as omicron subvariant BA.5 Continuing to drive the spread of the coronavirus in the United States, I’ve been thinking about what’s coming next. Omicron and its branches have Top in the Variation Chart Since last winter. before that, delta domination.
Scientists have some ideas about how the new variant could emerge. One involving a persistent infection — someone who has tested positive for the virus over an extended period of time. I’ll tell you about the strange case of a person who was infected with SARS-CoV-2 for at least 471 days, and what happens when the infection spreads uncontrollably.
In the summer of 2021, epidemiologist Nathan Grubaugh first noticed the prolonged infection. When Grubaugh discovered something he had seen before, his team had been analyzing coronavirus strains in samples from patients at Yale New Haven Hospital. This version of the virus was known only as B.1.517, and it never went by names like delta or omicron, nor did it wreak havoc in the community like its notorious relatives.
Instead, after appearing somewhere in North America in early 2020, B.1.517 became popular in a handful of regions around the world, even causing an outbreak in Australia. But after April 2021, B.1.517 seems to start to break down, and it’s one of those virus lineages that doesn’t know how many bursts and then ultimately fails.
B.1.517 may have long since been forgotten, tossed aside by the latest variant to gain a place in the local community. “But we still see it,” Gruber said. Even after B.1.517 faded across the country, his team noticed it showing up in patient samples. The same lineage, every few weeks, like clockwork, lasts for months.
One clue is the sample ID of the sample. Grubaugh’s team noticed that the code on the B.1.517 samples was always the same. They all come from one patient.
The patient was in his 60s with a history of cancer, which recurred in November 2020. That’s when they first tested positive for SARS-CoV-2. After seeing B.1.517 show up again and again in their samples, Grubaugh worked with a clinician to get patients’ permission to analyze their data.
Ultimately, the patient has 471 days infected (and counting), Grubaugh, Yale postdoctoral researcher Chrispin Chaguza, and their team reported on a preliminary study last month on medRxiv.org. The patients declined to be interviewed due to deteriorating health conditions and anonymity, and Grubb had no direct contact with them.
But all the samples collected these days tell an incredible story of viral evolution. The team’s analysis showed that at least three genetically distinct viruses evolved rapidly in patients over a period of about 15 months.
Each version has dozens of mutations that appear to coexist in patients. “Honestly, if any of these show up in the crowd and start spreading, we’ll call it a new variant,” Gruber said.
That’s probably rare, he said. After all, many long-term infections may have occurred during a pandemic, and only a few worrying variants have emerged. But the work does suggest that persistent viral infection could provide a playground for rapid evolution experiments — perhaps exploiting a weakened immune system.
Gruber’s work “may be the most detailed observation we have yet of a single persistent infection with SARS-CoV-2,” said Tom Friedrich, a virologist at the University of Wisconsin-Madison who was not involved in the work.
The study supports an earlier finding in another immunocompromised patient — one with persistent immunocompromised disease. Micron infectionIn that work, the researchers documented the evolution of the virus over a 12-week period and showed that its progeny infected at least five people.
Together, these studies shed light on how this infection may drive the emergence of the next omicron.
“I’m pretty sure that persistently infected people are an important source of new mutations,” Friedrich said.
Exactly who caused these infections remains a mystery. Yes, the virus can attack people with weakened immune systems, but “not everyone who is immunocompromised develops a persistent infection,” said Viviana Simon, a virologist at the Icahn School of Medicine at Mount Sinai who studies omicron infections .
In fact, doctors and scientists have no idea how common these infections are. “We just don’t have real numbers,” Simon said.That’s a huge gap for researchers, and Mount Sinai’s Pathogen Surveillance Program It is trying to solve by analyzing real-time infection data.
Studying patients with long-term infections could also tell scientists where SARS-CoV-2 is evolving, Friedrich said. Just because a virus evolves in one person doesn’t mean it will spread to others. But if certain viral mutations tend to appear in multiple persistently infected people, that could suggest that the next big variant might evolve in a similar fashion. Learning more about these mutational patterns could help researchers predict the future, an important step toward designing future coronavirus vaccine boosters.
Beyond virus predictions, Gruber said it’s important to identify people with long-term infections so doctors can provide care. “We need to give them access to vaccines, monoclonal antibodies and antiviral drugs,” he said. These treatments can help patients clear the infection.
But he noted that identifying persistent infections is easier said than done. Many parts of the world are not set up to detect these infections and have no access to vaccines or treatments. Even when these are available, some patients opt out. Patients in the Grubaugh study received a monoclonal antibody infusion about 100 days after infection and then declined all other treatments. They are not vaccinated.
Although the patients remained contagious during the study, their mutation never spread to the community, to Grubaugh’s knowledge.
While untreated chronic infections may give rise to new variants, they may also emerge in other ways, such as from animals infected with the virus, from human-to-human transmission from people not yet monitored by scientists, or from “other, perhaps, all of us.” didn’t think of it,” he said. “The evolution of SARS-CoV-2 continues to surprise us.”