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2021-01-30 -Signs, Portents, and the Weather-
Thoughts on the COVID vaccine
by Steve White

I was asked by TW to share a few thoughts on the COVID vaccine since that is a topic of intense interest both in American society and here on the Burg.

1. The current COVID vaccines are excellent. To ensure we're on the same page, a reminder that a vaccine is a way to provide protection from select viruses and bacteria. The concept is simple: we introduce an 'antigen', a snippet of protein (or protein+sugar) that cells in our immune system (known as 'antigen presenting cells') sense as 'foreign' and 'bad'. These APCs then teach our B cells (a type of lymphocyte and part of our immune system) to make antibodies when provoked in the future, and our T cells (another type of lymphocyte) to respond to that antigen in the future. If after vaccination (say to influenza) the virus then is found in our body (for example, in the lungs) our B cells make antibodies and our T cells react and enlist other parts of our immune system. That's the simplest explanation.

An antigen then is just a small portion of a protein in the virus or bacteria, what we call an 'epitope'. The more specific the epitope the better, and there are certain things about the epitope that provoke a better and more specific reaction. So it's all about generating an excellent antigen. Past efforts for every vaccine we've ever had from smallpox to today have revolved around getting that excellent antigen. We could use part of a virus or bacteria, we could use a dead virus or bacteria, or we could use a 'live attenuated', or weakened, virus, depending on what it takes to get a proper immune response. It's a time-consuming and expensive process because you don't want to generate a vaccine with an antigen that either doesn't work, or that provokes adverse reactions.

As many have read, the COVID vaccines from Pfizer and Moderna are a new type of vaccine based on 'mRNA': messenger RNA. Going back to Biology 101; DNA in our genetic code is translated into mRNA in a cell nucleus; that mRNA then goes to a ribosome where it is translated so that the ribosome builds a protein. This is how we go from genes to proteins. All the mRNA in the vaccine does is code for the antigen of interest. Cells in the body take in the mRNA and send it to ribosomes, where it encodes the translation of the antigen. Our immune system then reacts as usual. In this case the epitope is part of the 'spike protein' on coronavirus that does the work of binding a receptor on our cells. It's specific, always there, less likely to mutate in ways that wreck our vaccine, and absolutely necessary for the virus. Bingo.

One good thing about a mRNA vaccine is that the mRNA doesn't stay around long after it's been taken up by the cells. Over a couple weeks it elicits the generation of enough protein antigen to teach our immune system. Then it is degraded and generation of antigen ceases. This means that it isn't sticking around to cause problems for the future.

In addition, because we're creating a more specific antigen there is less risk of adverse reactions. Remember that a traditional vaccine (e.g., influenza, pneumococcus) uses a collected antigen (attenuated live virus, dead virus, etc.) so there's always the risk that we'll react to some part of that virus that isn't the epitope -- that is, the specific part of the virus/bacteria to which you want the immune system to react.

So a mRNA vaccine is a great idea. This is also the proof-of-concept that mRNA vaccines work. There's lots of possibilities in the future, and indeed a fair bit of the research that went into mRNA vaccines the last couple of decades came from DARPA and DoD, which wanted ways to immunize our military more quickly to various things (any veteran knows the numbers of injections they took prior to any deployment). It's also much quicker -- you can generate mRNA sequences in a day and test them in vitro in a laboratory in a week.

2. It's a well-tested vaccine. The Pfizer and Moderna vaccine phase III trials were well-run and published in high end medical journals (such as the New England Journal of Medicine) that are traditionally rigorous and good (not perfect) with their scrutiny. The numbers of patients in these trials are close to what one ordinarily does in any vaccine trial. The adverse event numbers were low and manageable. And the response is superb: > 90% protection (after two doses) from future infection is truly outstanding (for influenza vaccines, that varies from 50 to 70% year to year). That the trials were done quickly was because it was easy to generate the vaccine, and because Mr. Trump forced the FDA to move quickly (no one, no one has ever been fired at FDA for being too cautious). Recall that last May, people said we wouldn't have a vaccine until perhaps 2022 or 2023. We have it now because the vaccine makers had the incentive and the FDA got religion.

Both mRNA vaccines are two-dose vaccines. A single dose provided only 50-60% protection which was deemed insufficient for full immunity -- remember, the mRNA goes away in a couple of weeks, and for some of us that isn't enough to train our immune system. The 2nd dose fixes this problem. You'll have read that some advocates propose immunizing as many people as possible with just one dose, thus stretching the supply. While not providing as much individual protection, this strategy would get the U.S. to 'herd immunity' more quickly. It's an on-going discussion.

