During his youth, Stephen Cron was feeling helpless, as he watched his friends fall, one by one, prey to an unknown disease.
And when the disease, which we know as AIDS, became the body of his gymnastics partner Jerry Green, in 1978, Crohn expected that he would not escape his inheritance.
However, while Greene lost his sight and debilitated his body, Crohn’s had no symptoms. Within a decade, dozens of Crohn’s friends faced the same fate, and he survived.
The reason for his resilience remained unknown until immunologist Bill Paxton began his research on homosexuals fighting HIV in 1996.
Baskton was working at the Aaron Diamond Center for HIV Research in New York, and he was testing white blood cells that he had obtained from Crohn’s.
The scientist tried to infect those cells with HIV, which causes AIDS, in the laboratory, but all his attempts were unsuccessful.
It turns out that Crohn has a genetic mutation, which appears in only about 1 percent of the population, that prevents the AIDS virus from attaching to the surface of white blood cells.
Scientists simulated this breakthrough over the next decade to develop the “Maraviroc” anti-retroviral drug, which marked a breakthrough in AIDS treatment.
During the past twenty years, the discovery of Paxton has formed the core of research that includes cases like Crohn’s, who do not show symptoms of diseases despite exposure to viruses, with the aim of discovering new treatments. Some people have exceptional resistance to the Corona virus, which prompted scientists to examine their blood and genes, hoping to find the virus’s weaknesses.
For years, geneticist Jason Pope, a geneticist at the Icahn School of Medicine in Mount Sinai in New York City, has studied the reasons why some of them are so vulnerable to disease, from heart disease to Lyme disease, despite their exposure to risk factors that increase the risk of infection.
During the first wave of the Covid-19 pandemic, Bob immediately wondered about the possibility of finding people the virus could not infect.
Bob focused his research on families in which Covid-19 has afflicted several generations, with severe symptoms, while none of their members showed any symptoms. “Having an entire family might help us understand the genetic factors behind disease resistance,” he says.
New digital technologies helped Bob find families that could take years or decades to search for, at the height of the HIV outbreak.
Since June, Bob has been cooperating with groups on the Facebook platform and has also launched an online platform to search for asymptomatic Covid-19 patients.
Bob hopes that he will be able to decipher the necessary genetic map by analyzing blood samples from people without symptoms, looking for genetic mutations.
The results of this study may pave the way for the development of antivirals, which may prevent infection with Covid-19, and prevent future outbreaks of the disease.
Studies have linked O blood types with negative blood types and a reduced risk of severe complications from the disease. The researchers assumed that people who carry certain blood types may have antibodies capable of identifying some of the characteristics of the virus, but they have not yet been able to determine the nature of the link between the blood type and the complications of the disease.
Mayana Zatz, director of the Human Genome Research Center at the University of São Paulo, is conducting research on 100 couples between spouses and life partners, one of whom contracted Covid-19, and the other did not, despite living under one roof.
“We are trying to find the reasons why some people do not have Covid-19 disease despite their exposure to the virus, and the lack of antibodies to the disease in their blood,” says Satz. “We have noticed that this phenomenon is relatively common, as we have received about a thousand e-mails from people who say this description applies. on them”.
Zatz also examines the genes of 12 centenarians, over a hundred years old, who suffered slight symptoms, including a woman over the age of 114 in Recife, Brazil, who recovered from Covid-19.
These studies may help older people who are resistant to disease, find ways to protect those most vulnerable to disease from dying in the coming pandemics.
People with exceptional resistance to disease have attracted the attention of scientists in other fields, and over the past two months, they have reached important conclusions about the secret of the high numbers of Covid-19 deaths.
Deactivate the body’s alarm system
For twenty years, scientists at the Rockefeller University in New York have been studying the human genetic map, looking for evidence to explain why some people suffer from severe symptoms, just by contracting “usual” viruses, such as herpes or influenza.
“You may always find that some people suffer from severe and severe symptoms when they contract infectious diseases, because they have genetic mutations that make them more likely than others to develop complications,” says Qian Zhang, a geneticist at the university.
And when the Covid-19 pandemic broke out, it became clear that the elderly, especially those suffering from chronic diseases, were the most affected by the disease.
But scientists at Rockefeller, looking for the exceptional cases, such as healthy young men of 30 who ended up in hospitals on ventilators.
Last April, the team launched a global project in cooperation with universities and medical centers from Belgium to Taiwan, with the aim of identifying the reasons behind this.
And in the 1960s, scientists discovered an alarm system inside our cells to warn the body in case of a viral attack.
