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COVID-19 News - Mucosal Immunity  Dec 19, 2022  2 years, 6 days, 3 hours, 29 minutes ago

BREAKING! COVID-19 News: Russian Researchers Shockingly Finds That SARS-CoV-2 Infection Damages Mucosal Immunity!

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BREAKING! COVID-19 News: Russian Researchers Shockingly Finds That SARS-CoV-2 Infection Damages Mucosal Immunity!
COVID-19 News - Mucosal Immunity  Dec 19, 2022  2 years, 6 days, 3 hours, 29 minutes ago
COVID-19 News: A new study by researchers from Kazan Research Institute of Epidemiology and Microbiology of Rospotrebnadzor-Russia, Kazan State Medical University-Russia and Kazan (Volga Region) Federal University has shockingly found that SARS-CoV-2 infections can end up damaging the mucosal immunity of the human host!


 
The study findings have implications in terms of dysfunctional mucosal immunity contributing to the rise of RSV, Influenza and Strep A infections as the mucosa of the nose and throat are no longer able to fend off foreign pathogens. The findings also have implications of in terms of the possibility of nasal vaccines efficacy being affected!
 
Thailand Medical News, has already covered in previous COVID-19 News coverages that SARS-CoV-2 is able to damage the robust innate immunity system of children and also cause immune dysfunction and also COVID-19 induced immunodeficiency in both children and adults who have been exposed to the SARS-CoV-2 virus.
https://www.thailandmedical.news/news/covid-19-news-charlatans-promoting-immunity-debt-for-rise-in-pediatric-viral-infections!-sars-cov-2-destroying-children-s-robust-innate-system-is-the-
 
https://www.thailandmedical.news/news/why-is-no-one-warning-the-masses-that-the-sars-cov-2-spike-proteins-are-causing-major-immunodeficiency-issues-in-all-infected-individuals
 
Various studies have already validated the potential dysfunctions of systemic immunity as a result of COVID-19 infections.
https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(20)30138-9/fulltext
 
https://academic.oup.com/cid/article/71/15/762/5803306?login=false
 
Furthermore, it has been shown that the concentration of immune competent cells in persons with the history of SARS-CoV-2 infection does not return to pre-infection levels even a few weeks after recovery and sometimes for months.
https://academic.oup.com/cid/article/71/15/762/5803306?login=false
 
https://www.medrxiv.org/content/10.1101/2020.03.12.20034736v1
 
Also, SARS-CoV-2 virus-induced immune response dysregulation leads to significant phenotypic changes in peripheral blood lymphocytes, which persist as long as 4–11 weeks after the disease.
https://academic.oup.com/nsr/article/7/6/998/5804736?login=false />  
https://academic.oup.com/cid/article/71/15/762/5803306?login=false
 
https://www.medrxiv.org/content/10.1101/2020.03.12.20034736v1
 
It has been found that post COVID individuals have for a long time an increased percentage of pro-inflammatory monocytes (CD14 +, CD16 +) secreting a number of cytokines, including MCP1, IP-10, and and MIP1α, which contribute to the development of a “cytokine storm”. Cytotoxic lymphocytes (NK cells, CD8 + T-cells) show overexpression of activation markers.
https://www.biorxiv.org/content/10.1101/2020.02.12.945576v1
 
https://www.journalofinfection.com/article/S0163-4453(20)30223-1/fulltext
 
https://academic.oup.com/nsr/article/7/6/998/5804736?login=false
 
Now worrying, Russian scientists have also uncovered that the mucosal immunity is also affected in Post COVID individuals.
 
Prior to this study, in recovered COVID-19 patients, the state of mucosal immunity remains understudied.
 
Cytological, functional, and metabolic characteristics of neutrophils and the interleukin status will help to correctly assess the need for immune-rehabilitation measures.
 
The study team’s objective was to assess the state of mucosal immunity after COVID-19.
 
A detailed study of mucosal immunity included the assessment of nasal mucosal neutrophils with the monitoring of destructive and apoptotic changes as well as examination of the functional and metabolic activity of neutrophils entering the nasal secretions. Phagocytic activity was assessed using microbial suspension of Staphylococcus aureus, as well as intracellular oxygen-dependent biocidity, the functions of capturing, absorbing, and killing pathogens.
 
Comprehensive study of the secretory component included assessment of interleukin levels (TNF-α, IL-10, IFN-γ) and the content of sCD95 (sAPO-1/FAS), membrane marker of apoptosis, in the nasal secretions. Cell wall neutrophils in recovered COVID-19 patients show enhanced destructive and apoptotic processes within the cells.
 
Also, functional disorders due to inhibited phagocytosis of autoflora are recorded.
 
Functionally defective cells are brought into the nasal secretions; they demonstrate severely inhibited oxygen-dependent biocidity, rapid depletion of reserves, incomplete phagocytosis, and limited ability to capture pathogens, which can contribute to the growth of various pathogenic viruses and bacteria.
 
The study findings showed that in the nasal secretions, the concentration of sCD95 (sAPO-1/FAS), the membrane marker of apoptosis, is increased. Elevated level of pro- and anti-inflammatory cytokines (TNF-α, IL-10) downregulates IFN-γ, thus directly contributing to the formation of functionally defective neutrophils.
 
