Category: 2021

Categories
2021 COVID-19 Science Testing Vaccine

A Useful Model

Scientists create mental models to help understand the world around us.  Not that these models are reality; the real world is much, much more complicated.  Instead, these models are useful ways to think about reality.  Today I would like to create a mental model of the SARS-CoV-2 virus that will be useful as we learn more about the virus in coming weeks and months.

Think of the virus as an egg with spikes driven into the shell.  Now focus on two parts of this model: the spikes and the yolk inside the egg.  The spikes correspond to the S-proteins on the outside of the virus.  That’s easy to remember—S for spike.  The yolk corresponds to the nucleocapsid that covers the genetic material on the inside of the virus.  Let’s call the nucleocapsid “N” for short, which will also help us remember that N-proteins are inside the virus.  Now in our mind’s eye we see a virus shell with S-proteins on the outside and N-proteins on the inside.

When foreign proteins show up in your body, your immune system responds by making antibodies.  Therefore, when infected by SARS-CoV-2, your body will make at least two different types of antibodies: S-antibodies and N-antibodies. Blood tests are now available that can detect both kinds of antibodies, and both should be detected in someone who has been infected by SARS-CoV-2 in the past.

Vaccines expose the body to S-proteins only.  N-proteins are not part of vaccines.  Therefore, someone who has received a vaccine but has never been infected will have S-antibodies but not N-antibodies.  S-antibodies may come from vaccine or infection.  N-antibodies come from infection only.

Now we can use our model to predict antibody test results from four different groups of people, represented in the table below:

Previously InfectedNever Infected
VaccinatedS+ N+S+ N-
UnvaccinatedS+ N+S- N-

A simple model, but does it work?  To find out, I collected the results of antibody tests from four groups of people: people infected but not vaccinated, people vaccinated but not infected, people vaccinated and infected, and people never infected nor vaccinated.  Next time, we will review the results.

Categories
2021 COVID-19 Science Vaccine

New Clotting Disorder Caused by Vaccine

We’ve already discussed the rare clotting disorder associated with COVID-19 vaccinations, resulting in the pause of the Janssen vaccine last month.  It’s time to take a deeper dive to understand more about this disorder. To start, we must learn a little about platelets. It’ll be quick, I promise.

Platelets are bits of cells that circulate in the blood stream looking for leaks.  When a leak is found, platelets are activated and clump together to plug the hole.  There are lots of platelets in blood, so one hole usually isn’t enough to reduce the platelet count.  However, if all the platelets are activated at once, many clumps form, and the count of platelets goes down dramatically.  The reduction of platelet count is called thrombocytopenia. “Thrombocytes” means “platelets” and “penia” means “not enough”, so “thrombocytopenia” simply means “not enough platelets”.

Heparin induced thrombocytopenia (HIT) is a condition in which platelets are activated after the use of heparin, causing a suddenly drop in platelet count.  This is particularly dangerous because, as you may recognize, heparin is a “blood thinner” given to dissolve clots.  The formation of many clots is the opposite of what is desired.  HIT occurs because of an immune response in which antibodies to a molecule that forms when heparin is injected cause activation of platelets throughout the body.  The molecule is called “heparin-platelet factor 4 complexes,” but the name doesn’t matter. Most people don’t have those antibodies to this molecule.  This is a rare but life-threatening complication of heparin therapy.

The rare clotting disorders that have been rarely been observed after the Janssen vaccine have a similar mechanism.  Now referred to as vaccine induced thrombotic thrombocytopenia (VITT), it is like HIT because antibodies develop after vaccine administration that cause platelet activation.  The antibodies are similar enough to HIT antibodies that giving heparin will make the clots worse.  This is why heparin cannot be used to break down those clots.  

This seems to be the same clotting complication that has been observed with the AstraZeneca COVID-19 vaccine, not available in the U.S., but widely available elsewhere.  Both vaccines have in common the use of an adenovirus vector to deliver the vaccine.  A viral vector is not used in the mRNA vaccines. Is VITT related to the adenovirus vector in some vaccines? Nobody knows for sure. Yet.

