Monitoring chronic coronavirus infections may help forecast new variant threats, study suggests

A new study out of Israel suggests that monitoring chronic COVID-19 infections may be a means to predict future variants that could pose a threat.

Israeli researchers analyzed 27 chronically infected, immunocompromised patients

This transmission electron microscope image shows SARS-CoV-2, the virus that causes COVID-19, isolated from a patient in the U.S. Virus particles are shown emerging from the surface of cells cultured in the lab. (NIAID)

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As Omicron began its swift spread around the world, theories about its origins sprang up as well.

Did the heavily mutated coronavirus variant evolve within an animal host before spilling back into humans or in a COVID-19 patient being treated with a drug capable of spurring viral mutations?

Or, many scientists wondered, did the latest variant of concern develop during a protracted battle against the virus inside the body of someone with a compromised immune system?

While there are no clear answers just yet to the questions around Omicron's emergence, that third theory — tied to viral evolution inside immunocompromised hosts — is an area that's getting attention from researchers, with one new study suggesting that monitoring chronic infections may be a means to predict future variants that could pose a threat.

In early findings, published online as a preprint paper and not yet peer-reviewed, a team of Israeli researchers affiliated with Tel Aviv University looked at 27 chronically infected coronavirus patients.

All of those individuals had suppressed immune systems for various reasons, including certain cancers, high-dosage steroid treatment or low levels of T-cells from conditions such as AIDS.

"Presumably, these immune system disorders prevent clearance of the virus as compared to patients with an intact immune system, and thus the virus thrives for lengthy periods of time," the researchers wrote.

Mutations 'mirror' those in variants of concern

Typically during SARS-CoV-2 infections, viral shedding lasts anywhere from a few days to a few weeks.

But documented cases of chronic infections, such as those studied by the team, can last far longer, with replicating viruses detectable for lengthy periods of time. (That's notably different from long COVID, the researchers noted, in which the initial infection is shorter but symptoms persist.)

After analyzing the set of patients with chronic infections, the team concluded that the overall patterns of mutations observed in those cases "closely mirror" the patterns observed in variants of concern.

There were instances of viral rebound, for example, where the virus dropped to undetectable levels but then appeared to replicate throughout the body again — which may suggest mutations capable of evading antibodies, the researchers wrote, offering a possible signal that scientists can use to identify future variants.

Nurse Ashley De Lumen attends to a COVID-19 patient on a ventilator in the intensive care unit of Humber River Hospital, in Toronto in January. (Evan Mitsui/CBC)

But in their small sample of patients, the team didn't find instances of certain mutations that could drive virus transmission, prompting researchers to suggest that any variants emerging in chronically infected patients might lack that key capability. That's a potential trade-off, they argued, between the virus becoming more transmissible or more immune evasive.

"Overall, we suggest that extensive monitoring of chronic infections can be used for forecasting the set of mutations in future [variants of concern]," the team concluded.

'Critically important' studies

Jason Kindrachuk, an assistant professor in medical microbiology and infectious diseases at the University of Manitoba in Winnipeg, said these kinds of studies are proving "critically important," but he stressed that a small subset of patients isn't necessarily representative of what's happening more broadly with chronic infections.

Kindrachuk said he wasn't surprised that there were instances of immune evasion within the 27 patients studied, but noted that it will be crucial to understand why there weren't also mutations linked to increased transmissibility, which have helped multiple variants spread like wildfire.

"Whether those types of shifts in the virus are more random or related to a subset of chronic infections, that'll be important to say," he said.

WATCH | Virologist on Omicron's origins and what's next for pandemic: 

Famed virologist Angela Rasmussen on Omicron’s origins, what’s next for the pandemic

9 months ago
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Famed virologist Angela Rasmussen talks to Adrienne Arsenault about the origins of Omicron, what’s next for the COVID-19 pandemic and the death threats she’s received since taking over a top lab in Saskatoon.

Virologist Angela Rasmussen, who works with the University of Saskatchewan's Vaccine and Infectious Disease Organization in Saskatoon, questioned that element, noting it's hard to suggest that any trade-off is happening more broadly based on a sample of this size.

Omicron, she noted, may have arisen within an immunocompromised host and possesses a variety of mutations, making it both highly contagious and immune evasive, which throws a wrench in the Israeli team's conclusions.

"But otherwise, I think it's a very interesting study," Rasmussen said. "And it certainly adds a lot to our body of knowledge."

Crucial not to 'ostracize' patients

This latest research, as well as earlier findings on viral evolution within people chronically ill with COVID-19, suggests a need to monitor those kinds of patients, the experts who spoke to CBC News agreed.

"I do think that it is really important to start building networks like this to try to start understanding which mutations are going to be more likely to emerge in the case of persistent infection," Rasmussen said.

But doing so is easier said than done, Kindrachuk said, since much of Canada is loosening restrictions and limiting testing access, all while other countries are dealing with uncontrolled transmission.

"How do we manage patients with chronic infections? Not every person who has a chronic infection will have a variant of concern ... so what do you do?" he asked.

Monitoring those patients is crucial, given the need to both spot variants and stop their spread, Kindrachuk said.

"If it remains in that individual — even if it has all mutations it needs to be a better, fitter version of SARS-CoV-2 — if it stays out of someone else, it'll resolve over time," he continued.

But Kindrachuk said there's a razor-thin line between keeping an eye on those patients and further marginalizing people who may already have stigmatized conditions such as HIV/AIDS.

"We don't want to ostracize people," he said.


Lauren Pelley

Senior Health & Medical Reporter

Lauren Pelley covers health and medical science for CBC News, including the COVID-19 pandemic, Canadian health policy, and the global spread of infectious diseases. She's based in Toronto. Contact her at:

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