More severe courses from exposure to cold viruses?

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Immune memory Covid-19: more severe courses from exposure to cold viruses?

Many people had contact with other coronaviruses before the appearance of the new type of coronavirus SARS-CoV-2, e.g. as a trigger for colds. One hypothesis was that these contacts could also contribute to better immune protection against SARS-CoV-2 infection. But that is obviously not the case, as Kiel researchers have now found out. Rather, the immune memory could even contribute to severe Covid 19 disease courses.

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Contrary to a previous hypothesis, contact with cold viruses does not seem to offer any protection against Covid-19. (Symbol image)

Kiel – Covid-19 can run very differently, from symptom-free to life-threatening, especially in older sick people more often severe courses. The reasons for this are unclear. Many people already had contact with other coronaviruses before the appearance of the new type of coronavirus SARS-CoV-2, for example as a trigger for colds. One hypothesis was therefore that these earlier contacts could also contribute to better immune protection against SARS-CoV-2 infection.

Members of the Cluster of Excellence “Precision Medicine in Chronic Inflammation” (PMI) from Kiel investigated this. They were able to show that people who have not yet been infected with SARS-CoV-2 actually have certain immune cells, so-called T memory cells, which can also recognize SARS-CoV-2 as foreign bodies. However, these “pre-existing” memory T cells are apparently not very capable of recognizing a SARS-CoV-2 infection and fighting it, since they only bind the virus weakly.

Instead, these memory cells could even contribute to a more severe course of the disease. The research team led by Professor Petra Bacher and Professor Alexander Scheffold from the Institute of Immunology at the Christian-Albrechts-Universität zu Kiel (CAU) and the University Medical Center Schleswig-Holstein (UKSH), Campus Kiel, with colleagues from the University Hospitals in Cologne and Frankfurt has obtained these results recently published in the renowned specialist journal Immunity.

How our immune system stores information

In the course of life, a person’s immune system comes into contact with numerous foreign substances, such as pathogens. When it encounters a previously unknown pathogen, so-called naive T cells are activated, which after a learning phase of several days drive the immune reaction against the new pathogen.

This “knowledge” of the immune system about the specific pathogen is stored in the body in the form of T memory cells after the acute immune reaction. If the immune system comes into contact with the same pathogen again, these memory cells are activated and can fight the pathogen faster and more effectively than naive cells. These memory cells can also react to similar pathogens, for example different strains of coronaviruses, in a so-called cross reaction and also fight these more quickly.

Memory T cells without SARS-CoV-2 infection

“Previous work had already shown that people who have not had any contact with the novel coronavirus SARS-CoV-2 still have T memory cells that can recognize SARS-CoV-2 as a pathogen. But it was not clear where these come from and, above all, what influence they have on the SARS-CoV-2 defense. One hypothesis was that they came from contact with common cold coronaviruses and cross-react against Sars-CoV-2. Our focus was therefore on these already existing memory cells. We wanted to investigate whether these really lead to better protection against SARS-CoV-2 infection, ”explains Professor Alexander Scheffold, Director of the Institute for Immunology at CAU and UKSH, Campus Kiel, and member of the PMI Cluster of Excellence.

SARS-CoV-2 memory cells are not only created by colds

To do this, they examined the immune cells from the blood of donors who had previously had no contact with SARS-CoV-2. They were able to show that people without previous contact with the virus actually have these memory cells that also recognize SARS-CoV-2 as a foreign body. “However, contrary to expectations, younger people who get more common colds do not have a higher number of these cells. In addition, only a small part of these cells also react with the corona cold viruses. The memory cells apparently have little to do with previous contact with corona cold viruses, ”says Scheffold. “Rather, it seems to be the case that in the course of life the repertoire of memory cells against many different pathogens grows and thus the likelihood that some of them will also recognize SARS-CoV-2 by chance. This memory cell repertoire, which increases with every infection, can therefore also be referred to as “immunological age”, which actually increases with biological age, “continues Scheffold.

In COVID-19 sufferers with a mild course, the research team mainly found T cells that recognize the virus very well, while the T cells in sick people with severe courses recognize SARS-CoV-2 only poorly.
In COVID-19 sufferers with a mild course, the research team mainly found T cells that recognize the virus very well, while the T cells in sick people with severe courses recognize SARS-CoV-2 only poorly. (Bild: Immunity Cell Press)

However, although these memory cells are present in everyone, they are obviously not involved in the defense against SARS-CoV-2 infection. This is probably due to their quality: “These T memory cells recognize SARS-CoV-2 viruses, but they don’t do it very well. As a result, they are probably not in a position to ensure that the virus is successfully fought, ”explains first author Professor Petra Bacher, Schleswig-Holstein Excellence Chair, junior research group leader“ Intestinal Immune Regulation ”from the Institute for Immunology at the CAU.

Because the research team actually found T cells in Covid 19 sufferers with a mild course, which recognize the virus very well. “This could be based on an immune reaction based on naive T cells, that is, the T cells that support the immune reaction against the virus here could have originated from naive T cells and not from memory cells,” explains Bacher.

Immunological age may be a risk factor for severe disease

It was particularly interesting for the researchers that in patients with a severe course of the disease, the T cells recognize SARS-CoV-2 just as poorly as the “pre-existing” T memory cells. “This could indicate that these immune cells in the severe Covid cases originate from the poorly binding pre-existing memory T cells,” says Bacher. “This could provide a simple explanation for why older people are at higher risk of developing the disease more seriously. In many cases, they are also of a higher immunological age and thus a higher probability that the immune system will resort to these “incompetent” pre-existing memory cells, ”Bacher continues.

Physicists from the Westfälische Wilhelms-Universität Münster have shown in model simulations that the number of COVID-19 infections is falling significantly due to

“Our work shows that previous colds with coronaviruses do not offer efficient immune protection against SARS-CoV-2. In addition, it provides important evidence that immunological age could possibly favor a severe course of COVID-19 disease. Further studies are now necessary in order to check a direct connection between immunological age and severe COVID-19, and to analyze the influence of pre-existing memory cells on the immune reaction against SARS-CoV-2 in more detail, ”says Scheffold.

Originalpublikation: Bacher et al.: Low avidity CD4+ T cell responses to SARS-CoV-2 in unexposed individuals and humans with severe COVID-19. Immunity (2020). DOI: 10.1016/j.immuni.2020.11.016

* F. Buhse: Cluster of Excellence Precision Medicine for Chronic Inflammatory Diseases, 24118 Kiel

(ID:47016657)



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