The COVID Stew Keeps Bubbling

Keep an eye on what surfaces

In the last 24 hours the mainstream media has been lit up with stories about a newly discovered very highly mutated SARS2-Cov19 variant which is designated BA.2.86. As of yesterday only six sequences from four countries have been found—so why all the excitement? For starters this is the fastest the WHO has ever designated a new variant as a VOI (Variant of Interest). Thousands of different variants are found around the world all the time as the virus mutates, the focus of interest on this particular strain is that it has so many new mutations that it is just as different from anything we have seen before, as Omicron was different from any earlier virus. This BA.2.86 has 34 mutations separating it from its closest relative BA.2 (one of the original Omicron strains), and unfortunately a similar amount of evolutionary distance from XBB.1.5, which is the variant chosen for the new fall COVID booster shots. Exactly what that means in terms of the ability of this strain to transmit, and the severity of disease it might cause within the background of existing natural and vaccine immunity is anybody’s guess—but we know what happened when a similarly mutated virus called Omicron hit, so it certainly bears watching.

Based on the extremely limited data so far we can make a couple of logical conclusions. Several patients in Denmark have turned up with this virus in different locations, and with no history of contact with each other or common travel. The variant has also surfaced in Israel, the UK and one in Michigan. The genetic sequences are all (nearly) identical, with very minor differences felt to be due to sequencing errors or other technical issues. This tells us that it highly likely that this variant is already much more wide spread, (testing and sequencing efforts have markedly declined limiting data acquisition), that it does transmit, and that it likely has spread to other areas of the world. The possibility that a variant with this many mutations would simultaneously arise in multiple locations, with no intermediary relatives found is vanishingly remote. No viral fear porn is intended here, this is just to keep you up to date on interesting and perhaps, a bit down the road, important developments in the human versus COVID saga, which despite our best efforts is still fluid.

This is the scientific, extremely weedy portion, which some will appreciate, but if you skip to the next section I fully understand that you might find this about as interesting as I find the US tax code. When I said it’s anybody’s guess about how well this BA.2.86 variant will evade prior Omicron family immunity, or particularly XBB.1.5 vaccine immunity, I think we should look at speculation from a highly informed expert in Viral Evolution, like Jesse Bloom PhD, from the Fred Hutchinson Institute, rather than your bartender, dry cleaner, cable news talking head, or the guy on Twitter with a million followers. (No disrespect to the fine professions above—I certainly wouldn’t let Jesse Bloom clean my Kiton K50 suit). Below are some tables contained in a slide deck that Professor Bloom just put together, reflecting work from his lab and others, showing the mutations present in BA.2.68 and the interpretation of their likely impact on transmission and antibody evasion.

Some readers might recognize several of the mutations listed as sites that were responsible for antibody escape in earlier significant variant bad boys. Other mutations in this variant have been seen after treatment with monoclonal antibodies including sotrovomab. The final graph below shows work from Yunloug Cao’s lab showing that BA.2.86 is predicted to have as much antibody escape compared to the original Omicron as XBB.1.5 does. The critical information missing so far is how much this new variant will evade XBB lineage immunity. That won’t be important if BA.2.86 doesn’t transmit well enough to outcompete the XBB brood, or perhaps more importantly Eris EG.5, which looks like it is on a trajectory to take over top dog honors pretty quickly. Based on the discussion in the previous paragraph, I’m guessing it transmits reasonably well. How does a new variant like this just suddenly arise, seemingly out of nowhere? The most likely answer is prolonged infection in an immune compromised patient with persistent exposure to an antibody response which is not adequate to clear the infection. The evolution of such highly mutated variants has been observed in real time in several well studied patients over the course of the Pandemic, and it is widely believed among experts that Omicron was the product of this type of scenario.

Now that I’ve stumbled into a clearing in the viral woods, let’s have a look at where we are over the last two weeks with COVID hospitalizations and deaths. Remember we don’t count actual numbers of deaths anymore (at some point it was decided that didn’t play well on the evening news), but rather just relative percent change from prior week and COVID’s percentage of all deaths. As you can see below weekly hospitalizations are once again over 10,000, and the increasing curve of deaths is an inevitable consequence of that.

