three years in, pandemic mania has turned into a rumbling buzz. We go back to sweating each other out in nightclubs, blowing out birthday candles and sharing firm handshakes. Covid-19, although it is still very much alive, has become an everyday threat for most people, thanks to vaccines and treatments.
The same cannot be said for long-term covid, the mysterious life-limiting ailment that persists after an initial covid infection. For the millions besieged by him, their situation remains the same. “We don’t have tools in place yet to help treat patients,” says Linda Geng, co-director of the Covid-19 Post-Acute Syndrome Clinic at Stanford University. Estimates of how many people have Covid for a long time vary, but it has gotten as high as around 65 million—about the same as the population of France.
Only now, more than three years into the pandemic, has a consensus on the duration of Covid begun to solidify. And it turns out that what it is is a lot of things. Rather than a single disorder, it is more likely to be a smorgasbord of diseases that fall under one big umbrella. That means there probably won’t be a one-size-fits-all treatment, either.
What triggers prolonged Covid for you may not be what triggers it for another. Maybe your long Covid is caused by your immune system turning on you and attacking your body, a phenomenon called autoimmunity. So goes a theory. Or maybe it’s that the splinters of the virus are hanging around your body long after the initial infection, keeping the engine of your immune system revving to the point of exhaustion. Another theory is that SARS-CoV-2 causes lasting damage to certain organs or tissues. Maybe it’s a Covid infection wake up dormant virus your body has dealt with before, such as the Epstein-Barr virus, which causes mononucleosis.
All of these theories have some evidence to support them, and may not be mutually exclusive; For some people, these things could be happening at the same time. The idea that prolonged covid has different causes could help explain the great diversity of symptoms, the number of which more than 200.
Building on this, researchers are trying to kill two birds with one stone: test treatments that could alleviate prolonged covid while giving weight to certain hypotheses and beginning to unravel the puzzling condition. “The reality is that there is such urgency that we need to do these things in parallel,” says Geng. “He is building the ship as we sail it, but we have to sail it because people need help.”
But the jumble of symptoms makes clinical trial design much more complicated. Not everyone experiences all symptoms, and symptoms can vary in severity and duration. Also, there’s no consensus on how to define long-term covid, says Steven Deeks, an infectious disease specialist and physician at the University of California, San Francisco. “There is no magic biomarker, there is no X-ray, there is no test.” Therefore, it is difficult to decide who to include in a clinical trial. At this time, the long diagnoses of Covid work by exclusion: determining that the symptoms cannot be explained by another cause. Regardless, researchers are making progress.