Like a bad B-movie sequel, Omicron is back with more variants on the rise worldwide. BA.4 and BA.5 are the newest members of Omicron’s growing family of coronavirus subvariants that have been detected in dozens of countries worldwide.
These subvariants spread faster than other circulating variants, but so far, seem to be causing fewer deaths and hospitalizations than their older relatives. BA.4 and BA.5 carry their own unique spike protein mutations that enhance the virus’s ability to latch onto host cells and evade some immune responses.
BA.4 and BA.5 are able to infect people who were immune to earlier forms of Omicron and other variants. The size of BA.4 and BA.5 waves will vary from place to place due to differences in vaccination rates and infection exposure around the world. Overall, this has led to sustained hospitalization rates but a lower death rate when compared with earlier Omicron waves, such as Delta.
Studies suggest that antibodies triggered by vaccination are less effective at blocking BA.4 and BA.5 than they are at blocking earlier Omicron strains, leaving vaccinated and boosted people vulnerable to multiple Omicron infections. Due to the unique nature of the spike protein mutations, even people with hybrid immunity, stemming from vaccination and previous infection with Omicron, produce antibodies that are not able to fully incapacitate BA.4 and BA.5.
Over time, and given the patchwork of vaccination and infection, it is highly probable that additional Omicron variants will emerge. With Darwin hard at work, it’s possible that a further mutation could create a variant that is new to people’s immune responses, leading to increased immune evasion and escape. And while our recent experience suggests that successive COVID-19 waves are getting milder (at least for those who are immune-competent), there is no viral guarantee of future harmlessness.
Viruses don’t necessarily evolve to become less deadly. As we’ve been warned before about such mindless beings: “[Viruses] can’t be reasoned with. They don’t feel pity, or remorse, or fear. And they absolutely will not stop, ever, until you are dead!” Their only monomaniacal objective is to survive and reproduce.
The rosy scenario is that the future for SARS-CoV-2 is that it will become like the other four seasonal coronaviruses, reinfecting people every few years. The big question is whether symptoms will become milder over time and whether issues with long COVID will slowly disappear. Updating annual vaccines to target newer variants solve short-term problems of infection, hospitalization and death, but doesn’t address the ability of this single-stranded RNA virus to continue to reinvent itself in the “fresh meat” of the unvaccinated herd.
Evolutionary pressure and experience suggests a future more like the current cold viruses, but a small mutation in the wrong direction changes the game in potentially frightening ways.
David Segarnick Ph.D., is chief medical officer and executive vice president of MedEvoke, Lebanon, N.J., and assistant professor pharmacology, physiology and neuroscience, Rutgers Medical School, Newark, N.J.
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