After 35 years of sharing everything from a love for jazz music to tubes of lip gloss, twins Kimberly and Kelly Standard assumed that when they became sick with COVID-19 their experiences would be as identical as their DNA.
The virus had different plans.
Last spring, the sisters from Rochester, Mich., checked themselves into the hospital with fevers and shortness of breath. Kelly was discharged after less than a week, Kimberly ended up in intensive care.
Weeks after Kelly had returned to their shared home, Kimberly was relearning how to speak, walk and chew and swallow solid food she could barely taste.
Nearly a year later, the sisters are bedeviled by the divergent paths their illnesses took. "I want to know," Kelly said, "why did she have COVID worse than me?"
Since the new coronavirus first shuddered into view, questions like the one posed by Standard have spurred scientific projects around the globe. Among the 94 million infections documented since the start of the outbreak, no two have truly been alike, even for people who share a genetic code.
Identical twins offer researchers a ready-made experiment to untangle the contributions of nature and nurture in driving disease. With the help of twin registries in the U.S., Australia, Europe and elsewhere, researchers are confirming that genetics can affect which symptoms COVID-19 patients experience. These studies have also underscored the importance of the environment and pure chance: Even between identical twins, immune systems can look vastly different — and continue to grow apart over the course of a lifetime.
Dr. Mishita Goel, one of the doctors who treated the Standards, said she was surprised to see the different trajectories. "We were amazed."
At least some of the factors that influence the severity of a case are written into the genome. Tim Spector, a public health researcher and the director of the TwinsUK registry, said he and his colleagues reported that genetic factors might account for up to 50% of the differences between COVID-19 symptoms.
In at least some respects, identical twins are "genetically programmed to be similar," he said.
Twins Krista Burkett and Kasey Miller, 28, of Toledo, Ohio, fell ill after Thanksgiving. "Day for day, it was exactly the same," Burkett said.
What they experienced was not the norm. Many of the conditions that can raise a person's risk for severe COVID — excess weight, heart disease, diabetes, smoking — are highly influenced by environment and behavior, not just genetics.
Researchers have also floated the idea that the amount of coronavirus a person takes in may have an impact on the severity of disease.
Identical twins start as a single embryo that splits in two, creating carbon-copy babies-to-be. But from that time on, their developmental trajectories diverge, as their DNA accumulates often subtle, but unique, typos. A paper published in Nature Genetics reported that identical twins differ by an average of 5.2 early and naturally occurring developmental mutations.
Through adolescence, the biological chasm between twins deepens as distinct microbes colonize their guts, or subtle shifts in the environment squish or stretch parts of their genomes, making certain segments harder or easier to read. All of these changes can influence how a person responds to an infection, said Anita Pepper, a developmental biologist.
Mark Davis, an immunologist at Stanford University, said twins may start with the same genetic ingredients, but then "they roll the dice."