Coronavirus Variants Are Evolving – Even Inside A Single Person

Evolution is something many people visualize as a process that occurs outside, in your surroundings, but it also happens in the environment of the human body.

SARS-CoV-2 coronavirus is a clear example of evolution-in-action, and studies have now revealed how it causes new variants to emerge within a single person.

Mutation and Variation

Like a ticking clock, mutations appear continuously over time. They’re the fuel that ultimately powers evolutionary change in everything from viruses to humans.

Although some mutations are helpful because they make a species more successful — so SARS-CoV-2 gets better at infecting us or escaping our immune system, for instance — most mutations are harmful as they’ll stop an organism’s genes from working. Mutations are generally bad because “If it ain’t broke, don’t fix it.”

Mutations occur during reproduction, such as when cells divide or a SARS-CoV-2 virus particle replicates inside a cell. It’s often due to genetic material — DNA or RNA — being copied incorrectly. When that copying process introduces an error or typo, like substituting the chemical letter ‘C’ for ‘T’, it’s a ‘point mutation’ or substitution, while missing letters are called ‘deletions’.

Mutations create mutants, organisms that differ from a common ‘wild type’. When humans judge that a mutant is significantly different — say, because it escapes immunity — then it’s considered a new strain or variant, as in the case of the B.1.1.7 lineage first identified in the United Kingdom (or ‘UK variant’).

FIND OUT MORE: What’s The Difference Between A Variant, Mutant And Strain?

A new mutant will be genetically distinct from its parent — such as the virus version that initially infects you — but only by a few letters of DNA or RNA.

The likelihood of creating a ‘better’ variant is a numbers game: the probability that a given mutation will help SARS-CoV-2 is extremely small but it’s not zero.

While the chance may be less than one-in-a-million, thousands of virus particles are replicating in billions of cells inside millions of people, so odds of such a ‘rare’ event drop dramatically — to the point where it becomes very likely, even inevitable, that variants will emerge within the global human population.

Mutations accumulate relatively slowly. Among the trillions of virus particles in a single human body, the viral gene pool might only contain a couple of new mutations. That’s over the course of a normal acute infection with SARS-CoV-2, however, which lasts 2 weeks on average with a short infectious window (when an infected person can potentially transmit the virus) of only a few days.

Coronavirus can more easily accumulate mutations in one group, however: people with long-term chronic infections. That accumulation can happen if someone’s immune system is naturally compromized because they have an underlying health condition, for instance, or because it’s been artificially suppressed by drugs in chemotherapy.

Natural Selection

Nature selects among a variety of individuals based on their ability to survive and reproduce — whether that’s prey that evade predators or viruses that escape an immune system. That selective pressure from the environment is what can force a population of organisms to adapt, driving evolution by natural selection.

Several studies have tracked the evolution of SARS-CoV-2 variants in chronically-infected people. In such cases, researchers took samples from each patient and read the sequences in the viral gene pool to detect the presence of new mutants as they emerged. Through repeated sampling and sequencing, the scientists have identified variants that would provide the raw material for natural selection.

One study, led by Adam Lauring from the University of Michigan in Ann Arbor, described the case of a 60-year-old man with a history of lymphoma — cancer of the lymph nodes, which prevents the immune system’s B-cells making antibodies.

Over four months, the immunocompromized patient was in-and-out of hospital three times due to Coronavirus Disease, and that prolonged infection enabled a steady accumulation of mutations. Nine mutations became prevalent (or ‘fixed’) in the viral population between days 93 and 106.

The fact that the man was repeatedly readmitted put other patients at risk of Covid as he would have continued to shed virus particles. As the Michigan study concluded, “This case highlights challenges in managing immunocompromized hosts, who may act as persistent shedders and sources of transmission.”

Another study, led by Ravindra Gupta at Cambridge University, tracked SARS-CoV-2 evolution during treatment of an immunosuppressed man in his 70s. The patient’s viral gene pool was sequenced 23 times over 101 days, so the fate of mutations could be followed in detail. He was treated with remdesivir (not effective) and convalescent plasma containing antibodies from someone who recovered from Covid.

FIND OUT MORE: The Strange Story Of Remdesivir, A Covid Drug That Doesn’t Work

Convalescent therapy led to the emergence of a variant with the D796H mutation and a deletion of two amino acids — ΔH69/ΔV70 — in the spike protein, which is what coronaviruses use to break into a cell. According to the study, that mutant became the dominant variant following competition among the patient’s variants — evolution by natural selection.

The Cambridge study also used artificial viruses to show that the D796H mutation made spike proteins less susceptible to being neutralized by a matching antibody but also less effective at invading cells, whereas the ΔH69/ΔV70 deletion seemed to compensate by restoring the virus’ ability to bind a cell’s surface.

Interestingly, ΔH69/ΔV70 has also been deleted in the B.1.1.7 variant, which seems to have 50-70% higher transmissibility compared to the wild-type virus. So, as in the immunosuppressed patient, the deletion might have been favored by natural selection because it made the variant become more infectious and spread.

Based on a study led by Tanya Golubchik of Oxford University, the good news is that mutations that might help Coronavirus appear very rarely. According to the research, which used sequencing to measure genetic diversity across 1313 British people, most people carried distinct variants — but only one or two per person.

The Oxford study also examined transmission between people who come into regular contact — in the same household — and found that most variants are lost before they spread. That result suggests the vast majority of potentially dangerous new mutations are evolutionary dead-ends that are destroyed by the immune system.

The environment inside you — the human body — can be too harsh for Coronavirus.