Are We Creating Immune Resistant Variants Of SARS-CoV-2?

(Posted on Monday, January 11, 2021)

Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes, but changes in ways that are significant. This is the second in a series of articles on how the virus changes and what that means for humanity. Read the first piece here.

In May 2020, a man was hospitalized and, soon after, diagnosed with Covid-19. Within weeks he recovered and went home, only to be readmitted the following month when his Covid-19 symptoms came back with a vengeance. This time he was administered, at distinct yet overlapping intervals, a plurality of treatments, including the steroid dexamethasone; two rounds of remdesivir, an experimental drug therapy; and convalescent plasma from not one, not two, but three different patients. The man, his body unable to mount the resistance it needed to clear out the virus, succumbed to the disease in late August.

Over the course of the man’s hospitalization, researchers extracted, sequenced, and analyzed more than 20 different viral samples, a process they describe in a research paper currently undergoing peer review. They witnessed the virus evolving in real time, and over the course of 100-plus days noted the emergence of several mutations. One way to interpret this is that each time the man was given, via the blood plasma of previously recovered Covid-19 patients, a new mix of anti-SARS-CoV-2 antibodies, the virus found new ways to resist neutralization. In other words, we might be looking at a classic case of immune evasion, a term that refers to the sum total of strategies a virus uses to evade or otherwise overcome the immune system.

Immune evasion is a potential outcome of viral variation. I discussed the mechanisms by which viral variation occurs in the first piece of this series—the substitutions, deletions, insertions, and other alterations to genetic code that, multiplied sufficiently in all the right places, can change how a virus functions significantly. Why this happens—the subject of this piece—is why most adaptations happen. When the coronavirus finds itself in an inhospitable environment, it must either adapt or die. What this means for us more broadly is that our attempts to counter the virus, whether at the individual and population level, push it down new evolutionary pathways. Though for most organisms this is a matter of course, that doesn’t mean it occurs without consequence.

Notably, prior to his Covid-19 diagnosis the aforementioned patient was already living with lymphoma, a cancer of the blood that begins in the immune system, and receiving injections of rituximab, a treatment therapy that can have immunosuppressive effects. Over the course of several plasma fusions, his body became a sort of testing ground for new variants of virus—not unlike what is now happening to populations around the world. If a barrage of antibody treatments increased evolutionary pressure on the virus responsible for his infection, it can be said that the slow but steady amalgamation of vaccinated, recovered, and other partially immune individuals is doing the same for the virus out in the wild.

What is remarkable is that some of the mutations observed in this one man, like the H69-V70 deletion, we’re now seeing in European variants of SARS-CoV-2 that have circulated among millions, including the so-called UK variant B.1.1.7. The H69-v70 deletion is found in the N-terminal domain of the spike protein, the primary target of many Covid-19 drugs and some vaccines. Another study, published last month but also awaiting review, mapped how other kinds of spike mutations impacted the potency of antibodies in preparations of convalescent plasma. Those researchers found that mutations associated with E484, one of many sites pinpointed on the spike, had the biggest and most detrimental impact, reducing the protective capabilities of some antibodies more than tenfold. One of the variants to develop the E484 mutation is none other than 501.V2, also known as the South African variant.

Does this mean certain variants of SARS-CoV-2 will learn to evade our natural defenses against it, even in the majority of us who aren’t immunocompromised? Maybe, maybe not, but either way it remains a possibility we can’t afford to ignore. I already mentioned in my last piece that B.1.1.7 is far more contagious than its predecessor, and charts showing skyrocketing case counts across Britain elucidate the dangers of increased transmissibility better than words ever could. The explosive spread of B.1.1.7 foretells what might happen in the United States if we don’t patch up and ramp up our Covid-19 control measures, vaccine distribution included, sooner than later. In my next piece I’ll discuss the implications viral variation has for vaccines—and what we’ll have to do to make sure current vaccination campaigns proceed uninterrupted.

Read full article on Forbes

Originally published on Forbes (January 11, 2021)