Hello, this is Dr. Russell Kohl, chief medical officer at TMF Health Quality Institute with another installation of our Medical Minute. In today’s episode, we’re going to talk a little bit about the updated booster shots, and the emergency use authorization for those around the COVID-19 virus. So, with that, let’s jump right into it. On October 20, 2021, the U.S. Food and Drug Administration announced an adaptation to the emergency use authorization for the COVID-19 vaccines to allow for the use of a single booster dose. So, what they actually said was you may use a single booster dose for the Moderna COVID-19 vaccine, that needs to be at least six months after completion of the primary series, and it should only be given to those who are 65 years of age or older. If you’re 18 through 64, but at high risk for severe COVID-19 – so you have some of the different high-risk factors, or are 18 through 64, but have frequent institutional or occupational exposure to SARS-CoV-2, so this is probably the most non-specific of the requirements, but think of this as the likelihood that someone is going to come into contact. And, if you are in a situation where there is a high likelihood, such as a school teacher or something along those lines, then they recommend, under the emergency use authorization for that. In addition to the Moderna vaccine, they clarified for the exact same for the Pfizer vaccine, a third booster dose. And then around the Johnson and Johnson COVID-19 vaccine, they authorized that for anyone 18 years of age or older, and specified that instead of for the others, which are six months after your primary vaccination, this is a two month wait limit on the J&J. So, certainly those are big pieces of news. The biggest piece is the allowing of the mix and match booster dose. So in this, if someone has completed a primary vaccination of any sort of COVID-19 vaccine, then they are able to use any of the other vaccines for their booster dose. We’ll talk a little bit about the pros and cons of homologous versus heterologous vaccination a little bit later. But, first, let’s jump into the science. So, an article released in Mortality and Morbidity Weekly Report in September looked at the hospitalization effectiveness of each of the COVID vaccines as we have observed over the past year. And so they looked at within 14 to 20 days, or 14 to 120 days after receiving the vaccine. And then looked at greater than 120 days after having completed your vaccination series and what was the impact on reducing hospitalization. What they found was the Moderna vaccine actually was best at holding its long-term effectiveness in the 14 to 120 days after completing the vaccination series. Moderna had a 93 percent effectiveness rate against hospitalization. At 120 days after vaccination, that had only dropped to a 92 percent effectiveness rate. So, really high performance there. If we look at the Pfizer vaccine, that 14 to 120 day time period had a 91 percent effectiveness, but when you go out to 120 days, that had actually dropped to 77 percent effectiveness. So, still significant, but certainly not as impressive. When you get down to the J&J, or the Jansen vaccine, the single dose regimen at 14 to 120 days, it was 71 percent effective at reducing hospitalization, and really had very little change over time, such that at 120 days, it was at 68 percent effectiveness. So, we know there is a decrease in effectiveness over time. One of the questions that has been raised though is that a change in you or is that a change in the virus itself? So, fortunately, a study was published in October in the Lancet that came from Kaiser Permanente, that looked at the effectiveness of just of Pfizer, but looked at it against different variants. A little over 3.4 million people in their study, and it actually did differentiate between which variant the individual had received. Looking at the effectiveness against infection for the Pfizer vaccine, overall, over the entire time period, it was 73 percent effective, but against hospitalization it was 90 percent effective. Now, when you break that out by whether or not it was the delta variant or another variant, we do see that the delta variant, if folks acquired that illness, within the first month after their vaccination, it was still 93 percent effective. At four months later, it was only 53 percent effective at preventing infection. If you look at the other variants of the virus, within the first month, the vaccine was still 97 percent effective against being diagnosed with COVID-19. At four months, it had dropped to 67 percent. Now, the most important thing though is that even with the delta variant, which had the least effectiveness, if we looked out at six months, its effectiveness at preventing hospitalization was still 93 percent. So, certainly still, a highly effective vaccination. That Kaiser study does help us recognize that while there is a difference in the effectiveness against particular variants, there certainly is a time component associated with that. Taking to our third and final study we’ll talk about today, published in the New England Journal [of Medicine] in October, is a study in Israel that looked at 60 years old and older folks over a 60-day period and compared those who had received a third booster shot versus those who had not. The study included over 1.1 million folks and identified that at 12 days after receiving the booster shot, those who had received the booster shot were 11 times more protected than the folks who had just had the initial series of the vaccine. To put that in perspective, in the 60 days of the time period, there were 4,439 cases of COVID in those who were vaccinated that had not received a booster shot. There were 934 cases in those who had received a booster shot. But if you look at the severity, folks who actually had severe cases and had to be hospitalized, those with the primary vaccination series, only it was 294. Those who had received a booster shot, it was 29. It is important to keep in mind though that this is an over 60-year-old population, so they are certainly confounders associated with their likelihood of having severe illness. So, the big question folks have is about reactogenicity, or side effects as it is commonly called. So, essentially, they have found with the booster shots there is no real increased risk of side effects, particularly around the myocarditis, which is something that was looked at very closely. Fifty percent of folks who did get a booster shot reported either having sight pain, malaise, myalgia or headaches. Certainly, a fairly normal side effect profile, but actually a good thing from a medical perspective. The fact that you are reacting to it helps us know you are developing immunogenicity. The last thing to talk about today is homologous versus heterologous booster shots and what that really means. This is the mix and match component. If you had a Pfizer the first time, getting a Moderna booster shot or getting a Jansen booster shot, what are the potentials of doing that and what are the pros and cons. The difference in immunogenicity is really an interesting problem to deal with, because think about how the immune system works. You’re creating antibodies against whatever it is that you were exposed to, and so this is where natural immunity comes into it, this is where the different vaccines and presenting slightly different antigens, means that your body will create slightly different antibodies. A homologous booster shot will give you a higher antibody level; however, they will all be against the same component of the virus. This does increase your risk of being susceptible to a viral mutation in the future if your entire immunity is around a single antigen. However, a heterologous booster vaccine, or a booster from a different vaccine, will present to your body a slightly different antibody. What this means is you won’t get quite as high of an antibody level for any specific antibody, but you will have antibodies against multiple aspects of the virus. So, this can actually be a little bit more protective, actually, by giving you a little bit of protection against viral variants. If one of the antigens that you have an antibody against mutates in the virus, and no longer presents itself, you do still have some immunity left from the others. Certainly, just from my professional opinion, I am a big fan of heterologous boosters, just for the effectiveness they demonstrate over time. And it is notable that this is how the United Kingdom and the European Union have dealt with the vaccine from the very beginning. Certainly a safe and effective approach. I hope this information has been helpful to you. It certainly is interesting to dive back into some of the primary research on it. You might ask yourself, what is the real take away here? From my perspective, the real take away is that we have been able to show now that there is a waning immunity over time. That that is associated with your immunity itself and not just with variants of the vaccine, that there is effectiveness of the booster shot, but that there does remain a long-term effectiveness of the primary vaccination series. So, if you take all of these factors into account, what that means is that if you are at high risk of COVID infection or severe COVID there is probably some significant benefit to taking that booster shot as available through the EUA at this point. Those at regular risk it is still a bit more of a risk versus benefit analysis, but I will point out that there were very few risks associated with that additional booster shot. So, hope that’s helpful. I expect we’ll be doing another session fairly soon on the vaccination of children, but we’ll see what the FDA has to say about that at this point. So, with that, once again I’m Russell Kohl, chief medical officer and family physician at TMF Health Quality Institute. Keep up the good work, and don’t forget to keep making the world a better place.