Covid Updates

The Risks of At-Home Covid Tests

Dale W. Harrison — Sun, 22 Aug 2021 19:08:58 GMT

For the first time, there's widespread availability of over-the-counter Covid tests. The primary being the Abbot BinaxNOW antigen test.

This is also the first time most people have run their own at-home medical tests beyond perhaps a pregnancy test. As a result, there are some potentially dangerous fallacies about these tests and what the test results actually mean.

Key Takeaways for Home Covid Tests:

If the test is Positive you are absolutely infected!
Less than 2 tests per 1000 will return a false-positive1
There is NO reason to "confirm" the test-positive with a PCR test
If the test is Negative there's still a high chance you're actually infected2
Up to 680 tests per 1000 will return a false-negative if asymptomatic3
Up to 250 tests per 1000 will return a false-negative if fully symptomatic.4
These tests generally only work on people who are fully symptomatic
If exposed, Test-negatives should be confirmed with a laboratory-run PCR test5
These tests DO NOT tell you whether you're infectious!
There is NO test for "infectiousness" in existence
These tests are primarily useful for a confirmatory diagnosis on an already fully symptomatic patient

To Summarize:

If you have Covid-like symptoms and the test comes back POSITIVE, then you absolutely have Covid!
If you have Covid-like symptoms and the test comes back NEGATIVE, then you very likely have Covid but must confirm with a full laboratory-run RT-PCR test.
If you have been exposed, but are asymptomatic, DO NOT use this test, quarantine, and go to a clinic for a proper laboratory-run RT-PCR Test.

If you're using these Home Covid Tests in ANY other manner, then you're dangerously misusing the test!

Here are CDC6 guidelines for how these tests are to be used and not used:

The CDC recommends their use primarily in large congregant settings such as nursing homes, large warehouse distribution centers, schools, etc. NOT for keeping Covid out, for the sole purpose of slowing the rate of infection through those populations by isolating and quarantining people earlier during the infection cycle after known exposure through repeated daily testing.

These Tests Cannot be Used to Decide:

Whether the people coming to your party are "infectious" – this is how superspreader events happen!
Whether your child can go to school today – if Jr. has symptoms or has been exposed, then assume it's Covid until an actual doctor says otherwise
Whether or not you are "infectious" – these tests only register a reliable test-positive for patients with a Ct-count BELOW 20! So yes...you ARE infectious!

So if your kid has so much as a sniffle, don't misuse these tests as an excuse to send them to school. Get them to a real doctor for a proper test.

And please throw away the notion of using these tests for next your dinner party or birthday party or dance party!

If someone is sick and coughing they shouldn't be showing up at your party in the first place. If someone is infectious but asymptomatic, these tests will are very unlikely to reveal that.

These Home Covid Tests will provide no useful information that will allow an inherently risky event to be any less risky.

So if you're throwing a party, there's really only one scenario where these tests have utility. If you've already decided what you're going to do and just need some emotional justification for your dangerous risk-related decision, then just having the tests around can certainly make everyone feel much better about themselves!

And in that case, you probably don't even need to waste the tests by actually using them...just assemble them into a tasteful arrangement on the coffee table.

THE TECHNICAL DETAILS

Below, I will go into the reasons why these things are true and the source of these limitations. It does require some minimal level of understanding to be able to safely use these tests...

What Is A “Test”?

Before you can understand how to use a medical test, you need to understand a few things about these tests in general, including the Home Covid Test kits.

The first thing to understand is what a test actually is. A test is just a way to measure something. That "something" is generally NOT anything you're directly interested in, but it should be a reliable predictor of the information you're actually interested in.

You don't take a Covid Test to learn about how many viral fragments were on a nasal swab (what the test actually attempts to measure). What you want to know is whether you're INFECTED.

Unfortunately, what a test measures vs. what you want to know doesn’t always line up!

For example, the speedometer in your car is just a proxy for how fast your car is going. But the speedometer is just a needle that turns around a dial pointing at numbers...it's not "actual" velocity. And if your speedometer is misaligned and measuring 20 mph too slow, your car is STILL going at 80 mph even if the speedometer says 60 mph.

Medical tests are no different.

So, in a perfect world, the tests are flawless and it’ll find whatever is there, always returning a Test-Positive…and if nothing is there, it always returning a Test-Negative.

Unfortunately, that's a cartoon-level understanding of how this actually works! For a variety of often complex reasons, tests can fail to return results that accurately reflect the state of the condition you're interested in. In this case, whether someone is infected with the Covid virus or not.

How do You Test the Tests?

How good is one test versus another? How are they measured and compared?

You see people blithely saying things like "this test is 97% accurate". This is always a good indicator they don't have a clue what they're talking about.

First, when it comes to medical tests, there is no such thing as the word "accuracy". If you see someone using this term, then you can assume they do not understand how tests are evaluated nor how the test results should be properly evaluated.

All molecular tests (including Covid tests) are defined by three key measures:

LOD (Limit of Detection) – how much virus do you need for the test to work
Specificity – how sure are you the test found what it was looking for
Sensitivity – how sure are you the test didn’t miss what it was looking for

These can generally be reduced to a couple of important metrics:

False-Positive Rate – based on “Specificity”, it's an estimate of the fraction of Test-Positive results that are incorrect (meaning you're NOT infected, even though the test says “Positive”)
False-Negative Rate – based on “Sensitivity”, it's an estimate of the fraction of Test-Negative results that are incorrect (meaning you ARE infected, even though the test says “Negative”)

In general, the False-Positive rates for all such tests are EXTREMELY LOW. This is really never something you need to be concerned about.

As an aside...there's been a LOT of nonsense and outright lies ⁠about Covid tests having issues with false positives. This is complete fabrications being passed around by Covid-deniers. Anyone who is actually involved with designing and developing these tests knows this is never an issue with these sorts of molecular tests.

But there are a LOT of issues with False-Negatives and this is what can lead you astray in interpreting these test results! The rate of false negatives is directly tied to the particular type of test and how rapidly the test returns results (hint: faster = worse).

Types of COVID Tests

There are a variety of tests to determine whether you're infected with the SarsCov2 Covid virus. Each with various tradeoffs. But the key thing to understand is that there is NO FREE LUNCH when it comes to testing.

You cannot get a cheap fast test without sacrificing something critical!

And in general, what you're sacrificing is test Sensitivity. Meaning the faster your time-to-result, the higher the rate of false negatives. The faster the test, the more likely it will say you are NOT infected when you really ARE infected.

This is what led to multiple superspreader events at the White House last year. They were using a so-called 20-minute "Rapid Test" (the Abbott IDNow) and the false negatives were in the range of 30% to 40% percent. As result, they kept letting infected people into events.

Here's a summary of the major types of tests for SarsCoV2 infection and how they compare in these key metrics.

Table 1: Test Performance

Table 2: Examples & Usage

So if you want an answer in 10-minutes (which the Home Covid Tests promise), then you're going to have to give up a LOT. This is the problem with ALL rapid tests, faster results are uncertain results.

And the Home Covid Tests are at the very bottom of that pile!

Antigen Tests

The home Covid tests, like the BinaxNOW, are antigen tests. Meaning they're looking for protein fragments from the viral nucleocapsid. The shell containing the viral RNA.

All other molecular tests are what are called "nucleic acid amplification tests” (NAAT). Meaning they're looking directly for segments of viral RNA. Pieces of the virus's genetic material.

Antigen tests perform poorly because there's no way to amplify (makes millions of copies) of proteins during a test. With an RNA test, there's a chemical process called “polymerase-chain-reaction gene amplification” or PCR for making billions of copies of a specific target sequence so it becomes a great deal easier to reliably detect.

With a protein-based test, all you can do is try to purify away molecules that might get in the way of detecting the target protein. But all you have to work with is some fraction of the amount of protein that was first collected on the swab.

As a result, antigen tests require a MASSIVE viral load before being able to detect anything and reliably trigger a test-positive result. So a very high LOD or Limit-of-Detection.

This is why these sorts of lateral flow-strip antigen tests ONLY work reliably on people who are fully symptomatic within the first 5-days of symptoms. Before then, there's generally not enough virus present. After 5-days, the virus is being actively eliminated from the nose and throat and there's not enough virus.

This is also why you can be quite infectious to everyone around you even if symptomatic, especially with something like the Delta variant, and these tests can still return a false test-negative.

Again...there are NO tests for "infectiousness". The ONLY thing these tests can do is to potentially determine whether or not you're infected.

But the Package Insert Says Something Different!

There can be signficant differences between how these tests actually perform in the real world in the hands of untrained users and how they perform during FDA validation trials.

The validation data submitted to the FDA for getting these tests approved are collected under highly specialized and controlled conditions. Generally, the test subjects are chosen to give the most reliable test-positive (previously diagnosed fully symptomatic patients) or test-negative (fully asymptomatic patients with no know exposures).

And the sample collection, sample prep, and test interpretation are done by Ph.D.'s or at a minimum highly trained medical staff under close supervision by scientists.

The validation trials are meant to determine how well the test, in isolation, will perform under absolutely perfect and ideal conditions. It represents the far upper range of potential performance of the test in isolation from human factors.

Your Mileage May Differ…

And that's a perfect comparison. EPA Offical Average Highway Ratings are absurdly high. I'm pretty sure no one gets 25mpg in their F-150 pickup. Real-world mileage is likely closer to 10-12 mpg.

That's because the mileage tests are done under extremely contrived conditions that represent an ideal upper limit to engine performance, but have little or no bearing on how things will work in everyday usage in the hands of a normal driver.

FDA data is no different. And it's NOT that the FDA processes are somehow flawed...they are not! This sort of data is very important for comparing the relative effectiveness of various tests, for understand the core performance of the test in question and for understanding inherent limitations with different tests.

What's flawed are people’s assumptions about what that data means. It doesn't mean what you think it means!

Conclusion

These at-home Covid Tests have limited usefulness beyond confirming that what you’re in bed sick with is Covid versus a cold or the flu.

Their optimal use is for daily screening of large closed populations at a very low cost.

Screenings NOT to diagnose Covid infections, but to slow the rapid spread of infection through a closed population in places like nursing homes and massive warehouse distribution facilities by forcing early quarantining of exposed individuals.

As a good indication of these limitations, I know of NO biotech companies (who would best understand these tests) that are using these to screen their regular employees. They all rely on normal laboratory-run RT-PCR tests instead.

So definitely use these tests…they’re a valuable additional resource. But everywhere, I see people grossly misusing these tests out of ignorance of how they work and where they are and are not applicable.

Responsible use is knowledgeable use!

References:

https://www.medrxiv.org/content/10.1101/2021.08.04.21261609v1

https://pubmed.ncbi.nlm.nih.gov/33846714/

https://www.medrxiv.org/content/10.1101/2021.08.04.21261609v1

https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html

About the author:

I am a scientist with 20+ years in the biotech industry. I currently work as a consultant with companies involved in developing molecular diagnostics platforms, including some of the key testing platforms used to detect the SarsCoV2 virus.

So I bring an insider’s perspective that is scientifically oriented but directed to a general audience trying to make sense of the conflicting stories surrounding the Covid pandemic.

To learn more: https://www.linkedin.com/in/dalewharrison/

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Prior Posts...

There are NO "Breakthrough" Infections!

Dale W. Harrison — Sat, 07 Aug 2021 17:22:28 GMT

The term “breakthrough infections” implies that the vaccines have somehow failed to do their job. The vaccines are working exactly as expected.

What has failed is people’s understanding of how vaccines work and months of misguided public health messaging overselling what these vaccines are can and can not do.

This is a lengthy update, but it’s important to understand why we’re seeing vaccinated people getting infected and what this means for the future…

What Vaccines Do

There is a strong reaction in the virology community right now against the term "breakthrough infection" in regards to the Covid vaccines. The word "breakthrough" implies that infection after vaccination is something that was not fully and completely expected.

These are non-sterilizing vaccines. Meaning that they do not perfectly prevent infection of the mucosal tissues in the nasopharyngeal region (nose & throat) and upper lung.

The Covid vaccines work by keeping the virus out of the bloodstream and out of the lower lungs. This prevents Covid pneumonia and the permanent internal organ damage seen in more than 1/3 of natural infections.

Once pneumonia and internal organ damage have occurred, people need hospitalization. And this is why the rate of hospitalization after vaccination is extraordinarily low compared to the unvaccinated.

The Early Animal Trials

The early vaccine animal “challenge trials” from April and May of 2020 clearly showed that infection and transmission after vaccination could be common.

”Challenge trials” are where test animals are fully vaccinated and then deliberately exposed to varying levels of virus to see if they could become infected. These infected animals were then exposed to un-infected animals to see whether transmission could occur.

This is NOT new information but has been available for well more than a year now. I wrote about this extensively in this newsletter more than eight months ago and have written about it in other forums since June of 2020.

Covid Updates

Covid Vaccines Confer No Sterilizing Immunity

The new Covid vaccines are NOT like what most people imagine a vaccine to be! They will be nothing at all like the measles or smallpox vaccines that actually prevent infection. This is a topic I've been discussing since July when the initial vaccine animal studies went up on the pre-print servers. None of the current vaccine candidates confers "sterilizi…

6 years ago · 2 likes · 6 comments · Dale W. Harrison

That research showed that ~70% of fully vaccinated animals could be infected and re-infect others if exposed to a sufficiently high viral load.

Vaccination offers some level of protection against infection, but not a lot. Especially if the viral load is quite high and the level of contagiousness is high.

And this is EXACTLY the situation we have right now in the US with the widespread Delta-variant outbreak!

The Clinical Trials

This understanding was also made explicitly if you'd read the Clinical Trial Protocol documents from the human Phase III vaccine trials back in 2020.

Infection and re-transmission was ALWAYS seen as a possibility after vaccination and ALL the vaccines trials instead focused exclusively evaluate the vaccine efficacy based on reducing (but not eliminating) severe disease requiring hospitalization.

Infection after vaccination was seen in 100% of all the vaccine trials. So this is not a function of the vaccine, but rather a function of the limitations of the immune response to this particular virus.

