COVID twins help scientists unravel the genetic roots of the disease

The virus had various plans.

Early last spring, sisters in Rochester, Michigan checked in to the hospital with fever and shortness of breath. Kelly was discharged in less than a week, but her sister arrived in the intensive care unit.

Kimberly spent almost a month in danger, breathing through a tube, soaking in shock and getting out of shock. A few weeks after Kelly returned to her shared home, Kimberly was still re-learning how to talk, walk, chew, and swallow solid foods that she could hardly taste.

Almost a year later, the sisters suffered from a strangely different path that their illness followed.

“I’d like to know, why did she have a worse COVID than I did,” Kelly said.

Since the first appearance of the new coronavirus, questions such as those raised by Standard have spurred scientific projects around the world. Of the 94 million infectious diseases recorded since the outbreak, the two were not really the same, even for those who share the genetic code.

Identical twins provide researchers with off-the-shelf experiments to unravel the contributions of nature and promote disease. With the help of twin registries such as the United States, Australia, and Europe, researchers have confirmed that genetics can affect the symptoms experienced by COVID-19 patients. These studies also emphasize the importance of the environment and pure opportunities. Even among identical twins, the immune system can look very different and will continue to fall apart throughout life.

Dr. Misita Goel, one of the doctors who treated Standard Twins last spring, said he was surprised to see the virus follow such a different medical trajectory in each sister. “We were surprised,” said Goel, who published a case study on twins last summer.

Both sisters were overweight and had a history of metabolic status. If anything, Kelly, who suffers from asthma and more severe diabetes, may have had a slightly higher risk of entering the intensive care unit, Goel said. But even worse was Kimberly.

At least some of the factors that influence the severity of COVID cases are written into the genome. Recent studies suggest that, for example, people with ABO blood group may have a slightly lower risk of developing a serious illness with the coronavirus (experts say these types of findings). Is warned not to over-interpret). Other treatises focus on genes that influence the way cells warn about viruses, or genes that increase defense to ward off invaders.

Further fine-tuning of other genes can make it easier for the coronavirus to invade cells. Some people provoke an enthusiastic immune response to infection and can damage healthy tissue alongside sick tissue. This is a common feature of the worst COVID-19 cases.

Tim Spector, a public health researcher based in London’s St. Thomas Hospital and director of the Twins UK Registry, measures whether people experience symptoms such as fever, malaise, and delirium when attacked by the coronavirus. There seems to be a possible genetic effect. Last year, he and his colleagues developed a symptom tracking app to record how people dealt with their illness. In a study not yet published in a scientific journal, they reported that genetic factors may account for up to 50 percent of the differences between COVID-19 symptoms. One gene they are investigating is the code for a molecule called ACE2 that docks the coronavirus before it enters the cell.

“It’s a mistake to think that you can answer this just by decoding the gene,” Specter said. Nevertheless, in at least some respects, the bodies of identical twins are “programmed to be genetically similar.”

Twins Crysta Barquette and Casey Miller, 28, from Toledo, Ohio, fell ill shortly after Thanksgiving. Their illness staggered for about a week and hit Miller first. But “every day it was exactly the same,” Barckett said.

For both sisters, COVID began with an hour’s fever of 99.5 degrees Fahrenheit, followed by a few days of back pain and a strange humming sensation. On the 8th day, I was crescendo with a painful headache. After that, like a clockwork, the symptoms disappeared.

The virus encore did not offend the twins. “Honestly, that was a little good for her,” Miller said of her sister. “She knew exactly what would happen to her.”

What Barckett and Miller experienced was not standard. Many of the conditions that can increase the risk of severe COVID (overweight, heart disease, diabetes, smoking) are significantly influenced not only by genetics, but also by the environment and behavior. The history of people who have fought other coronaviruses that lead to the common cold can also affect their likelihood of developing serious cases of COVID.

Some researchers have also come up with the idea that the amount of coronavirus that a person ingests can affect the severity of the disease. This is a trend recorded with other infections.

Juliet Morrison, a virus expert at the University of California, said: “The difference is that it allows the immune system to actually suppress the infection, and it becomes much more difficult to fight the immune system if all cells are infected at the same time. Riverside.

Michael Russell, 29, says he suspects his twin brother Stephen may have sniffed more virus than this summer after he met his family on July 4.

Shortly after the celebration was over, when Stephen returned to his home in Arlington, Virginia, the two brothers began to experience symptoms. The virus saddled Stephen with an itchy throat and a headache — he said was a “mild, cold-like” illness.

