Kyle: Dr. Patrick, this question's for you, and it's about transmission. And we know that the Delta variant has been a game-changer, and we've seen the efficacy of vaccines drop to some degree with regards to do they prevent symptomatic COVID-19. And we're also aware that transmission of the Delta variant may be happening among...well, is happening among fully vaccinated people. So, what are your thoughts on this? Should this shake people's confidence in getting a COVID-19 vaccine?

Dr. Patrick: Well, I think people have...it's always easy to make generalized statements when you see a little piece of data coming in, which, by the way, new data every day, things are changing constantly, hard to keep up with. I think people have made this overarching statement that vaccines do not prevent the transmission of SARS-CoV-2 virus. In other words, they do not prevent people from contracting COVID-19. And, I think, to understand why that is not true, we need to start with the word transmission because there are two major types of transmission when we're talking about a viral illness here. First is called onward transmission, and this is the type of transmission that is more at the individual level. So a person becomes infected with a virus. They have viral particles in their nose, and, you know, they're basically shedding viral particles. And this can be transmitted through aerosols and large respiratory droplets to other individuals, right? So this is the transmission of the virus that most people think about. But there's also what's called its overall transmission, and that is the transmission in an overall population. This is the population level. So if we have a treatment or a vaccine that is able to prevent even a small percentage of people from becoming ill, then it still reduces overall transmission because fewer people are actually getting the illness.

And so as you mentioned, the Delta variant has sort of changed everything because, when, you know, we had the Alpha variant and even the Beta variant, we know that the vaccines in the United States were largely effective still and, you know, in many cases still 90%, 95% effective at preventing people from even getting COVID-19 symptomatic and seeking out health care. We know that in addition, people that did become...that did get infected with SARS-CoV-2 virus, they actually had fewer viral particles. They were not transmitting the virus like an unvaccinated person was. That's all changed with Delta. Now we have to aggregate new data, see, you know, what the data shows. And, I think, I would say that the data shows that in about July of 2021 is when the Delta variant in the United States really started to become dominant, sort of took over. And so there was a large study that was done out of the Mayo Clinic. Many states were involved in terms of like the sample population from many different states in the United States. And this was like 25,000 people that were vaccinated versus 25,000 people that were unvaccinated. What the Mayo Clinic study was looking at first was vaccine efficacy, like the ability to, you know, prevent people from getting COVID-19 and also looked at the efficacy of preventing hospitalization. So that's also very important.

And so when the Delta variant became dominant, it was clear that efficacy for preventing infection went down. So people that were fully vaccinated with the Pfizer vaccine went from an efficacy of like 88% to 93% or something like that down to 41%. So, there was still some efficacy. In other words, you know, 41% of people that were fully vaccinated were still not getting COVID-19, which means that the Pfizer vaccine still reducing overall transmission. And on a similar level, the Moderna mRNA vaccine also had reduced efficacy in terms of preventing infections, although it wasn't quite as dramatic. So the Moderna vaccine is about twice as protective as the Pfizer vaccine in getting a SARS-CoV-2 infection. So that was about 77% effective at preventing SARS-CoV-2 infection. So, again, overall transmission is reduced because, you know, a large percent of people that are fully vaccinated with Moderna are still not getting even infected. That was good news. Both vaccines were still quite effective anywhere from 80% to 97% effective at preventing hospitalizations, which is ultimately the most important thing. As Dr. Seheult pointed out earlier in this discussion, you don't want your hospitals overwhelmed with COVID-19 patients because, when your parents have a heart attack, or if you get in a car accident, or your child comes down with a severe form of RSV, you know, or fill in the blank, you're not going to get the care that you need and you deserve. So it's good to prevent hospitalizations because that protects our health care system from being overwhelmed, which is important for all of us.

