Rachel Robles contracted COVID in March 2020. The 27-year-old data analyst has not gone a single day without symptoms since. Most doctors did not believe her when she described how she had gone from running the Brooklyn Half Marathon the previous year to enduring such crippling fatigue that her couch felt like quicksand. How she suddenly struggled to put numbers together, despite her technical training. How no matter how many breaths she took, she always felt starved for air.
Three months in, one doctor told her, “COVID doesn’t last for 90 days. You either get over it or you die.”
That dichotomy—in which the only possible outcomes of COVID are either complete recovery or death—has turned out to be anything but true. Between 8 million and 23 million Americans are still sick months or years after being infected. The perplexing array of symptoms known as long COVID has left an estimated 1 million of those people so disabled they are unable to work, and those numbers are likely to grow as the virus continues to evolve and spread. Some who escaped long COVID the first time are getting it after their second or third infection. “It is a huge public health crisis in the wake of acute COVID infection,” says Linda Geng, a physician and codirector of Stanford Health Care’s long COVID clinic.
Though there is no longer debate that long COVID is a real phenomenon—both the Centers for Disease Control and Prevention and the World Health Organization have recognized its existence—the science is so new that many questions remain about how to define the condition, what causes it and how to effectively treat it. It has become clear, for example, that long COVID can assume a variety of different forms. “Not everyone has the same disease,” which means there are different causes, says Akiko Iwasaki, an immunologist at the Yale School of Medicine.
Scientists have proposed several different, yet interconnected, origin stories to explain these wide-ranging symptoms: The coronavirus could damage organs, spawn tiny blood clots, trigger autoimmunity, hide out in tissues or prompt new and ongoing symptoms in other, more subtle ways. To complicate matters further, these narratives are not mutually exclusive: Several could be occurring at the same time in a particular patient, or one could set off another in an unhappy sequence of events that keeps the patient in perpetual bad health. By teasing apart the theories one by one, researchers are gaining a greater understanding of this enigmatic illness and inching closer to therapies that don’t just mask symptoms but eliminate the root cause.
Listening to patients
Many of the earliest insights into long COVID have been gleaned from the experiences shared by patients. A survey by the Patient-Led Research Collaborative, a team of long COVID patients who are doing research into their condition, compiled a list of more than 200 different symptoms across 10 organ systems. These range from the most common complaints like fatigue, cognitive impairment, shortness of breath, irregular menstrual periods, headaches, heart palpitations, sleep problems, and anxiety and depression, to other afflictions like double vision, peeling skin, hair loss, tinnitus, tremors, food allergies, and sexual dysfunction. The constellation of reported symptoms can vary from person to person, even changing over the course of the condition.
Because there is no agreed-upon definition of long COVID, no simple diagnostic test, and no way to clearly distinguish one subtype from another, the various manifestations of this mysterious condition often get lumped under one big umbrella, confounding researchers. Yet emerging research is providing the first evidence for several promising hypotheses.
One theory blames the illness on lingering organ or tissue injury caused by the initial infection with SARS-CoV-2, the virus behind COVID-19. Though the coronavirus enters the body through the respiratory tract, it can travel through the bloodstream to infect the kidneys, heart, nervous system, and gut. In the process, it can set off waves of inflammation that reverberate throughout the body, causing collateral damage to multiple organs.
In one study, researchers at the University of Oxford compared brain scans of people before and after they got COVID and found that even mild cases can cause the brain to shrink by 0.2 to 2 percent more than in people who had not been infected. Because adults typically lose about 0.2 percent of their brain volume in regions related to memory every year, that translates to mental decline equivalent to 1 to 10 years of aging. It’s too soon to know if this effect is temporary or might set up people for age-related disorders later in life.
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