The Urgency of Normal
The State of COVID approaching Fall 2023
Though the federal government officially ended the Public Health Emergency in May, and some op-eds written by non-scientists have celebrated the end of the pandemic and normality returning, there’s no reason to believe that is the case.
COVID-19 remains a leading cause of death in the US, excess deaths among Americans 25–44 are 26.5% higher than they were in 2019, and a recent pre-print study from Australia suggests the risk of developing Long COVID is about 1 in 5 among the fully vaccinated. This finding is in line with other estimates of the prevalence of Long COVID, including the CDC’s own figures.
The notion that the pandemic is over rests on the idea that the population has finally achieved some kind of “herd immunity” which has made the virus less transmissible, but I’d like to go through the reasons that, not only is this not over, we may actually be vulnerable now to a prolonged period of high rates of illness this fall and winter.
“Herd Immunity”
First, let’s go over the brief but repetitive history of “herd immunity.”
No One Could Have Foreseen This™
Next, a trip through “herd immunity,” “hybrid immunity,” and “seasonality.”
Now that we’re all caught up, here’s why it’s a safe bet we are not done with COVID.
The numbers are no longer trending down
After a summer with much fewer COVID infections than we’d seen through all of last year, the latest data analyzing the concentration of SARS-CoV-2 in wastewater samples collected throughout the US shows that cases are rising again everywhere.
This is reflected in the latest US hospitalization data:
Although it became widely accepted early on that children were not as likely to get infected or transmit the virus, we have learned that they are, in fact, extremely reliable vectors for the spread of disease. In fact a study published in June that was conducted from October 2019–2022 found that about 70% of US household spread of COVID started with a child.
We should expect this trend to accelerate once the school year begins, along with a corresponding increase in the rate of absenteeism, hospitalizations, deaths, and disability.
Update 8/26/2023: I won’t continue to update this article, because I think it adequately explains everything that unfolds over the next several months, but I do want to acknowledge that the new school year has not even started everywhere, and hospitalizations are already increasing.
Meanwhile, the few schools that had already opened have already closed. Actually, not just schools, entire school districts:
Note in the headlines above that it’s not just COVID, but also flu (in August?) and strep A, which is often an opportunistic infection in people with weakened immune systems. This is particularly worrisome as apparently there’s a severe shortage of penicillin.
There’s a penicillin shortage (and shortage of other antibiotics) because there were so many severe bacterial infections last fall/winter that supplies of amoxicillin ran short by November.
There’s still a shortage and it’s not even fall yet:
End Update 8/26/2023
Everyone’s Immunity Has Waned
Since 2021 it has been apparent that the protection offered by the mRNA vaccines was not long-lasting, and would require booster shots at some regular interval to maintain their high effectiveness, especially as the virus mutates to become more immune-evasive. The last COVID-19 vaccine bivalent booster shots were made available in the fall of 2022 but only reached about 17% of the population, according to CDC data. I don’t fully understand why, but it was likely some combination of poor/inadequate messaging from the government and public health officials, as well as many (especially young) people thinking they did not need it.
The bivalent vaccines offered last year contained doses of mRNA for both the ancestral (Wuhan) strain of the virus, as well as the Omicron BA.4 and BA.5 sub-variants, which were the dominant sub-variants circulating in the population at the time. Because there were no clinical trials prior to the vaccines being approved, what we learned about their effectiveness came from real-world data, and it turned out to be less than impressive, as internal FDA/CDC data released this spring revealed.
While the boosters did provide additional protection against hospitalization relative to no vaccination and prior immunization with the original monovalent mRNA vaccines, within 120–179 days that effect had waned considerably, and in fact “crossed the null,” meaning that statistically it’s possible the vaccines had become 0% effective (within a very wide 95% confidence interval).
Also note that even at 7–59 days the bivalent boosters did not restore vaccine effectiveness to the 90–95% effectiveness we saw in the clinical trials of the original vaccines in 2020. A major flaw in the idea of combining the ancestral strain with BA.4 and BA.5 was that it contributed to something called immunological imprinting.
[U]nder certain conditions, the memory B cells with high affinity and specificity which are induced by a primary viral infection can block the development of B cells in response to the subsequent infection of a novel but related virus, which is being referred to as immune imprinting.
