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Migrates through the lymph and blood: how SARS-CoV-2 settles in the organs

How SARS-CoV-2 gets to different organs and what causes their failure in case of COVID-19, said Adkhamjon Abdullaev, researcher at the Laboratory of Molecular Hematology of the National Research Center for Hematology, and Vladimir Bolibok, an immunologist. Coronavirus penetrates from the lungs to other organs, spreading with blood and lymph, Russian scientists from the Federal State Budgetary Institution National Research Center for Hematology, Peoples' Friendship University of Russia and Moscow State University named after M.V. Lomonosov. However, severe impairment of liver, kidney and heart functions in COVID-19 is not always caused by direct infection of these organs with SARS-CoV-2. Adkhamjon Abdullaev, one of the authors of the work, senior researcher at the Laboratory of Molecular Hematology of the National Research Center for Hematology, spoke in more detail about the results of the study published in the journal Viruses.

“The study is devoted to the quantitative assessment of viral load in the tissues of the lungs, lymph nodes of the mediastinum, heart, liver, kidneys, spleen and brain,” the scientist said.

Earlier studies were limited to simply detecting infection in tissues, without quantifying viral load. The researchers decided to clarify what level of viral load is needed for SARS-CoV-2 to spread from the lungs to other organs.

Scientists analyzed tissue samples from 36 patients who died from COVID-19. In 30.5% of patients, the virus was present only in the lungs, and in 63.9%, several organs were affected at once. SARS-CoV-2 RNA was found in 86.9% of cases in the lymph nodes, in 56.5% of cases in the heart, in 52.2% in the spleen, in 47.8% in the liver, in 26% in kidneys and in 13% of cases - in the brain. The study showed that the spread of coronavirus particles from the lungs to other organs was typical mainly for patients who had an exudative (initial) phase of inflammation in the lung tissue and a high viral load of SARS-CoV-2.

“We assume that under conditions of impaired blood circulation in the lung, the main route for the spread of coronavirus particles from the lungs to other organs becomes the lymphohematogenic route, as evidenced by the high frequency of detection of SARS-CoV-2 RNA in the lymph nodes of the mediastinum,” says Abdullayev.

Such conclusions are quite natural, says the immunologist Vladimir Bolibok.

“The lymphohematogenous route for transmission of infection is a common route,” the expert said. - This is the next stage of spread, after the infection has overcome the mucous barrier. First, any infection transmitted by airborne droplets, penetrating through the integumentary tissues, enters the mucous membrane, primarily the respiratory tract - the nose, pharynx, oropharynx. Then a person can swallow it, it can enter the gastrointestinal tract with saliva. Or spread down the trachea into the bronchi. It settles on the mucous membrane, infects the cells of the mucous membrane, begins to multiply in them, and the next stage is lymphohematogenous spread throughout the body.

To find out how SARS-CoV-2 and viral load affect the development of multiple organ failure, the researchers turned their attention to the enzymatic composition of blood serum. However, the result was unexpected.

“In a healthy person, this composition is relatively constant, with a disease, the level of enzymes increases significantly, and this indicates pathology,” Abdullaev explains. “In our study, we planned to use them as a marker of the impact of COVID-19 on organs. Comparing the data, we found no relationship. In organs with signs of damage, there was no SARS-CoV-2 RNA.

It turns out that the cells did not suffer from the presence of a virus in them, but as a result of hypoxia due to a violation of their blood supply.

These data are consistent with existing knowledge about the consequences of COVID-19, confirms Bolibok.

“There are microthromboses, arterioles are thrombosed, blood supply is disturbed,” he says. -

If you imagine an arteriole as a tree trunk, then the cells adjacent to it are leaves. If the trunk of a tree is cut, then all the leaves will wither. And the cells that feed through this arteriole also die. That is, micronecrosis occurs.”

Other possible causes of multiple organ failure include cytokine storm, endothelial cell damage and vascular inflammation, sepsis, and impaired blood pressure regulation.

The researchers also encountered an unusual case of heart damage with COVID-19. An elderly patient was admitted to the hospital with a cough, intermittent fever, and low blood pressure. He died of cardiac arrest a couple of days later.

However, despite a lung lesion revealed at autopsy, indicating bronchopneumonia, SARS-CoV-2 RNA was present only in the tissues of the heart, and nowhere else.

Cases of penetration of SARS-CoV-2 into the heart have already been described in the medical literature. But heart damage without detecting traces of the virus in the lungs is a rare occurrence, Abdullayev notes.More complete data on the factors in the spread of SARS-CoV-2 from the lungs to other organs could be obtained using a genome-wide analysis of detected virus samples using the NGS (next generation sequencing) method.

“The coronavirus genome is constantly undergoing mutational changes, which contributes to the emergence of new, more infectious strains of SARS CoV-2,” Abdullaev explains.

In the future, it is necessary to continue studying cases of isolated lesions of individual organs - the heart, brain, and others.

Migrates through the lymph and blood: how SARS-CoV-2 settles in the organs