As reminders…

Alpha–Variant first identified in the UK

Beta–Variant first identified in South Africa

Gamma–Variant first identified in Brazil

Delta–Variant first identified in India

Also as a reminder:

–Yes, we have -another- Ebola outbreak. Late last week, an 18 year old in the Ivory Coast was traveling, treated presumptively for malaria, but ruled out on testing. Subsequently, her condition got worse with symptoms of hemorrhagic fever. There is at least one other patient who is known to be positive (her husband). Both are currently being treated and there are no reported deaths yet. The Ivory Coast has already distributed several hundred doses of Ebola vaccine the moment samples from the 18 year old were confirmed positive. There was a span of at least a week though where the patient was traveling and possibly symptomatic, so they may not have all the potential transmission chains isolated yet.

–Marburg in Guinea. Not much to update. No new cases so far. In fact, the WHO Africa report for this past week was much more focused on Lassa Fever in Nigeria. The current outbreak of what is an endemic disease hitting several hundred thousand there per year, as we discussed previously, has hit an approximately 20% mortality rate. They also spent some ink on cholera in Niger, which has affected several hundred people there with a mortality rate of about 3.9% (or approximately double the coronavirus CFR for the entire continent of Africa, recognizing that many cases of coronavirus are probably not being tested in less well developed rural parts of Africa).

–But bona fide Ebola and Ebola-family outbreaks continue apace, popping up more and more frequently. I am not sure if this is due to better detection (possible) or just an indication of increased risk of break out of this disease family. Coupled with known re-infection from Ebola Janes among the survivors, due to re-activation and spread of the virus, particularly, it seems, with sexual contact, and there remains a growing chance that an Ebola Jane or recently infected patient will hop on a plane to someplace with NO significant Ebola experience, and spread for a bit before anyone figures out what it is. I know widespread vaccination is a controversial topic and Ebola is indeed harder to catch than a coronavirus, but this is a disease with a 50%+ mortality rate–often double the Black Death. We have a vaccine for it. Prevention will be worth a pound of cure, and reserving Ebola vaccination for contacts of known cases (as it is currently being used initially in these outbreaks) seems increasingly risky.

–Alright, that’s the “rare, exotic yet contagious ways you will probably NOT die” portion of the update. Back to coronavirus.

–Leading off this week, we have a solid study from the Netherlands available as a pre-print that looks at recovery of viable virus from breakthrough infections. Similar to the South Korean study last year, they went to the initial positive sample from healthcare workers with breakthrough PCR positives (most were delta in the April-July span examined) and then tried to culture SARS-CoV-2 from the sample.

The long story short is that virus could be cultured from vaccinated patients only 68.8% of the time. Unvaccinated positives from the previous alpha wave, in the hands of these same researchers, could be cultured >85% of the time.

Further, the probability that the virus could be cultured went up the lower the Ct value of the PCR (and thus the higher the viral load). Interestingly, among vaccinated patients with symptoms, the Ct value fell for the first three days. Again, that implies that the viral load was increasing in that span–suggesting symptomatic breakthrough infection may have actively replicating virus while the immune system adjusts to delta’s spike protein changes.

So what do we learn from this?

• We need to differentiate symptomatic versus asymptomatic breakthrough infections. There is good reason to believe the latter do not have significant amounts of active virus present where they are a risk to others.
• So all the papers we have called out for NOT differentiating asymptomatic versus symptomatic infection absolutely deserve that callout because that difference almost certainly has a clinical and epidemiological impact.
• Even with symptoms, there is a significantly reduced chance of culturing active virus from breakthrough infections…even delta variant virus.
• Breakthrough infections in vaccinated patients are LESS likely to infect others. And that risk may largely be restricted to only symptomatic breakthrough infections. That would be consistent with cohort studies we have cited previously showing no transmission of prior SARS-CoV-2 variants from asymptomatic patients.

–To hammer home why it is absolutely criminal that the CDC, and other organizations that should know better, continue to NOT differentiate previously infected, unvaccinated patients among the SARS-CoV-2 naive unvaccinated patients AND then do comparisons with that whole “unvaccinated” group, pretending they have the same risk of hospitalization, we have a pre-print paper from a large hospital group in Israel.

Demonstrating research in this area done right, they had over 600,000 previously vaccinated but no known prior infection patients to compare to 63,000 unvaccinated previously infected patients and 42,000 with single dose vaccination. They matched for age, sex, socioeconomic data etc. to ultimately compare tens of thousands of matched patients among those three groups.

What did they find?

Vaccinated patients, who were COVID naive, were 13 times more likely to have breakthrough infection than recovered, unvaccinated (but now naturally immune) patients, more likely to have symptoms, and about 6 times more likely to be hospitalized.

I want to stress that breakthrough infection in either case was still rare.