In other words, if the body already has memory B cells for a virus, when a similar-looking virus comes along, the immune system will begin producing anti-bodies that were effective against the first virus, rather than take the time to create new B cells specific to the new virus. This is likely a gross oversimplification, but I think of it as some combination of “if it ain’t broke, don’t fix it” and “you go to war with the army that you have.”
A pre-print study from May 2023 found that antibodies created from the bivalent vaccines did not neutralize the newer Omicron sub-variants any better than the ones created from the monovalent vaccines targeting the ancestral strain, and both performed worse than the antibodies created from a breakthrough infection.
To be clear, we do not want breakthrough infections.
The authors determined that “inclusion of the ancestral spike prevents the broadening of antibodies to the BA.5 component in the bivalent vaccine, thereby defeating its intended goal.” Because of other studies that have supported this hypothesis and the FDA/CDC’s own data on the performance of the bivalent boosters, in June the FDA advisory panel voted unanimously to recommend a monovalent XBB COVID-19 vaccine for this fall.
We’ll return to XBB subvariants shortly.
In the US at least, SARS-CoV-2 prevalence was down significantly by the time the waning/imprinting would have been evident in the boosted population, but as I said earlier, fewer than 1 in 5 Americans even received a bivalent booster to get the temporary bump in protection, that rate varied significantly by region, and there was still a lot of infection/transmission in the winter of 2022–23 before it dropped to the lower levels we saw this summer.
The upside to the lower levels of viral transmission we’ve seen in the past months is, of course, fewer hospitalizations, deaths, less disability and lost productivity to illness. The downside is that it means the majority of the population likely has no recent history of being infected, and so has lost the temporary protection conferred by the presence of neutralizing antibodies created in response to infection.
And a recent study showed that prior infection with Omicron doesn’t really offer much protection, anyway:
“We found that some individuals had normal immune responses after the first infection, while others had very low levels of protective antibodies, which we believe was one contributing factor to why they got reinfected,” Bowdish said.
“Our current vaccine schedules are based on the assumption that having had an infection provides some level of protection to future infections, but our study shows that may not be true for all variants in all people,” Bowdish said.
Variant Soup
As the virus mutated throughout 2020–2021, variants were constantly being tracked and monitored, with the most transmissible/lethal variants getting Greek letter designations to easily refer to them. Everything since Omicron has been called “Omicron” despite significant genetic differences, which we will get to.
The whole history of the pandemic up to now can be told with this chart. The ancestral strain from Wuhan was responsible for the initial wave, and persisted through to early 2021 when the vaccines were first introduced (with some places unfortunately getting hit with the Alpha variant over the winter). There was a brief period where it looked like the virus might be suppressed until Delta emerged and proved to be both considerably more transmissible and decidedly more lethal, especially among younger people.
In terms of transmissibility, Omicron showed up at Thanksgiving and said, “hold my beer”. Despite being less lethal than Delta, Omicron was actually not much “milder” than the ancestral strain, but by nature of its incredible transmissibility it managed to kill way more people in that first wave than Delta did.
It also spread so fast that there was no time to create an updated booster specifically to target Omicron. Pfizer had said they’d need only 100 days to create and mass-produce an update, but would be almost a year before there was one available (and the FDA made them water it down with the ancestral virus, but I digress).
Let’s take a more detailed look at the rise and fall of different variants over the last two years. Since the WHO hasn’t assigned any Greek letters to any variants since Omicron, we’ll have to refer to the sub-variants that have emerged in the last two years using their PANGO (Phylogenetic Assignment of Named Global Outbreak) labels. You’ll note that each label starts with a combination of letters (A, B, C….AA, AB, AC, etc.), followed by numbers separated by periods, where each period means “descendent of.”
The first Omicron variant identified was labeled B.1.1.529, which means it was the 529th identified descendent of the 1st identified descendent of the 1st identified descendent of the “B” variant. For the sake of readability, a variant gets a new letter designation after three generations and the process starts again. The first descendent of B.1.1.529 was labeled BA.1, the second BA.2, and so on.
BA.5.3.1.1 was given the alias BE.1, then three generations later BE.1.1.1.1 was given the alias BQ.1
So BQ.1 is the alias of BA.5.3.1.1.1.1.1, which means it is a great-great-great-great grandchild of BA.5, which was a direct descendent of Omicron.
