The Lancet: What's new! The loss of 382 nucleotides may make SARS-CoV-2 infections milder!

!-- webeditor: page title . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . In a study by 2 genome on the severity of infection and the appy response: an observational cohort study, scientists from institutions such as the Singapore Science and Technology Research Agency (A-STAR) found genetic mutations that make the SARS-CoV-2 virus mild.
Like any other living thing on Earth, SARS-CoV-2 tends to be prone to natural genetic diversity because of mutations that have been feared since the SARS-CoV-2-induced COVID-19 outbreak swept the world. Contagious and lethal, however, the researchers found the opposite in this study, in which they analyzed a particular mutation that makes SARS-CoV-2 less pathogenic, resulting in a lower immune response, less infectious infection, and better clinical outcomes for infected people.
Previously, researchers have found mutations in the SARS-CoV-2 genome because genetic mutations such as these can be translated into different characteristics that affect viruses in different ways, so researchers are interested in studying these mutations and their effects; for example, mutations in areas where immune targets or viruses can be tested may have some serious effects on human hosts fighting viruses, and genetic mutations can also cause concerns about the spread and toxicity of viruses.
the study, researchers focused on a specific genetic mutation that researchers discovered during routine sequencing of the genome of SARS-CoV-2 isolated from cases in Singapore between January and February this year.
images: National Institute of Allergy and Institute of Diseases, US National Institutes of Health The mutation is missing 382 nucleotides, so researchers call it? The 382 mutant, which is located in a region of the genome called Open Reading Box 8 (ORF8), is a hot spot for coronavirus mutations and genetic mutations, in which case the absence of nucleotides causes the transcriptional adjustment sequence of ORF8 to be removed, which means that the ORF8 protein is not produced.
As early as the SARS epidemic in 2003-2005, the absence of 29 nucleotides in ORF8 led to mutations in the virus that could not replicate as efficiently as wild viruses, prompting some speculation among scientists that the mutation could lead to milder conditions in people infected with SARS, although scientists did not conduct further studies at the time.
so the researchers decided to delve into it? 382 mutants, who first screened 131 people diagnosed with PCR at seven hospitals in Singapore, found that 30 percent of patients carried the mutation, and 29 (22 percent) of the 131 patients carried the mutation. 382 mutant viruses, 10 people (8%) carrying both wild-type and ? 382 mutant viruses, and researchers have also found similar mutations of different lengths missing from ORF8 in countries such as Bangladesh.
based on the researchers' understanding of similar deficiencies in the ORF8 region and SARS-CoV, so they want to determine further? Whether the 382 mutation affects the severity of subsequent SARS-CoV-2 infections, the researchers triggered from the patient's clinical characteristics, comparing patients infected with the mutation with those infected with wild viruses using the patient's need for additional oxygen as a measure of the severity of the infection.
interesting to carry? Patients with the 382 mutation are less likely to need additional oxygen, and although all patient groups develop pneumonia at the same rate, do they only carry it? Patients with 382 viral mutants do not need additional oxygen, and are less likely to experience hypoxia, a dangerous condition in severe COVID-19 cases.
not only that, infection? The lower levels of inflammatory cytokines and coercion factors in the body of patients with 382 viral mutants, which are associated with severe COVID-19, and, notably, show low concentrations of growth factors associated with lung damage and regeneration, suggesting that the severity of the infection may not be sufficient to damage lung tissue.
besides, infection? Patients with 382 viral mutants also have better body immune responses, and further immunoanalysis results show that they have more effective plateplate regulation and T-cell response in the early stages of infection, which are often severely impaired in SARS-CoV-2 infections. Patients with 382 mutants are able to produce large amounts of cytokine IFN-cytosus, which helps the body produce a rapid and effective immune response.
Even after the researchers reclassified the age of the patient group and the presence of cogeneration, the findings remained the same, and because of this, the researchers speculated that the mutation could somehow lead to a reduced body's inflammatory response and a lower and less destructive cytokine storm that induced milder COVID-19 infections.
the results of this paper show that SARS-CoV-2 ? 382 mutants are directly related to milder viral infections and better clinical prognostication, but researchers do not know the cause or molecular mechanism behind the loss of 29 nucleotides in the SARS-CoV virus. Does the 382 mutation affect the replication outcome of the virus, which is carried or not carried? Similar viral loads observed in patients with 382 mutants seem to confirm this.
Although the exact role of ORF8 in SARS-CoV-2 is unclear, researchers believe it still plays a crucial role, with studies suggesting that it may help the virus evade host immune testing, while another study suggests that ORF8 was an early target for human antibodies during SARS-CoV-2 infections, based on which the researchers speculate that the lack of the immune function conferred by ORF8 is due to the lack of immune function. Infections caused by 382 mutants in the new host will be less effective, so the new strategy developed by late researchers may consider suppressing the function of ORF8.
!-- / ewebeditor: page -- !--webeditor: page:" -- so what does that mean? Speculating on the function and role of these genetic mutations may help researchers develop new targeted therapies or vaccines, if the absence of ORF8 can really translate into milder infections of the virus, as we have observed? Like 382 mutants, this is important for the development of late-stage vaccines, and later researchers will continue to delve into the role of analyzing mutants that drive different immune responses.
() Reference: Barnaby E Young et al. Effects of a major deletion in the SARS-CoV-2 genome on the severity of the infect and theegy response: an observational cohort study, The Lancet (2020). DOI:10.1016/S0140-6736 (20) 31757-8(2) The mutation making SARS-CoV-2 milderby Agency for Science, Technology and Research (A-STAR), Singapore !--/ewebeditor:page--.