Actually, we should not talk about the cold virus, since many viruses are capable of producing this disease, with nonspecific characteristics (there are no symptoms that are characteristic) and self-limited (the disease heals on its own, even without treatment). In fact, there are various families of viruses that produce it: rhinoviruses, which are the most frequent, adenoviruses, enteroviruses, respiratory syncytial and parainfluenza viruses, and coronaviruses.
Yes, yes, also some coronaviruses. Approximately 15-20% of all colds are caused by the HCoV-OC43, -HKU1, -NL63 and -229E coronaviruses, belonging to the same family as SARS-CoV-2. They even have, in some parts of their structure, a high homology with the latter.
The immune response we develop when a virus invades us is not just antibodies, although they are the ones we almost always use to assess a person’s response. Elements of the nonspecific response also participate, as well as T lymphocytes, responsible for specific cellular immunity. In fact, the latter have the most important role in the destruction of viruses, but their analysis is much more complex than simply detecting antibodies. This explains why the study of the role of the cell-specific response against SARS-CoV-2 has been somewhat slower and more complex.
The immune footprint that we have passed COVID-19
When a response is mounted against a pathogen and it is successfully eliminated, the elements responsible for its elimination progressively disappear. For example, antibodies produced by people who have passed COVID-19 tend to disappear quicklyTherefore, doubts remain about the duration of immunity of people who have overcome the disease. Of course, memory cells are always generated, both B lymphocytes (producing antibodies) and T (responsible for cellular immunity). Both retain information on how to respond to that pathogen, so if we come back in contact with it, the new response will be much more powerful, faster and more effective. So we vaccinated, to generate these memory cells.
SARS-CoV-2 continues to surprise us. When the cellular response of COVID-19 patients to it began to be studied, the researchers unexpectedly found that 40% of US individuals who had not had contact with the virus demonstrated that they had pre-existing immunity to it. Other studies carried out in Holland, Germany or Singapore They also detected that, according to the cohorts, between 20 and 50% of individuals not exposed to SARS-CoV-2 had reactivity to it.
An interesting detail is that the response promoted by helper type T cells was especially significant. The mission of these cells is to help the rest of the components of the immune system to carry out their functions, which includes both the production of antibodies and cellular antiviral responses.
So what is the origin of that pre-existing immunity and what does it mean? The most plausible, but not the only, explanation is that this reactivity could be the result of activation of memory cells that were generated years ago, at the end of a response to one of the coronaviruses that cause the common cold. If this is so, we could speculate that individuals who are asymptomatic or with a mild presentation of the disease would be those who had previous exposure to the cold coronavirus (not the other viruses responsible for it, obviously) and retain a good supply of cells. memory.
As respiratory infections are very frequent in childhood, these cells would still be recent and very active in children and young individuals. Therefore, contact with SARS-CoV-2 would provoke its cross-activation as the two alike, triggering a powerful and rapid immune response, which would explain the absence of symptoms in the younger population.
Although cross-reactivity usually takes place against the outer protein or spike, it has also been observed in front of the nucleus capsule. Evidence that we are not dealing with a laboratory device. On the other hand, the fact that this observation has been made in cohorts of different ethnic groups and countries supports a general mechanism in the population.
This cross reactivity is not the first time that it has been observed. For example, in the 2009 flu pandemic, older individuals were found to have a very mild clinical presentation (just the opposite of now). This was because the 2009 virus was quite similar to one that had circulated decades ago, indicating that the elderly they still had antibodies and memory cells generated in that infection. Therefore, we could be facing a similar situation.
Is pre-existing immunity good?
Of course, but it can also cause some problems for the future if we do not take it into account. For example, you might bias the results of clinical trials to demonstrate the effectiveness of vaccines against COVID-19. Especially since if we do not consider this factor, we could observe a powerful response in some individuals that, in reality, does not come from the vaccine but from the activation of memory cells that still survive.
This could lead us, on the one hand, that while the response to the vaccine would be more effective in those individuals with pre-existing cross immunity, it could also lead to erroneous conclusions about the efficacy of a vaccine, by overestimating its results.
On the other hand, there is another curious phenomenon called “original antigenic sin”, by which not very powerful immune responses are triggered when there is pre-existing immunity against a related pathogen. In this case, the effect would be clearly adverse.
Research on COVID-19 is progressing very rapidly and we have more and more information about this virus and the continuing surprises we find ourselves with. These rapid advances have been made possible by a robust science system. Maintaining and strengthening that robustness – and not imposing cuts – is essential to be able to respond with equal agility when the next pandemic arrives. What will come.
Ignacio J. Molina Pineda de las Infantas He is Professor of Immunology at the Center for Biomedical Research at the University of Granada.