Put differently, though, what they found is that natural immunity (which has spike protein antibodies and T-cells PLUS antibodies and T-cells to other SARS-CoV-2 protiens as well) outperformed the vaccine. Which, frankly, is not that much of a surprise. The magnitude of that effect is, though.

And that’s why all of these papers, where I have been bitching for weeks as they have rolled out, where they have not controlled for previous infection in the unvaccinated are flawed.

If you do not remove the previously infected from the “unvaccinated” group you are comparing, you will make the effectiveness of the vaccines LOOK worse than it actually is. Because in that unvaccinated group are people who will be HIGHLY resistant to breakthrough infection and hospitalization, make the “unvaccinated” group look “better” than it actually is.

And yes, Hypothetical Reader, this DOES make a mockery of mandates and vaccine passports which do NOT account for previous infection. This large, well executed study indicates that natural immunity from previous infection is probably more protective than the vaccine.

–The CDC has dumped more data about vaccine effectiveness over the past week, presumably that which informed its decision to encourage a third booster shot for everyone. We will cover this as briefly as I can.

The moral of the story is that while it seems reasonable and prudent for those at high risk (immunocompromised and elderly, plus etc.) from COVID to get a booster, this data is underwhelming in presenting a case for everyone getting a booster at 8 months.

First, the CDC released this as an early-to-print on Tuesday. This compares vaccine effectiveness in healthcare workers at 8 US locations between the alpha wave and the delta wave. The people in the study were screened weekly. Frustratingly, the authors considered “infection” again to be any positive PCR result in that span. To their credit, they do report which the percentage of unvaccinated and vaccinated positives that were symptomatic. They do NOT report hospitalizations, which, again, is the most relevant metric when we are considering vaccine efficacy. This is probably because the total number of positive PCR results (sorry–“infections” as they call them) is so small that hospitalizations were unlikely and probably so rare as to make meaningful statistical comparison impossible.

So the long story short here is that vaccines were ~80% effective in reducing positive PCR tests during the alpha wave, and there was NO statistically significant difference in that effectiveness based on how long ago you got the vaccine. If you adjust that to count ONLY symptomatic cases, the vaccine is even MORE effective.

In the delta wave, they top line a vaccine effectiveness of 66%. When I adjust their data for vaccine effectiveness in preventing symptomatic SARS-CoV-2, I get 79.2% vaccine effectiveness. Even the authors’ 66% has a confidence interval so huge it crosses that of the alpha wave, so the best interpretation is there is NO significant difference in vaccine effectiveness in the alpha versus the delta wave. Especially since I doubt the hospitals have been sending unvaccinated health care workers into COVID wards, so the vaccinated subjects in these studies are probably getting extra opportunities to pop a PCR test positive.

There is also NO reporting of how many of the unvaccinated subjects had previously recovered from COVID, since these should really be excluded from true vaccine effectiveness calculations.

BUT THEY STILL ARE NOT, AT LEAST NOT CONSISTENTLY, ACROSS THE LITERATURE.

For…..reasons? I guess?

If this makes sense to someone else out there, including the other docs on this list, please explain it to me. We know there is natural immunity from recovering from COVID, but we continue to ignore it when calculating vaccine efficacy–even though we can predict that it will make vaccines look LESS effective than they probably are. Other recurrent oddities in the literature I probably need explained to me as well include defining “infection” solely by SARS-CoV-2 assay positivity without bothering to separate symptomatic versus asymptomatic when the test was positive. Those all seem like important variables to me, and we seem to consistently be making these errors in definition in ways that are likely to make the current COVID burden seem worse.

We don’t need that–we have hospital occupancy rates and the knowledge that most of those are occupied by the unvaccinated to tell us how burdensome COVID is at the moment and to whom.

To their credit, the authors in their discussion paragraph say that their results need to be taken with huge caveats because the number of infections is low, making their estimates of vaccine effectiveness relatively uncertain. And prone to other “confounding variables.”

Sadly, this does NOT seem to be stopping folks from making huge leaps of faith on the data. Certainly not stopping headlines, either…

Other CDC papers on vaccine headlines included this one. Main finding here is that overall effectiveness against hospitalization (the main medical goal of the vaccines, remember!) is 91% against the delta wave in New York. That is a 10:1 reduction in hospitalization with the vaccine. Of course, most of the hand wringing in headlines about this paper is about a “drop” to 79% effectiveness against “infection.”

Which they defined as a positive test regardless of symptoms, and so yet again “infection” is best read as “vaccine effectiveness in preventing a positive PCR test.”

As to the 8 month booster recommendation, CDC released this on vaccine effectiveness 6 months after vaccination. There is NO change in the hospitalization rate at 6 months after the vaccine versus within 3 months of the vaccine (both are mid-80s effective against hospitalization; confidence intervals extend up to include the New York range above). In the immunocompromised though, effectiveness against hospitalization drops to 63%.

