After seven waves and without a trace of Covid in his body, Álvaro Lodares feels that he is “one of the few that has not had it” in Spain. “I am the only one among my friends; everyone asks me what material I’m made of,” jokes this 40-year-old from Madrid. Throughout the pandemic, he has followed health recommendations, and like many, he has practically returned to normal life in recent months. He has been going to the office for a long time, frequents bars and restaurants, takes off his mask in contexts where it is not mandatory, and has been in contact with people who fell ill shortly after. He has lost count of the tests he has done: all negative.
He belongs to a small group of the population that has not been infected with the coronavirus. Or at least, they are not aware of it. There are studies underway to try to find out if, beyond pure chance, there are genetic factors behind these “Covid virgins.” It is not known how many there are: there is no official figure, and it is not even easy to calculate how many remain uninfected. Even last Christmas, when all positive cases were still officially counted, there were many who remained off the radar, either by taking the test at home and not reporting it or being asymptomatic and not realizing they were infected. Since March, the under 60s are not even represented in the statistics because they are not given a diagnostic test.
The best approximation is drawn from two serological studies (studies that deal with the properties of blood serum) that are capable of distinguishing vaccine-induced and natural immunity. The first, carried out last April, took a representative sample from the Valencian community (a population on Spain’s eastern coast), resulting in 52% having been infected. The second is more recent and was carried out in Navarra (a region in northern Spain). It was announced on Friday with samples taken until the beginning of June: 62% have been infected.
Neither of these studies, which have not yet been peer reviewed, consider the latest wave, which is on a par with the sixth wave - that of last Christmas - in terms of infection rate, and though there is no official data, it caused millions of infections, far more than all of the previous ones. Salvador Peiró, one of the authors of the Valencian report, says that in his investigation, half of those infected had contracted the virus in the sixth wave and the other half in all the others. With these indications, he believes that it is possible that at this point three quarters of Spaniards have already been infected once or more, but it is an estimate that he will try to confirm with a similar study in a few months.
Both investigations show a great generational variation that suggests that older people are more protected against the virus. In Navarra, the percentage of young people who had contracted Covid before the last wave was much higher than that of older people: 85% among those between five and 17 years old and 26% of those over 80, with a linear decrease by age groups.
But among people of the same age there are positives and negatives with very different characteristics. A question on Twitter about how many people had not had the disease generated nearly 900 responses. From entire families who have never tested positive, using strict protection measures, to people who were the only ones who had never had Covid in their homes, despite leading a completely normal life and not being especially careful.
Sergio Pomares, a 35-year-old biologist from Elche (a city in southeast Spain), has been leading a normal life for some time: “I have gone to music festivals, with crowds of people; it was the same at the local festivals we had in February. I go to restaurants indoors. I am one of the few in my environment who has not tested positive. All my friends have had it. My husband too. So we slept in separate rooms, but wore a mask in common areas.”
Andrea Garriga, a 30-year-old midwife who has treated numerous pregnant women with Covid, is one of the few at her hospital (El Mar, in Barcelona) who has not had it. And she’s pretty sure she hasn’t because her job requires her to do regular diagnostic tests. Of course, she recognizes that her social life has been greatly reduced during the pandemic. Francisco Javier Ramos, a 63-year-old retired teacher, sees how “the circle is closing,” but neither he nor his family have had Covid - as far as they’re aware - despite going to restaurants or going on vacation.
People who have this “resistance” to Covid are often the victims of jokes: they’re asked if they have superpowers, that science should study them... Especially after the seventh wave, which has been like a street sweeper, infecting all those in its path that had resisted until now. Pedro Soriano, a 45-year-old lawyer who has not tested positive either, believes that his outdoor terrace has been able to help him, because he’s been holding most social gatherings there. Although he believes that it comes down to “pure and hard luck.” But the truth is that scientists do think that there may be an explanation behind these cases: certain genetic predispositions that make some people invulnerable to the coronavirus.
An international collaboration recruited more than 10,000 people who have lived in the same room for at least five days in direct contact with positive patients and have not been infected. Their genome needs to be sequenced in search of common patterns that differentiate them from the rest of the population that is susceptible to infection. One of the scientists working on this study is Aurora Pujol, a medical geneticist and ICREA professor at the Spanish Bellvitge Biomedical Research Institute (IDIBELL) and the Rare Diseases Network Biomedical Research Center (CIBERER). In Spain they have recruited 200 people with this profile to analyze their DNA, something that will still take between four and six months.
“There must be genetic components that do not allow the virus to enter,” says Pujol. “The idea is to better understand the mechanism to be able to develop new personalized drugs or use some that already exist. It is a genomic medical project to improve our response to pandemics. Beyond answering why some people don’t get it, we want to answer a bigger question: why is the human response to this virus so different? There is great discrepancy - from the majority who have no or very mild symptoms to patients who die in ICU, and not always because they are older or because they had previous pathologies, “she adds.
There are already some clues. Other studies have shown how mutations in the interferon pathway (a set of more than 20 genes that are the first barrier of the immune response to stop the virus) can affect the severity with which patients suffer from the virus. Marcos López Hoyos, president of the Spanish Society of Immunology, believes that “like everything in biology”, there will not be a single cause that explains why some people do not become infected, but there will rather be multiple ones.
Alterations in the ACE2 enzyme (the virus receptor) and in a protein called TMPRSS2, which influences the pathogen’s entry point into the body, could be the key behind a greater or lesser susceptibility to infection. The blood group has also been related in various studies: 0 with less possibility of contagion and A, with greater. There is also a whole series of genetic alterations that are being studied about the predisposition to getting seriously ill or dying. “There are surely still many factors of the immediate immune response that influence and that we still do not know,” says López Hoyos.
Protective mutations against pathogens are already known for other diseases. Against HIV, for example. Prostitutes who had numerous sexual encounters with infected people without any type of protection and were not infected began to be investigated. It was later discovered that it is something that happens to approximately one in 200 people, thanks to a gene that drives the production of more white blood cells needed to defend the body.
There is also a mutation that protects against malaria. It is known as sickle cell anemia, which is relatively common in Africa. Most of those who develop mild symptoms, without causing great damage to their health. Indeed, they are practically immune to Plasmodium, the malaria parasite. But in other cases, it becomes a very serious ailment and, far from being an advantage, it completely conditions their lives.
The challenge for science is to investigate all these phenomena to better understand how the interaction between pathogens and the human body works in order to confront them more effectively. In the case of Covid, knowing what produces natural immunity to the virus could be used to develop drugs that would most likely be given to the most vulnerable and immunosuppressed people.