People with weakened immune systems can retain reservoirs of SARS-CoV-2 – pools of the virus that survive the immune system’s attack – that create an “evolutionary pressure” causing the virus to mutate, says Jonathan Li. As a virologist at Boston’s Brigham and Women’s Hospital, Li was the first person to document ongoing viral evolution within an immunosuppressed person.
“It was crazy,” Li says, describing the large number of mutations. “At the time, we weren’t sure what it meant.”
That was August 2020. Since then, all the major COVID-19 variants being monitored – including Alpha, Beta, Delta and now Omicron – have shown similar characteristics to the variant detected by Li: namely, a “remarkable” number of mutations, all occurring at one time. This pattern has led some virologists to deduce that each of these variants evolved within single individuals.
The process of viral evolution replicates Darwinian evolution. Darwin’s finches evolved in response to environmental pressures on the Galapagos Islands. Random mutations – changes to beak shape or body size, for example – were passed on through generations if the mutations gave the individual host (and therefore the species) a survival advantage.
“For the virus, one person is the entire environment,” Li says.
Li breaks down the process: Immunosuppressed people can become chronically infected with SARS-CoV-2. This means their bodies only partially fend off the virus. For a while, they seem to get better; soon, though, the virus starts to surge again. That’s because the virus continues to reproduce within the body.
And as it reproduces, random changes occur in the genetic sequence; if a change confers an advantage – allowing the virus to more efficiently enter human cells, for example – that mutation will take hold. Over time, the evolved version of the virus thrives in the person, from whom it can spread.
“We’ve all been fearing this would happen,” says Bruce Walker, a Harvard University virologist.
The type of evolution seen with COVID is called “saltation,” where multi-mutational leaps occur all at once, not over time through the usual gradual evolutionary process. This will keep happening, Walker says, until vaccines are administered across the globe.
“Everywhere on Earth, people who are immunosuppressed need to be prioritized,” says Chris Beyrer. The Johns Hopkins professor of public health has been at the front lines of the global response to infectious disease for decades – first with HIV/AIDS and now with COVID-19.
The infrastructure for rapidly vaccinating immunosuppressed people in hot-spot regions around the world is there, Beyrer says. It was created for the HIV/AIDS epidemic, using funds from the U.S. PEPFAR program. COVID prevention efforts can leverage this groundwork, building on the trust developed over the course of 20 years, Beyrer says. What’s lacking is the strategic decision to try to prevent COVID mutation by vaccinating immunosuppressed people.
Some virologists have deduced that each of these variants evolved within single individuals.
If this strategy isn’t taken, COVID could present an “existential threat,” say both Beyrer and Walker. “What if the next variant is as infectious as the one we’ve got – and has the lethality of MERS?” Walker asks, referring to the Middle East Respiratory Syndrome, a coronavirus whose death rate was 35 per cent. “If one in three people dies, that’s an existential threat.”
The probability of further mutation is increased by two main drivers, says Li: high rates of infection in the general population and persistent cases in immunosuppressed individuals who aren’t being monitored.
Right now, both conditions are met in portions of the developing world: Only seven per cent of Africans are fully vaccinated – yet sub-Saharan Africa is home to 8 million people with untreated AIDS.
It is important to emphasize, Li says, that immunosuppression can be attributed to many causes, including cancer chemotherapy, rheumatoid arthritis drugs, untreated AIDS, and, as was the case for Li’s patient, an inherited autoimmune disease. The unifying factor is an immune system too weak to clear COVID.
Despite the conditions for further mutation, Beyrer and Walker agree that there is a pathway for containing viral spread and stopping the emergence of new variants.
This pathway requires not only vaccination – “these vaccines are magnificent,” Beyrer says – but also the use of new antivirals, such as Pfizer’s Paxlovid, which is slated to be reviewed by the U.S. Food and Drug Administration later this month.
“Imagine if you had oral antivirals stored in your medicine cabinet,” Beyrer says. In that scenario, people would take a rapid test as soon as they had the “slightest sense” they might be infected. Once receiving confirmation of infection, they could immediately start taking the pills, which, in Pfizer’s case, show a preliminary result of 89 per cent effectiveness against severe COVID.
Whether this full strategy is put into practice – global vaccination, rapid testing, antiviral therapies – depends on political decisions, according to the scientists interviewed. The medicines and infrastructure exist. The hitch, Li says, is political will: “Are politicians really going to say we should vaccinate people in Botswana over their own constituents?” Li asks rhetorically. “It takes a leader with foresight to say that.”