I wrote about this in this newsletter extensively eight months ago:

Covid Updates

Results from the AstraZeneca/Oxford Vaccine Trials

This is a longer article (about a 10-15 minute read) but contains some new and critically important information about how we can expect the vaccines to perform. Much of this will be counter-intuitive to the popular understanding of how vaccines work. I hope you are able to take the time to carefully read through the article…

6 years ago · 5 likes · 37 comments · Dale W. Harrison

Not only can you be infected, but you can ALSO transmit the infection to others after being vaccinated. This is true not only of vaccine-induced immunity but also of immunity after natural infection. This effect was seen early on before the public vaccination programs had even begun.

Again, this was discussed almost nine months ago:

Covid Updates

COVID Re-infections and the Vaccine

The implications of re-infection on vaccines is a significant issue. The viral-vector vaccines from AstraZeneca and Johnson & Johnson will likely be usable only once. These viral-vector vaccines rely on an engineered active monkey adenovirus, that once injected, will infect host (patient) cells and insert the RNA instructions for the patient’s own cells …

6 years ago · 4 likes · 1 comment · Dale W. Harrison

The Delta Variant Changed Everything!

So after months of being told that the vaccines would prevent you from getting infected, why are “breakthrough infections” now all over the news?

During most of the ramp-up in vaccination over the Spring and early Summer, the level of community infection was at an all-time low. And the Delta-variant had not yet emerged as the dominant infector.

When there are very few people infected, your chance of being exposed is very low. Whether you’re vaccinated or not. So few people who had gotten vaccinated had the chance to be exposed in those first few months.

But the Delta variant has changed EVERYTHING!

Not only are we seeing close to the highest levels of infection and community spread ever recorded, but this virus is extraordinarily more contagious. The viral load being expelled by an infected person is 1000x greater than with the original version of the SarsCoV2 virus.

This is the very first moment where large numbers of the population are vaccinated (~50%) and are being exposed to a large number of infected people with high viral loads.

What was seen in the earliest animal trials was that even after vaccination, if exposed to sufficiently high levels of the virus YOU WILL GET INFECTED!

What was seen in the animal studies 17 months ago is now being seen in the human population. There’s absolutely nothing surprising or unexpected about what’s happening.

Are These Vaccines Different?

No! Many vaccines are “non-sterilizing” and can permit infection and re-transmission.

This is NOT what vaccines are designed to do. Their job is to prevent disease or in the case of the Covid vaccines, severe disease requiring hospitalization. And the Covid vaccines are doing THAT job remarkably well.

Only about 5% of people being hospitalized are vaccinated. Close to 50% are specifically immuno-compromised patients where we know that ALL vaccines work poorly, if at all. And most of the remainder of those fully vaccinated but hospitalized are people in their mid-70s and older. Again, a group for whom vaccines, in general, tend to provide poor levels of immune protection.

But even these people, although requiring hospitalization, are seeing significantly reduced death rates. So even for those where the vaccine is working poorly, it’s still doing its primary job of keeping you alive!

Why Such Confusion?

Many people, even many MDs and healthcare workers, have a naive almost cartoon-like notion that vaccines all look like the MMR (measles) vaccine. A vaccine with near-perfect lifetime sterilizing immunity. This is simply not the case.

Even the polio vaccine is non-sterilizing and will permit infection and re-transmission. But even after 60 years, it has proven to be nearly perfect at disease prevention.

Localized micro-outbreaks of polio occur periodically in the US and Europe but are often never found until much later by immunologists because the infections cause NO disease symptoms.

Polio “the disease” ONLY occurs if the poliovirus jumps into the bloodstream. Polio is ingested orally and colonizes in the lower gut. It can then be expelled in feces and that contamination can re-infect others.

But as long as the vaccine prevents the poliovirus from entering the bloodstream, the person will be completely asymptomatic and never even know they were infected.

The Covid vaccines work EXACTLY like this. They prevent the SarsCoV2 virus from entering the bloodstream and replicating in the major organs (including the lower lung). This prevents Covid pneumonia and the permanent organ damage seen in many people with natural infection.

The vaccines prevent disease, that's what vaccines are meant to do…NOT prevent infection!

This is why the fully vaccinated MUST mask up, distance, and avoid high-risk venues during periods of extreme outbreak like what we're seeing right now across all the southern and southwestern states.

Dangers of “Vaccine Boosterism”

Early in the vaccine rollout, a LOT of irresponsible people made a lot of wild-eyed claims about how nearly perfect the Covid vaccines were.

Some of this was out of complete ignorance. A lot of doctors and medical personnel simply lack a full understanding of the subtleties of how different vaccines actually work.

But much of this was originating from scientific and public health experts who ABSOLUTELY knew they were lying (or at best being extremely “selective” with the truth) in a duplicitous belief that telling fairy tales would convince the vaccine resisters to get vaccinated.

Again, for those following this newsletter, almost eight months ago at the very beginning of the vaccine roll-out, this topic of “vaccine boosterism” and the dangerous precedence that was being set was discussed early on:

Covid Updates

Vaccine Boosterism

5 years ago · 4 likes · 16 comments · Dale W. Harrison

This is a classic mistake of highly educated experts. They imagine they can trick the stupid into doing the right thing without ever grasping just how deep down the well of stupid actually goes.

Lying to the ignorant and the uneducated isn't going to outsmart them...as we're seeing all too clearly in Arkansas and Texas and Florida and Louisana right now!

People should have been told the unvarnished truth from day one! It's never been a happy story and these vaccines were never going to be magical fairy dust.

Even now, the lying continues with the use of terms like "breakthrough infections", which continues to imply that the vaccines are somehow “broken”.

They are NOT breakthrough infections...they are fully normal and expected infections.

If the truth had been told from the beginning, people would NOT have been shocked at their "breakthrough" infections. And the vaccinated would have known that masking and mitigation were going to be a permanent part of their future.

Conclusion

Over the past 18 months, I've gotten a tremendous amount of pushback and outright attacks for being "too negative". What I've tried to do is communicate the emerging scientific evidence in a clear and non-sugarcoated way.

It has seldom been happy news, starting with the early vitriol over the explaining how herd immunity was going to be the magical glitter-farting unicorn that would come and save us all.

Covid Updates

Sweden Burns

Today Sweden reported 5,990 new cases. With a population of only 10M, that’s ~60 cases-per-100,000 population per day.This is now above the US rate and almost 2x the peak daily rates in Texas and Florida back in mid-July during the summer-wave. The Death of Herd Immunity…

6 years ago · 3 likes · Dale W. Harrison

But close to 100% of what I've written about over the past 18 months has now come to pass. And unfortunately, there's a LOT more unhappy news to come. But the sooner people come to grips with the actual reality that we're living, the sooner we can get control of this virus as a society.

The old normal is never returning...but the "new normal" can either be livable with a few precautions, or a non-stop living hell.

Things are entirely capable of getting VASTLY worse than they are right now today if people don't come to grips with what's happening.

And by “worse”, I mean a future SarsCoV2 variant more contagious than any virus ever seen in all of human history with the added ability to jump the vaccines. People need to be prepared for that within the next 2-3 generations of variants.

Right now, each new dominant variant appears and is replaced on a 6-month cycle. So 2-3 generations forward would be somewhere between July to December of 2022.

It's a collective choice...so far, we've chosen very poorly!

About the author:

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Prior Posts...

Delta Summer

Dale W. Harrison — Sun, 25 Jul 2021 17:34:28 GMT

We are now solidly into the 4th Covid wave in the US.

Based on past waves, it should take about 6 weeks to peak and another 8-10 weeks to return to baseline. Which means it's too late to get vaccinated (more on that at the end).

With a 2-week doubling rate (where we currently are), that would suggest a peak around the 1st week of September at or above 200,000 cases/day based on where we are at about 55,000 cases/day right now.

By comparison, last summer's wave peaked at 70,000 cases/day. We are already almost at that prior peak and things have just gotten started!

Last winter's wave peaked at 300,000 cases/day during the 1st week of January 2021 and this wave will likely push into that territory.

The Data

If you look at the graphics below, right now we see cases rising on a week-over-week basis for 100% of US states! With testing rising in 2/3 of states.

More ominously, the prevalence rate in the southern states is out of control. With most of the southern states running between 40 to 65 cases-per-100k population per day. Texas is at 25 cases per-per-100k! By contrast, the highly vaccinated northeastern states remain largely unaffected. So we are right now in the opening stages of the next major wave.

The Unvaccinated

I would expect to see about 10-12M Covid cases between now and early October, by which time we will return to a low baseline. That's equal to a THIRD of all diagnosed cases since January 2020! So this should be a major wave.

90% of that will be in the unvaccinated population with very little in the vaccinated population. Those most at risk in the vaccinated population will be everyone over 65 because vaccines in general work rather poorly in that age group, including the SarsCoV2 vaccines. As well as anyone with one or more co-morbidities, especially obesity and Type-II diabetes.

65%+ of these cases will be in only about a dozen southern red states. The US has 176M people unvaccinated with about 40% of those concentrated in just 12-15 southern and southwestern red states.

And if you take the under-12 population out of the picture, the divide is vastly starker than these numbers make it appear.

It's not 10-year-olds who are crowding into bars and gyms and restaurants. So the fraction of the adult population engaging in full-risk behavior in the southern red states is still quite high and still the overwhelming majority. More so than the raw percent-vaccinated numbers would indicate.

The Social Divide

There's increasingly a social divide between the two groups, the vaccinated and the those who refuse, with increasingly little social mixing.

Personally, I'm entertaining again, but I will not attend any events with unvaccinated individuals nor will I allow an unvaccinated person inside my house.

This seems to be a growing social pattern. Vaccinated socialize with vaccinated...while those who think the vaccine is the Mark of the Beast with Bill-Gates-Microchips® all flock together separately.

And because of these changes in social dynamics, the fully vaccinated population is probably near herd immunity, while the unvaccinated population will see ZERO social herd immunity benefits from those already vaccinated.

The social benefit of reduced prevalence and reduced risk of exposure that public vaccination programs confer only work if there's full social mixing between the groups.

This is why measles has been kept to as low a level as it has been...in spite of anti-vaxxer idiots. There's full mixing between the populations, so few at-risk targets ever come into contact because they're buffered by a largely vaccinated population.

Your Herd Immunity is Only as Good as the Herd You Hang With!

So the 176M unvaccinated, all crowding together maskless into restaurants, bars, and gyms will face an exposure risk identical to late last year before the vaccines were available.

Too Late to Increase Vaccinations

Finally, it's largely too late to get vaccinated. If you rushed out to get vaccinated today, it would be late August before you could get your 2nd shot, and early-to-mid September before you'd be protected.

You'd still have partial protection by the time things peak and would be protected during the wind-down phase in September and October, but time has largely run out.

People's best bet is to mask and dial back on most social activities (especially in indoor venues).

Personally, I'm fully masking again and switching to 3M 1860 respirators and am have stopped outside activity. So I'm increasingly just hunkering down until this thing runs its course by October.

The Winter Wave Next

Also, expect an even larger winter wave coming by late November through mid-January. What's increasingly clear, is this is NOT a seasonal disease, but a virus whose disease dynamics are almost entirely human-driven.

This is essentially an indoor virus. And summer is the indoor season in the South and winter is the indoor season in the North (and in the South during Jan-Feb).

It's that human dynamic coupled with political willingness to engage in mitigation behavior that explains almost all of the disease dynamics, including the political forces actively discouraging widespread vaccination.

We are on a 6-month full viral replacement cycle...where an entirely new adaptive variant appears and spreads to 100% of cases within a 6-month window. Only for that cycle to repeat again 6 months later.

So expect to see a matching every-six-month Covid wave for years to come. One in the summer hitting the southern and southwestern states...and one in the winter hitting all states except those at 80% to 90% vaccination levels.

This virus is now fully endemic and never going away and will likely remain an entirely new 3rd leading cause of death in the US for the remainder of our lives at 200,000 to 300,000 Covid deaths a year!

Places like Boston, Vermont, Connecticut, Seattle, San Francisco that are reaching 80%+ vaccination rates will be almost entirely spared.

Places like Texas and Florida with political leadership fighting to keep the virus spreading…and places like Mississippi, Alabama, Arkansas with only 1/3 of the population vaccinated will be 3rd-world hell-holes...

About the author:

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500,000

Dale W. Harrison — Mon, 22 Feb 2021 15:06:07 GMT

The US approaches a new grim milestone in the epidemic…

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Vaccine Boosterism

Dale W. Harrison — Sat, 06 Feb 2021 20:53:05 GMT

We are now entering a new phase of the pandemic with the arrival of the initial vaccines. Vaccines that have proven to be quite effective and quite safe.

For much of the pandemic, those trying to minimize the seriousness of the disease, the deniers and the anti-maskers, have relied on lies and fabricated “facts” to push their false-narrative in the face of an ever-increasing death toll.

What we should have learned over the past year is that the best attack against the lies and the denials is clear explanations of the unvarnished truth backed by hard data.

A truth that is not always happy, and not always what people would prefer to be told. And data that is seldom black & white. Part of explaining the science is also not stripping away the nuance and the complexity. Personally, that’s what I’ve tried to do with these articles.

But what never works is fighting the BIG LIE with your own lies and your own fabricated data. That seems obvious, but it’s clearly not a lesson that’s been well learned.

TL;DR: This is a longer article (~2500 words), but I want to discuss this particular piece of fraudulent vaccine boosterism that’s been making the rounds and why it’s both factually incorrect and meaningless as a piece of data…and how its sole intent is to deceive and not communicate truthful information…

The Vaccine Potential and the Obstacles

Vaccines are a key tool in the fight to bring the epidemic under better control. We are never going back to 2019, that door is forever closed. But we have the chance to craft a more livable 2022 or 2023 ahead of us.

For vaccines to have a chance of creating societal change, we need high levels of vaccine compliance. Likely above 90% for any chance of a return to normal social exchange given the new mutational variants.

But many experts correctly see both the anti-vaxxer movement and the newer anti-vaccine Covid deniers as key obstacles to reaching effective levels of vaccination. With well-funded institutions such as the AEIR and Hoover Institute (who gave us the genocidal policies of Scott Atlas) pushing anti-vaccine messaging.

With the CDC finally able to speak freely, we are beginning to see efforts at countering this anti-vaccine messaging with solid, albeit uninspiring, public health messaging. This is a positive step forward and should have started 10 months ago!

The Vaccine Cheerleaders

But increasingly, there’s a vocal group of “vaccine cheerleaders” amongst journalists, doctors, and even some scientists who have decided that telling lies and fabricating facts is the best way to combat people who…tell lies and fabricate facts!

