Category: COVID-19

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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.

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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%   ●
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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.

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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.

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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.
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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.

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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.

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2021 COVID-19 Vaccine

New Guidance for the Fully Vaccinated

Yesterday, the CDC published new guidance for fully vaccinated individuals.  In this article, we will summarize the key points of this new guidance.

First, we must understand what it means to be fully vaccinated.  The full effect of vaccine-induced immunity takes about 2 weeks, so an individual is considered fully vaccinated 14 days after the final vaccine injection.  The final vaccine injection is the second dose of the Pfizer or Moderna vaccine, or the single dose of the Janssen vaccine.

Last month, the CDC issued guidance lifting the quarantine requirements for fully vaccinated individuals following a COVID exposure, provided they remain asymptomatic.  Previously, this permission expired after 90 days.  Yesterday, the CDC affirmed its previous guidance, but lifted the 90-day expiration.  According to current CDC guidance, there is no longer an outer time-limit for the benefit of vaccine-induced immunity.  This is bound to change; we will follow closely.

To the removal of quarantine requirement, the CDC also added two additional liberties yesterday: (1) fully vaccinated individuals may visit indoors with other fully vaccinated individuals without wearing masks or social distancing, and (2) fully vaccinated individuals may visit with unvaccinated people from a single household who are at low risk for COVID-19 without wearing masks or social distancing.

Other COVID precautions remain in force for fully vaccinated individuals, including masking and social distancing in public except in the specific situations mentioned above.  If symptoms develop, fully vaccinated individuals should follow the same quarantine and testing recommendations of unvaccinated individuals.

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2021 COVID-19 Vaccine

New Vaccine

There were a couple of big changes in the COVID vaccine landscape last week.   On Thursday, February 25, the FDA reissued its EUAs for the Pfizer and Moderna COVID-19 vaccines, revising portions of their original EUAs.  On Saturday, February 27, the FDA issued a new EUA for the Janssen COVID-19 vaccine, commonly known as the Johnson and Johnson vaccine.  Lots of news, too much for one blog.  Let’s address the important information one bite at a time, starting with the Janssen vaccine.

Like all other COVID-19 vaccines, the Janssen vaccine has not been approved for use by the FDA.  Instead, these vaccines are authorized for use in the U.S.  This authorization is based on the FDA’s authority to make unapproved products available during an emergency when “there are no adequate, approved, and available alternatives.”  As stated in the EUA letter issued February 27, 2021, “It is an investigational vaccine not licensed for any indication.”  This means that clinical trails on vaccine safety and effectiveness have not been completed. Expect comprehensive analysis of clinical trials this summer at the earliest.

However, the Janssen vaccine differs from the other two vaccines in important ways.  First, it is not an mRNA vaccine.  Rather, it is a recombinant vector vaccine.  This vaccine is made by inserting genetic code for a protein of the target into a harmless virus (the “vector”).  When injected, this harmless virus presents the target proteins to the immune system, causing formation of antibodies, in this case antibodies to the spike proteins on the SARS-CoV-2 capsule.  This technology is not entirely new.  Manufactured (or “recombinant”) genetic code has been used to synthesize proteins for vaccines for nearly a decade.  Recombinant flu vaccines received FDA approval in 2013.  You may have received a recombinant flu vaccine in recent years. The difference between recombinant protein vaccine and viral vector vaccines has to do with where the antigenic proteins are made–either in your body (viral vector) or outside your body (recombinant protein). The harmless virus (the “viral vector”) cannot replicate within your body, so the effect is the same.

There are more differences. According to data submitted to the FDA, the Janssen vaccine is less effective preventing moderate to severe COVID-19 than the Moderna and Pfizer vaccines.  The Janssen vaccine requires only one doses compared to the two doses required by Moderna and Pfizer.  Storage of the Janssen vaccine is easier to accomplish than the other two. Vaccines features are compared as follows:

PfizerModernaJanssen
Vaccine TechnologymRNAmRNARecombinant Vector
FDA ApprovalNoNoNo
Effective rate95%95%66%
Minimum Age16 years18 years18 years
Doses221
Storage-70°C-70°CRefrigerated
Time between doses3 weeks1 monthNot applicable
Current comparison among authorized COVID-19 vaccines.

There is another difference.  In its reissued EUA, the FDA has required Pfizer to disclose post-authorization adverse events in its fact sheet to health care providers.  We will discuss that next time.

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2021 COVID-19

Vaccine and Quarantine

On February 10, the CDC updated quarantine guidance for vaccinated individuals exposed to COVID-19, giving some people a get out of jail free card.

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According to the new guidance, individuals who received their second FDA authorized mRNA vaccine injection between 14 and 90 days ago need not quarantine after exposure to COVID-19 provided they are symptom free.

An exposure is still defined as an encounter of more than 15 minutes and less than 6 feet with someone infected by SARS-CoV-2 when one or both individuals are not wearing a mask.  Provided that there is no fever or other indications of upper respiratory infection in the exposed individual, quarantine is not necessary for those who received both doses of either the Pfizer or Moderna vaccine more than two weeks before the exposure.  However, vaccinated individuals should monitor for symptoms (i.e., take daily temperatures) for 14 days after exposure, and should quarantine immediately if symptoms (i.e., fever) develop.  This reduced quarantine requirement does not apply to individuals who complete a vaccination series which has not receive an EUA from the FDA, such as vaccines approved in countries outside the United States.

If it has been more than two weeks since you completed a vaccine series, then you benefit from reduced quarantine requirements after exposure.  But you don’t get to party like it’s 2019!  You may still be able to spread the virus to others, so you must still mask and social distance in public.  Furthermore, no one knows how long vaccine-induced immunity will last.

The CDC maintains that natural immunity—immunity from infection—lasts for at least 90 days.  It may last longer, but the CDC is still unwilling to say so.  Since the CDC’s new quarantine exemption also expires after 90 days, it seems reasonable to infer that 90 days may be the outer limits of immunity, whether from previous infection or vaccination.  We may hope that it’s longer, but so far, the CDC has not said so.

So what does all this mean?  If it has been more than two weeks since you completed Pfizer or Moderna vaccination series, you have a get out of quarantine jail free card—you don’t have to quarantine after a potential exposure if you are symptom free.  However, a vaccination does not make you special in any other way.  You must monitor for symptoms for 14 days after exposure.  You must quarantine immediately if you have symptoms.  You must continue to mask and keep apart in public.  In other words, even if you have completed a vaccination series, you don’t have this card:

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At least not yet.