12/4: COVID-19 AND VACCINES: How It Was Not Rushed, How It Was Developed, Side Effects
Updated: Jan 13, 2021
So we've had some great news this past week. Both Pfizer and Moderna are seeing strong results from their vaccine trials, AstraZeneca and Johnson & Johnson are not too far behind, and more are coming. >90-95% efficacy is great news. However, given...well, everything, there is some understandable skepticism about the vaccine. Hell, I had expressed my own skepticism when Trump talked about vaccines by Election Day, or even the end of the year. However, as we see announcements and initial reports from the companies actually making the vaccines, there is reason for hope. Politics manipulating science is cause for alarm. Science driving politics is progress.
From multiple sources, the biggest concern I have seen is that this was a "rush job." People are concerned based on a few different circulating posts discussing how previous vaccines have taken at least ten years (one callous, and frankly rather cold-blooded post, titled "What's the endgame with 'rona?" discusses how "it took 25 years for a chicken pox vaccine to be developed" as if technology and medicine had not advanced in the 25 years since that vaccine was licensed in the USA). I have also heard many of my fellow healthcare workers express these concerns, for which I certainly don't blame them - we all need a healthy dose of skepticism when it comes to novel aspects of COVID-19 treatment and prevention. So I did some reading. Massachusetts General put out a terrific educational piece, so I'll be sprinkling points from it into this essay.
Today we'll talk about the concerns about the vaccine's speed, the scientific shoulders it stands on, and some details about how the vaccines and the trials work. First, know that all the vaccine creators have been conducting large trials - Moderna tested 30,000, Pfizer 44,000, and Johnson & Johnson 60,000. These were recruited in such a way that the vaccine vs. placebo were disseminated randomly but equally among similar-sized groups of many races, age groups, and preexisting conditions, to make sure it worked in a wide variety of bodies. These studies did not include children (at least one company is starting to recruit for the next phase which will include children) or pregnant/breastfeeding people, but mostly diverse beyond that, so reflective of the world population.
Below I've linked to an article in the Independent by a physician scientist named Dr. Mark Toshner, who runs many clinical trials. He discusses how most of that 10-year development period is spent doing a lot of waiting. He submits applications for grants, waits to get rejected, waits to resubmit to others, waits around to hopefully get the funding for his project. He waits through personnel changes at drug companies and the shifting winds of profitability estimates. If he gets the funding and the company approves, he gets to actually set up the trial, which in and of itself takes a long time find sites to administer the trial interventions, recruit people (the 30K, 44K, and 60K respectively mentioned above), and so on.
"It's not ten years because that is safe, it's ten hard years of battling indifference, commercial imperatives, luck and red tape,” he says. I would have included the Oxford comma there, but I'm quoting so I'm letting the article speak.
In the creation of this COVID-19 vaccine, they cut out a lot of those roadblocks. Funding has poured into these efforts, whether through Operation Warp Speed (Moderna, Johnson & Johnson, AstraZeneca) or from other sources (Pfizer), and the data is being shared and monitored cooperatively much more than it has been between previous competing drug development "races."
The next link is a BBC article about Oxford's vaccine creation. It also quotes Dr. Toshner. It discusses how this process really started nearly a decade ago. We had no way of knowing SARS-CoV-2 would become a global pandemic, but when SARS-CoV was a pandemic in 2002, and then a different coronavirus created MERS in 2012, science got to work. In studying those coronaviruses, we learned how that family of viruses works, including how they utilize a spike protein to unlock cells of the body to get in, replicate, and spread. They even made a MERS vaccine, but it didn’t go past phase 1 of the trial because the epidemic died down and financial interest waned. But between that and the H1N1 pandemic, the scientific community knew that it had to prepare for the next time.
Oxford made a vaccine template, an inactive virus that can be made to look like the virus for which immunity is needed. All you have to do is plug in the spike protein which can be presented to the body’s immune system (in a way that is without risk of replication, see below), so it can recognize that pattern if ever infected, and have antibodies ready. J&J and AZ are using this viral vector strategy.
Next, you’ve probably heard that some of the new vaccines are mRNA vaccines (Pfizer and Moderna), a fairly new type of vaccine. So what’s that about? For that we turn to Dr. Shane Crotty, virologist, vaccine scientist and professor at La Jolla Institute for Immunology. He compares mRNA to Snapchat messages (which is brilliant and I wish I had thought of it), as in they display their message to the right recipient (in the vaccine’s case, the recipient is the immune system) and then fade away (the way your own DNA’s mRNA would). A vaccine made from mRNA is designed to code for a single coronavirus protein (not the whole virus, so it can't replicate). So our cells will translate the message and create an immune response to the protein it creates. Our immune systems have evolved to recognize these types of proteins, and then the vaccine mRNA disintegrates and your immune system is now ready.
These mRNA vaccines do need to be kept ultra-cold, as you may have heard, and hospitals/public health distribution will rely on cold storage, among other things. That is due to the temporary nature of the mRNA.
Now, it’s not going to be all rainbows and butterflies. There will be side effects. 24-hour fevers and injection-site muscle aches, mostly, similar to the common side effects of the flu shot.
Dr. Paul Offit, in his op-ed in the Philadelphia Inquirer, addresses this. He points out that this process has been anything but rushed if you take out the bureaucracy and red tape (the equivalent of show-biz development hell).