Over the past couple of weeks, in the pages of the New York Times and Washington Post, as well as across Twitter and Facebook, we’ve been presented with some of the worst examples of what I’ve come to call “Vaccine Boosterism”.

And this has been abetted by some highly irresponsible corporate PR on the part of several of the vaccine companies, with Johnson & Johnson being the most disreputable.

And as an aside: It’s important to point out that lies can be told even when making “technically true” statements, as any lawyer can tell you.

It’s “technically true” that no one who’s been given a SarsCoV2 vaccine has yet died of Ebola. But a meaningless and irrelevant statement and highly misleading if said in a way to suggest any such protection.

Much of this misleading information, and outright lies, are being echoed on social media by people apparently smart enough to earn an advanced degree, but not smart enough to read the Clinical Study Protocol documents or even do a couple of simple Google searches to confirm their assertions.

What The Vaccines Trials Can Tell Us

It’s a useful exercise to actually read the Clinical Study Protocol documents that were the controlling documents for the vaccine Phase III trials as well as the FDA reports submitted for EUA certification of the vaccines.

The pharmaceutical companies are FAR less likely to play fast and loose with the facts in a legal filing with the FDA than what gets pushed out of the corporate public relations department.

These are not easy documents to read, but anyone with a high school education can grasp 90% of what they say. I will include below links to all of them.

The results from the vaccine trials have been promising, both in terms of efficacy and safety. But the vaccines DO NOT represent some miracle cure that will roll the clocks back to 2019.

Here is what the trials can tell us:
The vaccines appear to provide a fairly high level of protection for at least up to two months from mild-to-moderate symptomatic disease, though somewhat lower levels of protection for those above 65 years of age. And the vaccines appear to produce no short-term adverse effects within two-weeks of vaccination.

That is ALL the vaccine clinical trials can say with any reasonable certainty! Duration will probably last longer and side-effects will probably remain rare, but those are guesses based on absolutely no data available from the vaccine trials.

The bottom line is this: NO therapeutic has perfect effectiveness…and NO therapeutic is entirely devoid of risk!

These vaccines are one tool in the toolbox to fight the virus. Just like wearing a mask, it has the potential to be an effective tool if widely used, but not a perfect tool.

What The Vaccines Trials CANNOT Tell Us

In the FDA filing documents for EUA certification, certain conclusions were explicitly excluded because the data was simply lacking.

These included:

Impact of the vaccines on mortality
Effectiveness of the vaccines to prevent infection
Effectiveness of the vaccines to prevent hospitalizations
Duration of vaccine protection beyond 2-months
Vaccine adverse effects beyond 2 weeks (most vaccines adverse effects appear within 6 weeks)

They explicitly stated that the size of the study population and the duration of the studies, as well as the detailed nature of what was being measured prevented any meaningful statements about either infection or more severe disease leading to hospitalization or death.

To quote directly from the EUA filing Pfizer submitted to the FDA:

Vaccine effectiveness against mortality
“A larger number of individuals at high risk of COVID-19 and higher attack rates would be needed to confirm efficacy of the vaccine against mortality.“

”Benefits in preventing death should be evaluated in large observational studies following authorization.”

Vaccine effectiveness against transmission of SARS-CoV-2
“Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination.“

”Additional evaluations including data from clinical trials and from vaccine use post-authorization will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.”

Phase 3 follow-up
"Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt. Therefore, a 2-month follow-up period may allow for identification of potential immune-mediated adverse events that began within 6 weeks of vaccination.”
“From the perspective of vaccine efficacy, it is important to assess whether protection mediated by early responses has not started to wane. A 2-month median follow-up is the shortest follow-up period to achieve some confidence that any protection against COVID-19 is likely to be more than short-lived.”

It’s always useful to see what pharmaceutical companies have to say when submitting legal documents to Federal agencies under felony penalty for perjury!

Vaccine Boosterism

So back to the original graphic. This is one of the more egregious items being pushed by those who seem to think lies are the best tool to fight back against people who lie.

First of all, this graphic is factually incorrect! Secondly, it’s a lie by omission as ongoing data during vaccine deployment directly contradicts the false messaging this graphic is attempting to convey.

There have been both hospitalizations of those vaccinating (both during the trials and post-authorization) and at least two deaths due to adverse reaction to the vaccine, one of which has been fully confirmed.

But even if this was NOT fabricated data and was NOT being used to promulgate a lie, it would still be completely meaningless nonsense data. The size and duration of the vaccine trials meant that any data around the vaccines’ impact on hospitalizations, Covid deaths, or deaths directly from the vaccine could not be statistically distinguished from randomness.

Here’s an analogy. How can you tell if you’re holding a fair coin? By flipping it. Ok, you flip it and get “heads”. Is it a fair coin? Who knows?

You flip it again and get “heads” again. Is it a fair coin? You have NO idea!

The answer is, you haven’t flipped it enough to tell the difference between completely random events and what you might expect if it were not a fair coin. It takes a LOT more flips of the coin before you can distinguish a pattern from simple randomness.

Clinical study trials are EXACTLY the same…only a lot more complex.

Why ZERO Deaths a Meaningless Number

A bit of math, but easy to follow…

If you pick 1,000 random people who’ve been medically diagnosed with Covid, how many will end up being hospitalized? The answer is about 30 to 50 depending on region.

So another question. By the time the vaccine trials ended, how many of those who had actually gotten the vaccine had been diagnosed with Covid? This is the basis of the efficacy claims and the FDA EUA approvals.

Here’s a rundown:

Moderna – 11 Cases (94% vaccine efficacy reported)
Pfizer – 8 Cases (95% vaccine efficacy reported)
Novavax – 6 Cases (89% vaccine efficacy reported)
AstraZeneca – 63 Cases (76% vaccine efficacy reported)

Based on those rather low numbers, what’s the likelihood of seeing one or more of those Covid cases hospitalized during the study period based on a 3% hospitalization rate typical for non-vaccinated Covid cases:

Moderna – 28% chance
Pfizer – 22% chance (one case requiring hospital treatment, but not full hospitalization)
Novavax – 17% chance
AstraZeneca – 85% chance (they had two cases requiring hospital treatment)

And what’s the chance of at least one of those people dying from Covid:

Moderna – 10% chance
Pfizer – 8% chance
Novavax – 6% chance
AstraZeneca – 47% chance

All well less than the toss of a coin!

By comparison, across all four studies, in the placebo group, there were 553 Covid cases and 5 deaths. Out of 553 Covid cases, there’s a 99.7% chance of at least one death.

Versus out of the 88 Covid cases in the vaccine group, there was only a 58% chance of seeing one death. Not much different than the chance of a coin coming up head on a single toss!

Based on these numbers, it is simply impossible to distinguish randomness from something being caused by the vaccine. It’s like flipping a coin once and then asking if it’s a fair coin…no one can know!

Bottom line: The probability of seeing even a SINGLE hospitalization or much less a SINGLE death in the vaccine arm of any of the trials was quite low.

And this was explicitly stated in the Clinical Study Protocol documents. In fact, the stated expectation for the AstraZeneca trial was it would need to run for 730 days before vaccine impact on mortality could be measured! The trial results were reported out after running only 103 days.

The Noble Lie & Damaged Reputations

At least some of the people pushing this vaccine boosterism consciously KNOW they are pushing lies.

The journalists probably less so, they lack either the education or the minimal level of curiosity to know the difference but are certainly guilty of amplifying the lies. The MD’s promulgating this nonsense are harder to understand. Basically, doctors are not scientists and can’t be expected to be fully versant on any of the underlying science, but should still be capable of doing a Google search and knowing better.

People’s reputations are going to be damaged by pushing these lies and this false-narrative around these vaccines having 100% effectiveness and perfect safety. Neither is true. Plus, these are entirely unnecessary lies…the vaccines are reasonably effective and have proven to be quite safe.

That’s a perfectly acceptable story to tell. The deception and the lying is an arrogant disregard for the truth and an elitist assumption that people are too stupid to know they’re being lied to.

We should have learned the danger of the “Noble Lie” from the early days of the epidemic during the “no one should buy a mask” period in February and March.

Even someone as unimpeachable as Dr. Fauci has seen his reputation shredded by knowingly lying to the American public. And continuing to lie well after it was clear to everyone in virology that airborne aerosol transmission was probably the dominant route of infection.

Even though his motives were honorable in trying to manage access to PPE for medical personnel, the reputational damage has been long-lasting.

Conclusions

Encouraging widespread adoption of the vaccine is critical to bring some control to this epidemic. It will NOT bring about herd immunity and it will NOT return us to the world as it was in 2019. But it will save millions of lives and massively relieve the medical system.

But pushing the lie that this is the single miracle cure that will halt Covid and usher in herd immunity is incredibly dangerous and WILL backfire as we have already seen with masks.

Within the next six months, almost all of us will watch someone in our close circle of friends and family who had gotten the vaccine, go on to catch Covid, and potentially even land in the hospital. The vaccine will be effective, but not perfect.

How many of us know multiple people who came down with the flu after getting the flu shot. Once in widespread usage, these vaccines will look far more like the seasonal influenza vaccines than the measles vaccine. Important for diminishing risk, but not a complete safeguard from either infection or disease.

Managing the virus over the next decade will require an unprecedented amount of public health messaging. We will not get there by telling lies, fabricating “facts”, and engaging in happy-talk.

Uncomfortable truths, based on the best available data and science is the best way to tackle the conspiracy mongers, the grifters, and the charlatans. Reputation matters, it can’t be squandered…

Reference Links:

British Medical Journal article:
Will covid-19 vaccines save lives? Current trials aren’t designed to tell us
British Medical Journal article:
Covid-19 vaccine trial protocols released
Moderna Clinical Trial Protocol document:
https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf
Pfizer Clinical Trial Protocol document:
https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C4591001_Clinical_Protocol.pdf
AstraZeneca Clinical Trial Protocol document:
https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf
Johnson & Johnson Clinical Trial Protocol document:
https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol

About the author:

To learn more: https://www.linkedin.com/in/dalewharrison/

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Prior Posts...

Israeli Vaccination Data

Dale W. Harrison — Tue, 02 Feb 2021 17:17:20 GMT

Israel is leading the world in vaccinations with over half its population now fully vaccinated. And they are primarily using the Pfizer mRNA vaccine with a reported 95% vaccine efficacy based on the Phase III trials.

Here's a key statistic from the Israeli Ministry of Health report:

"...out of a group of 715,425 Israelis fully vaccinated, only 317 — 0.04% — got infected with the virus at least one week after their second shot, and 16 were hospitalized with serious symptoms."

Why is the data important?

This data is significant for two reasons:

This is the first large-scale tracking of post-vaccination Covid diagnoses in a general population
This is a large enough fraction of the total population that full-population comparisons can start to be made.

What we’ve seen so far are highly-controlled drug trials with carefully selected populations. Generally, when a therapeutic is rolled out to the general population, it will underperform the results seen in such highly-controlled studies.

With vaccines, what’s seen during a controlled trial is called “vaccine efficacy” versus “vaccine effectiveness”, which is what’s seen when that same vaccine is deployed across the general population. And “effectiveness” will always be less than the “efficacy” seen in the trials.

Secondly, Israel is the first country to go significantly beyond just vaccinating the elderly and high-risk populations. So their early data is valuable to get a sense of what a full vaccine deployment might look like in terms of actual vaccine effectiveness.

So what does the data say?

The tracking data looked very narrowly at a one week period following the 2nd vaccine injection. This was a cohort study, which means that one week of data for each individual participant is scattered over the roughly two months of the study.

But it’s still a single week of surveillance.

So if we annualize the case count, that's 317 cases x 52 weeks or ~16,500 cases expected over a one-year period. This is in a population of 715,425 or about a 2.3% rate of being diagnosed with Covid in a one-year period.

So to compare this with the US, let's assume we get 100% of the US population vaccinated and we scale the Israeli results up to the full US population of 330M.

That would imply about 7.6M diagnosed cases in a year with a fully vaccinated population. The US actually saw 26M diagnosed cases over the past year. This implies a "vaccine effectiveness" of only about ~70%.

So why the 95% vs 70% discrepancy?

"95% Vaccine efficacy" is what was reported out of highly controlled trials involving specially chosen test populations having the vaccine administered under highly idealized conditions.

"Vaccine effectiveness" is what happens when that same vaccine is administered to the general population. It is not surprising to a 30% drop-off, especially for vaccine trials involving upper-respiratory pathogens.

It’s also important to understand these are “population statistics” and can in NO way be applied to individuals. 70% might mean that everyone has an equal level of protection…or it might mean that 70% of those vaccinated have perfect protection and 30% have zero protection. Or anything in between…there’s simply no way to apply such population statistics to predict the risks any single person might face.

So the Israeli results cannot be called great or amazing (as many of the press reports have done)...but are certainly fully in alignment with expectations.

What about hospitalizations?

So the Israeli surveillance data also included hospitalizations and that data looks far less promising.

16 out of the 317 diagnosed cases resulted in hospitalization. That is a ~5% hospitalization rate.

By comparison, right now in the US, we are running between a 3% to 5% hospitalization rate for diagnosed Covid depending on region.

These numbers (just 16 cases) are fairly small and the time period of the data is quite short, but it looks like the vaccine is not offering any benefit if a vaccinated person actually goes on to develop Covid.

It’s important to remember that none of the vaccine trials looked at either hospitalization or deaths. The Clinical Study Protocols explicitly stated that the trials were too short and with too small a population to make any determination of whether the vaccines might reduce either hospitalization or death.

It’s not clear what this means, but one possible explanation is some fraction of those vaccinated ended up with very little protection and when infected look essentially like those in the unvaccinated population. But too early to draw any real conclusions.

Conclusions

This data is still quite preliminary and suffers from both a relatively small population (175,000 subjects) and short duration of follow up (1 week) but indicates that the Pfizer vaccine should be expected to:

Reduce the risk of diagnosed Covid by ~70%
But show no reduction in the risk of severe disease requiring hospitalization if the vaccinated person goes on to develop Covid.

If this 70% “vaccine effectiveness” number holds, and I think it likely will, then this will be the high-water mark of therapeutic protection for the foreseeable future.

This should be coupled with the experimental evidence that none of the vaccines confer effective sterilizing immunity. Meaning the vaccines will not effectively prevent infection and re-transmission, though such infection will be somewhat reduced and likely be asymptomatic or quite mild.

