Previous colds improve immune response to Sars-CoV-2

Coronavirus

Coronavirus Sars-CoV-2 (Image: Maksim Tkachenko / iStock)

Although the Covid-19 pathogen Sars-CoV-2 is a new pathogen, many people already have memory immune cells against the virus. The reason for this is apparently a cross-immunity due to previous infections with harmless cold coronaviruses. Researchers have now investigated how this immune memory affects the body’s response to Sars-CoV-2 and vaccination. According to this, previous cold infections could provide an explanation as to why many people only have mild or asymptomatic courses of Covid-19. In addition, the memory immune cells may make the vaccination more effective. However, cross immunity decreases with age.

If the immune system is confronted with a new virus, it usually does not yet have any specific defense mechanisms. The virus can multiply and cause damage in the body before sufficient antibodies have been formed. Sars-CoV-2 is one such new virus. Still, it doesn’t seem to have taken many people’s immune systems entirely unprepared. Only about five percent of those infected suffer severe courses. Many others, on the other hand, have only mild symptoms or no symptoms at all.

Resemblance to harmless relatives

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

So far, however, it was unclear how this cross-reactivity would affect the course of a Sars-CoV-2 infection. “We assumed that cross-reacting T helper cells have a protective effect, a previous cold with endemic coronaviruses that have been circulating in the population for many years, so alleviates the symptoms of Covid-19,” says Loyal. “But the opposite could also have been the case. With some viruses, a second infection with a similar virus strain leads to a misdirected immune response, with negative effects on the course of the disease. “

Colds can lead to milder courses

To find out how the cross-reactivity affects Sars-CoV-2, the researchers examined blood samples from people who had never come into contact with the virus. In fact, they found T helper memory cells in it that were able to bind to various surface structures of Sars-CoV-2, especially in the area of ​​the spike protein. On the other hand, they analyzed in detail the immune system of 17 patients from the study population who contracted Covid-19 during the study period. It was shown that the body T-helper cells, which it had formed against endemic cold coronaviruses, actually mobilized against Sars-CoV-2. In addition, the quality of the immune response against Sars-CoV-2 was better, the more these cross-reacting cells were present before the infection.

“In the case of colds with harmless coronaviruses, the immune system builds up a kind of universal, protective coronavirus memory,” explains co-author Claudia Giesecke-Thiel from the Max Planck Institute for Molecular Genetics in Berlin. “If it comes into contact with Sars-CoV-2, such memory cells are activated again and also attack the new pathogen. This could contribute to a faster immune response against Sars-CoV-2, which prevents the virus from spreading unhindered in the body at the beginning of the infection and thus presumably has a positive effect on the course of the disease. ”According to the researchers, the study thus provides one of several explanations, why a Sars-CoV-2 infection is so different in different people.

Immune memory supports the vaccination

At the same time, Giesecke-Thiel emphasizes: “However, the cross-reactivity does not mean that you are definitely protected from Sars-CoV-2 due to past colds. A vaccination is important in any case. ”But the memory immune cells from previous colds can also be important for the effectiveness of the vaccination. The researchers found this out when they examined the immune response of 31 healthy volunteers before and after vaccination. While normal T-helper cells were activated gradually over a period of two weeks, the cross-reacting T-helper cells responded very quickly to vaccination within one week. This enabled the body to produce antibodies against the spike protein as quickly as is otherwise only the case with booster vaccinations.

“Even with the vaccination, the body can at least partially fall back on an immune memory if it has already suffered colds with endemic coronaviruses,” says Loyal’s colleague Andreas Thiel. “That could explain the surprisingly quick and very high protective effect that we observe, at least in younger people, after a Covid-19 primary vaccination.”

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-reacting T cells and their binding strength decrease with age. According to the authors, this is due to natural changes in the aging immune system. “The advantage that a harmless coronavirus cold often brings younger people when fighting Sars-CoV-2 and also when building up vaccination protection is unfortunately less for older people,” says Thiel. “A third booster vaccination could presumably compensate for the weaker immune response in this more vulnerable population group and ensure adequate vaccination protection.”

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

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