Some People Have Had a Persistent COVID Infection for Years, Scientists Say

Scientists have stumbled upon a strange discovery — persistent COVID-19 infections that have likely lasted for years. However they have not been able to identify who the individuals are, and although they are likely ill, these people probably don’t know they still have COVID.

Marc Johnson, Ph.D., professor of microbiology and immunology at the University of Missouri, says he and his group found something they didn’t expect when testing wastewater samples in 2021. They call them “cryptic lineages” of COVID, which are mutations of the virus that have not yet spread through the population, and belong to a single individual.

These lineages, or unique viral sequences that are from an unknown, individual source, have since been identified in wastewater in Missouri, New York, California, Oklahoma, Virginia, Wisconsin, Michigan, Colorado, Texas, Florida, New Jersey, Kentucky, Ohio, Montana and Washington D.C., as well as Europe.

The discovery of persistent COVID is important not only to the people who may have it, but to the understanding of COVID in general. The samples foreshadow what the virus might do next by showing the trajectories it will likely take in order to avoid the human immune system. 

Persistent COVID likely has some similarities to long COVID, but Dr. Johnson does not think they are the same thing. 

“We really don’t know how big the overlap is between long COVID and persistent infection,” he says, “I don’t think all long COVID patients have a persistent infection. They have persistent symptoms, which is different because that can be caused by other things like your immune system being thrown out of whack, or many other causes. Some people clearly have a persistent infection and we don’t know what their symptoms are.” 

Without a list of symptoms, persistent COVID is not recognized as an official diagnosis in the same way that long COVID is.  

What the scientists do know is that some people have the viral load of an infected person for months, and sometimes years at a time.

“We know that some people are shedding the virus for a year, two years, and they’re shedding ridiculously high amounts, and the virus is very clearly mutating like crazy within these people. It’s not just random changes. These are clearly antibody escaped mutations,” he says, which means mutations that prevent antibodies from recognizing the virus. 

When Dr. Johnson first discovered the mutation in Wisconsin, he thought it may be from an animal. But then they tracked it to a human. 

“There was a lineage in a city in Wisconsin which was very consistent. And so we tracked it. We worked manhole by manhole starting from a city of over a hundred thousand all the way down to a single manhole where we figured out where the signal was coming in from,” he says. 

Researchers were able to narrow down the site where the wastewater originated, a single office building with 30 employees. That meant a person with the persistent infection was in that group. 

Dr. Johnson and his group requested to test the employees for COVID, and the health department offered the employees free COVID tests. About two-thirds of the employees participated, but they all tested negative.

“But it’s possible the infection is no longer in their nasal cavities. It could be in their gut,” Dr. Johnson says. “Then the health department didn’t really have a way to move forward because there was no standard test that the department could offer for stool testing.”

After a very long approval process, Dr. Johnson’s group was given the go-ahead to do stool testing, but by then the lineage they had been tracking for 13 months disappeared. Likely because the person finally got better, or the individual they were looking for may have simply moved on to a new job.

Dr. Johnson worries that the individual they found, and others like them, could be fairly ill and not know that they have a persistent COVID infection. 

He says the amount of viral shedding would suggest “a fair amount of tissue infected. I have a hard time believing it isn’t damaging them.”

But there is no easy way to test for a persistent COVID infection in the GI tract, so even if the individual is regularly going to the doctor, they may not be able to identify what is causing their illness. 

Further, Dr. Johnson suspects the people with persistent infections may have things in common, like certain pre-existing conditions, but there is no way to determine that at this time. 

There is a similar phenomenon with feline coronavirus, he says. “It causes a gut infection and they can shed virus for years and sometimes a really high amount of it. And most of the time they’re okay, but about five to 10% of the time the virus goes through this change and becomes feline infectious peritonitis.” The diagnosis used to be a death sentence for cats, but now they can be treated with COVID medicine, he says.

Dr. Johnson and his group know the mutations they have found belong to a single person because they are constrained to a single sewershed. “If it were from multiple individuals we would expect the sequences to branch off from each other, which they don’t,” he says.

“We don’t have irrefutable evidence that it is a single person in every case, but once we figured out how much a single person can shed, it became clear that it is by far the simplest and most likely explanation.”

“When the virus is in one person,” Dr. Johnson says, “it can just keep evolving every which way, and as a result, it evolves much faster. So a lot of the mutations we saw in crypto lineages very consistently, and we didn’t see them in any circulating lineages until years later. But now these mutations are seen in nearly a hundred percent of what’s circulating.”

He is working on other ways to identify these patients, since using wastewater to track is a slow process that brings up legal, ethical and privacy issues.

And the matter is of some urgency, since people with persistent COVID infections are likely circulating among the population and could be introducing dangerous variants to others. Further, they could be very ill or become very ill.

“I don’t know whether these are people who are going to die from a disease that could actually be treatable,” Dr. Johnson says.