Why are the elderly and people with certain underlying diseases particularly at risk? One of the reasons for the more severe Sars-CoV-2 infections in the risk groups could be a kind of “immune brake”, according to a study: In risk patients, defense cells calibrated to the pathogen are formed particularly often, but they are limited in their function. The results could help develop a therapeutic approach for severe Covid-19 courses, say the scientists.
“You should be particularly careful not to get infected!” As part of the corona pandemic, certain people hear this again and again. Because early on in the course of the spread of the virus, it became apparent that the disease is particularly critical in older people and people with health problems such as cardiovascular diseases or diabetes. You might think that these people are weakened. But the cause cannot be explained quite that simply. There are probably a number of medical reasons why the body in the risk groups copes comparatively poorly with the infection. One factor may be an adverse immune system response. The results of the interdisciplinary team around Arne Sattler from the Charité-Universitätsmedizin Berlin now provide new information on this aspect.
T-helper cells in sight
As part of their study, the scientists examined the blood of 39 patients who had been admitted to the Charité due to a Sars-CoV-2 infection. They extracted the so-called T helper cells from each blood sample. These are key elements of our immune system that are responsible for controlling the immune system. In the laboratory, the scientists brought the T helper cells of the respective patients into contact with artificially produced fragments of the Sars-CoV-2 pathogen. With the help of specific dyes, the researchers then specifically made those T helper cells visible that reacted to the virus fragments. In this way, they were initially able to determine whether there was a connection between the amount of activated T helper cells and the patient’s risk factors.
This led to an initially surprising finding: the older the patients were, the more virus-specific T helper cells were found in their blood. The same was true of the so-called comorbidity index – a measure of the severity of 19 different underlying diseases. The higher this classification value, the more Sars-CoV-2-specific T helper cells circulated in the blood of those affected. In other words: The high-risk patients even form a large number of T-helper cells that are calibrated to the pathogen.
Many – but “thwarted” immune cells
The further investigations then showed, however, that the T helper cells of the risk groups are apparently restricted in their function. With increasing age and with increasing exposure to underlying diseases, they produce less and less of the messenger substance interferon gamma (IFNγ). As the researchers explain, the immune cells normally release this messenger substance to activate other components of the immune system when they have detected a virus. “The excessive number of T-helper cells directed against the new coronavirus that we found in the blood of Covid-19 sufferers with risk factors are no longer fully functional,” says Sattler.
The scientists also found indications of what could be the basis of the effect: the well-known protein PD-1 apparently acts as a molecular “brake”. This factor is known to act on the surface of T cells to ensure that immune responses do not go crazy – for example, directed against one’s own body. The research results of the researchers now showed that the virus-specific T helper cells produce significantly more PD-1 during a strong Sars-CoV-2 disease than after an infection with comparatively mild symptoms. “The T-helper cells may be slowed down in people with risk factors. We assume that this could be a hindrance to efficient control of the pathogen, ”says Sattler.
He and his colleagues now see medical potential in the results of the study and earlier references: “Together with observations by other scientists, our data indicate that PD-1 could be partly responsible for the fact that the immune system in some Covid-19 sufferers is too low Releases messenger substances for defense against pathogens, ”says Sattler. “Covid 19 patients could possibly benefit from therapies that aim to release such an ‘immune brake’. Numerous studies are still necessary to clarify this, ”the scientist concludes.
Source: Charité – Universitätsmedizin Berlin, specialist article: J Clin Invest., Doi: 10.1172 / JCI140965