This is another example of unintended consequences resulting from the use of systems still in the early stages of development.  Life is full of risks; we accept that.  But wisdom demands that risks be acknowledged, quantified, and mitigated as much as possible.  Only the foolish follow science blindly.

Categories
2021 COVID-19 Science Vaccine

Why Vaccinate COVID-19 Survivors?

In these posts I use my experience as a practicing pathologist to present clear, simple, and understandable explanations of important issues relating to the pandemic amid the noise and misleading half-truths we encounter daily.  When I don’t know, I tell you.  Today, I’m asking you to help me understand something that’s been puzzling me for weeks. Why does the CDC adamantly insist that COVID-19 survivors be vaccinated?

The CDC’s statement is simple enough.  They say that there is a wide range of outcomes to SARS-CoV-2 infection, from no effect to death, and that there is a corresponding range of immune responses to infection.  Those who had mild disease, the argument goes, may not have built up the immunity necessary to fight future infections.  The vaccine, on the other hand, is a measured dose designed to stimulate an adequate immune response.  Furthermore, they assert that there is no data on how long natural immunity may last, saying, “experts do not yet know how long you are protected from getting sick again after recovering from COVID-19.”  So, they conclude, everyone must be vaccinated, even those who have recovered from COVID-19.

Simple enough, yes.  You will find this theory repeated on health websites and in the popular press, often citing compelling studies and medical experts.

But does it make sense?  Before the pandemic, did medical science ever assert that vaccine-induced immunity is superior to natural immunity?  I’ve looked.  I cannot find that assertion from any reputable source, nor can I find that assertion supported by any body of evidence.  I’m not saying that I’ve looked everywhere.  I’m saying I looked and came up empty.  If you know where it is, please tell me. 

Let me be clear about my question.  I’m not doubting that vaccine is an important tool in the war against infections generally and SARS-CoV-2 specifically.  Clearly, vaccines provide protection to individuals most vulnerable to bad disease outcomes.  Clearly, vaccines raise the overall immunity within the population, stemming the spread of infection.  An article published in Texas Medicine on the eve of the pandemic advocates for vaccine, especially childhood vaccines—mumps, measles, rubella, and the like—using a simple risk-benefit analysis.  This analysis, and many more like it within the body of traditional medical science, compare the risk of vaccine to the risk of disease.  Acknowledging that vaccines have risk and diseases have risk, vaccines generally have less risk than disease.  This is very different from introducing the risk of vaccine to individuals who have already survived the risks of infection by the virus.

There is a glaring flaw in the CDC’s argument.  True enough, experts do not yet know how long you are protected from getting sick again after recovering from COVID-19.  But neither do experts know how long you are protected from getting sick after completing a vaccine series.  How could they know either?  Neither COVID-19 nor the vaccines have existed long enough to be studied meaningfully, which brings me back to my question.  How can we say vaccine-induced immunity is superior to natural immunity?

I cannot think of any other example of this line of thinking.  We do not insist that children who have had chicken pox get the chicken pox vaccine.  We do not give hepatitis B vaccine to individuals who have had hepatitis B infection.  In fact, before giving a hepatitis B vaccine, we usually test for antibodies to make sure the individual has not been previously infected.  Why expose someone to an additional risk unnecessarily?

Are COVID-19 vaccines different from any other vaccine?  Has a new theory of immunology suddenly replaced years of observation and wisdom?  Why would the CDC, a place I know to be filled with smart, dedicated, and sincere physicians and scientists, be so insistent that COVID-19 survivors be vaccinated?  

If you know the answers, please tell me.  I would love to hear from you.

Categories
2021 COVID-19 Testing Vaccine

Herd Immunity

What is herd immunity and when will we get there?

Imagine a billiard table with balls racked at one end.  Smash a cue ball into the neat arrangement and all the balls will move.  That’s like the pandemic.  The energy spread from ball to ball is like the spread of virus from person to person.   

Now imagine the same table, except this time some of the balls are bolted onto the table so they can’t move.  Smash a cue ball into the rack and not as many will move.  The bolted balls are like people with immunity; they absorb energy and do not allow it to spread.  How many balls must be bolted onto the table to prevent spread of motion across the table?  That’s herd immunity; the percentage of people with COVID-19 immunity that it takes to stop the uncontrolled spread of virus.

