The SARS-COV-2 coronavirus is insidious and mysterious. The symptoms of the disease he causes are varied, and the portrait of his typical victim is not at all as obvious as it seemed before. 23andMe is going to use its unique genetic database to identify a possible link between patients' DNA and vulnerability to the virus.
The SARS-COV-2 coronavirus, which first surfaced last year in China, is an equal opportunity aggressor. If you are a human being, he wants to penetrate you. It seems that the virus infects people the same way regardless of their age, race or gender. This is logical, since this is a completely new pathogen from which no one has immunity.
But the virus-caused Covid-19 disease is more unpredictable in its manifestations. Very few people who are infected actually get sick. Patients have very different symptoms. Someone has a high fever and cough. Some have stomach cramps and diarrhea. Someone is losing their appetite. Someone ceases to distinguish smells. Someone is able to overcome the illness by sitting at home, consuming a lot of fluids and delighting themselves with TV shows. And someone ends up in intensive care, where many tubes are connected to him, which unsuccessfully pump air into his diseased lungs. The elderly with chronic diseases and men account for the majority of deaths. But not always. In the United States, a large percentage of those hospitalized with severe symptoms are under the age of 40. Children, especially infants, are also not one hundred percent protected.
Scientists are looking at scattered epidemiological data from hotspots such as China, Italy and the United States to understand what caused these differences. They look for characteristics and patterns in the age of patients, their race, gender, socio-economic status, behavior and the availability of medical services for them. Now they are digging deeper, trying to find clues in our DNA.
On Monday, 23andMe launched a new study to identify genetic differences that could explain why people with Covid-19 have such different reactions to infection. This consumer genomics firm has joined a string of new research projects seeking an answer to the same question. Previous research shows that certain gene variants put people at increased risk when they contract certain infectious diseases. Others provide them with protection, say, a mutation in the CCR5 gene, which makes the carrier immune to HIV. It is too early to say how significantly DNA protects against Covid-19, or vice versa, makes a person vulnerable. However, the information obtained can someday be used to identify people who are more at risk of infection,as well as for a targeted search for new drugs and treatments.
“We want to understand how our genes influence our response to the virus,” said Joyce Tung, vice president of research at 23andMe. “We hope that by collecting data from people who have been tested and diagnosed with Covid-19, we will be able to learn something about the biological characteristics of this disease and help the scientific community to treat patients more successfully.”
While other DNA research companies have converted their laboratories and are now testing people for Covid, 23andMe decided to use its unique asset - a database of more than 10 million customers, 80% of whom have agreed to use their genetic information and others for research purposes. data that they themselves reported. The company has been building this database for several years, which makes it easier to conduct mass surveys among potential research participants. As a result, each genetic profile includes hundreds of phenotypic pieces of information, such as how many cigarettes a client has smoked in their lifetime and whether any of their relatives have had diabetes. The huge amount of data that the company has,allowed her to begin her search for a cure and made her a powerful source of information in the field of genetic research.
The latest poll, published on the 23andMe customer portal, includes questions about where a person lives, what social distancing measures they follow, whether they have been tested for coronavirus, have had contact with infected people, and whether they have been diagnosed with Covid-19. (Only US customers of the company can participate in the survey.) 23andMe hopes to recruit hundreds of thousands of its customers to the study, including those diagnosed with Covid-19, who tested negative, who have flu-like symptoms, but who are being tested so far. did not pass, as well as family members of those infected. For people who test positive, an additional survey will be conducted about the severity of the illness, the manifestation of symptoms, and whether they have been hospitalized. This was told by the chief scientist of the company Adam Auton,which is leading a new Covid-19 study. All participants will be invited every month to a new survey with additional questions, allowing 23andMe to identify new cases among respondents.
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If the company collects enough responses from people infected with Covid-19, its research team will conduct a statistical analysis called Genome-Wide Association Search (GWAS). This method is widely used in genetic research. During GWAS, people are divided into different groups, in our case, most likely, based on symptoms. Their DNA data is then scanned to see if certain single-letter variations in the genetic code are more common among people with certain symptoms. If this happens often enough, it can be said with some degree of certainty that such variations are associated with these symptoms.