This means basic mitigation, wearing a mask, distancing, and avoiding high-risk venues will likely remain MORE effective than the best vaccines!

Btw…this mirrors the former CDC Director Dr. Redfield’s Congressional testimony back in late August after he’d seen the early Moderna and Pfizer data and the animal studies.

I want to state clearly, this is NOT a case against getting vaccinated!

I'm trying to take a hard look at the early available data and paint a realistic picture to counter some of the uninformed vaccine boosterism being promulgated in the press right now in a misguided attempt to counter the anti-vaxxer nonsense.

People aren't stupid and we'll all see this play out over the coming months as we witness friends and family who are vaccinated go on to catch Covid. Vaccines against upper-respiratory viruses will never be 100% effective.

We see this played out annually with the seasonal influenza vaccines…and we all know multiple people who went on to get the flu after having gotten vaccinated. This will not be substantially different.

But naive boosterism (even for the best of intentions) is a dangerous game that will come to backfire in the same way as the "don't go buy a mask" line did back in February and March.

Getting the vaccine remains absolutely vital…in addition to ongoing mitigation. The analogy I use is that if you're going into a gunfight, you have three choices:

show up in a snarky t-shirt
wear a bullet-proof vest
or duck behind cover.

Only an idiot would choose the snarky t-shirt. Smart people would take the bullet-proof vest (the vaccine) and still duck behind cover (the mask and mitigation).

Don't be foolish...do BOTH!

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Prior Posts...

Covid – YEAR 1

Dale W. Harrison — Fri, 01 Jan 2021 21:39:51 GMT

This is the first of a two-part series looking back at 2020, and forward into 2021.

Predicting the future is always fraught with risks. But I want to take a look back at 2020, discuss how I have made my prediction so far, and then in the next article look ahead into 2021.

Because I work in biotech and in infectious disease diagnostics, I was probably more aware than most of the start of the epidemic in Wuhan starting in December 2019. I had access to both data and to discussions with experts who had been on the ground during the early epidemic in China.

I also have the advantage of formal scientific training and more than 20 years of experience working in the biotech industry. So I have a solid grounding in molecular biology and virology, and good some good exposure to epidemiology and infectious disease. I also have a good knowledge of the history of infectious disease and virology.

This background gave me the expertise to follow the scientific literature and gave me access to knowledgeable colleagues to discuss what we were seeing and reading.

Predicting the Future

I rely on three key elements when trying to understand the future:

What are the underlying dynamics -
how do viruses work, how does infectious diseases spread, what do disease dynamics look like
What's happened historically -
how have similar epidemics functioned historically, how have similar viruses behaved, what has generally happened around the development of testing, vaccines, and treatments?
What's the human factor -
few can grasp change, denial in the face of overwhelming facts is the human norm. And denial always brings out the grifters, the charlatans, the opportunist, and the craven political actors.

The final element is to never attempt to make predictions while still in the grip of denial. The universal human tendency is to project our hopes and wishes and predict a fantasy world where the change we're facing is wished away.

My Journey

I follow a mailing list called ProMED’s that focuses on epidemiological surveillance. It tracks field reports of new emerging diseases and new outbreaks from around the world. So I became aware of the early outbreak in Wuhan in December 2019, through ProMED and through reports from colleagues coming out of China.

At first, I was in denial, thinking this would be isolated inside China, or contained regionally as SARS and MERS had been. But by early January, the level of infectiousness and the rate of spread was extremely alarming.

My personal “epiphany moment” was on January 21st, 2020. That was the date I knew with absolute certainty what was coming what it would imply. We were headed for the biggest global pandemic in a century!

Between late January and the end of February, I canceled all my travel for the year, and began stockpiling a multi-month cache of food, supplies, consumables, medical equipment, and pharmaceuticals that I thought would become in short supply during the coming epidemic.

And on March 10th, I decided to lock-down. I quit going into high-risk public venues, including grocery stores, restaurants, bars, and music venues, and began using a mask whenever I went out in public.

And in early March, I started writing about the epidemic and making predictions as to how things would progress. My initial warnings of what was to come faced an onslaught of derision and denial. But slowly as the year progressed, what had been seen as doom-saying because widely accepted as fact.

In fact, my predictions have consistently under-estimated the facts as they unfolded.

2020 Predictions

In the first three months of March, April, and May, I begin to write about what I saw as the unfolding course of events for 2020 based on my own evolving understanding of the rapidly progressing scientific literature. Most turned out to be highly accurate...

So here are some of my key early predictions:

Airborne-transmission would be the primary route of infection
Asymptomatic-spread would be a significant infection risk
The virus would have a high level of contagiousness just short of smallpox
Universal masking was the best hope for containing the spread
No seasonality - the virus would be active year-round through the warm months
Death rates 10x that of seasonal influenza
Waning immune protection within 3-6 month with the risk of re-infections
A rate of spread of between 1% to 2% per month of the US population (10-20M cases by the end of the year) even with unprecedented levels of mitigation
Hospitals and medical capacity would be overwhelmed by localized outbreaks
Between 300,000 to 350,000 deaths by the end of the year
Herd immunity was would NOT occur through natural infection
Even with a vaccine, herd immunity might still never be possible
There would be no magical cross-immunity from common colds
Viral mutation was NOT going to be an issue, coronaviruses are slow mutators
Effective vaccines would not be available until 2024 (entirely wrong on this one)

Most of this was based on a few facts and intuitions:

Early spread-rate in China meant extremely high levels of contagiousness (R0>3)
Coronaviruses durable immunity is always short (2-6 months)
Seasonality is based on low R-values, SarsCoV2 had a very high R0-value
No effective vaccine had ever been developed for a human coronavirus
The Spanish Influenza infected 20M people in 19 months (1% per month spread)
Early death rates in China, Italy, and Iran implied an IFR well above 1%
Exponential grown will ALWAYS overwhelm finite resources
There has never been a SINGLE case of naturally occurring herd immunity!
Coronaviruses are slow mutators due to its proof-reading enzyme
The shortest time to develop a vaccine in history was 4-years.

Most of the early predictions has turned out to be entirely correct:

20 Million cases in 10 months (2% per month spread)
350,000 deaths (on the high-side of my April prediction)
No herd immunity (an incredibly stupid idea from day-one)
Bodies in refrigerator trucks (because hospitals and morgues are overwhelmed)
Uncontrolled spread even in the face of significant mitigation efforts

The biggest miss was the unexpectedly rapid development of what looks like a series of highly effective and safe vaccines.

The key to early accurate predictions was based on:

Knowing the science
Knowing the history
Following the research as it evolved
Not being in denial – looking at the world without emotional blinders to see what's actually there, not what one might emotionally hope and wish for!

Predicting 2021

The next of this two-part series will look at predictions for 2021. I will go into depth as to what I see coming and the reasoning behind how things may play out in 2021.

But for now, here a short preview:

Things will NOT go back to “normal” next year!
There will be popular pressure to remove all mitigation measures
There will be a failure to convince large parts of the population to get vaccinated
Next year's death toll will be as high or higher than in 2020
There will be NO herd immunity next year...or in the future
The virus will likely go fully endemic with 20M cases/week by next Winter
As vaccination rates increase, the Covid death-rate will also increase
Masking will need to be a permanent fixture, even for those vaccinated.
Covid will remain the 3rd leading cause of death indefinitely
Covid will end up as a disease as common as the cold, but as deadly as the flu!

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New UK Coronavirus Variant

Dale W. Harrison — Sun, 20 Dec 2020 19:51:58 GMT

There is now new data from the Journal Cell on the new SarsCov2 variant being seen in southern England based on recent whole-genome sequencing studies.

Viral mutations are like selling real estate…it’s all about location…location…location.

Mutations are essentially typos in the viral genetic code. This most often occurs right after the virus enters a cell and makes copies of its RNA payload through a process called “RNA replication”. Coronaviruses are generally quite resistant to mutations because they carry what’s called a “proofreading enzyme” that can detect and correct for typos.

Most mutations are so-called “synonymous mutations” and are completely benign and don’t alter the meaning or function of the particular stretch of genetic code. But some can create significant functional alterations.

For example, the single-letter typo in “acceptable” vs. “acceptible” is far more acceptable than the single-letter typo in “duck” vs. “fuck”. Same amount of typos…very different results.

What we have with this new SarsCoV2 variant is the “oh duck” sort of typo…not good!

Preliminary Results

The new variant has been labeled VUI-202012/01 and has:

17 functional single-nucleotide variants (8 on the S-gene)
6 variants and 2 deletions in the S-gene (which codes for the spike protein)
6 “synonymous mutations” in ORF1ab and the M-gene (no big deal)
An Orf8 truncation that leaves the virus open to more mutations
71% increase in contagiousness
~2.5x increase in R-value (still very preliminary)
4x higher average viral load
exhibiting exponential growth even during full lockdown (bad!)
currently accounting for 62% of cases in London
no increase in severity of illness (which is a good thing)

So a couple of interesting points. First, this variant has accumulated a huge number of mutations in a very short period of time and this is quite surprising to see.

But the most concerning mutations are on the S-gene that carries the instructions for building the spike protein used by the virus to enter cells and used by the vaccines to target the virus.

What Does This Mean?

The virus is rather like a burglar with a lockpick trying to break into your cells. The lockpick is the spike protein that’s used to pick the lock on the front door.

Now let’s say there are a 1000 burglars in your town and suddenly 10 of them got hold of a set of REALLY good lockpicks that makes it a LOT easier to do a break-in. Pretty soon, those 10 burglars would be responsible for almost all the burglaries in town.

This is what’s happening in London right now! These S-gene mutations seem to let the virus break into cells far more efficiently and far quicker than before.

This means a few things:

this variant will be far more contagious
it will infect a person far faster
the viral load will grow faster and to higher levels

However, because the spike protein doesn’t play a role in disease severity, this mutation doesn’t appear to have created a more lethal version of the virus…just a far more contagious version.

Does This Effect the Vaccine?

In short…NO! It’s still a bit too early to know absolutely, but it’s almost certain to have no significant impact on the effectiveness of the vaccine.

The vaccine is designed to look for a large block of amino-acids (about 650+) that make up the head of the spike protein. These mutations result in 2 isolated amino-acid deletions and 4 amino-acid alterations. Such minor changes should have no impact on the ability of the vaccine to find and bind to the correct epitope (the part of the virus the vaccine is targeting).

How Did This Happen?

The sudden appearance of a large group of mutations in an otherwise slow mutating virus is concerning and raises the question of how it might have occurred.

The working hypothesis is that it came from a single infected individual. This person was likely immuno-compromised (due to some unrelated condition) and sustained a long-term severe infection from SarsCoV2. This would provide the right environment for a wide range of mutations to develop.

At some point, the patient was likely treated with Convalescent Plasma and/or Remdisvir. This cleared most of the more normal variants of the virus but left a more highly resistant and more aggressive strain behind that then fully re-infected the patient. And at some point, this variant got spread to other individuals and became a new highly contagious wildtype.

To quote from the research paper:

“What evolutionary processes or selective pressures might have given rise to lineage B.1.1.7?
High rates of mutation accumulation over short time periods have been reported previously in studies of immunodeficient or immunosuppressed patients who are chronically infected with SARS-CoV-2 (Choi et al. 2020; Avanzato et al. 2020; Kemp et al. 2020). These infections exhibit detectable SARS-CoV-2 RNA for 2-4 months or longer (although there are also reports of long infections in some immunocompetent individuals). The patients are treated with convalescent plasma (sometimes more than once) and usually also with the drug remdesivir. Virus genome sequencing of these infections reveals unusually large numbers of nucleotide changes and deletion mutations and often high ratios of non-synonymous to synonymous changes. Convalescent plasma is often given when patient viral loads are high, and Kemp et al. (2020) report that intra-patient virus genetic diversity increased after plasma treatment was given.”

“Under such circumstances, the evolutionary dynamics of and selective pressures upon the intra-patient virus population are expected to be very different to those experienced in typical infection. First, selection from natural immune responses in immune-deficient/suppressed patients will be weak or absent. Second, the selection arising from antibody therapy may be strong due to high antibody concentrations. Third, if antibody therapy is administered after many weeks of chronic infection, the virus population may be unusually large and genetically diverse at the time that antibody-mediated selective pressure is applied, creating suitable circumstances for the rapid fixation of multiple virus genetic changes through direct selection and genetic hitchhiking.”

“These considerations lead us to hypothesise that the unusual genetic divergence of lineage B.1.1.7 may have resulted, at least in part, from virus evolution with a chronically-infected individual. Although such infections are rare, and onward transmission from them presumably even rarer, they are not improbable given the ongoing large number of new infections.”

Reference Links

From the Journal Cell:
Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

From New Scientist:
What you need to know about the new variant of coronavirus in the UK

From the British Medical Journal:
Covid-19: New coronavirus variant is identified in UK

From the COVID-19 Genomics Consortium UK:
Update on new SARS-CoV-2 variant and how COG-UK tracks emerging mutations

Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations

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Results from the AstraZeneca/Oxford Vaccine Trials

Dale W. Harrison — Tue, 15 Dec 2020 21:59:13 GMT

The preliminary results from the Phase III trials of the AstraZeneca/Oxford Covid-19 vaccine were just published in the Journal Lancet. At a high level, the results closely mirror both the Pfizer and Moderna vaccine studies. The AstraZeneca vaccine is 90%+ effective at protecting against severe symptomatic illness.

But there are some really interesting additional data included in the study report that goes well beyond what was seen in the Pfizer and Moderna studies. Specifically, the very first data from human studies examining sterilizing immunity and some quite interesting data on re-infection rates.

TL;DR – the key findings in this area are:

The vaccine confers little or no protection from infection by the virus
Re-infection by the virus occurs at the same rate as first-time infections

These two findings point to some serious implications (discussed below):

No possibility of achieving herd immunity
Full endemic spread of the virus through the population
Potential to see the weekly death rate increase as vaccination levels increase!

I’ll explore each of these findings below, but first, let’s look at a quick summary of the key results of the AstraZeneca/Oxford vaccine trial…

Key Findings

11,636 participants were tracked over a 133-day period with a 90% vaccine efficacy against moderate-to-severe symptomatic disease. There was a high incident of short-term moderate-to-severe adverse reactions, but none that represented any health threat. There were no adverse effects that represented serious health or safety issues.