Epidemiologists differ on herd immunity targets for COVID-19, with estimates varying from 60% to 90%.  But these estimates are just educated guesses.  Herd immunity is something observed, not something predicted.  When the rates of disease reach a stable low level, herd immunity has been achieved.  

Now some observations from my point of view.  Last week, without a decline in the number of tests performed, there were only 6 positive SARS-CoV-2 tests in the laboratory where I work.  Until last week, weekly positives have been in the double digits going back to April 2020, with a peak of 475 during the first week of this year.  Since the last week in February, the weekly number of positive tests have been below 40.  The curve has flattened, despite the lifting of many restrictions designed to prevent spread of the disease in Texas.  We can no longer say that there is a COVID-19 epidemic in my community.  Instead, the disease appears to have reached endemic levels here.  

I need to pause to explain what I mean.  Disease prevalence, which we’ve defined before, means the rate of disease in a population.  Prevalence can be applied to any disease, not just infectious disease; thus, we can speak of the prevalence of diabetes, of breast cancer, of heart disease, and so on.  Epidemic simply means increasing prevalence, just like acceleration means increasing speed.  Endemic means that disease prevalence is stable and not changing.  Epidemics can be local, meaning confined to a house or a neighborhood or a city or a country, or epidemics can be global, meaning happening all over the world at once.  Global epidemics are called pandemics.  The term “global pandemic” is as redundant as “unexpected surprise” or “advance warning.”

Herd immunity is achieved once an infectious disease reaches endemic levels, but what is that number?  Assuming natural and vaccine-induced immunity are the same thing, then herd immunity is the percentage of folks who have either had the infection or the vaccine when disease becomes endemic.  Today, it is estimated that 10% of Texans (2.8 out of 28 million) have had COVID-19, and that 35% of Texans have been fully vaccinated.  Therefore, my area seems to have achieved COVID-19 herd immunity at 45%.

This all sounds like great news, so why not throw our masks in the air and celebrate?  There are still unanswered questions.  Vaccine-induced immunity is not the same as natural immunity, but is it the same enough for calculating herd immunity?  How long does immunity last?  Can herd immunity be lost once achieved?  What will be the impact of emerging variants on immunity of individuals and populations?  And, most puzzling to me, why is the virus surging now in India and Brazil despite previous waves of infection?  

We still don’t know as much as we would like to believe.

Categories
2021 COVID-19

More Variants Emerge

As new variants emerge, it’s time to update our charts so you will know what’s coming and what to watch for.  In its summary released last week, the CDC made minor terminology revisions and made some roster changes on the line-up cards.  In this edition, we will highlight the changes and update our charts with the latest information.

Variants of High Consequence.  Now called Variants of High Consequence instead of Variants of High Concern, these SARS-CoV-2 strains cannot be detected by tests, are not treatable by current therapies, or are not protected by natural or vaccine induced immunity.  A strain that fits any of these categories must be reported to the WHO and CDC immediately.  Thankfully, this list is still blank.

Variants of Concern.  Variants of Concern have reduced detection by tests, reduced response to therapy, reduced immune protection, greater transmissibility, or more severe disease.  Although there have been no additions to this list, there have been noteworthy updates to our understanding of these variants.  For example, B.1.1.7, the UK Variant, and B.1.351, the South African Variant, remain at the top of the increased transmissibility list at 50%; however, as we predicted in January, B.1.1.7 is also now the most prevalent lineage of the virus in most regions of the U.S. except the west coast. The California Variants B.1.527 and B.1.529 are now considered the most resistant to therapy of all U.S. variants.

Variants of Interest.  Variants of Interest are U.S. variants with the potential to become Variants of Concern based in the mutations within the variant, even though they don’t fulfill criteria to be a Variant of Concern based on observation.  Two changes have occurred.  First, B.1.525 is now believed to have first originated in the U.K. and Nigeria, even it continues to be most prevalent in New York.  And second, since last writing, a new variant, B.1.526.1 has spun off the New York Variant B.1.526.  This gives us the opportunity to briefly explain the classification system I have been using.

