Mutations and natural selection can help subsequent versions of a virus get stronger and stronger in different ways, which seems to be happening with the Covid-19 coronavirus. And Eric Topol, MD, founder and director of the Scripps Research Translational Institute, has called the currently spreading version, the Omicron sub-variant BA.5, “the worst version of the virus that we’ve seen.”

Topol used the “worst” word in a Substack post entitled “The BA.5 story” that he linked to in the following tweet

Spoiler alert. “The BA.5 story” ain’t a positive one for the U.S. right now, unless many more people and politicians can somehow change the “let’s pretend that it’s over and not around anymore” approach to the pandemic, which may work with zits but doesn’t work with Covid-19. As you can see, Topol wondered on the tweet why the Centers for Disease Control and Prevention (CDC) has not been issuing more warnings about the Omicron BA.5 subvariant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

After all, there’s nothing to suggest that BA.5 will be much less problematic than past versions of the virus. Data had already suggested that the BA.5 was more transmissible than its predecessors, which prompted the European Centre for Disease Prevention and Control (ECDC) to reclassify the BA.5 as a variant of concern (VOC). Therefore, it hasn’t been a surprise that the BA.5 has been moving towards becoming the dominant version of the virus in various parts of the world. About a week ago, on June 27, Eric Feigl-Ding, PhD, an epidemiologist and Chief of the COVID Risk Task Force at the New England Complex Systems Institute, tweeted out some graphs from an article written by John Burn-Murdoch for the Financial Times showing the BA.5-fueled rises in hospitalizations in Europe:

The BA.5 now appears to be fueling yet another Covid-19 surge in New York City (NYC). A tweet from Jay Varma, MD, Professor at Weill Cornell Medical School and former Senior Advisor for Public Health to the NYC Mayor, showed how things are high in NYC, but not in a good way. In this case, what happens in NYC won’t stay in NYC. Any wave in NYC will likely lead to similar waves throughout the U.S.

This has been the case throughout the pandemic with new and more transmissible versions of the SARS-CoV-2 replacing earlier versions and causing new surges. But what may be particularly concerning about the BA.5 is how different its structure is from those of the earlier Omicron subvariants that emerged this past Winter and how quickly those changes have occurred. Topol pointed to studies that have shown that the differences between the BA.5 Omicron subvariant and BA.1 and BA.2 Omicron subvariants are substantially greater than the differences between Delta, Beta, and Gamma variants and the original version of the virus that started this whole pandemic. Keep in mind that there was a whole year and a half between the original version and the Delta variant, whereas BA.5 has emerged no more than half a year after the first Omicron variant.

For example, a publication in Science Immunology cited by Topol presented an antigenic map of the spike proteins of the various major versions of the SARS-CoV-2 that have emerged since early 2020. An antigenic map is a diagram that shows how similar versus different the structures of various proteins are. The map makes it clear how different the BA.5 spike protein is from BA.1 and BA.2 spike proteins and how this different is much greater than the differences between the original virus’s spike protein and the spike proteins of the Delta, Beta, and Gamma variants.

As Topol indicated, the big concern is BA.5 potentially being what’s called immune escape. This has nothing to do with escape rooms and instead is a situation where the virus looks so different from previous versions that any existing immune protection that you may have doesn’t adequately recognize this new version of the virus. It’s kind of like you running into that acquaintance who has had a ton of botox and plastic surgery since your last meeting and asking him or her, “who are you? Have we met before?”

To understand the concept of immune escape, imagine dating someone earlier in your life like in college who turned out to be a nightmare. Say after the break-up, you imprint that person’s behaviors and superficial characteristics like his or her appearance in your head. You tell yourself never again, that you will recognize the warning signs much earlier. For example, if that person wore his or her hair in a shag, a mullet, or a shullet, which is a cross between a shag and a mullet, you may say that you are never going to date someone with such a hairstyle ever again. You may equate shullet with danger, for example. As former U.S. President George W. Bush once said, “Fool me once, shame on, shame on you. Fool me…you can’t get fooled again.” Well, what if someone else enters your life, someone with a very different appearance but a toxic personality similar to that of your college squeeze. If you are so focused on scanning for shullets, you may not recognize that this person sans shullet nevertheless has the same personality that caused you grief in college. Your guard may be down simply because the person looks different.

In a similar vein, will your immune system recognize the BA.5 since it is so different from the previous versions that your immune system may have been exposed to via either vaccination or prior infection? The differences aren’t just in the spike protein. As the Outbreak.info website shows, the BA.5 includes mutations changing other parts of the virus as well.

What’s the evidence that these differences may lead to “immune escape” for the virus? Well, Topol referenced a publication in Cell that showed how antibodies against the BA.1 subvariant didn’t neutralize the BA.4 and BA.5 subvariants very well. Although antibodies ain’t your entire immune response, this raises concerns that your immune system won’t be able to readily recognize the BA.5.

One way to deal with this immune escape subvariant is to update the Covid-19 vaccines to include mRNA for the BA.5 subvariant spike protein. But as Topol alluded to in his Substack post, there are several obstacles. First of all, Moderna and Pfizer have been focusing on updating the vaccines to account for the earliest Omicron variants, which Topol had pointed out were already very different from the BA.5. By the time these early Omicron-updated vaccines are available in the late Summer, early Fall, there could very well be a new subvariant, even more different than the BA.5. Rather than staying proactive and ahead of the curve, anticipating what may happen in the near future, the U.S. public health response had frequently been reactive. That is wait for it, wait for it, wait until it happens and then explain it away by saying something like, “oh, we didn’t expect this variant to arise,” which is kind of what happened with the Delta and Omicron surges.

Secondly, political leaders aren’t even convincing enough people to get boosters of the existing Covid-19 vaccines. As the CDC Covid Data Tracker shows, only 47.8% of the population had received the first booster dose, and only 33.7% of those 65 years and older have received the second booster. Without enforcing vaccination requirements, it is unlikely that these vaccination rates will increase significantly until after another surge has occurred and many more people have either died or contracted long Covid with an emphasis on the word after. Plus, how many people will end up getting an Omicron-updated vaccine soon enough to prevent another Fall and Winter surge?

Finally, with politicians ditching other Covid-19 precautions like face mask requirements as if they were soiled underwear, the lack of other Covid-19 precautions will allow the virus to continue to spread widely and new variants and subvariants to emerge more rapidly. After all, the SARS-CoV-2 reproducing is like trying to photocopy your butt while drunk. Each time it tries to replicate its genetic material and itself, the virus can make mistakes in the form of mutations. Thus, the more replicating or reproducing the virus does, the mutations may result, and the more different variants can emerge. It would be better for face mask wearing, higher vaccination rates, and other multi-layered Covid-19 precautions to slow down the spread of the virus so that vaccine development and manufacturing can catch up and instead stay ahead of the curve.

Again, it’s highly unlikely that the SARS-CoV-2 will get weaker over time. That would be like expecting different animal and plant species to get weaker over time. This just isn’t the case as evidenced by the fact that the hot dog eating records keep getting higher and higher. Instead, natural selection tends to work in the opposite direction, selecting for mutations that confer more fitness to the virus.

What might get stronger, though, is our immune protection against the virus, which can be best achieved through vaccination unless you happen to want all those dying and long Covid risks. There is a need for better and a greater variety of vaccines and vaccine approaches. Scientists just need the time, resources, and support of politicians to catch up and stay ahead of the curve. In other words, our national response to the Covid-19 pandemic should get stronger over time as well and not weaker.

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