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COVID-19 News - SARS-CoV-2 Causes Monocytes To Become Dysfunctional  Jan 01, 2023  1 year, 1 month, 3 weeks, 3 days, 8 hours, 21 minutes ago

COVID-19 News: Imperial College London Study Shows That SARS-CoV-2 Causes Monocytes From The Innate Immune System To Become Dysfunctional!

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COVID-19 News: Imperial College London Study Shows That SARS-CoV-2 Causes Monocytes From The Innate Immune System To Become Dysfunctional!
COVID-19 News - SARS-CoV-2 Causes Monocytes To Become Dysfunctional  Jan 01, 2023  1 year, 1 month, 3 weeks, 3 days, 8 hours, 21 minutes ago
COVID-19 News: A new study led by researchers from Imperial College London has shown that SARS-CoV-2 infections causes monocytes which are part of the innate immune system to become dysfunctional as a result of transcriptional reprogramming which also makes them adopt a pro-thrombotic signature.

Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions.
These study findings add to Thailand Medical New’s past COVID-19 News coverages that details how exposure to the SARS-CoV-2 causes damage to the innate immune system and also leads to the immune system becoming dysfunctional as well as the condition known as COVID-19 induced immunodeficiency!!-sars-cov-2-destroying-children-s-robust-innate-system-is-the-!-sars-cov-2-destroying-children-s-robust-innate-system-is-the-,-nsp-inhibits-stress-granule-formation
Thailand Medical News had also covered previous studies that showed how SARS-CoV-2 affects the monocytes.
This new study led by Imperial College London also had researchers from the Aix Marseille Université, CNRS, INSERM, Centre d’Immunologie-France and Wellcome Sanger Institute-UK who contributed.
Though alterations in myeloid cells have been observed in COVID-19, the specific underlying mechanisms are not completely understood.
The study team examined the function of classical CD14+ monocytes in patients with mild and moderate COVID-19 during the acute phase of infection and in healthy individuals.
Interestingly, monocytes from COVID-19 patients display altered expression of cell surface receptors and a dysfunctional metabolic profile that distinguish them from healthy monocytes.
Secondary pathogen sensing ex vivo leads to defects in pro-inflammatory cytokine and type-I IFN production in moderate COVID-19 cases, together with defects in glycolysis.
It was found that COVID-19 monocytes switch their gene expression profile from canonical innate immune to pro-thrombotic signatures and are functionally pro-thrombotic, both at baseline and following ex vivo stimulation with SARS-CoV-2.
Transcriptionally, COVID-19 monocytes are characterized by enrichment of pathways involved in hemostasis, immunothrombosis, platelet aggregation and other accessory pathways to platelet activation and clot formation.
The study findings identify a potential mechanism by which monocyte dysfunction may contribute to COVID-19 pathology.
The study findings were published in the peer reviewed journal: Nature communications.
The study team employed metabolic, transcriptomic and functional assays to identify a number of phenotypic and functional alterations in COVID-19 monocytes that characterize moderate disease and also provided the functional characteristics of monocyte responses in mild SARS-CoV-2 infections as an example of an efficiently and successfully cleared infection without excessive immunopathology.
Critical alterations in metabolism and transcriptional signatures characterize moderate COVID-19 monocytes and are important aspects of a global unresponsiveness phenotype upon pathogen sensing characterized by a transcriptional switch from canonical innate immune functions to a pro-thrombotic signature.
Importantly, this pro-thrombotic phenotype was further confirmed functionally, and is in agreement with clinical observations that patients with moderate and severe COVID-19 are at higher risk of developing hemostasis issues.
The initial inflammatory response mounted upon SARS-CoV-2 infection could potentially drive the changes in monocyte functionality, as inflammation is well known to activate the coagulation system.
While the study findings focused on the functionality of monocytes, previous data have shown that platelets from patients with COVID-19 are activated ex vivo during the acute phase of disease and have increased capacity to form monocyte-platelet aggregates, which supports the notion of inflammation driving the initial activation and functional switch of these cell types, promoting the initiation of hemostasis issues and potentially the diminished innate immune functions upon secondary stimulation.
Furthermore, the metabolic defects observed in COVID-19 monocytes probably underlie the observed diminished response to secondary stimulation, as they modulate innate immune functions including cytokine expression, activation, phagocytic capacity, etc.
The study team stressed that more mechanistic studies are needed to understand the link between coagulation and hyporesponsiveness to secondary monocyte stimulation in COVID-19 patients.
However, a key question that remains to be answered is the driver(s) of the described circulating monocyte dysfunction. Ex vivo isolated monocytes from moderate COVID-19 patients are pro-thrombotic while maintaining some innate immune functions. However, secondary pathogen sensing ex vivo triggers a switch in COVID-19 monocyte gene expression signature and functionality from canonical innate immune functions to pro-thrombotic phenotype.
It remains to be determined whether any soluble factors in the microenvironment contribute to this reprogramming, or even the direct infection of monocytes by SARS-CoV-2, which has been previously suggested.
Interestingly, the phenotype observed in circulating monocytes is in clear contrast with the functionality of monocyte-derived macrophages in the lung of COVID-19 patients.
In this regard, the study was limited by the lack of bronchoalveolar lavage fluid (BALF) paired samples to compare the phenotype and function of circulating monocytes with those infiltrating the target tissue. However, some previous publications examining paired airway and blood samples have shown differences in the signatures of circulating and lung innate immune cells, with low HLA-DR expressing, dysfunctional monocytes in the blood, and hyperactive airway monocyte and macrophages producing pro-inflammatory cytokines.
The detailed underlying mechanisms for these differences remain elusive. During the course of viral infections, circulating monocytes rapidly leave the bloodstream and migrate to target tissues, where, after pathogen sensing and/or other microenvironmental stimuli, they differentiate into macrophages and/or dendritic cells.
In this study however, the researchers only examined the functionality of monocytes during the acute phase of disease, early after symptom onset. It remains to be determined whether these dysfunctional monocytes have the capacity to migrate to the lungs and contribute to lung inflammation, or whether their dysfunction is such that migration is impaired and monocyte migration only occurred during the very initial phases of infection before monocyte acquired the impairments observed in this study.
Of note, some of the defective pathways displayed by COVID-19 monocytes, as for example glycolysis, have been shown to be essential for migration of other cells to target tissues.
The study findings beg the question of whether the functional impairments observed in monocytes during the acute phase of infection are COVID-19-specific. While stimulation with other viruses and bacterial products led to similar altered immune phenotypes in COVID-19 monocytes, it seems likely that these processes occur with other moderate respiratory viral infections, as has been shown in seasonal Influenza vaccination.
Further longitudinal studies of monocyte dynamics during SARS-CoV-2 and other respiratory viral infections using both blood and BALF samples are warranted to answer these questions.
For the latest COVID-19 News, keep on logging to Thailand Medical News.


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