Because SARS-CoV-2 mutates so quickly, new variants emerge rapidly.  The PANGO lineage system attempts to apply some order to this chaos.  Names begin with a letter designating a unique lineage, followed by a series of numbers separated by dots.  For example, the U.K. Variant B.1.1.7 is the seventh named variant of the B.1.1 lineage, and B.1.1 is the first named variant of the B.1 lineage, and so forth.  By looking at the name B.1.526.1 we know that this variant evolved from the New York Variant B.1.526, but that it has enough unique characteristics to merit its own name.  The variant’s family tree is embedded in the name.  For example, B.1.1 and B.1.526 are siblings, B.1.526.1 and B.1.1.7 are cousins, and B.1 and P.1 are from totally different families.  It’s a useful although not perfect system, and like everything in the pandemic, it continues to evolve.

Thousands of variants have been described.  The ones highlighted in the charts below are currently considered the most important in the U.S:

Variants of Concern
VariantFirst DetectionCurrent U.S. PrevalenceIncreased TransmissionIncreased SeverityReduced Detection by TestsResistance to Treatment
B.1.1.7UK44.7%50%●  
P.1Japan/Brasil1.5%   ●
B.1.351South Africa0.7%50%  ●
B.1.427California3.1%20%  ●
B.1.429California6.9%20%  ●
Variants of Interest
VariantFirst DetectionCurrent U.S. PrevalenceIncreased TransmissionIncreased SeverityReduced Detection by TestsResistance to Treatment
B.1.526New York6.9%   ●
B.1.526.1New York3.6%   ●
B.1.525UK/Nigeria0.3%   ●
P.2Brazil0.3%   ●
Categories
2021 COVID-19 Science Vaccine

Janssen Pause

These blogs advocate caution and skepticism, specifically in response to the COVID pandemic, but more generally in response to all “scientific” proclamations.  Don’t “follow the science” blindly.  Instead use your “smell test” before believing anything labelled as science.  Remember that science does not prove reality.  Instead, science proves what is not real.  We know much less than we would like to believe.

The sudden “pause” in vaccine rollout announced last week by Janssen is a case in point.  The pause follows reports of six cases of unusual blood clots following administration of the vaccine, tragically including one death.   

These unusual blood clots are called cerebral venous sinus thrombosis, or CVST, a condition which blocks the flow of blood out of the brain.  As a result, the blood vessels may burst causing a stroke which may permanently damage brain tissue.  So far, all patients are women under 50 years old with low platelet counts.   

An association between COVID-19 and CVST was noted before the Janssen vaccine was released.  In the August 2020 edition of the American Journal of Neuroradiology, Dr. D. D. Cavalcanti and associates reported three COVID-19 patients under 41 years old who developed CVST; all three patients died.  Others have reported similar associations between CVST and SARS-CoV-2 infection.  

This raises several questions.  Can CVST be caused by COVID-19?  Can CVST be caused by the Janssen vaccine? What about the mRNA vaccines?  And how is it that a vaccine causes a complication of the disease it’s meant to prevent?  Furthermore, six instances of CVST out of 6.8 million doses of the Janssen vaccine administered is a complication rate of less than 1 in 1,000,000.   The rate of anaphylaxis associated with the mRNA vaccines is 10 times as high.  Why so much concern for such a rare complication?

Something doesn’t smell right to me.

Categories
2021 COVID-19 Science Testing Vaccine

Antibody Tests after Vaccination

The CDC recently updated guidelines for interpretation of SARS-CoV-2 antibody tests after infection and vaccination.  There is currently no recommendation to measure antibodies after vaccination to determine vaccine effectiveness.  Despite this, I know vaccinated individuals who measure antibodies anyway, and they are surprised when antibody tests come back negative.

Okay, full disclosure.  It was me.  And my wife.  We took the Janssen vaccine in mid-March, and I checked our SARS CoV-2 IgG antibodies last week.  They’re negative.  For both of us.  What’s going on here?  Isn’t the point of vaccination to stimulate the production of antibodies?

The answer is a qualified yes.  The qualification comes in two parts: the “scientific explanation” and my opinion.  