The other thing that was found was that...not with the Mayo Clinic study, but there was another study, a large study that was done out of the U.K. and this study showed that this was...the most interesting thing in my opinion in this study, this also included AstraZeneca vaccine because AstraZeneca has largely been used in some European countries like in the U.K., that people that were fully vaccinated were still...you know, there was still some efficacy in terms of protecting against, you know, getting the virus as I just mentioned with the Mayo Clinic study something similar was found. But when you looked at peak viral load, in other words, when the virus is at its peak for replicating, the peak viral load was similar in a breakthrough infection from a vaccinated person versus a unvaccinated person that had contracted the SARS-CoV-2 virus. And so that sort of caused a media frenzy, you know, to sort of make this general statement that vaccines don't prevent transmission. And it's just not accurate to say that. For one, they're still preventing overall transmission as we just discussed. But two, you need to look at overall viral replication. So, you know, it's not just peak transmission that's important. You're transmitting this virus to other people at many different stages of being infected. And so that's exactly what this pre-print study out of Singapore, which was with the Delta variant showed that while initial viral loads were similar between a breakthrough vaccinated case and an unvaccinated person that had SARS-CoV-2 virus...infected with SARS-CoV-2 virus, those initial viral levels were the same. If you followed those individuals over time, the vaccinated people cleared the virus faster than the unvaccinated. So they actually had a shorter negative PCR time. If this was true, you would have the hypothesis that at any given time, if you were to take a random person out of the population and sample their viral load, then you would see vaccinated people at any point in time should have a smaller viral load because they're clearing the virus faster. And that's exactly what this real-time data that's being aggregated out of the U.K., it's called REACT Study, that study found that if you were to take a random sampling of people at any point in time, vaccinated breakthrough cases, they had a lower viral load than unvaccinated. So, I think, with this data, it suggests that not only do the vaccines still prevent...sorry, still reduce overall transmission, they also still reduce onward transmission. They're still affecting transmission on multiple levels. And so, I think, that's really important to keep in mind. In addition to that, understanding who gets the breakthrough infection. Why are 41% of people vaccinated with Pfizer still protected from even getting, you know, SARS-CoV-2 virus? And why are 77% of people fully vaccinated with Moderna not getting infected?

There was a big study that came out of Israel looking at breakthrough infections. Now, this wasn't necessarily when Delta was dominant, but I think it still is important to keep in mind that what's causing these breakthrough infections. We don't know exactly everything, but if you look at this Israel study, they were looking at health care workers. And there was about 15,000 of them basically. These health care workers, they took blood samples, and they could look at their antibody levels against...these were vaccinated health care workers. They could look at their IgG antibodies, and I'm not sure what other antibodies they looked at, but they could look at the levels of them and quantitate them. And then if they came down with a breakthrough infection, they could sort of use that data and go, "Oh, could we predict whether or not this person came down with a breakthrough infection based on their antibody levels?" And that's exactly what was found. People that had lower antibody titers were much more likely to get a breakthrough infection than people that had higher antibody titers. And there was another great study that came...it was a Miles Davenport group, and it published in "Nature Medicine." And he did this mathematical modeling to predict breakthrough infections. And what he found was that it seems as though, according to his model, people need a six-fold higher antibody titer level to be protected from contracting SARS-CoV-2 virus. Then they need to be protected from being hospitalized from the SARS-CoV-2 virus. In other words, you need a much lower antibody level or titer to prevent yourself from being hospitalized, but you need a higher level to prevent yourself from actually contracting the virus itself.

Dr. Seheult: So what Dr. Patrick has told us is that there is a difference that you have to look a little bit deeper. I was able to find a pre-print of an article that just came out a couple of weeks ago that looked at the quality of those viral particles that are shed from those that have breakthrough infections. So in other words, is it possible that the shedding of the virus that comes from unvaccinated are the same as vaccinated. And what this pre-print showed very interestingly if you look at this graph, here we have the amount of viral load being shed on the X-axis, and on the Y-axis, what they did was they tried to see what was the chances of these viral particles of actually growing in a viral culture, kind of a surrogate to successfully infecting the next person. What you can see here is the dark blue are those that are unvaccinated, and the light blue are those that are vaccinated. You can clearly see here that at any given viral load, the vaccinated health care worker in this study from the Netherlands was shown to have a less likelihood of infecting somebody based on viral culture. So, not only do we see with the vaccinated less breakthrough infections, and when there are breakthrough infections, they are cleared faster. But we're also seeing that the viral particles that come out of vaccinated people are less likely to infect. And that's important because there has been some talk going around that it's the vaccinated people that are transmitting the virus more and causing these outbreaks to those that are unvaccinated, and those are the ones that are showing up to the hospital. But clearly, here, the data is showing that is not the fact.

Dr. Patrick: Oh, just to add to that, Dr. Seheult, that is very interesting...that the study is very interesting because the way that researchers are measuring, you know, peak viral load is through real-time PCR, and real-time PCR can actually be detecting dead viral particles. That makes a hypothesis even quite likely that there are some dead viral particles, which you would even...you'd sort of, you know, theorize would be true because, if you do have antibodies against the spike protein, that your immune system would start to kill or to, you know, clear the virus that you're being exposed to since you have some antibodies, you'd think there would be some effect. So that's very interesting.

Dr. Seheult: Right. It boils down to the thing that I've heard that explains this as PCR is a way of looking...it's kind of like looking at dead body parts and assuming that those dead body parts are alive. All it's looking for is parts of the virus, and parts of viruses don't infect. They just make PCR positive.

Dr. Patrick: Right. Exactly. The question is, is like how many of those viral particles are actually even alive. If they were alive, you would imagine that when you put them in culture that they would replicate. So, very interesting study.