There is no information on duration beyond the 2-months of protection also seen in the other vaccine trials. These vaccines almost surely have a longer duration, likely 6-12 months, but due to the brief length of the trial, this is all the data available.

These results are nearly identical to what has been reported out of both the Pfizer and Moderna mRNA vaccine studies and show a potential 3rd highly effective vaccine candidate. This is very good news!

Vaccine Technology

This vaccine is a viral-vector type vaccine, a different vaccine technology than the Pfizer and Moderna mRNA vaccines. It is a recombinant replication-defective chimpanzee Ad5-adenovirus expressing the SarsCoV2 S-gene.

Essentially a chimpanzee adenovirus (Ad5 strain) that’s been genetically altered to prevent the virus from replicating, with additional genes inserted designed to produce copies of the SarsCoV2 spike-protein once the adenovirus has been injected and infects host cells.

One issue with this technology is those receiving this vaccine will develop an immune response to the chimpanzee adenovirus, rendering the virus unusable for future re-vaccinations. You literally develop an immune response against the vaccine itself in addition to SarsCov2. These chimpanzee adenovirus vaccines will also not be effective in sub-Saharan Africa due to the high prevalence of exposure to chimp adenovirus strains.

These are issues unique to viral-vector vaccines and not expected to a problem with the mRNA vaccines from Pfizer and Moderna.

No Sterilizing Immunity

Now for the interesting part of the study. This is the ONLY vaccine trial where participants were tested for SarsCoV2 infection on a weekly basis throughout the trial. That makes this the sole look at whether these SarsCoV2 vaccines are able to confer sterilizing immunity.

Sterilizing immunity is the ability of a vaccine to prevent infection and re-transmission of the virus. This is completely independent of “disease immunity” which measures how well the vaccine reduces symptomatic disease. So far, the prior vaccine trials have explicitly avoided looking at sterilizing immunity.

Sterilizing immunity is a feature of some vaccines such as the measles and HPV vaccines, but is lacking or entirely absent in others, such as the seasonal influenza vaccine.

The Data

The study was split into two sections based on vaccine dosage. One group received a lower dosage initially (LD) and then a larger standard dosage (SD) 3-weeks later. The other group received the larger standard dosage for both injections. Both the vaccine and placebo arms of the trial were then tested weekly for asymptomatic infection by the SarsCoV2 virus.

For those receiving the standard SD/SD protocol, the rate of asymptotic infection was identical between the vaccinated group and the placebo group. Zero sterilizing immunity.

For those receiving the modified LD/SD protocol, the rate of asymptomatic infection within the vaccine group was more than 40% that of the placebo group. Partial ineffective sterilizing immunity.

In addition, of the 66 total cases of infection in the vaccine group, 29 of these were asymptomatic, or 44%. This closely matches data from Moderna’s study.

In the just-released VRBPAC Report on the Moderna vaccine trials, they found a similar ~40% rate of asymptomatic infection. In the case of the Moderna trial, they only tested for infection at the time of each injection 28 days apart. So a less systematic study than AstraZeneca, but with nearly identical outcomes.

To summarize:

SD/SD dosage, equal asymptomatic infection rates between vaccine and placebo groups
LD/SD dosage, vaccine group had asymptomatic infection at 40% of the rate of the placebo group
44% of all infections in the AstraZeneca vaccine group were asymptomatic infection
~40% of Moderna vaccine recipients developed asymptomatic infection between the 1st and 2nd dosage

Evidence suggests that both the AstraZeneca and Moderna vaccines provide only limited sterilizing immunity with a post-vaccination asymptomatic infection rate at roughly half the level of the non-vaccinated population.

This is NOT an unexpected outcome. The early animal vaccine trials back in April and May 2020 with the Pfizer, Johnson & Johnson and AstraZeneca vaccines demonstrated no effective sterilizing immunity in either transgenic mice (genetically engineered mice designed to look like humans to the virus) or in rhesus monkey studies.

From the Lancet paper:

”Asymptomatic infections or those with unreported symptoms were detected in 69 participants. Vaccine efficacy in the 24 LD/SD recipients was 58·9% (95% CI 1·0 to 82·9), whereas it was 3·8% (−72·4 to 46·3) in the 45 participants receiving SD/SD”

From the article in the Journal Nature:

“Another lingering question is whether the vaccine is capable of fighting asymptomatic infections; an immunization that could do that could be key to shaping the course of the pandemic.”

”The data show that the low-dose vaccine regimen was about 60% effective at reducing asymptomatic infections, but it is unclear whether the standard dose significantly reduced them at all.“
“Researchers are concerned about asymptomatic infections because people who have them might unknowingly continue to transmit the virus to others, despite being vaccinated. “
“For now, this is the only study that’s given us data on that,” says Griffin. “And it’s a bit troubling.”

Implications of No Effective Sterilizing Immunity

Lack of effective sterilizing immunity means that asymptomatic infections will allow the continued spread of the virus, despite being vaccinated.

There are a few immediate implications to this lack of effective sterilizing immunity:

There is no possibility of ever achieving herd immunity
The virus will likely go fully endemic with widespread asymptomatic spread
The entire population must be vaccinated or face an extremely high likelihood of unprotected serious Covid-19 illness.
Masking, distancing, and other mitigation measures will have to remain in effect indefinitely to avoid infection and illness, even for vaccinated.

Because vaccinated individuals are only protected from severe symptomatic illness, but not from infection or mild-to-moderate illness, there will need to be efforts to avoid transmission. Especially until at least 90% of the population has been vaccinated.

The SarsCoV2 virus is an extraordinarily contagious virus. We have seen nothing in widespread transmission this contagious in 60 years. Not since widespread measles was eliminated in the early 1960s with the introduction of the measles vaccine. Because the measles vaccine conferred sterilizing immunity we were able to achieve effective herd immunity with only isolated outbreaks among those refusing vaccination.

SarsCoV2 is significantly more contagious than seasonal influenza and quite a bit more contagious than the common cold. We typically see about 40-60 million flu cases a year but over 1 billion colds each year. The average American gets 3 colds a year with ~93% of the population contracting at least one cold a year.

Without ongoing mitigation efforts and with the ability of the virus to continuously re-infect (see the next section), when this virus goes fully endemic, we should expect to see infection rates comparable to the common cold. But with Covid-19 mortality rates likely comparable to seasonal influenza (due to the effective reduction in severe illness once infected).

As common as the cold…as deadly as the flu.

Without ongoing mitigation efforts, this will be a DEADLY combination! Without continued efforts to reduce the spread of the virus, we could actually see the weekly death rate increase as vaccination levels increase. If the death rate drops by a factor of 10x (likely given the efficacy of the vaccines at reducing severe illness), but the overall infection rate rises by 10x or 20x, we would see death rates as high or higher than what’s currently being experienced.

Given the lack of good public health messaging around these issues and the intense political pressure to drop all mitigation requirements once widespread vaccination programs are in place, I fully expect just such an outcome.

If that happens, then SarsCoV2 will become the 3rd leading cause of death in the US for at least the next several years with annual fatality rates in the range of 300,000 to 400,000 per year. Covid-19 deaths will be exceeded only by heart disease and cancer.

Eventually, there will be therapeutics that should reduce the fatality rate, but even then the ongoing load on the health care system will be significant for years to come.

Re-Infection Occurs at the Same Rate as Initial Infection

Now for the second piece of VERY interesting data buried in the study.

All the other vaccine studies attempted to exclude people who had previously been infected. Potential study subjects were screened for seropositivity, meaning they had antibodies from a prior Covid-19 infection. The AstraZeneca study tested for seropositivity but included all these subjects directly into the vaccine study.

And because the AstraZeneca study included weekly testing for infection, this set up an interesting situation where previously infected people could be monitored for re-infection. And this re-infection rate could be compared to the initial infection rate seen in the placebo group.

There were 138 people in the seropositive group (previously infected with Covid-19). Of those, 3 were re-infected during the 4-month period of the study or just over 2%.

Of the 5,829 people in the placebo control group, 101 were infected during the 4-month study period or just under 2%.

These absolute numbers are low, but that has to be seen in the light of the small sample size (10,000 people) and the short duration of the study (~4 months).

Although the absolute numbers are small, this points to two key findings:

Re-infection is possible and not a rare event (otherwise there would have been none in such a small short-duration study)
The risk of re-infection is approximately equal to the risk of initial infection

This is entirely unsurprising given what’s understood about the short duration of immune protection from natural infection and the behavior of all other known corona-like viruses to re-infect (the average person gets 3 colds a year). But it’s nonetheless interesting to see this result drop out of a well-designed and well-controlled study.

Concluding Thoughts

Although these findings are quite counter-intuitive to the popular notions of how vaccines work, such outcomes are not uncommon for many types of vaccines.

As many as half of those who get the seasonal influenza vaccine will be infected, many as asymptomatic carriers of the flu virus. This is a key underlying mechanism behind what experts mean when they talk about the seasonal influenza vaccine being 10% to 40% effective. Although you are somewhat protected against severe illness, a large portion of those with the flu vaccine can and will still get infected each year.

So these outcomes are neither entirely unexpected. I first started writing about the risk of re-infection back in mid-February and I have been writing about the potential lack of sterilizing immunity since mid-June when the first vaccine animal studies showed identical infection rates between vaccinated and non-vaccinated animals during challenge trials (where the animals are deliberately exposed to the virus).

But the public policy implications are significant. If mitigation measures are discouraged or dropped, especially before reaching vaccination levels of 90% or more, we risk dramatically expanding the scope and lethality of the epidemic.

Companion Video

This is a short (4-minute) video of a segment from “This Week in Virology” where the co-hosts discuss the data from the AstraZeneca report and the implications of no effective sterilizing immunity.

It’s interesting to see how these concepts can be confusing and counter-intuitive, even for virologists who are actively involved in Covid and SarsCoV2 research.

Reference Links:

Journal Nature article:
Nature: Oxford COVID-vaccine paper highlights lingering unknowns about results
Journal Lancet peer-reviewed paper on the AstraZeneca vaccine trials:
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
ClinicalTrials.gov:
COVID-19 Vaccine (ChAdOx1 nCoV-19) Trial in South African Adults With and Without HIV-infection
Journal Science article:
More people are getting COVID-19 twice, suggesting immunity wanes quickly
FDA VRBPAC Committee Presentation of the Moderna Vaccine Trials:
mRNA-1273 Sponsor Briefing Document Addendum
Journal Cell peer-reviewed paper on transgenic mice vaccine studies:
A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2
Journal Nature peer-reviewed paper on rhesus vaccine studies:
ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques
This Week in Virology - Episode 693
https://www.microbe.tv/twiv/twiv-693/
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Covid-19 Death Toll

Dale W. Harrison — Fri, 11 Dec 2020 15:28:19 GMT

U.S. Covid-19 deaths hit an all-time high yesterday with 3,124 deaths. This is the equivalent of crashing 20 fully loaded 737-300 aircraft in a single day…one every 70 minutes.

From CDC Director Redfield:

“We are in the timeframe now that probably for the next 60 to 90 days we're going to have more deaths per day than we had at 9/11 or we had at Pearl Harbor,” CDC Director, Dr. Robert Redfield, said during an event hosted by the Council on Foreign Relations.

Links to Pfizer FDA Report & Original Clinical Study Protocol:

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Pfizer Vaccine Report to FDA

Dale W. Harrison — Tue, 08 Dec 2020 19:26:29 GMT

Pfizer has just released a full detailed 53-page report to the FDA reviewing the results of the Phase I/II/III clinical study trials for their Covid-19 vaccine BNT162b2. What follows is a high-level 5-page summary of what’s known and not known based on the Pfizer report.

Study Participants:

38,000 participants
Study Duration: 110 days
50% vaccine group: 50% placebo group

Age Range:

60% were under 55 years of age
15% were 55-64 years of age
25% were over 65 years of age

Health Conditions:

35% Obese
35% Overweight
45% With Co-Morbidities

Vaccine Efficacy:

95% vaccine efficacy at least 7-days after the second dosage, where efficacy is defined as a reduction in confirmed mild to moderate symptomatic Covid-19 illness.

From the Pfizer report:

“For participants with and without evidence of SARS-CoV-2 infection before and during vaccination regimen, VE against confirmed COVID-19 occurring at least 7 days after Dose 2 was 94.6%, with 9 and 169 cases in the BNT162b2 and placebo groups respectively. The posterior probability was >99.99% for the true VE being greater than 30%. The 95% credible interval for the vaccine efficacy was 89.9% to 97.3%, indicating that the true VE is at least 89.9% with a 97.5% probability given the available data.”

This graph shows the cumulative cases of Covid-19 for the placebo group (red-line) and for the vaccine group (blue-line). So good efficacy even after just a single dose!

Vaccine Ingredients:

VLP – virus-like particle (mRNA encapsulated in a shell of fat molecules)
- Nucleoside-modified messenger RNA (modRNA) encoding the viral spike glycoprotein (S) of SARS-CoV-2
- Lipids ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 2-[(polyethylene glycol)-2000]-N,N-ditetradecylacetamide, 1,2-distearoyl-sn-glycero-3-phosphocholine, and cholesterol)
Buffering Agents (to stabilize pH & provide an injection medium):
- sodium chloride (basic table salt)
- potassium chloride (an electrolyte found in sports drinks)
- monobasic potassium phosphate (also often found in sports drinks)
- dibasic sodium phosphate dihydrate (a common buffer salt)
Stabilizing Agent (used to stabilize the vaccine during storage & transport):
- sucrose (a common plant-derived sugar)
What is NOT in the vaccine:
- NO preservatives (not required for lipid-based VLPs)
- NO adjuvants (the mRNA molecules act as their own adjuvant)

As modern vaccines go, this is an incredibly simple and basic ingredient list!

Adverse Effects:

Adverse effects were generally mild to moderate and of short-term duration and generally worse following the second dose.

Most common adverse reactions were:

Injection site reactions (84.1%)
Fatigue (62.9%)
Headache (55.1%)
Muscle pain (38.3%)
Chills (31.9%)
Joint pain (23.6%)
Fever (14.2%)

Handling & Dosage:

The Pfizer BNT162b2 COVID-19 Vaccine is administered intramuscularly (IM) as a series of two 30 μg doses (0.3 mL each) 21 days apart.

