CLOTS...HORMONES...IMMUNE SYSTEM

In fact, the picture facing scientists about long COVID is still very complicated. There is no full consensus on the factors that cause this problem. One of the most prominent and controversial ideas is that long COVID is the result of abnormal particles called "micro clots" in the blood. This hypothesis was put forward by Resia Pretorius and colleagues at Stellenbosch University in South Africa. The researchers announced that they detected these particles in the blood of people with long COVID and characterized their biochemical structure. In addition, in a paper published online in 2021, the same team announced that they used a set of three drugs to destroy the particles and reduced symptoms. In some patients, they announced that they used apheresis, a method in which large needles are inserted into the veins to filter the blood.

This caught the attention of Tilly Fox and colleagues at the Liverpool School of Tropical Medicine in England. Fox reported that they first looked for a case study to see if there was any evidence of the efficacy and safety of this treatment, and that they could not find a controlled apheresis study for long COVID, and that they really did not understand where the evidence was coming from that would justify this treatment.

A second problem with the study in question is related to the microclots themselves. Rebecca Kuehn from the Liverpool School of Tropical Medicine states that microclots are not real clots, and in medical terms, clots are not just any particles in the blood, but a special type of clot that contains cells called platelets and proteins called fibrin or fibrinogen. It is also mentioned that microclots have these proteins but not platelets, and instead of platelets, they have another protein called amyloid. This means that treatments targeting classic clots will not work for them. On the other hand, other scientists researching long COVID are following Pretorius's study in South Africa. As a result, a definitive answer on microclots can only be obtained when the studies are repeated and confirmed.

The difficulty at this point, according to the scientists; He thinks the key to finding out which of these immune disorders are specific to long COVID, how they work, and how they relate to various symptoms. In a study published in September of last year, David Putrino of the Icahn School of Medicine at Mount Sinai in New York and colleagues profiled the immune systems of 275 people with and without long COVID, then used a machine-learning algorithm to look for signatures of long COVID. The team found a range of differences, from changes in white blood cell populations to changes in antibody responses.

However, the biggest changes in those with long COVID were in hormones. They had low levels of the hormone cortisol, which has many functions, such as suppressing some immune functions and boosting others, as a regulator of the immune response. Normally, cortisol levels would be expected to peak in the morning, but they were found to be low in the participants. Putrino thinks this result is related to long COVID.

Shortly after this study, last October, similar immunological changes were reported by a team led by Julia Berentschot at the University Medical Center Rotterdam in the Netherlands. The researchers examined the immune systems of 37 people with long COVID who were experiencing fatigue, 36 people without fatigue, and 42 people who had never had COVID-19. The long COVID patients had more signs of inflammation and evidence that some white blood cells were not functioning properly. In addition, those with more severe fatigue showed signs of chronic activation of white blood cells.

Co-author Hemmo Drexhage of the University Medical Center Rotterdam says there is growing evidence that immune system disorders can disrupt other body systems, including hormones and the brain, and can sometimes even lead to conditions like depression.

Many of these immune system studies have concluded that people with long COVID show signs of chronic overactivation, as if the immune system were still fighting an infection. But many researchers were unconvinced by this conclusion, calling it simple and asking: "Is the SARS-CoV-2 virus still in these people?"

Early in the pandemic, this idea was widely dismissed because the virus was not detected in blood samples after the first few weeks. But many now think this is a mistake. In a review published in September, Amy Proal of the PolyBio Research Foundation in Massachusetts and colleagues summarized evidence from biopsies and autopsies that the virus can persist in many tissues and organs, including the intestinal lining, skin and lungs. Similar viral persistence is said to be seen in other post-infection conditions, such as "post-Ebola syndrome." Another undesirable aspect of the issue is that many people have hidden viruses in their bodies, such as herpes viruses, which are extremely successful at hiding in our bodies.

There is evidence that reactivating these latent viruses may play a role in long COVID, as well as other chronic conditions like myalgic encephalomyelitis, also known as chronic fatigue syndrome.

According to Proal, the persistence of the virus in the body could explain the chronic immune activation seen in some people. Also, previous studies have shown that the spike protein in the virus causes clotting, so the possibility that the virus passes into the blood could also explain the microclots. Proal noted that between 30% and 60% of long COVID patients show spikes or other SARS-CoV-2 proteins in their blood.

The persistence of the virus was also highlighted in an October study by Maayan Levy of the University of Pennsylvania, which found that long COVID patients tend to have low serotonin levels. The researchers later identified a complex chain of events behind this. The persistent virus caused chronic inflammation, which disrupted the gut's ability to absorb a key precursor found in food, lowering serotonin levels and thus reducing serotonin storage. It is thought that these low serotonin levels may also affect the central nervous system, underlying some of the cognitive symptoms seen in long COVID.

Persistent symptoms have also been seen after other illnesses, including the 1918 Flu Pandemic and several Ebola outbreaks. According to a study conducted in October of last year, even common respiratory infections can cause long-term symptoms. All of this data also shows how far the scientific community has come in understanding the long-term effects of viral infections.

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What is this X Disease?

World Health Organization (WHO) officials addressed the issue of future pandemic risks at the annual meeting of the World Economic Forum held in Davos, Switzerland, and drew attention to the importance of anticipating and preparing for a possible risk rather than panicking. The WHO's list of pathogens and diseases with the highest pandemic potential in 2022 includes COVID-19, Crimean-Congo hemorrhagic fever, Ebola, Marburg, MERS, SARS and Nipah viruses, Lassa fever, Rift Valley fever, Zika and X disease. The DSO uses the term "disease X" to refer to an infection that has the potential to cause the next possible epidemic or a new global pandemic.

This term, coined in 2017, can also be used for a newly discovered pathogen or any pathogen that has been previously discovered but poses a risk of causing a pandemic. For example, according to the second definition, COVID-19 was the first X disease.

Coronaviruses, a large group of viruses, were seen as one of the main actors of the possibility of a new pandemic even before the COVID-19 pandemic. Because the new coronavirus that caused the pandemic was not the first dangerous pathogen in this group.

A different type of coronavirus called SARS, which causes a type of pneumonia, was first seen in China in 2002 and killed about 1 in 10 people before being stopped by strict infection control measures. Another, more deadly coronavirus called MERS emerged in recent years and killed about 1 in 3 of the people it infected. In fact, recent studies suggest that SARS and MERS are unlikely to easily trigger a new pandemic because most people now have antibodies to the virus that causes COVID-19. These antibodies are also known to provide partial protection against most other pathogens in the coronavirus family. However, experts stress that the possibility of a disease caused by many viruses, some well-known and some lesser-known, posing a global threat should not be ignored. So, is there a way to prevent a potentially risky disease X? Scientists are hopeful that the experience and knowledge gained from all the scientific studies conducted during the COVID-19 pandemic will allow for the rapid development of new vaccines, diagnostics and treatments for any future disease X.