Labels that start with “X” are recombinants, the mutant offspring produced by two different strains combining inside of an infected cell, which inherits characteristics of both. XBB was created from the recombination of BJ.1 and BM.1.1.1, and through mutations it has already produced several sub-lineages of its own, notably XBB.1.5, XBB.1.16, and EG.5 (XBB.1.9.2.5).
If you’re curious, you can see the current list of variants here.
The following chart shows the relative prevalence of each of the most common strains in the last two years.
Starting with Delta, we see a pattern of one variant dominating for a time before being outcompeted by a variant capable of evading immunity to previous variants. BA.1 replaced Delta, BA.2 replaced BA.1, then BA.5 replaced BA.2.
All the while the vaccines appeared to be becoming less effective:
This time last year BA.5 and BA.4 were clearly the dominant variants, which is why the boosters were updated to target them.
Within a few months, BA.5 was edged out by BQ.1 (a sub-variant which evolved from BA.5), which accounted for about half of all wastewater samples during last winter’s wave. It’s possible that enough people had developed temporary immunity to BA.5 from infection over the summer and that’s why it ceded ground to BQ.1; given the information I presented above on the bivalents’ uptake and efficacy I doubt they made much of a difference.
By April 2023, transmission was down considerably, to about a quarter of the winter peak, and XBB.1.5 (“The Kraken”) was dominant. XBB.1.5 evolved from BA.2 and as early as January 2023 was supposed to be an extremely transmissible sub-variant.
XBB.1.5 is the sub-variant that the fall boosters have been developed to target, but it reached its peak prevalence in early March of this year and has been in decline since.
There has been a similar decline in the apparent difference about how well the vaccine protects against death (and, we can infer, infections and serious disease).
Based on the CDC data above, during the first Omicron wave, you were 10 times as likely to die as a vaccinated person if you were unvaccinated (Note the difference between the red and blue lines — the further apart they are, the greater the difference vaccination makes).
By April 2023 that difference had shrunk to 4 times and appears to be converging.
It is now August 2023 and I cannot tell you how much better the vaccine protects you because the CDC has stopped publishing COVID-19 deaths by vaccination status in May.
This administration ended the Public Health Emergency on May 11.
Just to make this even clearer, when infections start rising again (and they are already rising), no one will not be able to tell you the vaccine still protects you against death and serious illness because they won’t have any data to support it.
Now let’s compare last year’s variant roster with this year’s.
It’s a competition between a variety of specific XBB sublineages, suggesting none has an inherent advantage of another in terms of transmissibility, but potentially just different enough to make it difficult to gain any sort of immunity. Even though all of the viruses circulating in the population are “Omicron”, it’s possible to become infected with a strain after or while being infected with another strain. It also makes trying to quickly identify more lethal variants because genetic sequencing is slow and there’s hardly any testing anymore.
The scientists and researchers tracking COVID mutations are on the lookout for something heavily mutated enough to evade existing immunity to previous strains or something with the mutation that made Delta so deadly. The nightmare scenario that haunts scientists is a strain with both properties.
Furthermore, newcomer EG.5 (“Eris”) has emerged as a descendent of XBB.1.9.2 and is set to become dominant according to a pre-print study from Japan:
First, we showed that EG.5.1 exhibits a higher effective reproduction number compared with XBB.1.5, XBB.1.16, and its parental lineage (XBB.1.9.2), suggesting that EG.5.1 will spread globally and outcompete these XBB subvariants in the near future.
The good news is that it does not appear to be inherently more transmissible or immune invasive than the other XBB subvariants:
Neutralization assay using the BTI sera of XBB subvariants (XBB.1.5, XBB.1.9 & XBB.1.16) showed that EG.5.1 is NOT resistant to these sera, suggesting that the emergence and spread of EG.5.1 is NOT due to the evasion from the XBB-induced humoral immunity.
In other words, EG.5.1 is spreading rapidly compared to the XBB subvariants, but immunity from those should protect you. It is possible a big reason for the spread of EG.5.1 is just population-level immunity waning from lack of recent infection as I explained earlier. What this means for the XBB.1.5 fall boosters is currently unclear. While EG.5.1 is not descended from XBB.1.5, they are both descended from BA.2, so genetically should be similar enough that the boosters will provide protection, but that will vary somewhat depending on the properties of each subvariant.