“The Pfizer-BioNTech COVID-19 Vaccine is supplied as a frozen [between -80°C to -60°C (-112°F to -76°F)] multi-dose (5-dose) vial. The vaccine must be thawed and diluted in its original vial with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to administration. After dilution, the vial contains 5 doses of 0.3 mL per dose. After dilution, the multiple-dose vials must be stored between 2°C to 25°C (35°F to 77°F) and used within 6 hours from the time of dilution.”

Risks & Unknowns - Summary:

Duration of Protection: Up to 2 months (study ran for only 110 days)
Immunocompromised individuals: Unknown, no data - too few participants
Individuals previously infected: Unknown, those with existing antibodies were excluded from the study
Pediatric Patients (under 16): Unknown, those <16 were excluded from the study
Pregnant or lactating individuals: Unknown, excluded from the study
Future vaccine effectiveness due to virus mutations: Unknown, study period too short to see the effect of potential mutations
Long-term effects of COVID-19 disease: Unknown, not looked at in the study
Asymptomatic infection: Unknown, not looked at in the study
Effectiveness against mortality: Unknown, study size too small and too short in duration to determine vaccine impact on Covid-19 death rate
Vaccine effectiveness against transmission of SARS-CoV-2: Unkown
Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination.

If efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask-wearing and social distancing could result in significant continued transmission.
Vaccine-Induced Disease Enhanced: Unknown
Risk of vaccine-enhanced disease over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further in ongoing clinical trials and in observational studies that could be conducted following authorization and/or licensure

Risks & Unknowns - Excerpts from the Pfizer Report:

Duration of protection

“As the interim and final analyses have a limited length of follow-up, it is not possible to assess sustained efficacy over a period longer than 2 months.”

Effectiveness in certain populations at high risk of severe COVID-19

“Although the proportion of participants at high risk of severe COVID-19 is adequate for the overall evaluation of safety in the available follow-up period, the subset of certain groups such as immunocompromised individuals (e.g., those with HIV/AIDS) is too small to evaluate efficacy outcomes.“

Effectiveness in individuals previously infected with SARS-CoV-2

“Therefore, available data are insufficient to make conclusions about benefit in individuals with prior SARS-CoV-2 infection. However, available data, while limited, do suggest that previously infected individuals can be at risk of COVID-19 (i.e., reinfection) and could benefit from vaccination.”

Effectiveness in pediatric populations

“The representation of pediatric participants in the study population is too limited to adequately evaluate efficacy in pediatric age groups younger than 16 years. No efficacy data are available from participants ages 15 years and younger.”

Future vaccine effectiveness as influenced by characteristics of the pandemic, changes in the virus, and/or potential effects of co-infections

“The study enrollment and follow-up occurred during the period of July 27 to November 14, 2020, in various geographical locations. The evolution of the pandemic characteristics, such as increased attack rates, increased exposure of subpopulations, as well as potential changes in the virus infectivity, antigenically significant mutations to the S protein, and/or the effect of coinfections may potentially limit the generalizability of the efficacy conclusions over time.”

Vaccine effectiveness against asymptomatic infection

“Data are limited to assess the effect of the vaccine against asymptomatic infection as measured by detection of the virus and/or detection of antibodies against non-vaccine antigens that would indicate infection rather than an immune response induced by the vaccine.
Additional evaluations will be needed to assess the effect of the vaccine in preventing asymptomatic infection, including data from clinical trials and from the vaccine’s use post-authorization.“

Vaccine effectiveness against long-term effects of COVID-19 disease

“COVID-19 disease may have long-term effects on certain organs, and at present it is not possible to assess whether the vaccine will have an impact on specific long-term sequelae of COVID-19 disease in individuals who are infected despite vaccination.

Demonstrated high efficacy against symptomatic COVID-19 should translate to overall prevention of COVID-19-related sequelae in vaccinated populations, though it is possible that asymptomatic infections may not be prevented as effectively as symptomatic infections and may be associated with sequelae that are either late-onset or undetected at the time of infection (e.g., myocarditis).”

Vaccine effectiveness against mortality

“A larger number of individuals at high risk of COVID-19 and higher attack rates would be needed to confirm efficacy of the vaccine against mortality. However, non-COVID vaccines (e.g., influenza) that are efficacious against disease have also been shown to prevent disease associated death.11-14 Benefits in preventing death should be evaluated in large observational studies following authorization.”

Vaccine effectiveness against transmission of SARS-CoV-2

“Data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination. Demonstrated high efficacy against symptomatic COVID-19 may translate to overall prevention of transmission in populations with high enough vaccine uptake, though it is possible that if efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask-wearing and social distancing could result in significant continued transmission.
Additional evaluations including data from clinical trials and from vaccine use post-authorization will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.”

Vaccine-enhanced disease

“Available data do not indicate a risk of vaccine-enhanced disease, and conversely suggest effectiveness against severe disease within the available follow-up period. However, risk of vaccine-enhanced disease over time, potentially associated with waning immunity, remains unknown and needs to be evaluated further in ongoing clinical trials and in observational studies that could be conducted following authorization and/or licensure.”

Phase 3 Follow-up

“Data from phase 3 studies should include a median follow-up duration of at least 2 months after completion of the full vaccination regimen to help provide adequate information to assess a vaccine’s benefit-risk profile. From a safety perspective, a 2-month median follow-up following completion of the full vaccination regimen will allow identification of potential adverse events that were not apparent in the immediate postvaccination period.
Adverse events considered plausibly linked to vaccination generally start within 6 weeks of vaccine receipt.7 Therefore, a 2- month follow-up period may allow for identification of potential immune-mediated adverse events that began within 6 weeks of vaccination. From the perspective of vaccine efficacy, it is important to assess whether protection mediated by early responses has not started to wane.
A 2-month median follow-up is the shortest follow-up period to achieve some confidence that any protection against COVID-19 is likely to be more than short-lived.
The EUA request should include a plan for active follow-up for safety (including deaths, hospitalizations, and other serious or clinically significant adverse events) among individuals administered the vaccine under an EUA in order to inform ongoing benefit-risk determinations to support continuation of the EUA.”

Links to Pfizer FDA Report & Original Clinical Study Protocol:

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Covid-19 Now Leading Cause of Death in the US

Dale W. Harrison — Sat, 05 Dec 2020 19:59:54 GMT

The US has reached another grim milestone. Covid is now accounting for 20% of all deaths in the US, exceeding both heart disease and cancer.

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Stark Recommendations

Dale W. Harrison — Thu, 03 Dec 2020 17:11:30 GMT

The US is currently seeing 430 Covid cases-per-100,000 population per week. This is a truly astonishing level of infectious spread!

In terms of your personal risk of being exposed to an infected person, it’s useful to compare this with the risk of being exposed to seasonal influenza. During a normal flu season, the equivalent risk level would 35 cases-per-100k population per week. The worse flu season in the past 25 years was only at an equivalent of about 100 cases-per-100k population per week.

So your current risk of exposure is 10x greater than in a normal flu season; more than 3x greater than the worst flu season most people have ever experienced. The current level of outbreak represents an infectious risk level beyond anything experienced in modern times…for at least a century or more!

Yesterday, December 2nd, we saw the highest recorded death toll in the US at almost 3,200 people. Over 200,000 new cases were reported with:

30 states have test-positivity rates above 10%
32 states reporting rising case levels

Whitehouse Coronavirus Task Force Report

The Whitehouse Coronavirus Task Force periodically releases a lengthy report with state-level review and guidance. The current Issue 24 dated Nov-29-2020 is 413 pages in length (link at the bottom of this article).

Their current recommendations are stark. Below are a few of the ones included in the report:

They begin with a direct rebuke to the extremely poor performance of many state governors and local officials:

If state and local policies do not reflect the seriousness of the current situation, all public health officials must alert the state population directly.

For anyone over 65 - do not enter indoor public spaces:

If you are over 65 or have significant health conditions, you should not enter any indoor public spaces where anyone is unmasked due to the immediate risk to your health; you should have groceries and medications delivered.

If you attended a Thanksgiving gathering then assume you’re already infected:

If you are under 40, you need to assume you became infected during the Thanksgiving period if you gathered beyond your immediate household.

Most likely, you will not have symptoms; however, you are dangerous to others and you must isolate away from anyone at increased risk for severe disease and get tested immediately.

A call for increased testing and identification of asymptomatic carriers:

The silent community spread that precedes and continues to drive these surges can only be identified and interrupted through proactive, focused testing for both the identification of asymptomatic and pre-symptomatic individuals. This must be combined with significant behavior change of all Americans.

A call for universal use of masks and distancing at all times:

Ensure masks at all times in public; increase physical distancing through a significant reduction in capacity in public and private indoor spaces, including restaurants and bars; and ensure every American understands the clear risks of ANY family or friend interactions outside of their immediate household indoors without masks.

Special vigilance for anyone over 65 who might have been exposed:

If you are over 65 or have significant medical conditions and you gathered outside of your immediate household, you are at significant risk for serious COVID infection
If you develop any symptoms, you must be tested immediately as the majority of therapeutics work best early in infection.

Report Summary for Texas

Texas had 248 new cases per 100,000 population – 38th highest rate in the US.
Texas has a test positivity rate at or above 10.1% – 27th highest rate in the US.
The following 3 counties have the highest number of new cases:
1. Paso County
2. Tarrant County
3. Harris County
These counties represent 33.5% of new cases in Texas.
During the week of Nov 16 - Nov 22 Texas had:
1. 21% of nursing homes had at least one new resident COVID-19 case
2. 38% had at least one new staff COVID-19 case
3. 7% had at least one new resident COVID-19 death.
Between Nov 21 - Nov 27, on average reported as newly admitted each day to hospitals in Texas:
1. 964 patients with confirmed COVID-19
2. 629 patients with suspected COVID-19

Key Recommendations

The COVID risk to all Americans is at a historic high. The national daily COVID incidence after Memorial Day, but before the summer surge, was fewer than 25,000 new cases/day and is now more than 180,000 new cases/day; COVID inpatients then were fewer than 30,000 but are now more than 90,000; fatalities have more than doubled.

We are in a very dangerous place due to the current, extremely high COVID baseline and limited hospital capacity; a further post-Thanksgiving surge will compromise COVID patient care, as well as medical care overall.
If state and local policies do not reflect the seriousness of the current situation, all public health officials must alert the state population directly.

It must be made clear that if you are over 65 or have significant health conditions, you should not enter any indoor public spaces where anyone is unmasked due to the immediate risk to your health; you should have groceries and medications delivered. If you are under 40, you need to assume you became infected during the Thanksgiving period if you gathered beyond your immediate household.
Most likely, you will not have symptoms; however, you are dangerous to others and you must isolate away from anyone at increased risk for severe disease and get tested immediately.

If you are over 65 or have significant medical conditions and you gathered outside of your immediate household, you are at significant risk for serious COVID infection; if you develop any symptoms, you must be tested immediately as the majority of therapeutics work best early in infection.
We are also seeing clear improvement in many European countries that implemented strong public and private mitigation but preserved schooling. We are also seeing states and cities that aggressively mitigated achieving a high plateau and early stability in less than 4 weeks.

However, in many areas of the USA, state mitigation efforts remain inadequate, resulting in sustained transmission or a very prolonged time to peak – over 7 weeks. All states and all counties must flatten the curve now in order to sustain the health system for both COVID and non-COVID emergencies.
The silent community spread that precedes and continues to drive these surges can only be identified and interrupted through proactive, focused testing for both the identification of asymptomatic and pre-symptomatic individuals. This must be combined with significant behavior change of all Americans.

Ensure masks at all times in public; increase physical distancing through a significant reduction in capacity in public and private indoor spaces, including restaurants and bars; and ensure every American understands the clear risks of ANY family or friend interactions outside of their immediate household indoors without masks.
Proactive weekly testing of groups representative of the community (teachers, community college students, county workers, staff in crowded or congregate settings, all hospital personnel, large private sector employers) will help identify the depth and breadth of community infection.

These cases should be triangulated with cases among long-term care facility (LTCF) staff to identify geographic areas with high numbers of asymptomatic and pre-symptomatic cases, which should then trigger widespread testing, identification, and isolation of positive cases among community members, stopping the ongoing spread.

These efforts to identify and reduce asymptomatic transmission should run concurrently with testing of symptomatic persons and contact tracing of cases.
Expand strategic use of point-of-care antigen tests for all individuals that gather across households. Antigen tests perform well in the highly infectious window and will be effective in the identification of asymptomatic and pre-symptomatic infectious cases. Antigen tests do not perform well after 8-10 days post-infection when nucleic acid cycle times are >30.
New hospital admissions in Texas are beginning to peak. Conduct aggressive impact testing of adults under 40 to rapidly identify those who became infected over Thanksgiving before they spread the virus to more vulnerable individuals, driving another round of increased hospitalizations and fatalities.

Full Report for Texas

Link to the Full Report for All 50 States

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How SarsCoV2 Reaches the Brain

Dale W. Harrison — Tue, 01 Dec 2020 17:04:22 GMT

Fully a third of all people with Covid-19 report neurological symptoms such as loss or change in their sense of smell or taste, headaches, fatigue, dizziness, and nausea. There’s been clear evidence of the SarsCoV2 virus being present in brain tissue, but the question has been how did the virus jump from the respiratory tract to the brain.

Recent research just published in the Journal Nature by Dr. Helena Radbruch of Charité's Department of Neuropathology, Dr. Frank Heppner, and a multidisciplinary team of researchers has now traced how the virus enters the central nervous system and subsequently invades the brain.

SarsCoV2 spike protein was found in certain types of cells within the olfactory mucous layer, where it may exploit the proximity of endothelial and nervous tissue to gain entry to the brain. Evidence suggested that olfactory sensory neurons may be directly infected, as well as in the brain areas that receive smell and taste signals. Which can explain a wide range of the well-documented neurological symptoms in Covid-19, including alterations of smell and taste perception well after recovery from the respiratory-phase of the disease.

Interestingly, SarsCoV2 was also found in other areas of the nervous system, including the medulla oblongata, the primary respiratory and cardiovascular control center of the brain. Researchers suggest this could exacerbate impact on respiratory function, adding to breathing problems due to SARS-CoV-2 infection of the lungs.

Quotes from the Lead Researcher

From Dr. Helena Radbruch:

These data support the notion that SARS-CoV-2 is able to use the olfactory mucosa as a port of entry into the brain," says Heppner. This is also supported by the close anatomical proximity of mucosal cells, blood vessels, and nerve cells in the area. "Once inside the olfactory mucosa, the virus appears to use neuroanatomical connections, such as the olfactory nerve, in order to reach the brain.