It is difficult to predict which genes will be found during these DNA search expeditions. But many of them are likely to be found in those parts of the genome that are responsible for the body's immune response, says Michael Snyder, who heads the department of genetics at Stanford University and has nothing to do with 23andMe and its research. “In general, we know that genetics influences the course of a viral infection,” he says. - There is nothing unexpected in this, since in the process of historical development, people in various environmental conditions were exposed to quite specific pathogens. It makes sense that different people have different immune systems.” (It must be said that an overprotective reaction, known as hypercytokinemia, has caused many deaths among patients with atypical pneumonia.that hypercytokinemia is also the cause of some deaths among young people with Covid-19.)
Another potential candidate is a gene for the ACE2 receptor. It is located on the surface of the lungs and other human cells, and is the molecular passage through which SARS-CoV-2 enters the body. Small changes in this gene can make it easier or harder to get through certain receptors. In addition, variations in the region of the genome that turn on or off the ACE2 receptor can also play a role. If genes are less active, human cells produce fewer receptors, making them harder for the virus to grab onto.
It's too early to speculate about the role genes play in determining the outcome of Covid-19 disease, Snyder says. But he is ready to bet that projects like those implemented by 23andMe are unlikely to provide a single genetic variant that decides whether a person will be in intensive care or not. “I'd be surprised if they find something as compelling as BRCA,” says Snyder, referring to one of the most powerful predictors of cancer that scientists have found. Mutations in the BRCA genes quadruple a person's chances of developing certain forms of breast cancer.
The point is that genome-wide association search is a numbers game. It is the best way to detect mutations that recur and reappear in the entire population, each having only a very small effect on a person's susceptibility to disease. And since a genome-wide association search is usually based on a limited set of genetic data, such as that collected by 23andMe (a static view of 600,000 genome locations), these common variants are easier to identify than rare ones.
However, it is very rare mutations that are likely to be the reason for the extreme exposure to Covid-19, says Stephen Chapman, a pulmonologist who works as a researcher at the Center for Human Genetics at the University of Oxford and is not involved in the 23andMe project. In the mid-2000s, he conducted the first genetic studies of bacterial pneumonia predisposition and discovered rare mutations in immune-mediated genes that made otherwise healthy children and adults highly susceptible to a particular bacterium entering the body. Chapman suspects that equally rare mutations involved in immune function and response to inflammation are being put to ICU beds for young, healthy people who have no other risk factors. “In my opinion, this is a serious drawback of GWAS,he says. "Genome-wide association searches overlook these rare, disease-causing mutations."
Finding them requires taking blood tests from non-standard patients and sequencing their entire genomes. If we decipher the DNA of a young adult who is connected to artificial lung ventilation, it is possible that it will be possible to reveal a unique genetic predisposition to Covid-19. On the other hand, the DNA of older people who have been diagnosed with coronavirus and Covid-19, but no symptoms, may contain protective mutations that protect against the most severe forms of the disease.
More than 90 such sequencing projects are already under way in laboratories around the world, and scientists are racing to understand the disease that has killed more than 76,000 people worldwide. Some of the projects are long-term genetic studies in the population, in which thousands of volunteers have been participating for a long time. Icelandic company DeCODE Genetics, which has been collecting data on the genomes and health of 364,000 inhabitants of this island country for decades, received government permission to publish the results of tests for Covid-19. There are also new studies being conducted exclusively among Covid-19 patients. To combine all the genetic data from various research teams,scientists from the University of Helsinki recently set up a clearing house called Covid-19 Carrier Genetics. As more data emerges, statistics become more convincing and reliable, and at the same time, the hope that mutations can be found that can change the impact of a new disease on a person, as well as the process of humanity's struggle against it, increases.
But it is hardly worth expecting that we will receive a genetic scorecard of susceptibility to Covid-19 in the near future. Chapman says it's likely that these studies won't be able to identify susceptible people based on their DNA. Rather, we will simply gain a better understanding of the molecular pathways through which the most severe forms of Covid-19 emerge. “This is a completely new and devastating human disease, and we urgently need to understand its biology,” explains Chapman. By isolating genes that regulate different immune responses, this will help determine what exactly needs to be treated with new drugs, and doctors will be able to more purposefully and specifically approach the treatment of individual patients. “GWAS and whole genome sequencing can play a very valuable role here,” notes Chapman.
Age, previous health problems, early testing, and quality care will all be central to determining who will survive and who will die from Covid-19. But DNA also probably plays a role in influencing the outcome of the disease. And here we still have a lot to learn and find out.
Megan MOLTENI