What omicron subvariant BA.5 continues to fuel the spread of coronavirus in the United States, I’ve been thinking about what might come next. Omicron and its derivatives have been topping the variant charts since last winter. Before, reigned delta.
Scientists have some ideas about how new variants arise. One involves people with persistent infections, people who test positive for the virus over an extended period of time. I am going to tell you about the curious case of a person infected with SARS-CoV-2 for at least 471 days and what can happen when infections get out of control.
That prolonged infection first appeared on epidemiologist Nathan Grubaugh’s radar in the summer of 2021. His team had been testing coronavirus strains in patient samples at Yale New Haven Hospital when Grubaugh spotted something he had seen before. Known only as B.1.517, this version of the virus was never given a name like delta or omicron, nor did it sweep through communities like its infamous relatives.
Instead, after emerging somewhere in North America in early 2020, B.1.517 appeared in a handful of regions around the world, even causing an outbreak in Australia. But after April 2021, B.1.517 seemed to sizzle, one of who knows how many viral lineages exploding and eventually fizzing out.
B.1.517 might have been forgotten long ago, sidelined by the latest variant to stake a claim in local communities. “And yet we were still seeing it,” says Grubaugh. Even after B.1.517 sold out across the country, his team noticed that it was showing up in patient samples. The same bloodline, every few weeks, like clockwork, for months.
One clue was the identification of the specimen from the samples. The code in the B.1.517 samples was always the same, Grubaugh’s team noted. They had all come from a single patient.
That patient, a 60-year-old with a history of cancer, relapsed in November 2020. It was just when they first tested positive for SARS-CoV-2. After seeing B.1.517 appear again and again in his samples, Grubaugh worked with a doctor to get the patient’s permission to analyze her data.
In the end, the patient has remained infected for 471 days (and counting), Grubaugh, Yale postdoctoral researcher Chrispin Chaguza and their team reported last month in a preliminary study published on medRxiv.org. Due to his deteriorating health and a desire to maintain his anonymity, the patient was unwilling to be interviewed and Grubaugh has no direct contact with him.
But all those samples collected during all those days told an incredible story of viral evolution. For about 15 months, at least three genetically distinct versions of the virus had rapidly evolved within the patient, the team’s analyzes suggested.
Each version had dozens of mutations and seemed to coexist in the patient’s body. “Honestly, if any of these were to emerge in a population and start spreading, we would call it a new variant,” says Grubaugh.
That scenario is probably rare, he says. After all, many prolonged infections are likely to have occurred during the pandemic, and only a few worrying variants have emerged. But the work suggests that persistent viral infections may provide a playing field for rapid evolutionary experimentation, perhaps taking advantage of weakened immune systems.
Grubaugh’s work is “probably the most detailed look we’ve had yet at a single, persistent infection with SARS-CoV-2,” says Tom Friedrich, a virologist at the University of Wisconsin-Madison, who was not involved in the work. .
The study supports an earlier finding about a different immunocompromised patient, one with persistent disease omicron infection. In that work, the researchers documented the evolution of the virus over 12 weeks and showed that its offspring infected at least five other people.
Together, the studies expose how such infections could potentially fuel the rise of the next omicron.
“I’m pretty convinced that people with persistent infection are important sources of new variants,” says Friedrich.
Who exactly develops these infections remains a mystery. Yes, the virus can attack people with weakened immune systems, but “not all immunocompromised people develop a persistent infection,” says Viviana Simon, a virologist at the Icahn School of Medicine at Mount Sinai who worked on the omicron infection study. .
In fact, doctors and scientists have no idea how common these infections are. “We don’t really have the numbers,” says Simon. That’s a big gap for researchers, and one that Mount Sinai Pathogen Surveillance Program is trying to tackle by analyzing infection data in real time.
Studying patients with prolonged infections could also tell scientists where the evolution of SARS-CoV-2 is headed, says Friedrich. The fact that the virus evolves inside a person does not mean that it will spread to other people. But if certain viral mutations tend to emerge in various people with persistent infections, that could indicate that the next big variant could evolve in a similar way. Knowing more about these mutation patterns could help researchers forecast what’s to come, an important step in designing future coronavirus vaccine boosters.
Beyond viral prognosis, Grubaugh says identifying people with long-term infections is important so doctors can provide care. “We need to give them access to vaccines, monoclonal antibodies and antiviral drugs,” she says. Those treatments could help patients clear their infections.
But identifying persistent infections is easier said than done, he says. Many parts of the world are not prepared to detect these infections and do not have access to vaccines or treatments. And even when they are available, some patients choose not to participate. The patient in Grubaugh’s study received an infusion of monoclonal antibodies approximately 100 days after infection and then refused all other treatments. They have not been vaccinated.
Although the patient remained infectious throughout the course of the study, his variants never spread to the community, to the best of Grubaugh’s knowledge.
And while untreated chronic infections can lead to new variants, they could also arise in other ways, such as from animals infected with the virus, from person-to-person transmission in groups of people that scientists haven’t been monitoring, or from ” anything else”. that maybe none of us have thought of yet,” he says. “SARS-CoV-2 has not stopped surprising us with its evolution.”