Russian scientists explained how human immunity is destroyed by the coronavirus, based on the data obtained during the new study.
Despite numerous hypotheses, it still remains unknown how COVID-19 decreases the number of the main cells of the immune system – lymphocytes. The latest study by Russian scientists from the National Medical Research Center for Hematology, Moscow State University, and other scientific organizations, published In the magazine Viruses, reveals the veil of secrecy over the mechanism of lymphopenia, says “Lenta.ru”.
The most common cause of death from coronavirus is a complex of three dangerous factors: bleeding disorders, acute respiratory distress syndrome and deficiency of certain types of blood cells (cytopenia).
In 80% of patients with moderate coronavirus and 96% with severe, there is a deficiency of lymphocytes – lymphopenia. In the event that their number is lower than 1000 per microliter, and a severe form of COVID-19 is observed.
Among several putative mechanisms for the onset of lymphopenia, one is that viral particles spread in the extrapulmonary environment, directly affecting the tissues of peripheral lymphoid organs: the lymph nodes of the mediastinum and the spleen, which filter lymph from the lungs.
The assumption about the penetration of coronavirus into the lymph nodes was confirmed by opening the chest wall of patients who died from covid with identified lymphadenopathy. Moreover, enlargement of lymph nodes was detected in 6% of patients hospitalized with coronavirus infection, and in 66% with severe COVID-19.
The development of lymphopenia after infection and the subsequent mass death of T-lymphocytes is described in other coronavirus infections – SARS-CoV and MERS-CoV. Coronavirus is able to have a direct effect on immune cells or cause their programmed death indirectly, through signaling pathways.
This is clearly seen in Iranian patients, who showed a correlation between the intensity of lymphopenia and increased programmed cell death of lymphocytes. But until now, the researchers did not have data that would prove the direct infection of lymphocytes with SARS-CoV-2 viral particles in patients with COVID-19.
In the course of their study, the scientists used tissue samples of the lungs and lymph nodes fixed with formalin and paraffin, taken for histological examination during the autopsy of 36 patients who died from COVID-19. RNA was isolated from them, which was then converted into complementary DNA through reverse transcription. The quantitative assessment of the genetic material of viruses was carried out using polymerase chain reaction (PCR). This approach made it possible to more accurately determine how SARS-CoV-2 has spread in the tissues under study.
Coronavirus can affect cells in the human body in different ways, depending on the strains, which differ by mutations in the so-called spike protein or S-protein, affecting the receptor-binding domain or its environment. This domain attaches to the ACE2 receptor on the surface of the infected cells and helps the viral particles to get inside.
As is known, organs and tissues, cells of which express ACE2, are primarily affected. Expression is the activity of genes, ACE2 is a membrane protein. Expression of ACE2 in lymphocytes turns immune cells into potential targets for coronavirus, different variants of which can act on them in a special way. Unfortunately, the results of the study did not provide any new data on how different strains affect lymphocyte damage. But scientists, in the course of direct examination of tissues and cells through an electron microscope, made an interesting discovery.
First, they tested the link between lymphopenia and viral load, dividing 36 patients into 3 groups, depending on the level of coronavirus in the tissues. The first included three patients in whom SARS-CoV-2 was not found in any of the organs. The second included patients with disseminated coronavirus lung disease. In patients of the third group, the coronavirus has spread to the lungs, lymph nodes and spleen.
The duration of the period spent in the hospital until death in the second and third groups was 18.5 and 7 days, and the frequency of lymphopenia was 58.3% and 71.4%. Shorter ICU stays were associated with higher levels of SARS-CoV-2 viral load in the lungs and extrapulmonary spread of the virus to secondary lymphoid organs.
The researchers found no correlation between the severity of lymphopenia and viral load in the spleen and lymph nodes. The result of the study showed: a significant deficiency of lymphocytes was noted even in patients in whom the coronavirus did not affect the spleen and lymph nodes, and vice versa – lymphopenia was not observed in some patients with dissemination of coronavirus in the spleen tissues.
However, transmission electron microscopy has allowed scientists to see something interesting: complete viral particles (virions) inside cells. In the cytoplasm of one of the lymphocytes, the researchers found a bubble with numerous SARS-CoV-2 viral particles.
As the authors of the study note, this is the first case of observation of direct infection of lymphocytes in patients with coronavirus. The discovery confirms the hypothesis that lymphopenia can occur not due to damage to lymphatic tissues, but due to the direct penetration of SARS-CoV-2 into lymphocytes and then active multiplication inside them, which is accompanied by a cytotoxic effect.