehabilitated patients. The researchers tested their neutralization ability against various variants of Omicron.
The paper said that vaccination + ba The infection history mainly activates the humoral immune memory induced by the original strain, and mainly produces the effects on the original strain and ba Neutralizing antibody with cross immune protection. These neutralizing antibodies with cross immune protection are easy to escape by mutations at the l452 site of spike protein, such as BA with l452q mutation 2.12.1 and BA with l452m mutation 2.13 and BA with l452r mutation 4/BA. 5, etc.
This also explains that the mutation of l452 locus occurs frequently in the sub lineage variants of Omicron. In fact, it is in response to ba 1. Immune pressure of patients recovering from infection.
The Ohio University team selected the sera of medical workers who had been vaccinated with two or three doses of mRNA vaccine and tested ba 2.12.1 and ba The immune escape ability of BA1 and Ba2 virus was found 2.12.1 it has stronger neutralizing antibody resistance and stronger escape ability.
Specifically, the serum of health care workers vaccinated with two doses of vaccine was sensitive to ba 1、BA. The neutralizing antibody titer of 2 was 20 times lower than that of the original strain The neutralizing antibody titer of 2.12.1 was 36 times lower than that of the original strain.
The serum of medical workers vaccinated with three doses of vaccine was sensitive to ba The neutralizing antibody titer of 2 was 2.9 times lower than that of the original strain The neutralizing antibody titer of 2.12.1 decreased by 3.7 times compared with the original strain.
Stronger immune escape ability means vaccinated or previously infected with Omicron ba 1、BA. After 2 strain, it is still possible to be infected by Ba again 2.12.1 infection.