Shots in the Foot
So last year we were able to identify the overwhelmingly dominant variant to immunize against, but the booster campaign was a failure because:
- the vaccines became available when that variant was already in decline
- the vaccine got watered down with a strain of the virus that was long-extinct and created an imprinting problem
- there was limited demand / low awareness
Now we’ve got updated monovalent vaccines which hopefully will create less of an imprinting problem, and the vaccine producers, for their part, were prepared to deliver at the end of this month. The government, however, was not:
And to make matters worse, COVID does not appear to be a priority for the current leadership at CDC:
You are reading this now because I have no faith in this government or media to properly inform you about any of this, so I am doing my best to get the word out.
Update 8/26/2023: Public health officials appear to have taken notice of rising hospitalizations, but here we have the Director of the Center for Disease Control and Prevention explaining that you can protect yourself FROM AIRBORNE RESPIRATORY VIRUSES BY WASHING YOUR HANDS.
This is politics, not science.
Update 8/26/2023: In mild defense of Cohen, her boss, the Secretary of Health and Human Services Xavier Becerra, is an unqualified former district attorney, who senior administration officials have said ought to be replaced, but won’t be for political reasons:
Several administration officials voiced similar displeasure with Becerra’s leadership, although they would not do so on the record because they were not authorized to speak with the media. The health secretary “is taking too passive a role in what may be the most defining challenge to the administration,” said one senior administration official.
The Nightmare Scenario
When we had widespread testing, travel restrictions, and public protections in place, the spread of variants was slow enough that we had a good lede time to gather data before it would spread throughout the world. Now, sub-variants have a chance to spread widely.
While I was in the process of drafting this, 6 cases of a previously unidentified variant were sequenced in London, Denmark, Michigan, and Israel — all locally acquired and completely unrelated.
The variant is called BA.2.86 (“Pirola”) and the WHO declared it a Variant Under Monitoring after just the first 3 cases were sequenced.
BA.2.86 is a descendent of BA.2 that is so heavily mutated you would need to add an extra ring to the family tree above in order to show its relationship to the ancestral strain (I’ll update this whenever someone creates that radial chart).
Update 8/26/2023: See below
So a new variant has appeared out of nowhere and may already be everywhere.
And it’s not just the number of mutations that has gotten everyone’s attention.
Update 8/26/2023: We are now actually up to 10 cases on 4 continents, indicating at least 2 distinct sublineages of a common ancestor. While they appear to have an advantage in antibody evasion, but may not be more transmissible than other variants, it would be bad were it to recombine with a more transmissible strain. In other words, we may not have to worry about BA.2.86, per se, but rather its offspring.
Whack-a-Variant
Is BA.2.86 a nightmare variant — as transmissible as Omicron and as lethal as Delta? I don’t know. Is it already circulating? Probably. Will it become the dominant variant or will it get outcompeted by something fitter? That’s impossible to predict. The only certainty is that the virus will continue to evolve
As long as transmission of SARS-CoV-2 continues unabated, this story is going to continue repeating. This virus makes so many copies of itself that it’s capable of mutating inside one person before it’s passed on to the next. The planet is now full of millions of people at any given moment literally providing space for viral R&D by producing trillions of copies of the virus and testing its fitness by exposing others.
The mRNA vaccines do not offer long-lasting protection against infection. Technically speaking, they can be updated to the latest variant very quickly, but in practice we’ve seen these companies can’t react quickly enough to a sudden genetic leap like we saw in BA.1 (or now BA.2.86), and even if they do, the government has a proven track record of slowing them down even further.
We need to stop If you prevent infection, you prevent transmission, if you prevent transmission, you slow the rate of mutation. We need a vaccine that prevents infection and is variant-proof.
Novavax
We already have a vaccine that prevents infection and is variant-proof.
It is called Novavax, and rather that give this section a cutesy title I’m going to call it Novavax so that you read the word Novavax as many times as possible.
Novavax was developed along with the other vaccines as part of Operation Warp Speed, and even though its approval has been slow-walked by the FDA, it received Emergency Use Authorization in July 2022 and was approved and distributed last fall as a booster at the same time as the bivalents.
