Undefeated for Covid and people with multiple reinfections intrigue scientists

On April 7, 2020, doctor Marcelo Sapienza, 55, began to feel a fever. Two days later, he couldn’t smell anything. The picture was reminiscent of Covid-19, a disease discovered months before and which, at that moment, was already a pandemic.

Marcelo took an exam on April 10, and the result was positive. The fever continued, as well as muscle and hip pain. “Near the seventh day of the condition, I became more anxious to know that there could be an exacerbated inflammatory picture, but fortunately the symptoms were progressively improving”, he says.

The doctor lived with his wife, Maria Tereza Sapienza, 57, and their son. Marcelo isolated himself inside his house from the day he lost his sense of smell. Even so, they knew there was a chance that transmission had occurred earlier, not least because no vaccine was available at that time.

The reality, however, was different: both Maria Tereza and her son tested negative for the disease.

The scenario repeated itself, now in 2022. Already vaccinated, Marcelo again had Covid, but Maria Tereza did not present the disease. “Again, we were a little surprised that she didn’t get sick,” says the doctor.

The couple is part of a study by the Center for Studies on the Human Genome and Stem Cells, also known as Genome USP. Researchers at the institution identified other couples who went through the same experience and sought to understand the reasons why one of the partners got sick and the other did not.

In parallel to this investigation, another one was taking place with a similar purpose. In this second study, the objective was to understand why some elderly people over 90 years old had mild cases of Covid-19 when they were sick. By the end of 2020, there were already more than one hundred people monitored by the survey, some even centenarians.

“If you think of a 100-year-old elderly person who experienced Covid before the vaccine with the strain that came from China and spread around the world, the data showed that the chance of this person having complications was very high”, says Mateus Vidigal, researcher of the Genome.

The explanation, both for the elderly without complications and for couples in which one of the partners was not infected, may be genetic.

In the case of older ones, genome analyzes were performed, and some genes associated with the immune system were found more frequently. One of these is the MUC-22 gene. He is responsible for the production of mucin, a protein associated with mucus. This, in turn, plays an important role in combating Covid.

The researchers even compared the genomes of the elderly with those of adults up to 50 years old who had died from Covid-19. In these adults, changes were not observed.

In couples, genome sequencing was also performed, with results similar to those seen in the elderly. “We also identified these resistance genes”, says Vidigal.

The answer, however, is not yet definitive. The next stage of the research involves cellular assays to conclude whether, in practice, these genes really provide a differentiated response to Covid-19.

Another point concerns the numerous factors involved in a person’s immune system. An example is another investigation, also from Genome, about twins. Vidigal reports the case of two identical twins who had Covid at the beginning of the pandemic. After that, one of them became infected with the disease again, having a more serious condition, while the sister did not experience it.

“In theory, they share the same DNA, so we would expect a similar presentation of the disease, except that this girl ended up being reinfected and the identical twin sister did not”, he explains.

The case demonstrates how, far beyond genetics, several factors can influence someone’s immune response. Smoking, practice of physical activities and food are just a few examples that affect a person’s defense system. “All this ends up modulating the immune response, which is unique for each individual”, explains Vidigal.

Reinfections also raise questions

In November, consultant Ana Carolina Oyafuço, 27, went on vacation in Spain. Still in the European country, she began to experience flu-like symptoms, such as sore throat and fever. Back in Brazil, Ana took two self-tests for Covid-19 – both with positive results.

She is not sure if the infection happened in Spain, but suspects so. “I arrived on a Monday, and on Tuesday I already tested positive”, she says.

Ana says she was anxious and afraid. Her grandfather died of the disease in July, and the sequels worried her. But a positive Covid test wasn’t exactly new – in fact, this was the third time that the consultant had results confirming the infection.

As with people who never caught the disease, examples of reinfections like Ana intrigue scientists, but some hypotheses already indicate why this occurs.

Cristina Bonorino, immunologist and professor at UFCSPA (Federal University of Health Sciences of Porto Alegre), says that one explanation involves polymorphism, the idea that individuals have different immune responses. People with reinfection, for example, may have a pattern of immune response that makes repeated cases of the disease possible.

Another reason relates to the virus’ ability to mutate. When this occurs, the pathogen develops mechanisms that can bypass the defense mechanisms already acquired in previous infections or even with vaccination. Therefore, cases of reinfection would be more likely to occur.

These two explanations, however, still lack further evidence. Bonorino claims that there is a shortage of studies on reinfections, both for Covid and for other diseases.

“In general, we don’t do these studies for any virus, and perhaps it would be a good idea to program research for all these vaccine target viruses in order to implement public health policies”, he says.