Offit also talks about the rare major side effects, but also points out that any of those side effects (Guillain-Barré Syndrome in the influenza vaccine, for example, which is exceedingly rare) occur within six weeks of the vaccine, which means with these large numbers, and with the eyes of the world watching, we will definitely see if that happens (as we already did early in AstraZeneca's trial, which was paused to investigate an adverse event, and then subsequently restarted). The vaccine doesn't get Emergency Use Authorization by the FDA until we hit that time frame (post-second dose) and the safety data is strong.
Speaking of which, you may have heard and wondered about the fact that the vaccine is two doses. That’s not new, we have multiple vaccines that require multiple doses. Two doses gives your immune system even more pathways to a systemic immune response - the first provides some protection, but the second confirms that your system has many immune pathways to get a full response (security has a better chance of recognizing and kicking someone out if they've been shown who it is multiple times). At this time, no one has tested if the vaccines are interchangeable. So after you get your first shot, your second shot must be the same vaccine from the same company.
By the way, before this rumor tries to spread - you will not be able to get COVID-19 from the COVID vaccine. Just like you cannot get the flu from the influenza vaccine.
We don't know all the answers yet, because it is still early. But I hope this assuages some of the concerns that have been expressed. I urge you not to get caught up in conspiracy theories or the myth that a governor is trying to impose on your freedoms with this when they are really trying to combat this pandemic without a clear national message. Instead I urge you to consider your fellow humans. So many of you want to protect the vulnerable (even though everyone is vulnerable) - whatever your definition of vulnerable is, this is how we protect ourselves and each other. We will still need to keep our masks on and maintain distance and avoid large gatherings for some time...but this is going to be the first step. This is how we eventually defeat this pandemic and find a real "new normal." As always, I welcome your questions.
Update: I posted this to Facebook and other questions came up, as they should. My good friend, physician scientist Dr. Arthur Chang, came in with the assist: as of 12/4/2020 since things evolve quickly.
1) The current COVID-19 vaccines in children: there has been no published or preliminary reports of vaccine performance in kids. With that said, the current "front runners" have either designed or are enrolling trials to test the vaccine on adolescents. This is a very typical vaccine strategy given the extra general safeguards about testing medicines / vaccines in the pediatric population. They take a step-wise approach first making sure healthy adults tolerate it well, then healthy adolescents, and then healthy school children. Infants, immunocompromised, and pregnant are often the last groups to have testing done in general. I'm not aware of specific plans to test in these populations yet beyond "Let's see how adolescents / kids do first."
2) Do any of the vaccines contain a live virus: The short answer is both yes and no. the mRNA vaccines not contain any virus (be it COVID or others). The merely contain the instructions for a protein and our body does the work.
That said, there are a few "front runners" (AstraZeneca, Russia's sputnik vaccines, and some of the vaccines out of China) use what's called a "replication deficient viral vector" in otherwords the protein that they're making is from COVID, but to get the protein into people they use another virus to bring that instruction into cells. Most of them use Adenovirus that, again to stress, is unable to replicate. This is "similar" to the live attenuated vaccines we use for other diseases, but unlike those other vaccines in this case the Adenovirus is genetically altered to express COVID proteins. Thus we're piggy backing on the adenovirus weak ability to infect while expressing COVID to get the body to learn to fight COVID.
There are several others that are also in the pipeline that are more typical protein vaccines, and way further down the pipeline are people experimenting with live attenuated COVID vaccines, some being designed to be given as a nasal spray like FluMist. Suffice it to say we do not have clinical data on these yet.
3) The corollary to the previous questions, can immunocompromised people get the vaccine?: The short answer is we don't know yet. If the question is is it safe to give, there's little to no reason to suspect that it wouldn't be safe for most (but not all) of the vaccine candidates, especially for the mRNA based vaccines. however, the larger question of "will it work for immunocompromised people" is an open one at the moment regardless of type of vaccine since we do not have data to say definitively yet.
4) Is it possible that this virus can lay dormant in a body similar to herpes type viruses: Fortunately this is not the case with coronaviruses as a family (including COVID-19). These are not viruses that integrate into our genome or hide in our body like the herpes family of viruses (which notably includes VZV (chicken pox), HSV (cold sore / ulcer), CMV and EBV (the mono-like viruses). They do not have the same machinery or propensity to hide in our body. If anything our body is relatively good at getting rid of it which dove tails into the other question...
5) will it continue to mutate slightly with the need for a vaccine that will be tweaked yearly to try to guess the newest strain like the flu vaccine? This is mostly an open question, but largely hypothetical. Coronavirus does mutate like the flu, but not as fast as the flu. It actually tends not to mutate very quickly because it has machinery that reduces the mutation rate for a given strain. The way several of the vaccines are currently designed suggests that we may make immunity to a "common" portion of the virus which means our immunity may be relatively robust to minor mutations. Take for example, the mutations we have observed in the mink strains in europe. Current evidence suggests that the vaccines may do as good or better against that strain.
Articles I referenced:
Dr. Chang's sources:
Mutation rates of coronaviruses: https://www.nature.com/articles/d41586-020-02544-6?fbclid=IwAR1NKKuzoOI5NhCFVXIl3HB-Erfisy9XuggYY7jV_zM34n03qjrrVAPJEkc#:~:text=A%20typical%20SARS%2DCoV%2D2,the%20University%20of%20Basel%2C%20Switzerland
Talk by Dr. Falsey on current vaccines (relatively technical, aimed at researchers / physician-scientists): https://ub.hosted.panopto.com/Panopto/Pages/Viewer.aspx?id=a52e7e71-c6f1-4a2f-9240-ac7c010cea8c&fbclid=IwAR3F9KIOt-BAyAsuBkoRo1X8q5aNWk8BwV9COydaom4kYNVFGc68pEA5L_M