So again, good support for boosters for specific, at risk populations. If there is no change in effectiveness against hospitalization after at least 6 months after vaccination for everyone else though, well, it’s not exactly clear why everyone else needs a booster–at least based on this data.

If we are following the current data, at least.

As for giving boosters to the elderly (and why that might be a good idea), CDC put out this. This paper is also difficult to interpret, because they are misusing “infection” once more, so all we can conclude is that there is reduced effectiveness against positive PCR tests in nursing home patients. Which headlines (and, in fairness, the authors in the introduction for why they did this study) again try to generalize for vaccine effectiveness over time, since the elderly were generally vaccinated first. To the authors’ (reduced) credit, the list in the limitations of this study explicitly state their results are “not generalizable to the broader population” because elderly people in a nursing home do not have the same immune system function as an otherwise healthy 22 year old on a beach in Cabo. I may be the only reading that far though.

Overall, at least, this does provide some data support for the argument for the elderly and select at risk populations.

To your “should I get a booster?” question, hypothetical reader, the answer depends. Are you already a person with known at risk conditions for severe COVID? Are you 65 or older? Cancer patient? Diabetes? High blood pressure? Compromised immune function? Compromised heart or lung function? As important as age, are you obese? Be honest–and don’t worry. A shocking percentage of the population is, and is growing, around the world. If those apply to you, then yes, I would think about getting a booster when it comes available to you.

You will reduce your personal risk.

I also recommend Layne Norton’s “Return to Shred” playlist (really, the first “episode” of it) in his “Biolayne” YouTube channel for diet steps you can take if weight modification to reduce your risk of COVID and other diseases where excess pounds are a risk factor is of interest. Diet is overwhelmingly the biggest bang for the buck there. Zoe is also a consideration for personalizing recommendations, but the key via Biolayne is to get portion and calorie control with foods you like to eat first.

Enough of the diet tangent though.

If you are NOT an at risk category for severe COVID, and have already been fully vaccinated, do you need a booster?

Well, I, personally, am NOT in any of the at risk categories, and will NOT be running out to sign up for a booster. I don’t see compelling data for need right now. It would be a nice to have, and I’m not even sure how much of my risk for severe COVID would even be modified by the booster. Do I think there will be social pressure through employer mandates, travel mandates etc. for a booster? Very likely. Because “science.” And I will be very annoyed when they happen.

Further, boostering me and those like me will do NOTHING to stop the pandemic portion of SARS-CoV-2.

Remember, >90% of current hospitalizations due to COVID are in the unvaccinated (yes, Hypothetical Reader, we will get to Israel down below).

You eliminate the risk of health care system collapse and ICU “bed’s taken” from COVID by reducing hospitalizations. That can be through herd immunity (previous infection or vaccination) and/or effective treatment of acute cases.

So the most bang for the buck is NOT wasting shots on boosters for the low risk young’uns out there–it’s getting the still unvaccinated, who have not already recovered from COVID, vaccinated.

And I am not the only one who thinks so!

Bloomberg talked to one set of infectious disease experts who basically said the same thing. Evidence for boosters for everyone is underwhelming so far, and greater public health effect would be in focusing shots on the unvaccinated:

https://www.bloomberg.com/news/articles/2021-08-20/biden-plan-prods-scientists-to-back-boosters-despite-murky-data

–Yes, I did see that Pfizer’s vaccine finally got full FDA approval. Moderna is likely to follow, but they have small hiccups we will get into momentarily.

Will that help move vaccination needles? I doubt it. I think that was more an easy excuse for those who have decided, for other reasons, to delay vaccination. And frankly, I don’t think their opinion of the FDA is so high that they “believe” this approval either.

So how do we move the vaccination needle? Well, I made suggestions on how to have those conversations before. Here’s a family medicine doc who also shows you how it’s done in a way that respects the patient and their autonomy.

Make sure you click through for the whole thread.

–Lastly, on the vaccines, the risk for myocarditis from the Moderna vaccine may be higher than initially suspected based on Washington Post reporting:

https://www.washingtonpost.com/health/2021/08/19/moderna-vaccine-myocarditis/

The FDA is reviewing. However, at worst, this merely doubles the likelihood of myocarditis from the vaccine. It is more common in younger males.

Even with this doubling, a young male is -at least- 5 x more likely to get myocarditis from SARS-CoV-2 itself than from the vaccine. Both are still literally lottery level events.

That’s not the only Moderna news, however. Japan has halted Moderna vaccinations for contamination concerns after finding “fine particulates” remaining in the vial after the shots have been distributed. So that will take some investigating over the next week plus.

–But if you read our “Choose Your Own Black Death Adventure” update last year, you already knew what a Harvard immunologist is now telling you:

Key pandemic learning (all the way back from the Middle Ages): Once a pandemic agent is out, it’s out, and everyone will get exposed eventually. In fact, once the first case is in your town, safest to assume you have already been exposed.

