Category: COVID-19

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2021 COVID-19 Vaccine

A New Vaccine Warning: Guillain-Barré Syndrome

Last week, the FDA added a new statement to the Janssen vaccine Factsheet for Healthcare Providers, warning of an increased incidence of Guillain-Barré Syndrome among vaccine recipients. This warning was issued after cases in India and the United Kingdom were published in the Annals of Neurology.  Although the warning only applies to the Janssen vaccine, at least one case has also been reported following Pfizer vaccination.

Guillain-Barré Syndrome is a condition in which the immune system attacks peripheral nerves, the nerves responsible for sending signals for motion and sensation between the body and the brain, resulting in pain and weakness, and in severe cases, paralysis and death.  Although most people recover, symptoms may linger for a long time.  Guillain-Barré Syndrome is triggered by various conditions that cause inflammation, including infection, surgery, trauma, and cancer.  Rarely influenza and childhood vaccines have been associated with Guillain-Barré Syndrome.

Guillain-Barré Syndrome was identified as a complication of COVID-19 early in the pandemic.  Subsequent studies demonstrate that these cases are “not due to a direct attack of the virus, but rather to an immunological reaction to the virus.”  Now we learn this long-recognized complication of COVID-19 can also be an adverse effect of a COVID vaccine.

The warning for Guillain-Barré Syndrome is the third FDA statement of an immune mediated vaccine complication, adding to the precautions previously issued for myocarditis and clotting disorders.  Interestingly, myocarditis and clotting disorders have also been recognized as complications of COVID-19. 

It’s becoming increasingly clear that COVID-19 has two separate disease pathways.  The first is the direct effect of the virus.  The second is the response of our immune system to the virus.  Vaccines intentionally stimulate this immune response.  Is it surprising that adverse vaccine effects overlap with COVID-19?  Expect more examples of autoimmune complications of COVID vaccines.

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2021 COVID-19 Vaccine

COVID and Autoimmune Disease

Some individuals infected by SARS-CoV-2 experience brain damage.  Although it sounds like science fiction, “COVID brain fog” describes a very real condition in which infected patients experience memory loss, strokes, and other nervous system lesions.  How can this happen?

In an article published last week in Nature, Michael Marshall, a free-lance science journalist from the U.K., describes the current areas of research into the causes of this condition.  One possible mechanism is autoimmune disease.

The immune system’s job is to protect the body from agents of disease (“pathogens”) without damaging the body’s own cells.  Like the military guarding the border of a sovereign nation, the constituents of the immune system carry lethal weapons meant to destroy an invading enemy.  But what if the military can’t tell the difference between friend and foe?  Those lethal weapons might be unleashed on its own people, and the citizens of that nation would be at risk of harm from their own government.  Let’s say for example that the U.S. learned all its enemies wear red hats.  If the army was ordered to seek and destroy anyone wearing a red hat, many innocent Americans unwittingly wearing red hats could be killed in an effect to stamp out a threat to our nation.  

The immune system works by learning something about the pathogens that threaten the body—not the color hats they wear, but the shape and composition of molecules on the invaders.  When the shape and composition of those molecules are similar enough to the shape and composition of molecules on the cells in our own body, the immune system can’t tell the difference, and it attacks us.  That’s autoimmune disease.

Autoimmune disease is highly individualized.  Although we lump these diseases into categories ranging from lupus to rheumatoid arthritis, each person with an autoimmune disease has a disease that’s uniquely his or her own.  There’s a lot of overlap, but no two individuals have exactly the same disease manifestations.  

There are many examples of autoimmune disease targeting specific organs.  Hashimoto’s thyroiditis is a disease in which the immune system targets the thyroid gland.  In Crohn’s disease the immune system targets the cells of the gastrointestinal tract.  Multiple sclerosis is an autoimmune disease of the central nervous system.   COVID brain fog may also be, at least in part, an autoimmune disease of the central nervous system in which an immune system primed to destroy SARS-CoV-2 causes collateral damage to the brain.

If that’s the case, we have yet another reason to avoid COVID-19.  But we may also want to avoid stimulating the immune system to fight SARS-CoV-2, which is precisely the goal of a COVID vaccination.  We know that everyone who has had COVID-19 develops antibodies to the viral spike protein.  We also know that everyone who has received a COVID vaccine develops antibodies to the same viral spike protein.  What if these are the autoantibodies associated with COVID brain fog?

