Myth: I Had Mild COVID, I’m Fine

This preprint study has some stunning findings. The short version is that even among those who had COVID but no symptoms, there is tissue damage.

When cells die, their contents are released into the surrounding tissue. Parts of the DNA of the cell are also released and can be detected in the bloodstream. That’s what is meant by cell-free DNA (cfDNA). Epigenetic liquid biopsies study the cfDNA and can determine the type of cells that it came from, based on characteristic molecular structures. The authors state “Patients with severe COVID-19 had a massive elevation of circulating cell-free DNA (cfDNA) levels, which originated in lung epithelial cells, cardiomyocytes, vascular endothelial cells and erythroblasts, suggesting increased cell death or turnover in these tissues.”

Cardiomyocytes are the muscle cells of the heart that contract to provide the heartbeat. When a large area of these become damaged, it is called a myocardial infarction, or commonly called a heart attack. This is normally due to either fatty plaques forming in the blood vessels that feed the heart or a clot that enters one of them. Keep that in mind for the part on vascular endothelial cell damage.

Endothelial cells line the inside of tissue. Epithelial cells line the outer surface. Damaged lung epithelium means that the cells that take up oxygen in the air sacs of the lungs (alveoli) which gets diffused into the bloodstream and carbon dioxide to flow into the alveoli no longer function. Erythroblasts are the cells that become red blood cells when mature. The damage to these just these two cell types means that other tissues will be supplied less oxygen, but that is just part of the widespread damage.

The damage to the vascular endothelium is really one of the most critical things to understand about COVID. It is the layer of cells lining blood vessels.

Capillaries become small enough that they only allow for a single red blood cell to pass at a time, as illustrated.

That is the problem with endothelial damage. When that occurs, capillaries can be occluded, which would lead to reduced (or no) oxygen flow to the tissue supplied by the capillary. These blockages are what are referred to as microthrombi.

An important finding of this study is “Patients with severe COVID-19 have a higher concentration of cfDNA, originating in affected tissues.” When endothelial damage occurs and microthrombi form on a large scale, such as in severe COVID, it leads to acute organ damage and potentially organ failure.

The damage of clot formation is evident in a stroke. (The other common type of stroke, where a blood vessel ruptures, is called a hemorrhagic stroke). When a clot causes a stroke, it’s called an ischemic stroke, because the clot deprives the downstream brain tissue of oxygen, as illustrated in this animation.

There was an autopsy study of patients who had died of COVID. “151 autopsies were included, and 91 cases presented microthrombi in the lung (73%), heart (11.2%), kidney (24%), and liver (16.3%). The age range was between 27 and 96 years.” Clearly the COVID microthrombi risk is real across many organs.

Endothelial damage is not only dangerous due to clot formation, but also because the endothelial cells are responsible for the transfer of oxygen from red blood cells into the surrounding tissue, which can also lead to that tissue being starved of oxygen and potential death of those cells, which is called ischemia.

The preprint also refers to erythropoiesis, which is simply the production of new red blood cells. Why would this increase? Because the body recognizes that parts of it are starving for oxygen.

There is more to the study, but this is the basic biology that is important to understand in how COVID causes damage.

I suspect that part of the reason that COVID seems less damaging in younger or healthier populations is that they can more easily handle some tissue damage since the surrounding unaffected tissue can take on some of the load of the damaged tissue. However, as that unaffected tissue ages, it won’t work quite as efficiently as when it was young and healthy, and the impacts of the COVID infection will start manifesting themselves as a number of chronic diseases. The fact that we are seeing many of these in such a short time is extremely concerning. It suggests that we will see massive amounts of chronic diseases among people who had COVID infections in the future. You can find information on some of these broken down by organ system on this page. Click the link of the system to see some of the studies.