A few days later, Michael, who lived home with his parents, complained of much more serious symptoms such as sore throat, chills, shortness of breath, and malaise, and was forced to bed all day. It’s been about two weeks before he smells and tastes cinnamon-coated popcorn, which he regularly eats.

The twin parents also collapsed with bad COVID symptoms, so Michael had to be isolated from the other two infected adults. The brothers said he could have been exposed to a large number of viruses when he was hankering together in the same house. But they added, it’s just a guess.

For some twin pairs, there is no clear explanation for the course of their different illnesses. Malena and Vivian Har, 17-year-old identical twins from Jackson Hall, Wyoming, have spent their lives close to each other, linking the tastes of In-N-Out Burger and Taylor Swift.

“We share drinks, hang out in each other’s rooms and have the same friends,” Vivian said. But she and her sister never seem to have the same illness.

When my sister got sick with COVID a week after attending the Halloween party, her symptoms split. Malena lost her sense of taste and smell, and Vivian fought a debilitating flu-like illness, neither of which returned after two months.

Identical twins begin as a single embryo that divides into two and give birth to a carbon copy baby. However, from that time on, their developmental trajectory diverges as their DNA is small and often accumulates subtle but unique typos. A paper published this month in Nature Genetics reported that identical twins differ by an average of 5.2 early spontaneous mutations.

From childhood to adolescence, the biological gap between twins deepens as separate microorganisms settle in the intestine, and subtle environmental changes crush or stretch parts of the genome into specific segments. Makes it harder or easier to read.

Anita Pepper, developmental biologist and vice president of the Wistar Institute in Philadelphia, said all these and other changes could affect a person’s response to infection.

Even the DNA at which the cell begins does not stick to the stone. Certain immune cells, called B cells and T cells, are, in some respects, particularly impervious to the genes from which they begin. Part of the job of these cells is to produce proteins such as antibodies that recognize pathogens that can be harmful to the body. The more these suspicious forms that cells and antibodies can find, the better a person can avoid the disease.

However, it does not make sense to encode a separate gene for each possible iteration of the antibody. There are too many. Instead, immune cells build a defense repertoire through a process called recombination. This process mixes and collates DNA segments to create billions, trillions, and even 4 trillion unique gene stretches.

Marion Pepper, an immunologist at the University of Washington and an identical twin of Anita Pepper, compared the process of grouping words on a scrabble board. This is a way to generate diverse vocabulary without having to carry the dictionary from place to place.

“Once these cells are out of the body, we hope they are diverse enough to recognize everything,” says Pepper. “great.”

Because these processes are random, it is nearly impossible to replicate from person to person, even if the initial Scrabble tiles are all the same.

Mark Davis, an immunologist at Stanford University and an immunologist at Stanford University who studies the genetics of the immune system, said that this immune adaptability is to prevent even pathogens that have never been seen before. The advantage is that you can prepare your body. .. The twins may start with the same genetic component, Davis said, but then “they roll the dice.”

Yet another researcher turned to twins to study another effect of the pandemic: Global fraying in psychological well-being. Emanuela Meda, an Italian twin-registered researcher, is leading an effort to track the stress, anxiety and depression of thousands of twins scattered across the country. On a remote continent, public health researcher John Hopper, director of Twins Research Australia, has embarked on a similar project to monitor how families are navigating the world transformed by the coronavirus.

According to Hopper, the pandemic has created a significant proportion of challenges. However, the initial findings collected through a series of studies provide a faint light of hope. In the turmoil, some feel that difficulties have brought them closer to their loved ones.

In Michigan, Kimberly and Kelly Standard recall their illness last spring as one of the longest stretches they’ve ever spent apart. During the first few days they spent in the hospital, the sisters facetimed each other from separate rooms. This was the best alternative to meeting each other in person.

Kelly struggled to calm her mind while Kimberly’s condition was fluid, even after she was released from care. She became afraid of the phone ringing, knowing that every time the screen flashed the hospital’s 734 area code, it could bring news that her sister had died.

After Kimberly woke up in the intensive care unit, it took several days before he could speak more than a file. She reached out to the hospital phone without a cell phone and called her sister. She was the only one who really knew her number.

When the Standard sisters finally met again, they wept and wrapped each other in a close hug. It was a blessing, Kimberly said: “Finally, I felt like myself again.”

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