Importantly, compensatory increase in the IL-10 anti-inflammatory cytokine under the influence of SARS-CoV-2 virus proteins downregulates IFN-γ and is a cofactor of depression of intracellular biocidity of neutrophils.
 
It was also observed an increased level of the TNF-α pro-inflammatory cytokine which increases apoptotic and destructive changes in neutrophils entering the nasal secretion.
 
The study findings showed SARS-CoV-2-induced, functional, and metabolic impairment of neutrophils of the mucosal immunity system develop in recovered COVID-19 patients, thus providing a scientific rationale for immunomodulatory therapy.
 
The study findings were published in the peer reviewed journal: BioNanoScience (Springer)
https://link.springer.com/article/10.1007/s12668-022-01020-x
 
The key findings of the study are:
 
-In post-COVID-19 patients, the cell-bound component of mucosal immunity reveals lympho- and eosinopenia. The neutrophils population shows cytodestruction, increased apoptosis, and decreased functional and metabolic activity of the cell.
 
-Impaired cytokine profile at the level of the MALT system in recovered COVID-19 patients shows an imbalance of pro-inflammatory cytokines (TNF-α/IFN-γ) and a pronounced increase in the level of IL-10, anti-inflammatory cytokine.
 
-Pleiotropic effects of cytokine imbalance on the neutrophils systems of mucosal immunity are associated with two types of changes, i.e., cytodestructive and apoptotic changes causing the inhibition of functional and metabolic activity of the cell, as well as direct effects on oxygen-dependent microbicidal activity, functions of pathogen uptake, capture, and killing.
 
-SARS-CoV-2-induced functional and metabolic disorders at the neutrophils level require lengthy rehabilitation and provide a scientific rationale for immunomodulatory therapy in recovered COVID-19 patients.
 
The study findings are also consistent with the results of past studies of the important role of TNF-α in the regulation of neutrophils functions at the level of local immunity.
https://jamanetwork.com/journals/jamasurgery/article-abstract/596077
 
The study team found in ‘recovered’ COVID-19 patients, a severe decrease in the content of IFN-γ (1.16 pg/ml, p < 0.05). It has been shown that the most important aspects of IFN-γ pleiotropic effects are a dramatic increase in the antimicrobial and anti-inflammatory activity of Ns due to increased production of superoxide radicals by cells, an increase in immune phagocytosis and antibody-mediated cytotoxicity of phagocytes, which is due to increased expression of IgG-Fc receptors.
https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0603252
 
In post COVID individual, correlation between the level of IFN-γ and almost all parameters of the functional activity of neutrophils entering the nasal secretions was found, including pathogen capture, i.e., PIA (r =  − 0.53; p < 0.05), PNR (r =  − 0.57; p < 0.05), PN (r =  − 0.57; p < 0.05), and pathogen killing – % D (r =  − 0.57; p < 0.05) and DI (r =  − 0.57; p < 0.05), the level of intracellular biocidity – spontaneous NBT (r =  − 0.57; p < 0.05), and stimulated NBT (r =  − 0.57; p < 0.05).
 
In COVID-19, a successful activation of the cascade of interferon-producing reactions should lead to virus replication control and suppression of SARS-CoV-2 dissemination.
 
However, at the same time, it should be noted that, along with the activation of immune cells, SARS-CoV-2 expresses proteins that suppress the synthesis of interferons (IFN-α, IFN-β, IFN-γ), thereby weakening the antiviral immune response. A pronounced decrease in IFN-γ in recovered COVID-19 patients seems to be the result of two immunopathological processes, i.e., pleiotropic effects of increased levels of pro- and anti-inflammatory cytokines (TNF-α/IL-10), as well as depletion of the mechanisms of IFN-γ synthesis in the acute period of disease, which have not been not restored by the time of early COVID-19 recovery.
https://jlb.onlinelibrary.wiley.com/doi/full/10.1189/jlb.0603252
 
Importantly, a low level of IFN-γ during the recovery period is a cofactor of inhibition of almost all functional capabilities of neutrophil, i.e., oxygen-dependent microbicidal activity, functions of pathogen uptake, capture, and killing.
 
The detailed etiopathogenesis of immune disorders at the level of mucosal immunity in recovered COVID-19 patients can be explained schematically as follows: impaired balance of the cytokine profile, which started during the acute stage, persists during the recovery period. Increased content of pro- and anti-inflammatory cytokines (TNF-α/IL-10) downregulates IFN-γ, which directly contributes to the development of functionally inferior neutrophils of the mucosal immunity system in terms of oxygen-dependent microbicidal activity, functions of pathogen uptake, capture, and killing.
 
Furthermore, the compensatory increase of the anti-inflammatory cytokine IL-10 under the influence of COVID-19 proteins downregulates the level of IFN-γ and is a cofactor of depression of intracellular biocidity and mucosal immunity.
 
Also, increased pro-inflammatory cytokine TNF-α results in enhanced apoptotic and destructive changes in neutrophil entering the nasal secretions, thus contributing to the suppression of cell functional and metabolic activity, as well as the development of lymphopenia and eosinopenia at the level of the cellular elements of the MALT system.
 
Hence, virus-induced functional and metabolic disorders at the level of Ns of the mucosal immunity system develop after COVID-19, requiring lengthy rehabilitation and immunomodulatory therapy.
 
For the latest COVID-19 News, keep on logging to Thailand Medical News.

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