MUST READ! COVID-19-News: Study Shows That Type Of SARS-CoV-2 Mutated Strains Dictates COVID-19 Disease Progression And Severity
: Researchers from Semmelweis University and Pazmany Peter Catholic University in Budapest-Hungary, in a news study shows and echoes the same hypothesis that Thailand Medical News has been stating since the start of the pandemic: COVID-19 disease progression and severity and even Post-COVID-19 effects are all dictated by the various mutated strains and variants of the SARS-CoV-2 coronavirus which is mutating and evolving at rapid rates contrary to stupid so called ‘virologist’ or ‘experts’ and so called scientific writers that have been spreading misinformation that the SARS-CoV-2 coronavirus is not mutating or that even if it does it is has no bearing on the disease or is becoming weaker.
The study findings which shows the relationship of specific mutations on the disease's outcome are published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2020.10.16.20213710v1
The ongoing COVID-19 pandemic is characterized by unpredictable clinical phenotypes, with the majority SARS-CoV-2 infections being asymptomatic or mild but with an array of Post-COVID medical conditions arising.
Important however in a subgroup of patients ie about 15 to 18% of all COVID infections, the condition leads to moderate or severity conditions, of which leads to the death of over a quarter of those in this subgroup.
It should be noted that the SARS-CoV-2 coronavirus's genome is a large one, about 30 kb in length, with 25 genes. Phylogenetic analysis reveals three variants, A, B, and C, distributed differently in Asia, Europe, or the American continents. The genes encoded in this genome include the envelope protein, an RNA dependent RNA polymerase (RdRp), a spike glycoprotein, and the membrane glycoprotein.
Constant mutations in any of the structural and functional genes may impact the virus's characteristics, including its virulence. Mutations in the untranslated genomic regions may also have significant effects. As new SARS-CoV-2 mutations in the virus continue to emerge, their functional impact is being studied.
For example, some mutations lead to variation in the RdRp enzyme, while others increase the transmissibility. The latter type of mutations may enhance the survival advantage of the strain, allowing it to become the dominant strain following its introduction into an area, as seen with the spike D614G mutant, which has largely replaced the original strain in most areas.
This new study focused on identifying those viral mutations that were associated with different outcomes in the patient. For instance, if a mutation reduced the virus's virulence, the resulting mild infection might allow the virus to spread widely. At the same time, those which result in death may cause intensified attention to virus containment, resulting in the fadeout of the outbreak.
In order to achieve this, the researchers linked the mutations to all the outcomes across a large patient cohort. Of the over 72,000 complete sequences available, clinical data were available in only just over 5,000 sequences and follow-up data in ~3,200 patients. The limited proportion of sequences include
d in this study may have caused sampling bias, say the researchers.
For the study the majority of samples came from Asia, while ~27% were from Europe, ~9% were from Central America, ~6-7% from the Americas, and ~5% from Africa.
The disease progression and severity break-up was as follows: 625 with mild, ~2,300 moderate, and ~220 severe.
To date there were about 2,100 identified mutations in all, of which 463 were not represented in the clinical samples
The study team estimated that each sample has, on average, 2.8 mutations. The average sample size for the wild-type virus with a mild outcome was 623, while it was 2.336 and 217 for wild-type virus and hospitalized vs. severe outcome, respectively.
The study team found 141 mutations, which had a significant correlation with the clinical outcome.
Interestingly looking only at mutations observed in 2% or more of the samples, they found 64 samples correlated to 6 mutations in the ORF8, ORF3a, nsp4, nsp6, and the L and N proteins.
Meanwhile in samples from patients with moderate to severe disease, the study team found 9 mutations related to seven genes, including the D614G and L54F in the spike protein, one in the RdRp, and others in other structural and non-structural proteins.
The study team also explored all mutations that were present in 10 or more severely ill patients. This showed two more mutations in the spike protein and the nsp7 gene, present in 28 and 11 severely ill patients.
Significantly the prevalence of mutations correlated with a mild outcome was lower than with severe outcomes, at ~1,500 vs. 6,700 mutations. There were over 5,000 mutations that were not linked to any clinical outcome.
The study team found that of the 17 mutations thought to be significant, the greatest number (5) of them were in the nucleocapsid phosphoprotein, which was associated with both types of outcomes. Several mutations in the N protein were linked to a mild and severe outcome, respectively. One of them increased the outcome severity from a 76% chance of a mild outcome to less than 1%.
It was found that most of the mutations were closely linked in position, being mostly found in a small region of the phosphoprotein mutations between positions 194 and 204.
Interestingly this region is phosphorylated and is located in a serine-rich region of the protein.
Also it should be noted that Phosphorylation activates host RNA helicase DDX1, thus enabling the production of longer fragments of subgenomic mRNA.
Importantly the discovery of the role of phosphorylation in the N protein could be useful in designing drugs against it at these sites. It also shows that this approach could help identify more important mutations in the genome of the virus.
It should also be noted that the structural proteins were found to be more prone to mutations than the non-structural proteins. The destabilization associated with some non-structural protein mutations might have led to the divergence of SARS-CoV-2 from the SARS-CoV lineage.
Most importantly another important finding is that mutations in the SARS-CoV-2 genome can shift the virus towards either greater or lesser virulence in the future, which justifies keeping a watch over the rate, location, and effect of mutations.
Currently studies are already indicating that the SARS-CoV-2 coronavirus is evolving smartly not just to evade host immune response but also in terms of characteristics to help its spread and infectivity and even to remain in the human host for a longer period while it causes untold gradual damage.
The SARS-CoV-2 can be described as a supervirus that mankind has never seen or dealt with so far.
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