The Sars-CoV-2 coronavirus is a new pathogen for mankind – before the pandemic, our immune system did not know this virus. Nevertheless, some people’s immune cells react to the new corona virus, as a study has now revealed. About a third of the healthy volunteers had T helper cells that recognized parts of the Sars-CoV-2 viral spike protein. Closer analyzes indicated that this reaction could be due to a previous infection of the test subjects with one of the common cold coronaviruses. It is still unclear whether this cross-reaction will protect against Covid-19 or promote it.
Our immune system plays a crucial role in how well our body copes with infections like Covid-19 and whether a severe course is imminent or the disease is mild or even asymptomatic. The immune system has various strategies to combat pathogens. In addition to the specific antibodies, which can dock precisely on certain surface structures of the virus, various defense cells also help to make viruses such as Sars-CoV-2 harmless. These include T-helper cells, white blood cells, which are responsible for the control and coordination of the immune response. Activated T helper cells ensure that other immune cells can fight the pathogen directly and form tailored antibodies. T-helper memory cells also “remember” the characteristics of the pathogen and can then trigger a faster and more efficient immune response when they come into contact with the pathogen, similar to the specific antibodies.
Unexpected cross reaction
Researchers around Julian Braun from the Charité – Universitätsmedizin Berlin have now investigated in more detail what role these T cells play in the reaction to the new Sars-CoV-2 coronavirus. For their study, they isolated T cells from the blood of 18 Covid-19 patients and 68 healthy people who had never been shown to come into contact with the new coronavirus. The defense cells thus obtained then confronted them with small, artificially produced fragments of the Spike protein from Sars-CoV-2. This surface protein forms the protruding “crowns” of the virus and plays a crucial role in penetrating human cells. This test showed that the T helper cells from 15 of the 18 Covid patients responded to the viral protein fragments. “We did not expect that otherwise, the patient’s immune system was fighting the new virus and therefore reacted to it in a test tube,” explains co-author Claudia Giesecke-Thiel from the Max Planck Institute for Molecular Genetics in Berlin.
To the scientists’ surprise, however, the T helper cells of some healthy comparison subjects also reacted to the protein structures of Sars-CoV-2. In 24 of the 68 tested – and thus a good third of them – there were memory cells that recognized the viral proteins. Accordingly, there are people who have never been in contact with the new corona virus, but whose immune system still seems to recognize this new virus. A possible explanation for this was provided by closer analyzes of the T cell reaction. The researchers found that the defense cells of the Covid 19 patients were activated by almost all sections of the viral spike protein. In healthy individuals, however, the T cells only reacted to sections that also occur in other, closely related coronaviruses such as Sars and the common cold coronavirus. “Corona viruses cause up to 30 percent of seasonal colds in Germany,” says co-author Andreas Thiel of the Charité. “It is estimated that an adult gets an average of one of the four native corona viruses every two to three years.”
Protection or aggravation?
According to the scientists, this suggests that the healthy subjects in their study had previously had contact with the common cold coronavirus – and that their immune system therefore recognizes matching parts of these viruses with Sars-CoV-2. “Because one of the properties of the T helper cells is that they can be activated not only by a precisely fitting pathogen, but also by sufficiently similar intruders,” explains Giesecke-Thiel. In fact, supplementary analyzes showed that the T helper cells of the healthy volunteers who responded to Sars-CoV-2 were also activated by various common cold coronaviruses – they showed a cross-reaction. It is still unknown whether this “prior knowledge” of the immune system protects its wearers and how the cross-reaction influences the course of Covid-19. If the former is the case, this could possibly explain why some people develop only mild or no symptoms when infected with the new coronavirus.
“Basically, it is conceivable that cross-reactive T helper cells have a protective effect, for example by helping the body to produce antibodies against the new virus more quickly,” explains co-author Leif Erik Sander from the Charité. “In this case, recent coronavirus colds would likely alleviate the symptoms of Covid-19. However, it is also possible that cross-reactive immunity leads to a misguided immune response – with negative effects on the course of Covid-19. We know such a situation, for example, in the case of dengue virus. ”The scientists now want to know whether an earlier cold can protect against a severe course and how the presence of the“ prewarned ”T cells affects the infection with Sars-CoV-2 in a follow-up study. “If we assume that these cold viruses can actually confer a certain immunity to Sars-CoV-2, people who have often suffered from such infections in the past and for whom we can detect cross-reactive T helper cells should be better protected than others “Says Thiel. “We will therefore pay particular attention to these groups of people in the Charité Corona Cross study.”
Source: Julian Braun (Charité – Universitätsmedizin Berlin) et al., Nature, Preprint, doi: 10.1038 / s41586-020-2598-9