–Alright, going around the horn…

Believe it or not, the US Epiforecasts Rt has been < 1 for most of the week and only just bumped up to about 1 yesterday. This means that the nation as a whole is likely at the delta wave peak.

Yes, approximately when we said previous delta waves in the UK and India suggested we would hit that peak <waves world’s tiniest flag>.

That said, it’s an imbalanced top. For example, cases in Louisiana, Texas and Missouri, all early delta wave hotspots, are now in decline. Late delta wave states like Indiana, for example, probably have another week or two to see their top. South Dakota, which has been the last state to get major delta activity, is on the rise, but I would expect an overall fall to June/July new case numbers for the US as a whole by the end of September. Good news for football, I guess?

Elsewhere, China is starting to re-open a bit, suggesting their draconian closings have blunted the numbers enough for official purposes. Australia is shooting dogs lest the workers in the shelter dare, dare, go outside to drive and rescue the dogs.

That is some North Korea and China level ‘ish, there Australia.

The hell is wrong with you people, Australia?

New Zealand has also largely barred people from going outside after one delta case became 10 on the island. That has (predictably) failed, as they are now up to 148 cases, and I doubt they stop there.

Worth mentioning that both Australia and New Zealand have had markedly less success in vaccination than many of their developed peer nations.

On the other end of the spectrum, very vaccinated Israel is near the top of their own delta wave (current Epiforecasts Rt of 1). “OMG…the vaccine is useless! We iz all gonna lockdown again and/or die! DOOOOOOOOOOMM!!!! DOOOOOOOOOOOOOMMMMMMMM!” I hear you say, Hypothetical Reader of Many Headlines.

Look, as of August 15th, 59% of the hospitalizations in Israel were fully vaccinated. Now, that is, indeed, quite different from the 5% or less vaccinated hospitalizations in much of the rest of the world. Of those hospitalized in Israel who were fully vaccinated…

…would it surprise you if I said the vast majority of them were older than 60? And of the rest, most of them had underlying immunocompromise?

No? That doesn’t surprise you? Because you have been reading my scientific paper breakdowns the last three weeks and know that all the data suggests that older patients and immunocompromised are most likely to be hospitalized on breakthrough and the data suggests boosters are a good idea in them?

Especially if you also noticed that “59% of hospitalized Israelis” is less than the percentage of total vaccinated Israelis, and thus even their current outbreak heavily skews to the unvaccinated based on relative abundance in the population.

Vaccines still work. Selective boosters, for those with the known risk factors and especially the elderly and immunocompromised, seem prudent. Those are the two strongest messages from the international data at the moment.

–Speaking of which, a reader sent this super scientific, short video illustrating how vaccines work: https://mobile.twitter.com/briansolis/status/1429946252729348110?s=21

–Apologies to the reader with the epic survival story of their (barely) symptomatic bona fide vaccine breakthrough infection who contacted us with the details this past week.

We ran out of time this update…

–Jeffrey Epstein died a little over 2 years ago, after being convicted of sexual exploitation of underage girls, with credible reasons to believe he was not the only one involved, and may well have been blackmailing a number of wealthy, well-connected people. Your chances of catching Marburg are equivalent to the chances they have followed up on statements from the guards the night he died in prison, or CCTV failures during that period.

–Your chances of catching Ebola are equivalent to the chances there have been subsequent arrests from all of the evidence collected in the searches of Epstein’s Virgin Islands, New York home (rumored to have its own surveillance suite), his New Mexico ranch (never actually searched as far as I can tell), testimony from Ghislaine and other reported co-conspirators–all collected over the last two years.

Arrests any day now, right guys?

–Your chances of catching coronavirus, in most places in the world, remain equivalent to the chances this was going to happen given the on-going catastrophe in Asia.

Humanity has generally emerged from its pandemics to find the world a changing, and ultimately changed, place. We mentioned some of that, in brief, around the Black Death here and here. Unsurprisingly, perhaps, we seem to be rhyming–even though the mortality hit in the Black Death was much higher.

Ironically, historians might one day argue that our institutions, society, and global system was perhaps less robust, less anti-fragile, than the 14th century world–despite the major difference in technology.

If it seems like the dial is on maximum stupid, that there is just an unrelenting wave of new causes for concern, of major changes, if everything feels stressful and unbalanced… well… it is unbalanced.

The good news is that you will play a role in shaping what the Other Side of This becomes.

With every thought, every decision, every action you will take.

You will get through. You will get others through. You have the courage and capability to stand tall in the maelstrom.

You do.

Just know that change is coming, fairly fast now. In fact, the Other Side of This is only just getting started. From here to there is some wild territory…

<Paladin>