I am asked several times daily what my opinion is of the COVID-19 vaccination. I am happy to share that as well as how my opinion has been formed. My training and career have been based on keeping up with the immense field of research relevant to my professional career. Forming opinions in this area has been on the same basis.
First, I appreciate that there are other factors that may go into a decision about vaccination and that the science with this infection and the vaccines for them at any time is incomplete. The best we ever have with hard science on any subject is what is available at that point in time which is always somewhat incomplete.
An example is that in the early days of the pandemic, it was thought that a significant mechanism by which the virus was spread was contact. We now know while that is still a minor part of it and care with hand washing, disinfecting surfaces and using hand sanitizer helps some, the primary mode of spread is through airborne particles. If I had a choice between only a mask or hand sanitizer, the former wins. Fortunately, both can be followed and are advisable.
I have always looked at vaccination based on a risk/reward analysis. The seasonable flu vaccines are typically 50-60% effective, and a healthy adult will almost always get through the seasonal flu with a week to 10 days of just feeling bad. This equates to not much risk and not enough reward with a 50-60% effective vaccine.
COVID-19 is a different risk/reward analysis. It has killed over 2.5 million worldwide and estimates suggest we will hit 500,000 in the U.S. by February. Although the deaths bias towards the older, less healthy population, they have not spared any age group. A more common residual disorder associated with COVID-19 infection is long haul syndrome. The long haulers have persisting fatigue, symptoms in the brain, lungs and other body symptoms that become chronic and impairing. By most analysis, this is high risk. The mRNA vaccines have an effectiveness of 95% which is an excellent reward analysis.
Some new research has shed a lot more light on all of this. Under normal conditions, an infection will trigger an initial inflammatory response, a “first responder” to try to limit the infection but also to attract another immune cell, a T follicular helper cell (TfH). (See (1) in diagram) They learn the viral signature called an antigen and then should migrate to regional lymph nodes (2) where B cells which produce antibodies are. (3) The TfH cells give the specific antigen signature of the virus to naive B cells who have not been trained what to kill yet. They make antibodies (4) against that specific viral antigen which then attacks the infection. These B cells reproduce others to do the same task peaking in number between 3 and 4 weeks. Some enter the circulation as long-lived potentiating cells (LLPCs) (5) who have the sole job going forward to make more of the specific antibody quickly if the infection is detected again. These cells are the ones that gives us long-term immunity.
With the above mechanisms in mind, how efficiently this whole process goes forward determines both how effective the initial response to the virus is but also how effectively do we maintain a long-term antibody response to give us continued immunity. There appear to be multiple places where this process of initially battling the infection as well as producing enough ongoing antibodies to give us immunity can go wrong.
The first is that those who get severe symptomatic COVID-19 infections get an initial inflammatory response but do not appear to develop high numbers of T follicular helper cells. This limits the ability to transfer the message about what to make antibodies against to the B cells in the lymph nodes. They tend to get a weak initial antibody response leaving the inflammatory activation to battle the infection on its own. The result is “cytokine storm” which is an overabundance of inflammatory activating chemicals that damage the lungs and other organs trying to fight the infection.
The second problem that occurs is that the lack of training B cells in the lymph nodes leads to poor levels of long-lived potentiating B cells that produce the long-term immunity. The mRNA vaccines appear to facilitate the migration of T follicular helper cells to the regional lymph nodes better than the infection in many people both creating a good initial antibody attack and long-term antibody driven immunity.
For most, the decision between vaccination or risking infection and hoping for a good outcome appears to favor the vaccination. One of the common arguments against vaccination is that it can result in adverse effects. Vaccine reactions such as autoimmunity do occur, but infection is a more common trigger so same comparative risk analysis. Early studies are beginning to document that autoimmunity is fairly common in those with severe COVID-19 infections and is the likely mechanism of much of the long hauler symptoms. Type 1 diabetes is well known to be triggered by viral infection as is rheumatic heart disease, an autoimmune attack of the heart triggered by a strep infection.
Each of us should make our own decision about the COVID-19 vaccination. I think making it from an informed position will produce the best decision.
Kanko et al. Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19. Cell, 2020;183:143-157.
Woodruff et al. Clinically identifiable autoreactivity is common in severe SARS-CoV-2 Infection. MedRxiv. Preprint. 2020 Oct 23.