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COVID-19 News - SARS-CoV-2 Evolving To Evade T Cells  Mar 29, 2023  1 year, 8 months, 1 week, 3 days, 8 hours, 17 minutes ago

COVID-19 News: Is SARS-CoV-2 Evolving To Evade T-Cell Immunity And Also Destroy T Cells With The Debut Of XBB.1.16, EG.1, EU.1.1 And FD.1.1 Variants?

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COVID-19 News: Is SARS-CoV-2 Evolving To Evade T-Cell Immunity And Also Destroy T Cells With The Debut Of XBB.1.16, EG.1, EU.1.1 And FD.1.1 Variants?
COVID-19 News - SARS-CoV-2 Evolving To Evade T Cells  Mar 29, 2023  1 year, 8 months, 1 week, 3 days, 8 hours, 17 minutes ago
COVID-19 News: In the course of the COVID-19 pandemic, we have seen the SARS-CoV-2 virus constantly evolving and spawning newer variants and sub-lineages and, in some cases, even recombining to evade the various antibodies induced by the vaccines or even by the previous infections. The various monoclonal based therapeutics and convalescent plasma protocols are no longer effective to deal with the current range of variants and sub-lineages causing the ongoing COVID-19 onslaughts.


Image Credit: Getty
 
The SARS-CoV-02 virus has even evolved to create drug resistant strains via mutations that can cause the various antivirals like remdesivir, paxlovid and molnupiravir to become ineffective.
 
Already we have seen through numerous past studies that the SARS-CoV-2 is not only disrupting and stopping both innate and adaptive immune responses so that it can evade their inhibitory effects, but it some cases it also causes the damage of various important components of the human immune system, making many to suffer from a dysfunctional immune system or worse in some cases to suffer from COVID-19 induced immunodeficiency.
(Note; Supporting studies for everything mentioned above can be found in the Thailand Medical news repository of SARS-CoV-2 studies…use the TMN search function.)
 
However, what is now concerning researchers, scientists and healthcare professionals is whether or not the SARS-CoV-2 virus is now continuing to find ways to not only totally evade the T-Cell immune responses but also destroy or damage the T Cells even more effectively.
 
Considering the integral role of T cells in SARS-CoV-2 immunity, the potential exists for selective pressure to lead to T cell escape, although the extent to which SARS-CoV-2 mutations affect T cells is currently poorly understood.
 
Functional T cell responses are directed against multiple virus proteins, with the magnitude of response correlating with viral protein expression levels. Responses to spike protein, N protein and M protein dominate, with appreciable responses also seen against ORF3a and the non-structural proteins NSP3 and NSP12.
https://pubmed.ncbi.nlm.nih.gov/33521695/
 
As the T cell response targets epitopes across the SARS-CoV-2 genome, the footprints of T cell escape are more broadly distributed than antibody-driven changes, which are concentrated within dominant epitopes of the spike protein.
 
Few studies have documented intrahost evolution within T cell epitopes, which would serve as direct evidence of T cell escape. Mutations within CD8+ epitopes in N protein (M322I and L331F), M protein (L90F) and the spike protein (L270F) were noted within minority variants in one study during the course of acute infections, resulting in loss of epitope-specific responses.
https://pubmed.ncbi.nlm.nih.gov/33664060/
 
Interestingly, prolonged SARS-CoV-2 infections in immunocompromised hosts may offer greater opportunities for T cell escape, akin to the extensively described examples in HIV-1 infection.

< br /> https://pubmed.ncbi.nlm.nih.gov/19487423/
 
The emergence of the NSP3 T504P mutation resulting in loss of a CD8+ epitope response has been reported in multiple individuals with impaired humoral immune deficiency but preserved T cell responses in the context of chronic SARS-CoV-2 infection113,114.
https://pubmed.ncbi.nlm.nih.gov/35996593/
 
https://www.researchsquare.com/article/rs-750741/v1
 
Although these findings are limited to a few cases, there is an urgent need for more prospective cohort studies systematically evaluating the risk of T cell escape in certain patient populations and with newer emerging sub-lineages.
 
