“Usually, when people recover from acute viral infections, their immune response kills the cells affected to eliminate the virus,” says Diane Griffin, a virologist at the John Hopkins Bloomberg School of Public Health. But when viruses infect long-lived cells, such as neurons, the immune system can’t afford to destroy them. That means “you don’t actually get rid of all the virus genome,” she says; instead, the virus might hide in parts of the body for long periods.
If so, this persistence may actually be key to long-term immunity. Griffin says that even if the virus isn’t spreading profusely, if its proteins are still being produced in a small number of cells, its fragments may force your body to maintain an immune response—keeping you from getting sick again.
That’s true even for infections such as measles, where long-living neurons aren’t a major target. In monkey studies, Griffin found viral RNA in immune system cells called lymphocytes for six months after apparent recovery. The virus could last even longer in human cells, she says. Meanwhile, measles produces life-long immunity, and Griffin suspects persistent RNA may help explain that effect.
Others agree with her. “Some aspects of the immune system exist as they are because we are chronically infected,” says Skip Virgin, executive vice president and chief scientific officer of the biotechnology company Vir.
Avindra Nath, the clinical director of the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, says that a “possible persistent immune function” may be detrimental to COVID-19 patients, and may play a role in so-called cytokine storms where the immune system kicks into damaging overdrive. Such immune responses may help explain the potential relapses and some of the emerging long-term complications, says Nath, who has begun developing a long-term study on the topic
However, individuals may exhibit myriad levels of viral persistence and immunity, which could make vaccine development and deployment more challenging. “The same viral particle won’t have the same effect in every person,” says Santosh Vardhana, a medical oncologist at Memorial Sloan Kettering Cancer Center. That’s why few vaccines provide universal immunity, says Vardhana, who’s researching how adaptive immunity might help COVID-19 patients.
This variety in responses can also make it harder to recommend how long sick people should stay isolated. The U.S. CDC currently recommends COVID-19 cases isolate for 10 days after they start feeling ill, and three days after their fever dissipates. If you never have symptoms, the 10-day window starts after you get a positive result on a COVID-19 test.
Both for vaccine efforts and to better treat patients, Vardhana says, “we have to think about the immune response with COVID with more complexity.