“When a virus enters a cell, the infected cell produces proteins called interferons, and releases them outside the cell. When the rest of the cells receive the signal, they take preparations to fight the virus. If the infection is serious, the cells produce enough interferons and release them into the bloodstream to alert the whole body that it is,” Zhang says. Is being attacked. “
But sometimes a genetic defect can disrupt this system. In 2015, Rockefeller scientists noticed the presence of genetic mutations in healthy young adults that lead to severe acute respiratory syndrome (PEP) associated with influenza. Because of this genetic mutation, cells do not release interferon proteins. “If the alarm system is turned off, the virus may spread and multiply rapidly in the body,” Zhang says.
Studies published in September 2020 compared 987 patients with Covid-19 who had pneumonia and who were less than 50 years old or older than 50 years and had no pre-existing diseases, and with Coronavirus patients who had no symptoms.
Studies discovered that about 3.5 percent of patients in the first group had a genetic mutation that prevents cells from producing and releasing interferon, and that 10 percent of them have autoantibodies in the blood, that is, antibodies that target proteins produced by the body.
These antibodies bind to interferon proteins released by cells and remove them from the bloodstream before the signaling signal reaches the rest of the body.
Ignacio Sanz, an immunology expert at Emory University, says that these results support the results of other studies that have shown that autoantibodies play an important role in developing serious Covid-19 complications, by disrupting the body’s ability to defend itself.
The Rockefeller scientists intend to use this information to search for people at greater risk of severe symptoms of Covid-19 disease and other respiratory diseases such as seasonal influenza.
Zhang says that anyone who is discovered to have a genetic mutation that disrupts the production of interferon in response to the viral attack can be treated with type 1 interferon proteins, either as a preventive treatment or in the early stages of infection.
She says: “Three patients in Paris, who had these genetic mutations, received an interferon injection, after they were confirmed to have Covid-19. The results were wonderful, and none of them developed severe symptoms.”
The team is also collaborating with blood banks around the world to count the number of people who have autoantibodies that target type 1 interferons. “We want to know the number of people who have autoantibodies, because many of the participants in the study appeared normal and did not suffer from any health problems, until they contracted Covid-19,” Zhang says.
In only 14 percent of patients with severe complications of Covid-19, autoantibodies were responsible for disrupting the interferon response.
“A small number of patients develop severe complications of the disease because they have a mutation in one major gene, while the vast majority of patients interact with several genes, which make them more susceptible to developing complications of Covid-19,” says Alessandra Raineri, professor of medical genetics at the University of Siena. Acute “.
Scientists from the University of Edinburgh studied the genetic map in 2,700 patients in intensive care rooms in the United Kingdom, and compared it to the genetic map of healthy volunteers.
They observed that the genes that are associated with interferon production and predisposition to pneumonia were more or less active in patients who developed severe complications of Covid-19 disease, compared to healthy people.
“The defect in the activity of these genes allows the virus to spread easily in the body and may also cause lung damage,” says Irola Bayrou Castenera, the geneticist who led the study. Castiniera expects these results to change types of treatments during future pandemics.
In February 2020, algorithms predicted that the drug paricetinib, used to treat rheumatoid arthritis, would be effective in treating COVID-19. This is because this anti-inflammatory drug suppresses the activity of at least one of the genes that contribute to lung disease.
Clinical trials have shown that giving patients a combination of parisetnib and the antiviral remdesivir helps Covid-19 patients recover in a shorter time.
In collaboration with researchers from The Rockefeller University, University of Edinburgh scientists are conducting broader studies on patients who are genetically predisposed to developing complications from Covid-19. These studies may help scientists to identify the reasons that make people with blood type A more likely to develop severe complications.
These studies helped scientists unveil the mystery of the difference in the impact of Covid-19 between the sexes. “These studies revealed how important the role of interferon is to stimulate the body,” says Rainieri. “Men have an increase in the male hormone testosterone in the blood after puberty, and this hormone affects the activity of the genes that control the production of interferon. That is why men who already have a defect in these genes. More susceptible to infection with the virus. “
These answers may not make much difference in the current pandemic, but they may definitely contribute to saving lives in future ones. The outbreaks of acute respiratory syndrome, swine flu, Ebola and Middle East respiratory syndrome in the past twenty years have proven that viruses will continue to be transmitted from wild animals to humans. We are now in dire need to develop new ways to treat people most at risk of developing disease complications.
Zatz’s team uses stem cells to convert blood samples taken from centenarians who have had exceptional resistance to Covid-19 disease, into lung tissue, and to infect them in the laboratory with several viruses, to explore the ability of genetic mutations to protect them from these viruses.
Similar to the study on Stephen Crohn’s blood sample, this study may aid the development of new antivirals.
“Our goal is to discover the genetic differences that enhance the resistance of some of them, not only against the Corona virus, but also against other viruses or diseases. We hope that this discovery opens new horizons for treatment for us,” says Zatz.