Category: Vaccine

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:

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.

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:

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

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.  

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:

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.

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.