Three years in, the pandemic mania has settled to a rumbling hum. We’re back to sweating on each other in nightclubs, spluttering out birthday candles, and sharing firm handshakes. Covid-19, while still very much alive, has for most people diminished to an everyday threat, thanks to vaccines and treatments.
The same can’t be said of long Covid, the mysterious, life-limiting ailment that lingers on after an initial Covid infection. For the millions besieged by it, their situation has remained much the same. “We still have no established tools to help treat patients,” says Linda Geng, codirector of the Post-Acute Covid-19 Syndrome Clinic at Stanford University. Estimates of how many people have long Covid vary, but it’s been put as high as around 65 million—about the same as the population of France.
It’s only now, over three years into the pandemic, that a consensus on what long Covid is has started to solidify. And what it is, it turns out, is a whole bunch of things. Rather than a single disorder, it’s more likely a smorgasbord of diseases that fall under one big umbrella. That means there likely won’t be a one-size-fits-all treatment either.
What triggers long Covid for you may not be what sets it off for another. Perhaps your long Covid is caused by your immune system turning on you, attacking your body—a phenomenon called autoimmunity. So goes one theory. Or maybe it’s that splinters of the virus are hanging around your body long after the initial infection, keeping your immune system’s engine revved up to the point of exhaustion. Another theory is that SARS-CoV-2 causes long-lasting damage to certain organs or tissues. Maybe it’s that a Covid infection reawakens latent viruses your body has encountered before, such as the Epstein-Barr virus, which causes mononucleosis.
All these theories have some evidence to support them, and they may not be mutually exclusive; for some people, these things could be happening at the same time. The idea that long Covid has different causes could go some way toward explaining the sheer diversity of symptoms, which number up to 200.
Working off this basis, researchers are trying to hit two birds with one stone: trialing treatments that could alleviate long Covid while at the same time lending weight to certain hypotheses—and beginning to defog the mystifying condition. “The reality is that there’s such an urgency, we need to do these things in parallel,” says Geng. “It’s building the ship as we sail it—but we have to sail it because people need help.”
But the jumble of symptoms makes designing clinical trials much trickier. Not every person experiences every symptom, and those may vary in severity and duration. Plus, there’s no consensus on how to define long Covid, says Steven Deeks, a physician and infectious disease specialist at the University of California, San Francisco. “There’s no magic biomarker, there’s no x-ray, there’s no test.” Because of that, it’s tough to figure out who to put into a clinical trial. Right now, long Covid diagnoses work by exclusion: determining that symptoms can’t be explained away by another cause. Regardless, researchers are plowing ahead.