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- Fat data: everyone who has had COVID-19 may be at risk of bone destruction
Fat data: everyone who has had COVID-19 may be at risk of bone destruction
Anyone who has had a coronavirus infection can suffer from a dangerous disease — postcovoid osteonecrosis, researchers at Sechenov University have warned. Russian scientists were the first to uncover the causes of the bone-destroying disease that develops after COVID-19 and leads to pain, loss of mobility and the need for endoprosthetics. It turned out that mast cells, which are involved in allergic and inflammatory reactions, play a central role in the development of pathology. Details about the dangerous symptom can be found in the Izvestia article.
How coronavirus destroys bone tissue
Scientists at Sechenov University, together with colleagues from other research centers, have uncovered specific pathological changes in osteonecrosis of the femoral head (ONGB), which develops after COVID-19. A study published in Pathophysiology has shown that this serious disease is caused by a massive accumulation of mast cells in areas of severe vascular fibrosis and thrombosis.
This is a disease in which a violation of blood supply leads to death of bone tissue, pain, loss of mobility and the need for endoprosthetics, doctors explained to Izvestia. Before the pandemic, long-term steroid use, alcoholism, and injury were considered the main causes, they said. However, since 2020, the number of cases has increased dramatically in patients who have suffered even a mild form of COVID-19 and have not taken high doses of hormones. This raised the question of a possible direct role of the virus in the development of the disease.
To answer this question, the scientists conducted a pathomorphological analysis of bone tissue samples removed during endoprosthetics in 88 patients: 41 with post—cystic fibrosis and 47 with a disease of a different etiology.
The main difference was the 9.1 times higher content of mast cells in the areas of necrosis, fibrosis and around blood vessels. In patients who had an infection, the volume of fibrous tissue was 5.6 times higher, and thrombosis was 2.6 times more common than in the control group. There was also a pronounced giant cell granulomatous reaction, that is, a sign of inflammation, in which granulomas containing multinucleated giant cells form in the lesion. This contributes to the destruction of the bone.
Moreover, anyone who has suffered from COVID-19 can suffer from post-calcareous osteonecrosis, scientists warn.
— The potential risk group is significant and includes those who have had COVID-19, regardless of the severity of the disease, gender and age. Our study included patients aged 22 to 70 years who had suffered both mild and severe form. Clinical and laboratory diagnostics of the content and activity of mast cells in the joint tissues of COVID-19 patients may become a promising approach to identifying the risk," said Natalia Serezhnikova, a leading researcher at the Laboratory of Digital Microscopic Analysis at the Institute of Regenerative Medicine.
The findings point to the central role of mast cells in the development of post-calcareous osteonecrosis, the scientists said. Activated by the virus through the ACE2 and HRH1 receptors, they release pro-inflammatory, profibrotic, and prothrombotic substances such as histamine, tryptase, and others. This leads to impaired microcirculation, thrombosis, and bone death. Most of the patients had no other risk factors, which indicates a direct involvement of SARS-CoV-2 in the pathogenesis.
There are drugs that can control the formation of mast cells, but it is not yet known whether they can help with post-cystic osteonecrosis.
— Mast cells are involved in many body processes, including allergic reactions, and many antiallergic drugs are directed at them — they stabilize the membranes and prevent degranulation. However, there is currently no evidence to confirm their effectiveness in post-calcareous osteonecrosis. Previously, mast cells were simply not considered in the context of this disease," Natalia Serezhnikova explained.
Further research by the team of scientists will be aimed at identifying the pathogenetic mechanisms by which mast cells are involved in the formation of complications in various organs and tissues. This will significantly expand the understanding of the role of these cells in the development of kidney syndrome and apply the results of scientific research in clinical practice.
The consequences of the coronavirus
For the first time, the authors have shown in detail the special "handwriting" of post-COVID osteonecrosis of the hip. The lesions turned out to have about nine times more mast cells, noticeably more fibrous tissue, and more often microthrombs than in osteonecrosis of a different nature. Such a set suggests the mechanism of "inflammation — microthrombosis — impaired blood flow — death of bone tissue," said Albert Rizvanov, head of the Center for Excellence "Personalized Medicine" at Kazan (Volga Region) Federal University. Moreover, most of the patients in this series did not receive steroids, which increases the suspicion of an independent contribution of COVID-19.
— Mast cells are the "signaling" of immunity. In COVID, mediators (histamine, tryptase, cytokines) are activated and released, which can increase inflammation, fibrosis, and thrombosis. This has long been discussed in the context of coronavirus infection and Long-term COVID, and the new work adds morphological confirmation specifically in bone tissue," the specialist noted.
For science, this is a foundation for pilot tests of biomarkers of mast cell activation and the design of research on targeted approaches, he noted.
At the beginning of the pandemic, SARS-CoV-2 seemed dangerous only because of the high risk of death. However, as the study progressed, it became clear that it can affect various organs and tissues, which makes it even more dangerous, Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian Gerontological Research and Clinical Center at Pirogov University, told Izvestia.
Thus, the classical entrance gate of the virus, the ACE2 receptor (angiotensin converting enzyme receptor 2), is mainly distributed in blood vessels. This explains the wide variety of organs that the virus can infect.
— An alternative pathway is H1 (histamine receptor 1, the one for which many different antihistamine allergy medications have been invented). And since the role of mast cells carrying this receptor has been proven in the mechanism of osteonecrosis, scientists' interest in the growth of this disease after COVID-19 is logical," the scientist said.
This once again underlines the importance of controlling infectious diseases, which do not affect everyone, but only the most susceptible people, Mikhail Bolkov emphasized. At the same time, each person's susceptibility is individual, including due to differences in the shape of the receptors, and this also requires further research, the specialist added.
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