First the “scientific explanation”, simplified.  An individual may produce three types of antibodies against SARS-CoV-2: N, S or RBD. Infection stimulates the production of all three types of antibodies, but vaccine stimulates the production of S antibodies only.  Therefore, vaccinated individuals who have never been infected will be S-antibody positive, but N and RBD antibody negative.  If the antibody test is designed to detect N or RBD antibodies, but not S antibodies, then the result will be negative in those individuals.  On the other hand, detection of N or RBD antibodies in a vaccinated individual means that the individual has been exposed to the virus, either before or after vaccination.  The trouble is that the antibody tests available today by emergency authorizations do not specify which type of antibody is measured.   We do not know which antibody we are measuring unless we know details about the test, details that are usually not listed on the report from the lab.  

This explanation has precedent.  We know, for example, that Hepatitis B infection stimulates the production of two different types of antibodies: core antibody and surface antibody.  Hepatitis B vaccine only stimulates production of surface antibody; it does not stimulate production of core antibody.  Therefore, someone who is positive for surface antibody only has been vaccinated but has not been infected.  On the other hand, someone who is positive for both surface and core antibodies has been infected by Hepatitis B in the past.

All well and good for hepatitis, but what about SARS-CoV-2?  In the case of SARS-CoV-2, the “scientific explanation” is a hypothesis, meaning it is an educated guess.  Before we can say that we know something, we must compare our hypothesis to real-world observations.  There has not been enough time to observe the response that our bodies really have to vaccine.  It doesn’t make the hypothesis wrong, but it doesn’t make it right either.

My opinion?  The “scientific explanation” is still an opinion.

Categories
2021 COVID-19 Vaccine

Anaphylaxis

In the revised EUA issued for its COVID vaccine on February 25, 2021, the FDA required Pfizer to updated its “Fact Sheet for Healthcare Providers” to include post-authorization adverse effects. As a result, Pfizer’s fact sheet now states, “Severe allergic reactions, including anaphylaxis [emphasis added], and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema) have been reported following administration of the Pfizer-BioNTech COVID-19 Vaccine during mass vaccination outside of clinical trials.”  Moderna did not receive the same mandate to revise its fact sheet, which still does not include a similar warning about anaphylaxis.  What is anaphylaxis and what are the facts about this life-threatening vaccination complication?

Anaphylaxis is a severe allergic reaction in which your body releases a flood of chemicals designed to modulate the immune response all at once.  The result is a sudden drop in blood pressure and narrowing of airways which can lead to fainting and death.  Some people are more prone to anaphylaxis than others, and some stimuli are more common causes of anaphylaxis than others.  Peanuts and bee stings are common examples.  The allergic response can be effectively reversed by an injection of epinephrine.  Susceptible individuals (and you know who you are) often carry EpiPens to self-administer a dose of epinephrine in case of a reaction.

Anaphylaxis can occur anytime something is injected in the body, although the risk is exceedingly low.  However, the rate of anaphylaxis after the mRNA vaccines is about ten times higher than the rate of pre-COVID vaccines.  If this is the case, then why did Pfizer’s new EUA highlight this potential complication and Moderna’s did not?  The answer may be related to initial experience with the two vaccines.  Since Pfizer received authorization for its vaccine first, increased anaphylaxishad already been observed in association with the Pfizer vaccine before Moderna even received its EUA.  The reputation stuck.  Although initial reports suggested that Pfizer caused more than twice as many anaphylaxis reactions as Moderna, subsequent experience has shown that both mRNA vaccines have about the same rate of anaphylaxis.  According to a March 16 CDC report 1,913 deaths have been reported associated with vaccine administration after more than 109 million doses.  Reports of recent VAERS data searches, the FDA database collecting vaccine adverse events, suggest that the rate of anaphylaxis deaths are similar for the two vaccine manufacturers.  The Janssen recombinant vector vaccine appears to be associated with fewer cases of anaphylaxis than the mRNA vaccines; time will tell whether this observation sticks or is skewed by the fewer number of vaccines administered so far.  The CDC recommends that all vaccination administration sites be prepared for potential anaphylaxis reactions, including educating staff on the signs and symptoms of anaphylaxis and having at least three epinephrine doses on hand at all times.