Bear in mind that coronavirus can mutate, and mutate quickly. It's an RNA virus; its genetic code is in a single strand of RNA as opposed to the double strand of DNA in human cells, bacteria, and some other viruses. Influenza is also a single-strand RNA virus and is well known to mutate frequently. If the RNA coding for the spike protein mutates sufficiently the Pfizer and Moderna vaccines (and any other vaccine based on the spike protein) won't work anymore -- we will have taught our immune system to watch for something that won't be there.

3. It's a well-manufactured vaccine. Because it's an mRNA, the solvent, stabilizing agents, etc. in the vial are somewhat different than for a protein antigen vaccine. It was easier to formulate, though as we've seen, it has to be kept frozen. RNA is susceptible to breakdown at room temperature. But the manufacturing process otherwise is simpler, and that led to it being available more quickly (and the vendors were subsidized to get this 'process chemistry' going up-front).

4. The anti-vaxxers will have their usual concerns; they are as wrong here as they are in general. I won't get into their neurotic arguments. Experience to date shows that the vaccine has about the same safety profile as (say) influenza vaccine. As with any vaccine, some number of people will have modest reactions (arm pain, low-grade fever, fatigue) and a very few will have a severe adverse reaction. Fortunately the two vaccines for COVID have had very few severe adverse events to date.

There is a cautionary note for both vaccines that relates to the reports of people with multiple allergies having some increased risk of an anaphylactic reaction to the COVID vaccine; this is not unexpected. There's also a concern of receiving the vaccine for people who've had COVID infection in the past, and the emerging recommendation is to wait 90 days after infection before receiving the vaccine.

5. You'll have seen in the news that other vaccines are coming. These are different from the Pfizer/Moderna mRNA vaccines. Johnson & Johnson has a vaccine nearing FDA approval that requires a single dose and does not require freezing. It's effectiveness is in the 66-75% range. That's equal in efficacy to the yearly influenza vaccine, and is adequate to help us respond to the pandemic. This vaccine uses a modified cold virus variant to deliver the mRNA for the spike protein; the virus infects cells and delivers the mRNA. It too is susceptible to COVID mutations. As a side note, this same technology was originally developed to deliver a HIV vaccine (that isn't out yet), but the technology was then used to develop a vaccine for Zika virus and now for COVID. This technology also will be around to generate new vaccines to benefit society.

6. In short: I've had the Pfizer vaccine, my family is getting the vaccine when eligible to do so, and I strongly encourage all my patients to receive the vaccine. I encourage the public at large to do so when available. You should talk with your primary care doctor about any concerns you might have, what your risks are to both the vaccine and COVID infection, and about how your overall health may influence your risks.

Full disclosure: I am a pulmonary specialist and teach medicine at the University of Chicago. My opinions here are my own.
Posted by Steve White 2021-01-30 00:00|| || Front Page|| [1 views ]  Top

#1 Thanks for the info, Steve.
Posted by Mercutio 2021-01-30 08:18||   2021-01-30 08:18|| Front Page Top

#2 A lot to read, but very well done. I'll share it with my family, since you have addressed some of their concerns and pointed out cautions I of which I was unaware.

Bravo!
Posted by Bobby 2021-01-30 08:31||   2021-01-30 08:31|| Front Page Top

#3 "There's also a concern of receiving the vaccine for people who've had COVID infection in the past, and the emerging recommendation is to wait 90 days after infection before receiving the vaccine." I have found no evidence published supporting this recommendation. My sister, 78, came down with a mild case of COVID 27 Nov. She received dose #1 of Pfizer immunization 7 Jan. and had a sore arm for a day or so, no other ill effects. Her physician is a geriatrician with a teaching appointment at a university medical center. Her PCP's recommendation at the time was that if the patient has no ongoing symptoms of COVID, the shot is not contraindicated. Sis is on the schedule to get shot #2 within the next week or so, about 62 days after she got COVID.
Posted by Thineger Sproing6704 2021-01-30 11:49||   2021-01-30 11:49|| Front Page Top

