Earlier colds improve the immune response against Sars-CoV-2

Although the pathogen Covid-19 Sars-CoV-2 is a new pathogen, many people already have memory immune cells against the virus. The reason for this is apparently cross-resistance to previous infections with harmless cold coronaviruses. Scientists have now investigated how this immune memory influences the body’s response to Sars-CoV-2 and vaccination. Hence, previous cold infections may explain why many people have only mild or asymptomatic courses of Covid 19. In addition, memory immune cells can make vaccination more effective. However, cross resistance decreases with age.

When the immune system is confronted with a new virus, it usually doesn’t have any specific defense mechanisms yet. The virus can therefore multiply in the body and cause damage before it has produced enough antibodies. Sars-CoV-2 is such a new virus. Even so, it doesn’t seem like many people’s immune systems are completely unprepared. Only about five percent of those infected suffer severe mileage. On the other hand, many others have only mild symptoms or not at all.

Similar to harmless relatives

‘There is now strong evidence that there is cross-reactivity with antibodies against the harmless cold coronaviruses,’ explains a research team led by Lucie Loyal of the Charité Universitätsmedizin Berlin. This cross-reactivity is based on the fact that some Sars-CoV-2 surface structures, including the spike protein, are very similar to other, harmless corona viruses. If the body has already produced antibodies against such cold coronaviruses in the past, they may also attack the new Sars-CoV-2 coronavirus.

So far, however, it has not been clear how this cross-reaction affects the course of Sars-CoV-2 infection. “We assumed that cross-reactive T-helper cells were protective, that a previous cold with endemic coronaviruses, those that have been circulating in the population for many years, alleviated the symptoms of Covid-19,” says Loyal. “But it could also be the other way around. For some viruses, a second infection with a similar virus strain leads to an inappropriate immune response, which has a negative impact on the course of the disease. ‘

Colds can help with milder dishes

To find out how cross-reactivity affects Sars-CoV-2, researchers examined blood samples from people who had never been exposed to the virus. In fact, they found helper memory T cells in it that could bind to various Sars-CoV-2 surface structures, particularly in the area of ​​the spike protein. On the other hand, they analyzed the immune systems of 17 patients in the study population in detail who developed Covid-19 during the study period. It has been shown that the body actually mobilized the helper T cells it formed against the endemic cold coronavirus, against Sars-CoV-2. Moreover, the immune response against Sars-CoV-2 was qualitatively better, the more of these cross-reactive cells were present before infection.

“In the case of a cold with harmless coronaviruses, the immune system builds up a kind of universal, protective memory for the coronavirus,” explains co-author Claudia Giesecke-Thiel of the Institute of Molecular Genetics Max Planck in Berlin. “If it comes in contact with Sars-CoV-2 now, such memory cells are reactivated and also attack the new pathogen. This could contribute to a faster immune response against Sars-CoV-2, which prevents the unimpeded spread of the virus in the body at the onset of infection, and therefore presumably has a beneficial effect on the course of the disease, ‘the researchers say. The study therefore provides one of several explanations for why Sars-CoV-2 infection varies so differently from person to person.

Immune memory supports vaccination

At the same time, Giesecke-Thiel emphasizes: “However, cross-reactivity does not mean that you are definitely protected against Sars-CoV-2 from colds. Vaccination is important in all cases. ” But memory immune cells from previous colds may also be important for vaccination effectiveness. The researchers found this by examining the immune responses of 31 healthy volunteers before and after vaccination. While normal T helper cells were progressively activated over a two-week period, cross-reactive T helper cells responded very quickly to vaccination within a week. As a result, the body was able to produce antibodies against the protein spikes as quickly as possible with a booster vaccination.

“Even with vaccination, the body can at least partially revert to immune memory if it has already had a cold from corona endemic viruses,” says Loyal’s colleague Andreas Thiel. “This may explain the surprisingly quick and very high level of protection that we see, at least in younger people, after the first vaccination against Covid 19.”

Cross-reactivity decreases with age

However, older people seem to benefit less from immune memory. Blood samples from 568 healthy volunteers showed that both the number of cross-reactive T cells and their binding strength decreased with age. According to the authors, this is due to natural changes in the aging immune system. “The advantage that the harmless coronavirus cold often brings young people in the fight against Sars-CoV-2 as well as in building protection against vaccines is unfortunately smaller in the elderly,” says Thiel. “A third booster dose could possibly compensate for the weaker immune response and provide adequate protection against immunization in this more sensitive population group.”

Source: Lucie Loyal (Charité Universitätsmedizin Berlin) et al., Science, doi: 10.1126 / science.abh1823

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