Although there is no proof this is the case, there is evidence suggesting that the idea is plausible.  Last week, we learned that vaccines may cause myocarditis and pericarditis, essentially an autoimmune disease affecting the heart.  VITT, a condition in which vaccination causes blood clots, is also immune mediated.  We must consider the possibility that stimulation of immunity against viral spike proteins causes autoimmune disease in some vaccine recipients.

As we connect more dots, an image emerges from the haze of the pandemic.  As the picture becomes clearer, will we have the courage to believe what we see?

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2021 COVID-19 Testing Vaccine

Which Vaccine Causes the Greatest Antibody Response?

It’s not even close.  In terms of generating the highest S-antibody response, Moderna is the clear winner.  Pfizer comes in second, and Janssen (Johnson & Johnson) finishes in last place.  Here’s the data that backs this up.

The same volunteers we tested to figure out antibodies after vaccination and disease were separated by vaccine type and evidence of infection.  Evidence of infection includes either a positive SARS-CoV-2 test during the pandemic or the unexpected presence of N-antibodies.  We did not count two individuals who had only one dose of mRNA vaccine, nor did we include people who had both vaccine and infection.  Then we measured the antibody levels of the individuals in each group.  Here’s what we found:

VaccineLowHighAverage
Moderna8.49.18.7
Pfizer4.27.66.2
Janssen1.43.92.6

Clearly, Moderna vaccine stimulates the highest antibody response.  Then we graphed the antibody response caused by vaccine compared to the immune response of infection.

Chart, box and whisker chart Description automatically generated

Previous infection is better than the Janssen vaccine and nearly as good as the Pfizer vaccine.  If we eliminate those overachieving Moderna people, we get a chart that looks like this:

Immunity SourceLowHighAverage
Pfizer or Janssen1.47.66.2
COVID1.28.44.3

Graphically, the data looks like this:

Chart, box and whisker chart Description automatically generated

It’s nearly identical. 

Let me summarize the findings and restate the question that’s been puzzling me for weeks.  Two of the three vaccines authorized in the U.S. stimulate S-antibody levels that are no better than SARS-CoV-2 infection.  Yet the CDC still insists that infected individuals be vaccinated with any of the three authorized vaccines, even if the person starts out with S-antibody levels at least as high as the expected levels resulting from vaccination.  Why?

Let me be clear.  I’m not asking whether a person who has not had COVID should be vaccinated.  That’s a legitimate question that deserves more than knee-jerk consideration, but it’s not the question I’m asking here.  I’m asking why vaccination is in the best interest of a person who has already been infected?  Maybe the answer is obvious to you; if so, please help me understand.  It doesn’t make sense to me.

Last time, I asked you to consider that the answer may be in the prioritization of population health over individual health.  This time I ask you to consider something else.  When things don’t make sense to me, I have a snarky, cynical side that asks, “Who’s profiting?”  

Something to think about.

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2021 COVID-19 Science

The Delta Variant

The Delta Variant is one of several new strains of SARS-CoV-2 recently added the variant zoo.  Why has this new variant received so much attention lately, and why are we referring to variants with Greek letters now?  

The CDC still groups variants into categories of High Consequence, Concern, and Interest.  Thankfully, there are still no Variants of High Consequence.  The WHO has assigned Greek letters to certain variants to aid in communication.  The Delta Variant, B.1.671.2, is a new entry on the list of Variants of Concern.  Three cousins of the Delta Variant, B.1.671, B.1.671.1 and B.1.671.3 are now on the Variants of Interest list.  All these new strains originated in India.

What makes Delta different? It’s the first addition to the Variant of Concern list since April, and it’s prevalence in the U.S.is increasing.  Although it’s not nearly as prevalent as the Alpha Variant, aka the U.K. Variant, B.1.1.7 which we first learned about last December, some reports suggest that the Delta Variant is even more easily transmitted, meaning that it may soon replace the Alpha Variant as the most common form in the U.S.  The Delta Variant shows some resistance to treatments, although not more than other variants.  It does not escape detection by tests, and S-antibodies, either from disease or vaccine, seem to provide immune protection.  The Delta Variant is just the ‘new kid on the block’; we need to take this in stride.

I’ve updated variant reference tables, sorted by U.S. prevalence.

