Categories
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.

Categories
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 ConsequenceConcern, 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%   
Categories
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.

Categories
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. 

Categories
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.