The phase-III clinical trials showed test subjects immunized with Novavax had a 90% reduction in symptomatic infection and 100% reduction against moderate and severe disease. The study was conducted during the Alpha (B.1.1.7) wave in the UK at the end of 2020 and found that protection still held up against Alpha, an early indication that the vaccine would hold up well against variants. Here is a video breakdown of that study.
Novavax is not an experimental mRNA vaccine, it is a traditional protein-based vaccine that is adjuvanted, which means a substance has been added to it which enhances the body’s immune response.
As discussed earlier, the mRNA boosters, both the monovalent and bivalent versions targeted at seemed to have an imprinting problem. Meanwhile, the M-Matrix adjuvant in Novavax actually appears to improve the immune response with each subsequent dose, making it somewhat “variant-proof.”
Recall the radial “Circle of Variants” or “COVID Family Tree” and how distance from the center means more mutation and less immune recognition. Successive doses of Novavax broaden the bodies recognition of new variants and shrink the distance.
The other aspect that makes Novavax superior product is that it targets a different part of the spike protein that is less prone to mutation over time. When scientists talk about mutations to the virus, they are usually referring to changes in the S1 region, as opposed to the S2 region that is more stable over time.
The data is in from a Phase-II trial started in September 2021 on Novavax’s effectiveness as a booster shot for those who have previously had mRNA, and the study found that:
Heterologous and fractional dose COVID-19 vaccine schedules in adolescents are safe, well-tolerated and immunogenic [mixing and matching vaccines is safe, has few side effects, and works]
Neutralising antibodies against Omicron BA.1 and BA.2 were higher after [Novavax] than a two-dose 30µg [Pfizer] schedule.
The lowest rate of SARS-CoV-2 breakthrough infections occurred in participants who received [Novavax] as their second dose.
Remember, two doses of Novavax held up during the phase-III trials against the Alpha variant in 2020. This Phase-II trial during the first Omicron waves showed that a Novavax booster shot provided superior protection to a second mRNA shot.
As a protein-based vaccine, Novavax would have been ideal for skeptics of mRNA technology, and it has considerably fewer side effects, which would appeal to me and everyone else who got knocked down for a day from the Pfizer/Moderna shots.
The fact that you are currently limited to using it as a booster if you’ve already had an mRNA shot is unfortunate because, as I pointed out above when talking about broader recognition, it looks like you really need to get multiple doses spread out over time to reap all the benefits of the platform.
For more information on the benefits of Novavax and why it really is a three-dose vaccine, I highly recommend reading this entire article:
Update 8/26/2023: Novavax has released a press statement asserting that their XBB-targeted booster “induced neutralizing antibody responses to the EG.5.1 and XBB.1.16.6 subvariants in small animal and non-human primate studies.” As of August 9 wastewater analysis from Biobot Analytics, XBB.1.16 had become the dominant sub-variant and accounted for a quarter of all cases nationwide, while EG.5.1 at 11.8% appeared to still be the fastest-growing. There is still no date when the boosters are expected to be available.
Update 8/31/2023: https://www.biorxiv.org/content/10.1101/2023.08.30.554497v1
This is not the end
To recap, SARS-CoV-2 is not gone and continues to mutate. The mRNA vaccines are limited by their targeting of the S1 region of the spike protein, which is the part of the virus that is continually changing. Updates to the mRNA vaccines are not happening quickly or getting approved enough to make a difference, and continued boosting with older variants causes immunological imprinting.
The good news is that, while it is not a silver bullet, there is a vaccine available that is superior at protecting infection and durable against viral mutations.
The problem is that you had not heard of it, didn’t know to look for it, and probably thought you did not need it. Since Novavax is still under EUA in the US, the company cannot market it to you (in July 2023 it received full Marketing Authorization by the European Commission in the European Union under the name Nuvaxovid).
But now you know about it, and you might even know more about it than your PCP or the pharmacy tech who will inject you with it. Try asking your doctor, don’t just take my word for it.
Regardless of your prior vaccination status or how mild your last COVID infection was, you’ll want to get this vaccine.
It goes like this: If your immune system is able to recognize the virus based on the signature of the spike protein despite continued mutations in the S1 region, then it can efficiently produce antibodies to bind to the spike protein and prevent it from binding to cells with the ACE2 receptor in your body.