Variants of Concern
VariantWHO LabelFirst DetectionCurrent U.S. PrevalenceIncreased TransmissionIncreased SeverityReduced Detection by TestsResistance to Treatment
B.1.1.7AlphaUK69.7%50%●  
P.1GammaJapan/Brasil8.4%   ●
B.1.617.2DeltaIndia2.7%140%  ●
B.1.351BetaSouth Africa0.7%50%  ●
B.1.429EpsilonCalifornia0.6%20%  ●
B.1.427EpsilonCalifornia0.4%20%  ●
Variants of Interest
VariantWHO LabelFirst DetectionCurrent U.S. PrevalenceIncreased TransmissionIncreased SeverityReduced Detection by TestsResistance to Treatment
B.1.526IotaNew York5.0%   ●
B.1.526.1 New York2.5%   ●
B.1.525EtaUK/Nigeria0.1%   ●
B.1.617.1KappaIndia0.1%   ●
P.2ZetaBrazil0.0%   ●
B.1.617 India0.0%   ●
B.1.617.3 India0.0%   ●
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2021 COVID-19 Science Testing Vaccine

Vaccinate the Previously Infected? A Risk without Benefit

Vaccination of the previously infected is a risk without benefit because there’s no significant difference between S-antibody levels stimulated by SARS-CoV-2 infection when compared with vaccine.  

Using the same group of volunteers from our study to determine antibody types stimulated by vaccine and/or COVID, we measured the level of S-antibodies in the people who had them.  To make the comparison fair we did not consider the people who were both vaccinated and infected; instead, we only counted people who were vaccinated but had no evidence of disease, and we compared them to unvaccinated people with evidence of infection.  Here’s what we found:

IndividualsLowHighAverage
Vaccine171.49.16.6
COVID81.28.34.2

There were 17 people vaccinated without disease.  Their S-antibody levels ranged from 1.4 to 9.1 with an average of 6.6.  There were 8 unvaccinated individuals with evidence of infection.  That evidence could with be a positive SARS-CoV-2 test sometime during the pandemic, a positive N-antibody test, or both.  Their S-antibody levels ranged from 1.2 to 8.3 with an average of 4.2.  Any level above 1 is considered positive.

Graphically, the data looks like this:

Give a slight edge to vaccine, but really the difference between the two groups is negligible.  The COVID group includes a couple who previously had asymptomatic infections, implying that even asymptomatic infections cause the formation of S-antibodies just like vaccines.

Which causes us to return to the question we asked in early May.  Why vaccinate COVID survivors?  I still see no evidence for doing so, but there are reasons for not vaccinating previously infected people.  Our study includes two previously infected people who took the first dose of an mRNA vaccine and experienced vaccine complications so severe that they couldn’t take the second dose.  One of the two developed a debilitating condition that has not yet resolved and may persist for life.  Through June 7, 2021, VAERS received 5,208 reports of death associated with vaccine administration in the U.S.  Clearly the vaccine did not cause every reported death, but just as clearly, the vaccine death rate is greater than zero.  Death is the most serious of complications.  There are more common but less serious complications that range from inconvenience to discomfort to debilitation.  If there is no benefit, why take a risk?  That’s why my advice is that previously infected people should not be vaccinated without a compelling personal indication. 

Some researchers are beginning to agree with me.  As early as February, a study subsequently published in Nature suggested that a second dose of mRNA vaccine is unnecessary for people previously infected by SARS-CoV-2.  More recently, a pre-publication report of a study conducted at the Cleveland Clinic concludes that vaccinating individuals who have had SARS-CoV-2 infections has no benefit.

So why does the CDC still adamantly insist that COVID-19 survivors be vaccinated?  The answer lies in perspective.  The vaccination rate in a community is the single greatest factor in controlling the spread of disease and achieving the goal of herd immunity, which has already been reached in many parts of the country.  If you prioritize the good of the population over the good of any individual, then you advocate for universal vaccination even when the vaccine has no benefit, or worse yet, may cause harm to individuals.

That is not my focus as a physician.  My focus is the individual, the patient in front of me.  Health care is not a commodity that can be mass-produced without hurting individuals.  I have urged that vaccine decisions be made individually, not collectively, and I continue to do so.  I believe that the people with greatest risk of unnecessary harm from vaccine are the previously infected and the young.

The suggestion that even asymptomatic infections cause the formation of S-antibodies has implications in the ongoing debate regarding the vaccination of children, the group most likely to have asymptomatic infection.  During this debate, we must first resolve whether our priority is the population as a whole or the individual boys and girls subject to vaccination.  We may reach different conclusions depending on the priority we choose.

Here’s an idea.  Why not check S-antibody levels before vaccination?  Something to think about.

