One million, three hundred and seventy-eight thousand, eight hundred and thirty-nine. The number of lives lost due to SARS-CoV-2 (as of writing this). That's 1,378,839 too many people. Over the last year, the way we live has changed drastically - masks and lockdown have become a fact of life and Zoom has become something that we can't live without. But on a biological level, what is happening that makes COVID-19 so deadly? Firstly, it is a virus (which are incredibly dangerous), but coronavirus also makes specific changes to the structure of the cells it infiltrates to make it even more deadly.
COVID-19 causes illness in two ways: an inflammatory cytokine response and the cytopathogenicity of the virus. The first of these, the inflammatory cytokine response, is actually something I have mentioned before in a previous post. A cytokine is a protein that is secreted by specific white blood cells that signal to the immune system that something is wrong and that there needs to be an immune response. The type of cytokines I am talking about, inflammatory cytokines, are the ones that promote an inflammatory response in the body. A response like this may be deadly, as cytokine production by the macrophages may lead to a feedback loop (where the cytokines just keep on being produced), and eventually lead to a cytokine storm. In this case, the inflammation that normally helps to remove pathogens starts to become dangerous to important organs, like the kidneys, your liver and your lungs.
Much more dangerous than a cytokine storm, though, is the fact that new research is suggesting that COVID-19 is hijacking the affected cells and turning them into 'virus-copying factories'. The virus does this by changing the physical structure and function of some of the organelles inside the cells and altering their function to make the replication of the virus as effective as possible.
The main organelles involved in protein synthesis are the nucleus, the rough endoplasmic reticulum (RER) and the Golgi apparatus. In infected cells, you can see vesicles (sacs full of cell products or cytoplasm) connected to a network of endoplasmic reticulum throughout the cell. The RER is the site of protein synthesis - it has ribosomes on its surface, which allow it to synthesise proteins quickly and effectively, so if it has been changed by COVID, it may be that the virus is using it to create copies of its RNA (its genetic material), and turn them into functioning viruses.
As well as this, the Golgi apparatus was altered in shape and position. The Golgi apparatus is key in a cell, as it allows polypeptides (which are chains of subunits, making up a larger protein) to be turned into a functional protein. With its new shape, it seems as if they are being used as assembly stations for the virus to replicate efficiently.
The changes didn't stop there, though. The mitochondria have also been changed, making them thinner and much less effective at respiration. The positioning and density of mitochondria in the cytoplasm was radically changed, with the level of folding in the cristae (the inner membrane of mitochondria) reduced dramatically, but the space between the external and the inner membrane increased. The concentration of ATPase, the enzyme used in aerobic respiration, which is the process by which your cells transfer energy and make use of glucose, was also drastically reduced, meaning the level at which your cells could respire was lowered - this might be the reason behind people with COVID feeling fatigued or have difficulty breathing - their cells can't make enough ATP (adenosine triphosphate, the cell's way of storing and transferring energy which is produced by aerobic respiration in the mitochondria) to cope with the body's demands.
Lastly, the cytoskeleton, which is the cell's transport system, was reconstructed too. The cytoskeleton is made up of 3 types of fibres/tubes: microfilaments, microtubules and intermediate filaments, with motor proteins helping with the movement of organelles, etc. From what was seen in the study done, the intermediate filaments are the part of the cytoskeleton most highly affected. They seem to make a cage of sorts around the vesicles that are situated near the nucleus, which suggests that they are being used to scaffold around the vesicles so that they can be transported around the cell to the different 'stations' after being produced by the nucleus and chained together by the RER. This means that COVID has turned the cytoskeleton into a conveyor belt of sorts, to transport the different parts of RNA and viral subunits around the cell to be ultimately assembled at the Golgi.
In conclusion, viruses are deadly. They can create problems around the whole body, or in specific cells to specific organelles. In the case of coronaviruses like SARS-CoV-2, it can do both. But by understanding the specific changes that the virus makes to the cells, it makes it easier to create therapies and treatments to try and make the patients' experience of the illness more manageable.
If anyone would like to read the study which I used for research it is here.
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