#4 "There's also a concern of receiving the vaccine for people who've had COVID infection in the past
If this is a serious concern should people be tested before receiving the vaccine? It seems like mild cases would easily be overlooked or ignored without ever learning they were COVID. Or is it only severe previous infections that provoke concern?
Posted by Glenmore 2021-01-30 12:20||   2021-01-30 12:20|| Front Page Top

#5 He sure ticked off all of the "neurotics" out there.
Posted by Clem 2021-01-30 13:01||   2021-01-30 13:01|| Front Page Top

#6 Very helpful. My own doctor has recommended the vaccine, and so I am scheduled for March (the soonest they can get me in.)
Posted by Tom 2021-01-30 13:20||   2021-01-30 13:20|| Front Page Top

#7 Strong endorsement. Thank you.
Posted by swksvolFF 2021-01-30 13:46||   2021-01-30 13:46|| Front Page Top

#8 Thank you very much.
Posted by magpie 2021-01-30 13:57||   2021-01-30 13:57|| Front Page Top

#9 "previous infections that provoke concern?" This concern may well turn out groundless, just have to wait and see.
Posted by Thineger Sproing6704 2021-01-30 14:46||   2021-01-30 14:46|| Front Page Top

#10 Thank you Steve W. One of the sad things these days is the utter lack of credibility doctors and scientists have these days due to the abuses of a few (Climate Change, Covid-19, etc...)
Good to have advise from someone I consider 'credible'.
Posted by CrazyFool 2021-01-30 15:31||   2021-01-30 15:31|| Front Page Top

#11 My question is: if I have had the vaccine, why do I still need to wear a mask? Same question for someone who has had COVID19?
Posted by Rambler in Virginia  2021-01-30 15:58||   2021-01-30 15:58|| Front Page Top

#12 Mr. Wife gives you a thumbs up, Dr. Steve. Thank you for doing this for us.
Posted by trailing wife 2021-01-30 15:59||   2021-01-30 15:59|| Front Page Top

#13 If we've already had a mild case of the virus (and don't know it), what are the affects of piling on with the vaccine? What is Dr. Steve's take on Hydroxychloroquine (marlaria meds)? I have taken that stuff numerous times without side effects. Took it for periods of a year overseas twice, shorter tours as well.
Posted by Besoeker 2021-01-30 16:07||   2021-01-30 16:07|| Front Page Top

#14 I neglected to mention...Yes, thank you very much for your analysis Dr. Steve.
Posted by Besoeker 2021-01-30 16:12||   2021-01-30 16:12|| Front Page Top

#15 I know better! I watch Youtube and I stayed in a Holiday Inn Express last year.

OK, maybe you should believe a real Doctor
Posted by Frank G 2021-01-30 16:58||   2021-01-30 16:58|| Front Page Top

#16 I'm glad these vaccines exist, and appreciate the thoughtful and well informed commentary. Personally, I won't be getting vaccinated. At least for several years.

1. I have already had and cleared the disease. Not only do I believe that has left me naturally vaccinated, but I haven't seen any studies on the safety and efficacy of the vaccines in people who have already had the disease. That's because those studies do not exist. I don't mind waiting.

2. The risks of the disease have been grossly exaggerated. In my age group the survival rate is 99.98%. And treatment options continue to improve. That has to go into my own personal risk/reward analysis.

3. The track record of the experts has been dismal. I point to, for example, the 2 retracted hit job studies on HCL. I also point to the WHO admitting their CT guidelines for testing were producing false positives ONE HOUR after Biden was inaugurated. So, yeah, Credibility of those telling me to get vaccinated is pretty low right now. Remember when we were all going to die because there weren't enough ventilators?

4. These are still experimental agents. There are no 5 year safety studies. Not even published animal studies. Again, I'm happy to wait.

For those who are at high risk or frightened, I am thankful you now have this option.
Posted by Angstrom 2021-01-30 17:26||   2021-01-30 17:26|| Front Page Top

#17 Dr Steve, you left one thing out: the mRNA vaccine is pretty specific to one set of proteins on the spike, and you did mention that, and the fact that if the virus mutates away from that protein the immunity will not be there. What you left out is: the people making the mRNA pick a protein that is vital for the virus to have in order to attach to the ACE-2 receptors, so if the virus mutates away from that protein it may no longer be viable to infect via the current route. In shor English: if it mutates to where the vaccine will not be effective, that same mutation may make the virus unable to infect humans.
Posted by Deadeye Jaiting7534 2021-01-30 22:06||   2021-01-30 22:06|| Front Page Top










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