BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: blood clot

Blood Clotting Proteins Predicting Signs of Long COVID

Many individuals experience sickness after they have already been cured of COVID. This is called long COVID, symptoms include cognitive problems also referred to as brain fog. Having these issues leads to a decreases in memory and concentration making it harder to function in everyday life. Now imagine still feeling sick even though you really are not sick with the virus, not a good feeling. These symptoms are now believed to come from blood clots triggered by the virus. The blood clots leave behind proteins in the blood so researchers are able to find and diagnosis patients who think they have symptoms after they have had COVID.

A study by Nature Medicine found that blood tests could point signs of long COVID. 15 % of people who contracted the virus develop long COVID symptoms. Symptoms of long COVID could last for months and possibly even years. This condition is difficult to treat and diagnose due to the wide range of symptoms it causes. These symptoms include brain fog, chest pain, dizziness, and joint pains. We all know what it is like having these pains so are able to understand how difficult it is to go through your everyday life with long COVID. Scientists are still trying to figure out if the virus stick around in the body or if it leads to other reaction, like having an autoimmune response.

The lead researcher Maxime Taquet, along with others from the University of Oxford, conducted an experiment in the United Kingdom. They tracked over 1,800 hospitalized COVID patients between the years 2020 and 2021. After six and twelve months the scientists conducted cognitive assessments and took blood samples. These are tests you still want to do good on. The blood tests revealed that the patients dealing with brain fog had specific proteins in their blood, proteins that we all have in common. The first protein is called D-dimer, which is present when blood clots breakdown. The patients with this protein did not do poorly on their cognitive tests so their memory and concentration is in tact. On the other hand these patients experience shortness of breath. This could be a sign the blood clots are taking place in the lungs causing the brain to not get enough oxygen levels. The second protein found in some patients is called fibrinogen. This protein is synthesized in the liver and stops bleeding. The patients who had this protein complained about memory impairment and sadly they also did not do well on the cognitive test.

D-dimer

D-dimer Formation

Another test was conducted, analyzing around 50,000 people in the United States looking for D-dimer and fibrinogen. Higher D-dimer levels were only found in people who previously had COVID, while high levels of fibrinogen correlated with brain fog whether or not a person previously had COVID. This indicates that fibrinogen is involved in other cognitive conditions.

Human fibrinogen structural scheme

Human Fibrinogen

Although scientists know there is a relationship between blood clots and long COVID, there still needs to be more research done. Even the blood in your body could help research! Research is currently being done on how the SARS-CoV 2 spike protein affects the fibrinogen protein, and research treatments for clot dissolving medications. This is challenging though since the symptoms and diagnosis of long COVID is still difficult to spot. Scientist will continue studying blood samples and patients suffering from long COVID to better understand the sickness.

The research being conducted can be related to the AP Bio class about the role of the immune system is response to the virus. The immune system is very responsive when COVID is introduced to the body and when it is gone in long COVID patients. A study was conducted and it was found that participants with long COVID had higher levels of non-conventional monocytes and activated B lymphocytes. They had lower levels of type 1 conventional dendritic cells and central memory T cells. The B cells are responsible for attacking pathogens that are free floating, and T cells are responsible for attacking pathogens in infected cells. The dendritic cells break down pathogens and present the antigen on its surface for it to then be found by the T helper cells to pass on the information. These participants’ antibody responses is also stronger against the SARS-CoV-2 spike protein. Those who do not have long COVID do not have responses as strong. Long COVID participants also are more susceptible to other diseases. Other disease, once in the body can trigger the body to have more and worse symptoms. All these specific parts of are immune system all work together in all of our bodies to form the way we each combat infections. We should all be grateful for processes our bodies go through to help us get through our everyday lives.