Following is what you will recognize as my favorite graph, showing US waste water COVID RNA levels. There’s a reason the expression, “What’s the real Poop on this situation”, has been popular for so long. You will see the continued slow increase in viral burden for the total US, which started way back at the end of June.

The burden of disease is quite variable around the country, as it is around the entire world. This indicates to me that we are not in the early stages of a huge wave of COVID right now. Those large scale eruptions, like Delta or Omicron spread very rapidly with more uniform involvement of our country in short order. Here is a several week old graphic from CDC of relative increases or decreases in hospitalizations by state. We will see shortly if my prediction of the magnitude of the XBB’s and EG.5.1 wave is correct—if not feel free to have some Gell-Mann amnesia and continue to read this blog anyway. Also feel free to make up any explanation you want for the varying amounts of COVID in different parts of the country (the weather, vaccination enthusiasm, racial make up, politics, religion), at this point your guess really is as good as the experts.

It’s the last few weeks of summer, and that of course means more outdoor time, and more mosquito encounters. This has been an unusually hot, and in some locales rainy summer, the perfect combination for a bumper crop of these pests. 2023 so far is on track to be a massive year for Dengue in South and Central America, with over 3 million cases reported so far, and on track to surpass the record from 1980. Here in the US, Dengue has reestablished endemic transmission in several warmer states with yearly cases reported in Florida, Texas, Arizona and Hawaii. If you don’t live or plan to visit there then West Nile, which is far more wide spread around the country, should be reason enough to reach for the proven insect repellants like DEET, Picaridin, Oil of Lemon Eucalyptus or PMD. Below is a map of US states with reported West Nile cases this year, but cases have been reported in other states in prior years, and basically you can assume it can occur anywhere in the US—anywhere there are Culex species mosquitoes. If your reaction to the graphic below is, “What?—only 190 cases”, consider that 80% of infections are asymptomatic and most of the others are flu-like illness that don’t get diagnosed. Only 1% of cases are neuro-invasive and that’s what these 190 cases so far this year represent. If the term neuro-invasive sounds bad, you’re correct—20% of such patients die and many that survive are left with severe brain damage. The highest risk of severe disease is in young children and people over 60, plus the immune compromised. Go ahead and use the insect repellant.

The news from Maui this week has been devastating. It certainly looks like the loss of life may have been worsened by a serious error in judgement by the emergency services department not to sound the warning siren system. I listened to the Director of Emergency Services explain that the sirens are “PRIMARILY” used to warn people of tsunamis, and that they were afraid people would think there was an imminent tsunami, and flee backwards from the coast in Lahaina for higher ground. That explanation seemed reasonable for about the time needed for 3 or 4 synaptic relays. My first thought was, “Oh, what else are the sirens supposed to be used for now that we know their “Primary” function. My next deduction was that folks aroused and going outside to find dense smoke and fire bearing down on the city from the grasslands surrounding it are not terribly likely to flee into the visible fire, instead of heading for the water. After expressing at the press conference that he had no regrets about this decision, the Director resigned the following day. This is perfect example of what can come from placing too much confidence in the government’s ability to protect you. Remember the government is simply people, and on any given day one or more of them may do no better or worse than the person filling your drive through order. Politicians and government functionaries today all seem to have one common trait—when is the last time you heard anyone of either party say, “I’m sorry about that serious error in judgement”?

This week I’m running a special, anyone who correctly guesses the number of charges in Donald Trump’s next indictment will receive a free subscription to this newsletter. Entries based on private party or other pre-release information before the Grand Jury has voted will not be counted. Finally, I’m asking that the person who keeps subscribing to “Clear and Present Thinking” using the email robert.L.peters@pci.gov cease and desist—neither I nor President Biden find this amusing. (He already has his own subscription.)