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2021 COVID-19 Science

THE PANDEMIC IS OVER

What gives a Texas pathologist practicing in a suburban community the right to declare THE PANDEMIC IS OVER in screaming headlines?  Shouldn’t such a pronouncement come from an official institution like the NIH or the CDC or the WHO or a prestigious university?   Read on, I’ll tell you.

The graph of the number of positive tests resulted each week by the laboratory where I practice gives you a fair image of the pandemic in my community:

There were two waves, a small one last summer and a bigger one in the winter.  But since the end of February, the number of positive tests has been low and constant.  Positive tests have not disappeared, but the rate of positives is not changing.  Search for rates in your community, and I bet you’ll find a similar graph.

Recall that epidemic means an increasing number of cases in a community, and that pandemic means an epidemic all over the world.  From the graphs it’s obvious that the number of cases is not changing, and it hasn’t been for several months.  If there’s no epidemic in my community and there’s no epidemic in your community, then there’s no more pandemic.  The pandemic is over.

The graphs also tell us that the virus is still here, and probably will be for a long time, maybe forever.  Epidemiologists call this the endemic rate—the rate of disease that is always present in a population.  People will still get sick, and some may even die, but it’s no longer an epidemic.  We reached herd immunity more quickly than many “experts” predicted.   

So now what?  We have to learn to live with the virus. Know your immunity status.  If you are not immune, continue COVID precautions if you wish to avoid contracting the virus.  The pandemic may be over, but the virus and its variants will be with us for a long time. 

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2021 COVID-19 Science Testing Vaccine

Antibodies after Vaccination and Disease

Last time, we built a mental model of the SARS-CoV-2 virus and used that model to make predictions of antibody test results.  This time we will see how that model squares against real-world observations.

Here’s the table we created last time:

InfectedUninfected
VaccinatedS+ N+S+ N-
UnvaccinatedS+ N+S- N-

With their permission, I tested more than 40 individuals who fit into one of the four categories.  Here’s what I found:

InfectedUninfected
Vaccinated4 S+ N+
7 S+ N-		17 S+ N-
3 S+ N+
Unvaccinated4 S+ N+
2 S+ N-		4 S- N-
2 S+ N+

Previously Infected and Vaccinated.  There were eleven people in this category, but only 4 had both the S- and N-antibodies that our model predicted.  Surprisingly, nearly two thirds of the people in this group lacked N-antibodies.  This is not what our model predicted.  It seems some people may not form N-antibodies.  Let’s keep looking.    

Previously Infected but Unvaccinated.  There were six people in this category.  Four had both S-antibodies and N-antibodies, but two had only S-antibodies.  Again, we’re missing some of the N-antibodies predicted by our model.  What’s going on here?  I’ll offer some speculations later.  

Vaccinated without Known Infection.  There were twenty people in this category, and all but three of these individuals had the expected S+ N- antibody pattern.  All outliers were S+ N+, suggesting they had asymptomatic infections sometime during the pandemic.  Is this suggestion reasonable?  I think so.   During the pandemic we tested healthy patients before elective surgeries and found a significant number of asymptomatic infections, so we know this can happen.

Unvaccinated without Known Infection.  There were initially five people in this category, and they had neither S nor N antibodies detected in their blood.  Except for one person.  She was surprised to learn she of a silent previous infection based on the finding of both S and N antibodies in her blood.  Subsequent testing of her husband, who also is unvaccinated without previously known infection, found S and N antibodies in his blood too, bringing the total number of people in this group to six with two outliers.  

We can summarize what we’ve learned as follows:

  • Both SARS-CoV-2 infection and vaccine stimulate the production of S-antibodies, 100% of the time in this study.
  • A significant number of people, about 20% in this group, had silent SARS-CoV-2 infections during the pandemic.
  • SARS-CoV-2 infection does not seem to stimulate the production of N-antibodies consistently.  This is a pesky observation that does not fit our model.

Could it be that N-antibody production relates to the severity of disease?  Probably not since quite a few of the S+ N+ individuals in this study had asymptomatic infections.  Could it be that variant viruses cause N-antibody negative infections?  Or is the N-antibody test not very good?  All are possible, but, as we’ve said so many times since the outbreak of the pandemic, we really don’t know for sure.   What we can say is that tests for “COVID antibodies” are more complicated than they seem at first glance.  Laboratories should clearly label the antibodies measured when reporting SARS-CoV-2 antibody results.

How do the antibody levels caused by disease compare with the antibody levels caused by vaccine?  And which vaccine provides the best immune response?  We will examine these questions next time.  

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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.

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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.

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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.