Why are some people protected from Covid-19 without having contracted the disease?

After months of uncertainty and grim headlines, some scientists are hesitantly recognizing what could be good news. During the first weeks of the Covid-19 pandemic, it was estimated that around 60% of the population would need to be exposed to the coronavirus to achieve herd immunity, which occurs when a high percentage of the community is immune to a disease.

A large-scale antibody study in Spain found that around 5% of the population had contracted the coronavirus, with significant differences between the regions – in the Soria province, the figure was more than 14%, compared to 1.2% in Cádiz. The hope of achieving herd immunity seemed like a long shot. But as time passed, a growing amount of research began to suggest that more people are protected against the coronavirus, or at least its most serious versions, than the antibody studies indicated. Experts, however, do not want this news to be used as an excuse for the relaxation of coronavirus safety measures.

When there is an infection from a virus of the same family there could be a cross-reaction and the immune system could develop antibodies similar to the ones that neutralized the other virus

Juan Pablo Horcajada, the head of infectious diseases at Mar hospital

“We have been living with coronaviruses for a very long time. Most of them cause minor respiratory problems [like the common cold], while others are more serious, like SARS and MERS,” explains Juan Pablo Horcajada, the head of infectious diseases at the Mar Hospital in Barcelona. Four viruses in the coronavirus family cause around 25% of colds, and “it is well known that when there is an infection from a virus of the same family there could be a cross-reaction and the immune system could develop antibodies similar to the ones that neutralized the other virus,” he explains. “What we don’t know yet is if these antibodies can offer protection and if so, to what extent.”

A study recently published in the journal Science estimated that at least 20% or perhaps up to 50% of people who have never contracted SARS-CoV-2 have some kind of cellular protection against the disease. It is likely this has been generated by previous contact with one of the coronaviruses that cause colds. The research, however, has been done on cell samples and the hypothesis still needs to be tested out in real situations and on real people. For now, the authors of the study, researchers from La Jolla Institute for Immunology in the United States, acknowledge that it is “very speculative” to link the better prognosis of some Covid-19 patients with their previous exposure to the coronaviruses that cause the common cold.

Similar research from other groups has found the presence of protective T cells, the white blood cells that destroy infected cells in the body, in between 40% and 81% of samples. “This would explain the behavior of the pandemic in the last few weeks,” says Manel Juan, the head of immunology at Clínic hospital in Barcelona. “Although there is concern about the rise in cases, we are not seeing a repeat of the situation in March [when there were hundreds of daily deaths and hospitalizations] and this could be because a greater percentage of people are protected than is reflected in the antibody tests.”

According to one study, up to 50% of people who have never contracted SARS-CoV-2 have some kind of cellular protection against the disease

Luisa Villar, the head of immunology at the Ramón y Cajal hospital in Madrid, says that “more infections would have been expected,” given that only 11% of people in the Madrid region have had the coronavirus, according to the serological study.

According to Villar, the response of T cells, developed by contact with similar viruses or a person’s very immune system, could also explain the heterogeneous impact of the disease. “In young people, T cells are more active, but this response starts to decline from the age of 70,” she says. “That’s why young people may have a minor case or even be asymptomatic, while seniors have much more serious symptoms.”

One of the reasons why coronaviruses can cause colds is that they share a viral spicule protein that is used to colonize host cells. The laboratories working on a vaccine for Covid-19 see this spicule as the key to developing an immunological response.

While the research may explain why young people have less serious cases of Covid-19, it does not explain the gap in the contagion rates between Spain’s 17 regions. “I would have thought that there would have been more protection in the north of Spain, because you would think there would be more colds there, but that’s not what we are seeing,” says Juan.

In young people, T cells are more active, but this response starts to decline from the age of 70

Luisa Villar, head of immunology at Ramón y Cajal hospital

Jesús Rodríguez Baño, the head of infectious disease at the Virgen Macarena hospital in Seville, also backs the hypothesis that people have more immunity to Covid-19 because they have been in contact with similar diseases, but says there still needs to be epidemiological confirmation of the data. “It’s a similar situation with the flu. There is a certain degree of immunity after contracting a virus like the flu,” he explains, adding that given the virus has led to a global pandemic it’s unlikely that the immunity is widespread.

A better understanding of the immunity of a population could shed light on the mysteries that remain about why Covid-19 affects people so differently. But measuring real immunity, beyond the presence of antibodies, requires tests that are expensive and difficult to carry out. In Barcelona, Manel Juan is leading a European project to develop an easier and faster test for determining who has immunity from T cells. This information could be used to help find out who is protected and to what extent, and also help design new vaccines, which help the body to generate a more efficient reaction against the coronavirus. For the moment, however, the good news that people who have never had contact with the virus can be protected needs confirmation via research.

English version by Melissa Kitson.