COVID-19 May Be Behind Dangerous Blood Clots in Patients

According to an article by Erin Garcia de Jesus, a new study shows that some of COVID-19’s lethal blood clots may originate from the immune system attacking the patient’s body instead of the virus. These clots form due to excessive inflammation from an overactive immune response in severely ill patients. Researchers are now trying to figure out how this response happens. Currently, the belief is that some of the clottings may come from auto-antibodies that go after the cell membrane-forming molecules instead of the foreign invader. This attack would prompt neutrophils to release a “web of genetic material geared at trapping virus particles outside the cells.” While this process may control infections in tissue, it causes clotting in the bloodstream. Cardiologist Yogen Kanthi and her colleagues at the National Institutes of Health in Bethesda, Md., reported that “some blood clots may form when the webs trap red blood cells and platelets, creating a sticky clump that can clog blood vessels.” Blood clots in the lungs have become a significant cause of death for COVID-19 patients.

Auto-antibodies that recognize phospholipids can cause antiphospholipid syndrome (APS). APS is an autoimmune disease in which auto-antibodies can activate clot-forming cells, putting patients at a higher risk of blood clots. Extremely ill COVID-19 patients sometimes have high levels of neutrophils as well as phospholipid-binding antibodies in their blood. The belief is that antibodies may be causing the neutrophils to release traps that create clotting.

According to the study, of 172 hospitalized COVID-19 patients, more than half had auto-antibodies that recognized one of three various types of host phospholipids. When the researchers combined auto-antibodies taken from six COVID-19 patients with lab-grown neutrophils, the neutrophils cast their nets. Furthermore, when the researchers injected the same patient auto-antibodies into mice, the mice formed blood clots.

While this research is promising, Thomas Kickler, a hematologist at Johns Hopkins School of Medicine, states that “it’s unlikely that phospholipid auto-antibodies are the whole story.” Other inflammatory immune responses can also trigger clots, so the antibodies may only be part of the mystery.

On a brighter note, a process called plasmapheresis (filtering the liquid part of blood), could assist severely ill COVID-19 patients by removing the problematic antibodies.

This topic relates to our AP Biology study of the immune system. COVID-19 is a threatening virus that penetrates our immune system, and it can cause various problems in our body once it makes its way past our defenses. One of our main defenses is antibodies. Antibodies are specialized, Y-shaped proteins that bind to a foreign invader inside the body. The immune system uses the antibodies to search and mark the invader. Antibodies are a humoral response in part of the adaptive immune system which learns to recognize and eliminate specific invaders. People recovering from COVID-19 may have antibodies that are effective against the virus. Another bodily defense system is inflammation. Inflammation is an internal defense that is part of innate immunity. During inflammation, cells release histamine, and macrophages secrete cytokines. The histamines dilate local blood vessels and increase capillary permeability and cause the area to swell with fluid. Cytokines attract neutrophils and dendritic cells, and natural killer cells kill damaged or infected cells. A fever (a common symptom of COVID-19),  is a systematic inflammatory response triggered by pyrogens released by macrophages.

Low Iron, Sticky Blood, and Strokes

Photo taken by BruceBlaus http://en.wikipedia.org/wiki/File:Blausen_0088_BloodClot.png

Photo taken by BruceBlaus
http://en.wikipedia.org/wiki/File:Blausen_0088_BloodClot.png

Scientists at Imperial College London discovered that low iron levels make blood “stickier” and thus, result in a higher risk of having a stroke.  The most common type of stroke, ischaemic stroke, is a result of a lack of blood supply to the brain caused by small clots.  These researchers found that iron deficiency increases stickiness of platelets, which cause clotting when stuck together (original article).  This connection between iron deficiency and stickier blood was made previously, but its implications are just now being identified.

In this recent study, about 500 patients with a disease called hereditary haemorrhagic telangiectasia (HHT) were studied because their condition allows small blood clots to travel to the brain more often than clots in people without the condition.  The patients with low iron were more likely to have a stroke, and their platelets stuck together to form a clot more quickly than those of patients with higher iron levels.  More specifically, having a moderately low iron level (about 6 micromoles/liter) about doubled the risk of stroke when compared to the risk with a normal iron level.  This is a strong start to proving the link between iron levels and strokes, but more research must be done to fully prove the connection because there are more steps that occur between the clot forming and the stroke occurring.

Scientists are hoping that the newly discovered implications of this research could help lower the risk of stroke in high-risk patients through the monitoring and regulation of iron levels.  Could simply raising a person’s iron level help prevent strokes? I believe that further research will reveal a more complex solution involving a process that occurs between the clotting and the actual stroke.

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