Donnerstag, 27. Februar 2020

Do SARS-CoV-2 viral infections influence the maturation of dendritic cells and T-Cell Priming of the immunesystem?

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Dear friends of freedom and peace,
dear friends of love and happyness,
dear patients,
Coronavirus diseases like SARS or MERS-CoV or COVID-19 is leading to death in many cases as a result of ARDS - so called acute respiratory distress syndrom of lung failure - especially in older patients. For example at the first SARS epidemic 50 percent of the patients older than 65 years died.
Similar effects can be observed at MERS-CoV infected patients.
In all these coronavirus infections researchers found a significant down regulation of the adaptive immune response which is regulated by dendritic cells and Langerhans Cells. Further is was observed that a dysregulation of cytokines are propably the cause of the severe COVID-19 lung disease and lung failure leading to death of the patients. I think this is the result of less maturation of dendritic cells which is leading to low B-Cell activation and low levels of anitiviral neutralizing antibodies.
Using neutralizing antibodies against the protein S is able to protect against the SARS-Virus. This has been shown in the SARS-CoV epidemic at 2003 and later - and even in many other emerging viral diseases like Ebola...
If we predict similar immune dysregulation at the COVID-19 disease which affects dendritic cells as keyholder of the response of the adaptive immune system we should try to improve the function of dendritic cells in order to improove the activation of the CD-4 T-Cells in the body of infected patients and to enhance the B-cell activation for production of neutralizing antibody against the virus and to lower the viral load within the body.
Using CD-40 agonist mAb could be a solution in the treatment of the dysregulation of the immune system in elderly patients by increasing the maturation of immaturate dendritic cells to maturate dendritic cells - causing better stimulation of B-Cells which are producing neutralizing antibodies against the virus and rebalancing the cytokine dysregulation caused by the viral load of the Coronavirus.
An effective adaptive immune response against emerging viral diseases could be the result of such an intervention therapy preventing T- and B-Cells from aptotosis and in the follow up improoving viral elimination from the body.
The rebalancing of the immune system and abnormal Cytokine levels in ARDS-patients, which leading in 52 percent of affected patients to death, seems to be the key role from my point of view to combat high mortalitiy of ICU-delivered SARS-CoV-Patients.
Further studies are needed to find out if mAbs agonist against CD40 are able to reduce viral load of dendritic celles and their infection by the SARS-CoV-2 Virus and then rebalancing the dysregulated Cytokine levels.
All the best to you.

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