More details for the answers to these questions can perhaps be found in more comprehensive studies involving the newer SARS-CoV-2 sub-lineages that have emerged including the XBB.1.16, EG.1(XBB.1.9.2.1), EU.1.1(XBB.1.5.26.1.1), FD.1.1 (XBB.1.5.15.1.1) and even the CH.1.1.12.
 
From a preliminary perspective, most of these new sub-lineages are now having more emphasis on mutations in the N proteins and not spike mutations and are using various mutations on the various ORF proteins that are involved with silencing or disrupting immune responses to achieve its goal of further evading any last left T Cell immunity responses and also damaging them so that it can help when the next line of sub-lineages emerges for the ‘great kill’!
 
The XBB.1.16 aka Arcturus for instance is a lineage with 5 additional mutations E180V, K478R, and S486P, ORF9b:I5T and ORF9b:N55S. XBB.1.5 doesn’t have these mutations in ORFb.
 
Studies and COVID-19 News coverages have already shown that the mutations in ORF9b assists with innate immunosuppression.
 
https://pubmed.ncbi.nlm.nih.gov/33567255/
 
https://pubmed.ncbi.nlm.nih.gov/33913550/
 
https://www.thailandmedical.news/news/shandong-university-study-uncovers-that-sars-cov-2-orf9b-antagonizes-type-i-and-iii-interferons-by-targeting-components-of-signaling-pathways
 
https://www.thailandmedical.news/news/breaking-covid-19-research-coronavirus-study-reveals-that-sars-cov-2-orf9b-protein-binds-to-human-host-mitochondria-protein-tom70
 
The exact consequences of the mutations in this variant remain unclear; however, it is evident that both XBB.1 and XBB.1.5 have managed to elude antibodies generated from previous infections, the bivalent booster, and monoclonal antibody therapies. Consequently, our reliance on T-cells for protection has increased. For T-cells to effectively defend us, the virus must first infect a cell, which then triggers the T-cells to eliminate the virus-infected cell. This process inadvertently hastens cellular aging with each subsequent infection.
 
Viral infections that bypass antibodies can be highly damaging, as they infect various cell types, including immune cells. T-cells must eliminate virus-infected cells, which can lead to cell death and the need for uninfected cells to divide and restore the population. However, cells can only divide a limited number of times, with cellular aging indicated by the shortening of telomeres. Women tend to produce more naive T-cells and have longer telomeres, which may contribute to their longer lifespans compared to men. Telomere shortening affects tissue regeneration and homeostasis, and continuous immune reactions can lead to replicative senescence.
https://www.mdpi.com/1422-0067/22/11/6151
 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835063/
 
There is a very high possibility that XBB.1.16 and the rest of the newer SARS-CoV-2 sub-lineages ie EG.1, EU.1.1, FD.1.1, and CH.1.1.12 may be more capable of evading T-cells, the last line of defense for our immune system via using mutations o their various N proteins or ORF proteins.
 
Initial findings indicate that XBB.1.16 seems to be increasingly adept at disrupting the communication between infected cells and T-cells, making it harder for T-cells to identify and target infected cells. In essence, this means T-cells may struggle to detect infected cells. If T-cells fail to recognize more infected cells, it allows COVID to replicate, spread, and persist in regions inaccessible to T-cells.
 
If this scenario unfolds, a larger number of individuals will have difficulty eliminating the virus, leading to increased infections, persistent inflammation, and related autoimmune disorders, as well as musculoskeletal, neurological, cognitive, and vascular dysfunction.
 
As more emerging sub-lineages evolve to better suppress or infect T-cells, the overall impact on the global communal physical, mental, and economic well-being will be substantial.
 
The pandemic is far from o