It is important to emphasize, however, that the COVID-19 patients involved in this study had what would be defined as severe disease, belonging to that small group of patients in whom the disease proves fatal. It is not necessarily possible, therefore, to transfer the results of our study to cases with mild or moderate disease.

Our data suggest that the virus moves from nerve cell to nerve cell in order to reach the brain. It is likely, however, that the virus is also transported via the blood vessels, as evidence of the virus was also found in the walls of blood vessels in the brain.

SARS-CoV-2 is far from the only virus capable of reaching the brain via certain routes. Other examples include the herpes simplex virus and the rabies virus.

In our eyes, the presence of SARS-CoV-2 in nerve cells of the olfactory mucosa provides good explanation for the neurologic symptoms found in COVID-19 patients, such as a loss of the sense of smell or taste.

We also found SARS-CoV-2 in areas of the brain which control vital functions, such as breathing. It cannot be ruled out that, in patients with severe COVID-19, presence of the virus in these areas of the brain will have an exacerbating impact on respiratory function, adding to breathing problems due to SARS-CoV-2 infection of the lungs. Similar problems might arise in relation to cardiovascular function.

the anatomical structures sampled for histomorphological, ultrastructural and molecular analyses including SARS-CoV-2 RNA measurement from fresh (non-formalin-fixed) specimens of deceased individuals with COVID-19. Specimens were taken from the olfactory mucosa underneath the cribriform plate (anatomical region R1, blue, n = 30), the olfactory bulb (R2, yellow, n = 31), the olfactory tubercle (R3, n = 7), different branches of the trigeminal nerve (including conjunctiva (n = 16) and cornea (n = 13)), mucosa covering the uvula (R4, n = 22), the respective trigeminal ganglion (R5, orange, n = 22), the cranial nerve nuclei in the medulla oblongata (R6, dark blue, n = 31), the cerebellum (R7, n = 24) and the carotid artery wall (n = 13)

Additional Scientific References

Research Paper from the Journal Nature:
Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19

Reporting from Genetic Engineering News:
SARS-CoV-2 May Enter the Brain through the Nose

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COVID Re-infections and the Vaccine

Dale W. Harrison — Mon, 30 Nov 2020 19:01:18 GMT

The implications of re-infection on vaccines is a significant issue. The viral-vector vaccines from AstraZeneca and Johnson & Johnson will likely be usable only once.

These viral-vector vaccines rely on an engineered active monkey adenovirus, that once injected, will infect host (patient) cells and insert the RNA instructions for the patient’s own cells to manufacture copies of the SarsCoV2 spike-protein.

The vaccine-induced production of SarsCoV2 spike-proteins then induces a host immune response leading to the production of antibodies in the bloodstream capable of neutralizing the SarsCoV2 virus upon later infection.

But the injection of the adenovirus also induces a separate vector-response. An immune response directed against the adenovirus carrier. Future vaccinations with any of the viral-vectors vaccines will be ineffective as the viral-vector will be neutralized before being able to reach and infect host cells.

Essentially, your own immune system will destroy the vaccine before it can work!

Vaccine boosters will likely be required every 6-12 months indefinitely given the short duration of neutralizing antibodies in the bloodstream (3-6 months) and the uncertainty of the effectiveness of long-term t-cell / b-cell immune memory.

Based on recent work out of the La Jolla Institute for Immunology, some people showed high antibody levels up to 8-months after infection, but others exhibited only a short-lived antibody response. So the immune response to the virus seems quite variable and the researchers were not able to identify any predictors for when a patient would exhibit shorter or longer immune duration.

Due to such variability in immune-response, rather than a fixed time-window for getting a vaccine booster, people will likely need to test themselves monthly for antibody levels (with a simple home test-strip) and schedule a vaccine booster when antibody levels drop below a prescribed level.

And in such a case, the only remaining vaccine option would be one of the mRNA vaccines such as the Pfizer or Moderna candidates. This is the importance of having multiple vaccine candidates based on different vaccine technologies approved and available.

Addendum: The Johnson & Johnson vaccine is built on a rarer adenovirus subtype Ad26. The AstraZeneca vaccine is built on the Ad5 subtype. So it should be possible to still rely on the other viral-vector vaccine for subsequent boosters.

A Covid Researcher Who Re-Infected Himself

Below is an excerpt from an article about the Russian research Dr. Chepurnov and his experience with Covid re-infection.

Prof Chepurnov, who says he first caught coronavirus on a skiing holiday in Italy, became famous in Russia when he used himself as a guinea pig.
He said his personal experiment showed he had antibodies for three months after his first infection, after which they reduced.
He then deliberately exposed himself to Covid patients while not wearing protective gear - and caught it again.
The second bout was worse and he ended up in the hospital with double-pneumonia but has since recovered, he said.
The experiment led him to conclude hopes of "herd immunity" in a population are "overblown" and even that vaccines relying on antibodies might only work for a few months.
He said: "We need a vaccine that can be used multiple times, a recombinant vaccine will not suit.
"Once injected with an adenoviral vector-based vaccine, we won't be able to repeat it because the immunity against the adenoviral carrier will keep interfering."

Link to article:

Covid scientist who ‘infected himself with virus TWICE’ warns of ‘wave of mass reinfections’ as antibodies vanish

Additional Scientific References

Excellent introduction to mRNA vaccines:
RNA vaccines: an introduction

CDC article on the different types of Covid-19 vaccines:
Understanding How COVID-19 Vaccines Work

Recent paper from La Jolla Institute for Immunology on SarsCoV2 immune duration:
Immunological memory to SARS-CoV-2 assessed for greater than six months after infection

Immune response to adenovirus vector:
Adeno-associated viral vector-mediated immune responses: Understanding barriers to gene delivery

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Covid Vaccines Confer No Sterilizing Immunity

Dale W. Harrison — Fri, 27 Nov 2020 19:48:57 GMT

The new Covid vaccines are NOT like what most people imagine a vaccine to be! They will be nothing at all like the measles or smallpox vaccines that actually prevent infection.

This is a topic I've been discussing since July when the initial vaccine animal studies went up on the pre-print servers. None of the current vaccine candidates confers "sterilizing immunity" to the SarsCoV2 virus!

A non-sterilizing vaccinated means that a person can:

Still get infected with the virus
Can absolutely infect others around them
Can still get sick and even die.

The vaccines DO offer "disease immunity" in which the virus will be prevented from jumping to the bloodstream due to the production of neutralizing antibodies. This reduces the chance the disease will have severe effects on the vascular system and major internal organs.

This means your chances of developing severe illness and death are significantly reduced, but not eliminated. You can still get sick and it can still develop into pneumonia and you can still die just like with the flu. But severe illness will be significantly reduced for most people who get vaccinated.

From Moderna’s Chief Medical Officer

Here's a quote from Dr. Tal Zaks, Moderna’s Chief Medical Officer -

“I think we need to be careful, as we get vaccinated, not to over-interpret the results. When we start the deployment of this vaccine, we will not have sufficient concrete data to prove that this vaccine reduces transmission.”

This non-sterilizing effect has been demonstrated in the Moderna, Pfizer, and AstraZeneca vaccines and is likely a feature of all 1st-generation Covid vaccines.

#AxiosOnHBO to not \"over-interpret\" vaccine results: \"They do not show that they prevent you from potentially carrying this virus...and infecting others.\"\n\nAdding, we shouldn't \"change behaviors solely on the basis of vaccination.\" ","username":"axios","name":"Axios","profile_image_url":"","date":"Tue Nov 24 04:22:34 +0000 2020","photos":[{"img_url":"https://cdn.substack.com/image/upload/w_728,c_limit/l_twitter_play_button_rvaygk,w_120/tsqokwji4rqrzwyzmw9n","link_url":"https://t.co/qrwQkjLf3Y"}],"quoted_tweet":{},"reply_count":0,"retweet_count":205,"like_count":322,"impression_count":0,"expanded_url":{},"video_url":null,"belowTheFold":true}" data-component-name="Twitter2ToDOM">

Implications for the Future

This means that the use of masks, distancing, limited closures, and other mitigation efforts will STILL be required long after the vaccines are introduced. This will be the case at least until we exceed 70%-to-80% vaccine compliance and may still be required for those over 60 well after full vaccine compliance.

If we drop all mitigation efforts, even with full vaccine compliance, the virus will go fully endemic and almost everyone will catch Covid-19 once or twice a year.

In such a scenario, Covid will be as widespread as the common cold but kill like seasonal influenza. The average person gets 3 colds a year with over a 1-billion colds a year in the US versus only about 30M to 50M cases of seasonal influenza.

Because Covid vastly more infectious than seasonal influenza, we should expect 6x to 10x as many cases of Covid as the flu, but with a death rate comparable to the flu.

Even after full vaccine compliance (80% plus), with a fully re-opened economy and no mitigation measures, Covid-19 will likely remain the 3rd leading cause of death in the US after heart disease and cancer with an annual death toll of >300k deaths per year.

This is why maintaining mitigation measures like mask usage, distance, reduced social density may be necessary for the next several years. Unfortunately, there will likely be a strong political push to drop all mitigation measures shortly after the vaccine is widely available.

In a scenario where there’s a 50% vaccination rate and no mitigation measures, the death rate could easily be 2x-to-3x higher as it becomes increasingly difficult for those unwilling to take the vaccine to avoid infection...but without any of the protections of the vaccine!

If we drop mitigation measures with only half the population vaccinated, then by this time next year, the epidemic could be at levels vastly above where we are today!

Concluding Thoughts

Widespread support for vaccinations will be crucial for the economy and society to resume to any sort of reasonable level. And because the SarsCoV2 virus is so contagious, a vaccine compliance level of 80% will be needed before we see a full return to more normal levels of social interaction.

It will be important for the broad population to understand exactly how these vaccines will and will not work. And to understand the distinctions and implications of concepts like “sterilizing immunity” and “disease immunity” and “immune duration”.

All these distinctions are VERY important for people to understand to push back on popular pressure to drop mitigation efforts.

Links to References:

LANCET: What can we expect from first-generation COVID-19 vaccines?

These observations suggest that we cannot assume COVID-19 vaccines, even if shown to be effective in reducing severity of disease, will reduce virus transmission to a comparable degree. The notion that COVID-19-vaccine-induced population immunity will allow a return to pre-COVID-19 “normalcy” might be based on illusory assumptions.

CELL: A Single-Dose Intranasal ChAd Vaccine Protects Upper and Lower Respiratory Tracts against SARS-CoV-2

Intramuscular dosing of ChAd-SARS-CoV-2-S induces robust systemic humoral and cell-mediated immune responses and protects against lung infection, inflammation, and pathology but does not confer sterilizing immunity, as evidenced by detection of viral RNA and induction of anti-nucleoprotein antibodies after SARS-CoV-2 challenge

STAT: The world needs Covid-19 vaccines. It may also be overestimating their power

Vincent Munster, who leads the team that conducted that study, said a vaccine that could mitigate the severity of the Covid-19 pandemic would still be a significant contribution in a world struggling to co-exist with a dangerous new virus.

Michael Mina, an infectious diseases epidemiologist at Harvard’s T.H. Chan School of Public Health, thinks achieving sterilizing immunity with a vaccine will not be possible for Covid-19. Experience with human coronaviruses — and with multiple pathogens that cause colds — shows immunity that develops after infection with respiratory tract infections is not lifelong. In some cases, the duration is measured in months, not years.
“If [infection with] natural coronaviruses doesn’t do it, I don’t think that we should necessarily expect or have the anticipation that we’ll be able to get there with the vaccine,” said Mina, who is also associate medical director of clinical microbiology at Boston’s Brigham and Women’s Hospital.

Scientists Warn Americans Are Expecting Too Much From a Vaccine

“Everyone thinks COVID-19 will go away with a vaccine,” said Dr. William Haseltine, chair and president of Access Health International, a foundation that advocates for affordable care.
But the trials, which will study 30,000 to 60,000 volunteers, will be too short in duration and too small in size to prove that the vaccines will prevent what people fear most — being hospitalized or dying — by the time the first vaccine makers file for emergency authorization, expected to occur later this year, Haseltine said.

BIORXIV: ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques

Viral loads in BAL fluid and lung tissue of vaccinated animals were significantly reduced, 162 suggesting that vaccination prevents virus replication in the lower respiratory tract. Despite this 163 marked difference in virus replication in the lungs, reduction in viral shedding from the nose was 164 not observed

Researchers: COVID-19 Studies Should Also Focus on Mucosal Immunity

"We think it is a serious omission to ignore the mucosal immune response to SARS-CoV-2, given its initial sites of infection," said Michael W. Russell, PhD, emeritus professor, Department of Microbiology and Immunology in the Jacobs School of Medicine and Biomedical Sciences at UB, and senior author on the paper. "Clearly the response of the systemic immunoglobulin G antibody [the most abundant circulating antibody] is important—we do not deny that—but on its own it is insufficient."
Russell noted that naturally, the initial focus of research on the disease was on cases of severe disease when the virus descends into the lower respiratory tract, especially the lungs, where the cellular immune responses exacerbate the inflammation rather than fight the infection.
But since the upper respiratory tract, including the nose, tonsils and adenoids are the initial point of infection for the SARS-CoV-2 virus, the immune responses that are triggered there are of special interest.

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An American Tragedy...

Dale W. Harrison — Wed, 25 Nov 2020 17:46:42 GMT

This is the first-person’s account of one family’s fight with Covid-19 as it sweeps through their extended family with tragic results…

Diary of a Sad Woman - why I hate COVID

by Hina Patel @hinapatelRx

Sun, Oct 15th

My brother picks up my mom who has just spent 2 weeks in Florida staying with my aunt post uncle’s death. Mom/dad had both attended my uncle’s funeral 2 weeks earlier. Mom comes back feeling sick.

Oct 16-26th

My family has “flu-like” symptoms. Mom has been in bed since she got home. My brother and dad start feeling weak later in the week. Mom/dad see their primary care physician on Oct 25th where he tested them for COVID antibodies which came back negative on the 28th.