A few sensible conclusions may be drawn from this information.  

  • Ask the person administering your vaccine what would happen if you had an anaphylaxis response.
  • If you have an EpiPen, bring it with you when you get your vaccine.
  • If you have had a severe allergic reaction in the past, consider deferring vaccination or taking the Janssen (Johnson and Johnson) vaccine instead of an mRNA vaccine.
Categories
2021 COVID-19 Vaccine

Breakthrough

As more Americans are receiving COVID vaccinations, there are reports of COVID occurring in individuals who have been fully vaccinated.  Can this really happen?

Yes, you may still become sick from a SARS-CoV-2 infection even if more than two weeks have passed since your final vaccine injection.  “Breakthrough” is the term for this type of infection, and many state health departments have reported breakthrough infections.  According to current CDC reports, over 50 million Americans have been fully vaccinated, accounting for 15.1% of the total U.S. population, yet 7-day rolling averages for new COVID-19 cases and hospital admissions for COVID are up 6.7% and 2.6% respectively.

We know that breakthrough infections occur with other vaccines.  In years past, many patients were admitted to the hospital for flu even though they received a flu vaccine earlier in the season.  We may be seeing a similar phenomenon with the COVID vaccine.  Furthermore, we still do not know whether most breakthrough infections are caused by the original SARS-CoV-2 virus, or one of the emerging variants.  It is possible that vaccine is less effective against one or more variants.

We have a lot to learn about breakthrough infections, but this much is clear: the pandemic is not over, and the vaccine is not a panacea.  While vaccine may provide an added layer of protection against dying from COVID, it does not prevent contraction of disease.  For now we must continue to do what we know keeps us safe: mask in public and keep apart, even if you have received a vaccine.

Categories
2021 COVID-19 Testing Vaccine

New Variant Classification

Last week the CDC revised its classifying terminology for SARS-CoV-2 variants.  To have clarity in our thoughts and debates, we must be precise in our language.  Poor decisions often descend from muddled and incomplete understandings.  I know that readers of these posts strive to be current in models of understanding and language, so they will not be caught flatfooted in conversation and reasoning.  That’s why I summarize the essential points here.

There are now three types of SARS-CoV-2 variants: Variants of Interest, Variants of Concern and Variants of High Concern.  I will discuss the definitions, lists of variants and their characteristics in reverse order.

Variants of High Concern.  Variants of high concern are those SARS-CoV-2 variants that cannot be detected by tests, are not treatable by current therapies or for which natural or vaccine induced immunity offers no protection.  Any one of those three criteria is enough to place the variant on the High Concern list.  Scary stuff.  The good news is that there are no variants on this list.  At least not yet.

Variants of Concern.  Variants of Concern have reduced detection by tests, reduced response to therapy, reduced immune protection, greater transmissibility, or more severe disease.  Again, any one of these criteria is enough to land a variant on this list.  The bad news is that the number of variants on this list has exploded since the last time I wrote about it.  In addition to the B.1.1.7 variant first detected in the UK last fall, four other variants have been added to the list:

These Variants of Concern have all been identified in the United States.  The B.1.427/429 Variants of Concern are most prevalent in the western United States, now responsible for more than half of infections in California.  The B.1.1.7 Variant of Concern is most prevalent in New Jersey and Florida, approaching 10% of the new viral infections there.  Click here to view the current numbers and distribution in the United States.  To see worldwide cases of COVID-19 caused by variants, click here.  These maps are updated at least weekly.

Variants of Interest.  Variants of Interest are being watched closely because they have the potential to become Variants of Concern based in the mutations within the variant, even though they don’t fulfill criteria to be a Variant of Concern based on observation.  This may be because the variant is too new or because too few of the instances of the variant exists to make meaningful observations.  The current Variants of Interest and their potential, but not observed, effects are listed below:

Like the Variants of Concern, all the Variants of Interest are currently present in the United States.  

There are a number of other variants which have been identified and named, but which have not yet been classified as a Variant of Interest, Variant of Concern, or Variant of High Concern.  Expect the members of these variant classification lists to change and shift as more becomes known about variants.