Binding to ACE2 receptor opens to the door to the cell. Some background knoweldge you need to understand the next graphic is that necrosis in your heart muscles is bad.
This maybe the first time you’ve heard about the ACE2 receptor, but this one fact about SARS-CoV-2 explains the mechanism of damage to heart tissue caused directly and indirectly by the virus, but the virus can do this anywhere in your body where the ACE2 receptor is present.
Which is everywhere.
If you understand that, this graphic makes a lot more sense:
The comparison between Omicron and Delta in terms of severity in the media back in 2021, had to do with whether the primary site of the damage was in the lungs, which can cause death within days. Cardiovascular problems and blood clots, on the other hand, can take months or years to manifest, and usually very suddenly.
In other words, based on our understanding of the mechanism by which SARS-CoV-2 infects the body, we would expect COVID-19 to result in problems that will end up being listed as a cause of death other than COVID-19 later.
And if that were the case, and if the vaccines waned in effectiveness over time, then we would expect to see a lot of people dying for reasons not attributed to COVID on death certificates, especially among those most likely to survive the acute phase of the infection because of their health/age.
Now try to reckon articles saying “we don’t know why this is happening” with an article published the same week explaining “this is why this is happening”:
This article is from February 2023:
In fact you can go back to any point in 2020 and find detailed explanations of phenomena which are being described as new or a mystery but are actually neither.
Besides heart attack, stroke, and diabetes, we’ve also got studies on neurodegeneration and significant declines in sperm count that are straightforward to explain as COVID-related and difficult to make sense of otherwise.
What’s Next
Pfizer, Moderna, and Novavax are all supposed to have updated boosters next month. It’s good that the Novavax shot will be more effective against BA.1.15 because presumably that will help protect against the other XBB variants along with EG.1. The real benefit is the second/third dose, because the virus will continue to mutate gradually or it will will mutate abruptly the way it did with BA.2.86, and the mRNA shots have not proven effective at keeping up.
I’m going to try to do what I can to make it possible for everyone to start over with 2 doses of Novavax, but the shareholders at Pfizer and Moderna may have some issue with that.
In the meantime the course of action I would recommend is:
1Buy NIOSH-approved N95 respirators that fit your face and wear them everywhere you go, starting yesterday. Masks are variant-proof.
2Avoid large unmasked gatherings indoors with poor ventilation until you’ve at least had the Novavax booster. That would be the bare minimum.
3Do your own research on the Novavax booster and consider getting it as soon as it is available. As a non-medical professional, I can’t give medical advice, just pass along information.
4 Share this information with anyone and everyone you can and encourage them to take precautions and look into Novavax. For some people, it will be enough to point out that cases are rising again. If you’re thinking, “gee, no one else is wearing a mask, guess I don’t need to,” see if you can’t get a couple of your friends and coworkers on board and watch how quickly some of the people around you start thinking “gee, a lot of other people are wearing a mask, guess I need to.” Be the change you want to see.
5Assume it’s COVID. If you feel absolutely terrible, but a rapid antigen test (RAT) / home test says you’re negative, keep testing, or do a PCR test to check, if you can. The tests haven’t been updated in forever and weren’t that good to begin with. Having a COVID+ test will make it easier to establish a link between the infection and any post-COVID or persistent COVID symptoms.
6 Stay abreast of developments concerning BA.2.86. First reports are always wrong. Be wary of predictions based on conclusions made from incomplete data. Keep in mind that any media organization committed to presenting “both sides” is never going to take a stance on any issue until both sides agree, and whatever they agree on may not be true.
7 Look into HEPA filters for your home/office/classrooms. For less than $100, you can build your own Corsi-Rosenthal box out of a box fan and MERV-13 filters, which can be even more effective than a consumer-grade air filter. You can also purchase next-generation boxes that use computer fans (and are much quieter) but they are also more expensive. Air filtration is also variant-proof.
That’s the best I have at the moment. I’m waiting on consumer-grade far-UVC lights in the 222nm range and breathalyzer tests that can detect infection with SARS-CoV-2 within 1 minute. Nothing by itself will solve this, and it certainly won’t be possible to reverse course without the public’s involvement.