Thurs, Oct 29th

I received a call from my sister stating that when she spoke to my dad that morning, he sounded short of breath. I’m sitting at Panera bread working because I had lost power overnight due to a storm. I FaceTime dad and ask him to check his pulse ox. I can see his hands shaking as he was trying to install the battery into the pulse ox. I stay on FT until he gets his reading. 89%. I panic. I tell him to get to the ER right away. In hindsight, I wish I would have kept my cool.

I call my bro/sister-in-law (SIL) to rush him to the ER. As they prep him, I jump in the car to drive 6h to come home. My SIL has to drop dad off at the ER and is unable to go in with him. He is admitted and sits in the ER for the next 36h until they find a bed on the COVID unit.

He gets a CT scan of his chest. ID is consulted. His test results come back positive and he is started on remdesivir, dexa, and enrolled in a trial for CSL-312.
I arrive home late early evening. Mom seems ok, just weak. My brother looks like absolute shit.

Fri, Oct 30th

Dad gets a room on the COVID floor. He is placed on high-flow oxygen. Meanwhile, bro is feeling awful so SIL takes him to the ER. He’s home within a few hrs with a z-pak. His test comes back (-). I disinfect everything in the house top to bottom daily.

Sat-Sun, Oct 31-Nov 1 - brother with high fevers (up to 102.8°) all weekend. We give Tylenol around the clock. He isn’t keeping up with food/water intake. 1° care MD changes antibiotics to Ceftin. He’s starting to feel “loopy”.

Mon, Nov 2nd

SIL takes bro back to ER. His test is still (-). They ask if he wants to be admitted. He says yes. SIL and I are thankful so we can get some rest. His room is a few doors down from dad. We don’t tell my dad to avoid additional stress. I’ve been FT’ing dad daily. He hates it in the hospital. He says that he will be finishing up 5d of tax and coming home.

Tues-Fri, Nov 3-6th

Father and son both getting treated. Dad is now going b/t CPAP/high flow. ID decides dad should get a total of 10d of tx. Dad is frustrated. He tells me he’s scared multiple times. It breaks my heart. I tell him to be patient and let the drugs do their thing and let his lungs heal. I head back to ATL for a few days and come back by the end of the week. My older sister comes to stay for a week.

Sat, Nov 7th

Brother comes home. He feels much better. Meanwhile, dad still alternating between CPAP and high flow. He has positional desaturation. They can’t really prone him or put him on his side. He is counting down the days to come home.

Mon, Nov 9th

I’m back in ATL. Dad FTs me and shows me the dry erase board. “Look at the date, look at the date, I’m supposed to be home! Pick me up right now!” I want to cry. I try to reassure him that he just needs more time for his lungs to heal.

Tues-Wed, Nov 10-11th

RN lets me know dad isn’t eating due to cont. CPAP. He has another CT scan to rule out a PE b/c his sats are down. Again, he tells me he is scared. I hate that no one can see him and that he is alone. Wed. evening, dad can barely open his eyes. Panic sets in

Thurs, Nov 12th

As his healthcare proxy, I get a call in the morning that they are having trouble bringing up his sats. He had been pulling off his mask the past few days. The rapid response team is in the room. “Would you like for him to be intubated?” I say yes.

We, as a family, had discussed his living will earlier in the summer. I knew what his wishes were. Dad is transferred to the ICU that day. He gets another CT scan. He undergoes a bronchoscopy.

They pull a few mucus plugs. “His lungs look fibrotic”. Dad is on 85-90% FIO2. I pray, and pray, and pray that the vent will give your lungs time to heal. Dad’s labs look awful. Elevated d-dimer, ferritin, LDH; very low platelets and albumin....all markers of disease progression.

Fri, Nov 13th

We learn that my aunt died from COVID. She too had been admitted 10 days before him. We never told dad how sick she was. This was the same sister who had lost her husband just a month earlier (non-COVID). Our families are devastated. (Cont)

Dad is fluctuating between 70-90% FIO2 on the vent. He has severe ARDS. His P/F ratio is <100. As a former CCM pharmacist, I know his lungs are like a brick. The attending shows us his 2 CT scans and I see the progression and the ground glass opacities. He barely has any functional lung.

Over the weekend, he develops acute renal failure. He receives CRRT to remove fluids. He is requiring minimal pressors. I pray, and pray, and pray that he pulls a Tom Brady and comes back to beat this.

Sat-Sun, Nov 14-15th

We see dad daily via WebEx. It breaks my heart to see dad intubated. He’s not the same man. Prior to all this, dad was 100% functional. He could walk miles with no problems. Dad was with me hiking in the Himalayas less than a year ago. How did we get here?

Mon, Nov 16th - I fly home again from ATL. All the driving was too much. My older sister flies home to ATL and my younger sister goes home to her kids.

Tues-Wed, Nov 17-18th

Dad is fluctuating between 70-100% FIO2. He is still requiring minimal pressors and low dose sedation/analgesia. I’m still hoping dad gets through this. He’s always been a fighter.

Thur, Nov 19th

The attending calls with an update. He has a new RML and RLL consolidation. They start vanc/meropenem. The worst update......dad is not waking up at all. A head CT has been ordered. The pharmacist in me says it’s lingering sedation. I’m in denial.

Fri, Nov 20th

The CT scan is done today. It shows multiple infarcts with an SAH. I call my sisters to come home stat. We decide to wait to tell mom until Saturday when we are all together. We decide not to discuss the strokes. (Cont)

I break it to my bro that dad has a very poor prognosis and that we should discuss the next steps knowing that dad would have hated being stuck on a vent. My bro is in denial. He calls his MD friends who all say give it a few days. We decide to give my bro the time he needs to cope.

Sat, Nov 21st

We tell mom. She doesn’t quite understand everything and holds on to hope that dad will wake up. We take the time over the next few days to let family/close friends pay their respects via WebEx. Many great stories. We decide as a family to withdraw care on Monday.

Mon, Nov 23rd

The worst day of my life ever. I had called to nurse at 8:00 am to figure out the logistics. They were only going to allow 4 of us to come into the hospital but we convinced them to let 5 of us in. We hate that my SIL and BIL couldn’t see dad one last time.

The COVID ICU is like Fort Knox. “You can only come in one at a time”. How is mom going to do this alone? The staff is kind enough to let mom be in the room while the siblings rotate. When it’s my turn, I go in and sign the paperwork for withdrawal of care.

I go into the room, I lose it. I want to crawl into a hole. I hold your hand and stroke your head. I tell you how much I love you, how much you meant to me, how you were the best daddy in the world, and that God couldn’t have given me anyone better. I promise to take care of mom.

I promise to carry on your legacy. To always be smiling and to always help others as you did. To always look at the bright side of things, to never have hate in my heart. I thank you for everything you have done for me. The staff let my brother be in your room after extubation.

You passed within seconds. It was clear you were ready to leave us. I pray you didn’t feel anything. I pray you weren’t scared.

Final thoughts:

There were 3 different outcomes from these 3 cases. My SIL remained throughout this. Why? B/c she wore a mask the whole time. She wore it as soon as my parents returned from Florida. To all the naysayers/non-believers, I hope you never have to go through this.

I am eternally heartbroken. This was not fair to my dad who brought joy to those around him. My parents were careful all year. They wanted to support my aunt during her time of need. That was always my dad’s priority...his family.

We pleaded for them not to go but he always did things his way. Dad, you lived a wonderful life and I know you had no regrets. I love you!!! #WearAMask

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A Comprehensive List of Covid Resources

Dale W. Harrison — Tue, 24 Nov 2020 19:36:16 GMT

It can be frustrating to not have a central hub of all information for SarsCoV2 and COVID-19. Below is a comprehensive list of links to data & resources covering the categories of:

Cases (Infections)/ Hospitalizations/Deaths
General Public Health Information:
Patient Registries & Special Populations
Support Groups (Patients)
Support Groups (Health Care Professionals)
Information on Clinical Trials
Current Research

Please feel free to share this with anyone who would benefit.

Thanks to Erin C. Sanders (twitter:@ErinSandersN) for compiling the original list.

Cases (Infections)/ Hospitalizations/Deaths

General Public Health Information:

Patient Registries & Special Populations

Support Groups (Patients)

Support Groups (Health Care Professionals)

Information on Clinical Trials

Current Research

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Testing Won't Make Thanksgiving Safe!

Dale W. Harrison — Mon, 23 Nov 2020 19:31:37 GMT

Having everyone get a Covid test this week will NOT make your Thanksgiving gathering safe!

The only way to manage risk for Thanksgiving is to keep the events to only people already in the household. As soon as people from outside join, the risks escalate. The entire group is only as safe as the least-safe member.

All it takes is inviting a single person who thinks masks are stupid, the virus is fake, and going to bars is a good idea and the entire group now has a risk-level equivalent to that person!

And as the White House learned after the Rose Garden super-spreader event, inviting risky people and then relying on same-day testing to keep everyone safe is a dangerous fantasy.

There are several issues with using testing to create safe events:

Time-lag between infection and when a test will show positive
Time-lag on getting test results back
High false-negative results from same-day rapid tests

Time-lag after Infection

People will test negative for SarsCoV2 for 3-5 days after the initial infection. It simply takes time for the virus to replicate to a level where it can be detected by even the most sensitive tests.

That’s generally thought to be a minimum of 3-days for a laboratory-run RT-PCR test and 10+ days for a rapid antigen test.

You can easily have gotten a negative on a test yesterday and be fully infectious to others today and still have not developed any symptoms.

Time-lag on Getting Test Results Back

Test results for an RT-PCR test generally take 2-5 days to return results. You can test today, be infecting people tomorrow, and not get a test-positive result until a couple of days later. In general, a test result will lag an infection event by a week or more.

This is especially critical if you think you’ve been exposed. NEVER wait for test results to come back, quarantine immediately.

High False-Negative Results from Same-Day Tests

Using a same-day rapid test to avoid delays in getting results back will not solve the problem either. All rapid tests have issues with very high rates of false-negatives. This means you can be fully infectious, but the test says you’re fine.

There are two categories of rapid test:

RT-LAMP (Isothermal-PCR) Tests like the Abbott ID NOW
Antigen tests like the Abbott BinaxNow lateral-flow strip test

In actual clinical practice, the RT-LAMP tests will run as high as 40% false-negative. Meaning that out of 10 infected patients tested, only 6 will be identified.

The antigen tests are even worse. In actual clinical practice, they will return 50%+ false-negative. Meaning that out of 10 infected patients, only 5 or fewer will be identified.

However, if you get a test-positive on ANY of these rapid tests, then you are 100% absolutely guaranteed to be infected and likely to be extremely infectious to others!

Always believe a test-positive and take action!

Always be skeptical of any test-negative!

Why So Many False Negatives Results?

There is a direct relationship between how fast you get results and how well a test is able to identify infections. There is simply NO free lunch…faster tests mean less sensitivity and more people will slip through undetected.

In addition, the rapid antigen tests are ONLY approved for testing fully symptomatic patients. If you’re not fully expressing symptoms of illness (fever, cough, difficulty breathing) then taking a Covid antigen test will almost always return a negative result.

As a result, none of the antigen tests have been validated on non-symptomatic patients, and none have FDA approval for use on non-symptomatic patients. They are designed only to test people who are already ill to rapidly determine whether the illness is Covid-19.

So don’t imagine that you can have everyone get an antigen test ahead of the big Thanksgiving gathering…that’s a recipe for a very unhappy Christmas!

Abbott BinaxNOW lateral-flow strip antigen test

Abbott BinaxNOW ID NOW RT-LAMP test

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Science by Press Release is Not Science

Dale W. Harrison — Sat, 21 Nov 2020 19:41:26 GMT

So far we know very little about either the Moderna or Pfizer vaccines other than what's been pushed out by their corporate PR groups.

There's still NO data and no scientific papers for peer-review from either company. So we still have no clear understanding of their definition of "effective" or their definition of "95%".

These are NOT terms with objective definitions but rely on the original study design and how the statistical analysts interpreted the intentions of the study design.

This is why seeing an actual paper outlying those details along with a full release of data is critical before ANYONE can make an informed decision.

End of Phase III Trials Announced

More concerning is that they're ending Phase III trials after just over 90-days in. Wrapping up five months early without ever achieving full enrollment. That is an insanely short period of time for a novel vaccine trial. And a very small test population especially if you're interested in observing adverse effects.

Again, perhaps there is evidence that's not yet been released to justify such a move, but with vaccine trials that typically last 5+ years, a 90-day timeline seems extraordinary.

Confidence of Corporate Leadership in their Vaccines

My other concern is the behavior of senior leadership at both Moderna and Pfizer.

Just since the Phase III trials have started, the top three corporate officers at Moderna have dumped over $100M of Moderna stock. These stock trades are required to be reported to the SEC and are then made public through the SEC Form 4 reporting site.

At Moderna, no one has been buying stock, but those with direct access to the vaccine trials data have been dumping stock on a weekly basis for months now.

Meanwhile, over at Pfizer…one day after the Pfizer vaccine announcement, the CEO dumped over 60% of his Pfizer stock along with the Chief Corporate Affairs Officer.

Again, during this time period, not a single member of the senior leadership team in either company has purchased a single share of their company's stock. It’s been exclusively sell-orders. These are very people who have actually seen the full data and the full details on the vaccine trials.

There are many valid reasons for senior leadership in a publicly-traded company to be dumping their stock, but it’s generally NOT an indication that the senior executives believe their companies are poised for positive news over the coming few months.

Concluding Thoughts

Given that all we have access to are a few paragraphs written by some PR consultant, I remain skeptical of the scientific backing that supports these vaccine claims. Perhaps that view will change over the coming weeks if and when these companies share their data and offer their findings for formal scientific review.

These are entirely new categories of vaccines, never before used with humans. And these never-before-deployed vaccines are being approved after only a bit over 90-days of trials. Trials that have been terminated early! Absolutely everything about this process has been extraordinary and entirely unprecedented.

But here’s the deal…extraordinary claims require extraordinary proof!

All we have at this point are glowing press releases pushed out by corporate communications departments.

Personally, in the absence of seeing some extraordinary data, my benchmark for taking the vaccine is 6-months after the first 20M people have been vaccinated...until then, I'm going to just keep doing what I've been doing to stay safe…

Source Documents:

Moderna Press Release:
https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy

Pfizer Press Release:
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine

SEC Form 4 - Moderna:
https://www.secform4.com/insider-trading/1682852.htm

SEC Form 4 - Pfizer:
https://www.secform4.com/insider-trading/78003.htm

About the author:

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