Learn about the Science of COVID-19 with Dr. John SantaLucia (Part 2)

I want to say a little bit about the different types of testing that are available. So there are nucleic acid based tests and there are antibody tests. So the nucleic acid tests are detecting the RNA from the virus. Remember we talked about the components of the virus. There’s an RNA genome and it has protein components. Well, the nucleic acid tests are the ones that when you see people doing a nasal swab or giving saliva, they are doing a test for the nucleic acid. There are different flavors of these nucleic acid tests. They’re called rapid tests or isothermal tests or the polymerase chain reaction tests or multiplex tests that can detect multiple viruses at once. These are very different than antibody tests. Antibody tests are a blood test that detects the immune response to the virus. And these antibody tests have usually a control and then they are actually detecting two different types of antibodies, so-called IgM and IgG antibodies. So antibodies are testing the human response to the virus.

All right, so, shown here is a really important set of graphs that really sort of show why there is some confusion about testing. So what’s shown here is day zero, if you were to become infected with this virus, if you were to do a PCR test on day zero, your chance of getting a positive test would be 40%. So that means that in the early stages of the virus infection, the PCR tests and the immunology tests would be negative, even though you have the disease. So as virus replicates and there are more and more copies of that virus circulating in your blood and in your respiratory tract, then what happens is you see more and more of that viral RNA present. So at day four the PCR based test will detect about 80%. All right? So even then, the test is still not perfect at its highest point. So the PCR test is determining do you have active infection currently going on?

Now, at that point in time, when you are most infectious and producing the most virus, the PCR test will be positive. But if you went and got an immunology based test, it’d be very likely to be negative, either for IgM or IgG. Either one of those antibodies would be negative. But later on in the course of the infection … your immune system starts kicking in, it starts defeating the virus. When that happens, the virus in your body starts decreasing, the amount of virus. And so the PCR based tests get worse and worse at detecting the virus, and now, your body’s response, the antibodies grow with time. And so after about two weeks, the antibody tests would be positive and the PCR tests would be negative.

At this point in time, you’d still have some residual viral RNA in your system, and you may still even be infectious, mildly infectious after a few weeks, but eventually, you would see, later on, you would see that the light blue curve is the IgM or, I’m sorry, IgG, and that antibody would be in a high amount, indicating you had a previous infection. And the initial IgM would now decrease. This is a sign that you are no longer contagious, basically. [The antibody] tests do not tell you if you are immune. They tell you if you’ve been infected, but they don’t necessarily indicate yet if you are immune to a future infection.

So the PCR based tests, as I mentioned, detect a viral RNA directly. That is, do you have infectious RNA agent running around in your blood? If so, the PCR tests do a test called reverse transcription to turn the viral RNA into DNA and then they do DNA replication many times to make many copies, and this is called the polymerase chain reaction, or PCR. This polymerase chain reaction is just a method of taking an original sample of RNA or DNA and making an exponential number of copies. So the temperature is cycled. Every cycle, the amount of DNA double. So it goes from one molecule of DNA to two molecules to 4 to 8 to 16, 32, 64. This method exponentially amplifies the amount of DNA and then that DNA can be detected by fluorescence. So if you see DNA amplification occur, then you had the virus.

Okay, so I’ll skip this stuff about multiplex PCR just to get into some of the other topics here. How do we develop immunity against this virus? Well, the coronavirus, once it gets into your cell, I mentioned it [earlier], the spike protein interacts with the ACE2 receptor. That makes the virus get into the cell. The virus is then uncoated and replicated. And then what happens is the virus is released from your cells, and then those viruses come up against your immune system, and the immune system has these cells, called macrophages, for example, and those chop up the viral proteins into little pieces. Those little pieces then become the signals that tell your body to respond by making B cells and antibodies or doing cytotoxic T cells to kill cells that are infected. Now, the B cells eventually create memory cells that can allow you to become immune later on. But this is a basics of how your body responds. So, the important point is your body takes parts of the virus and it utilizes that to immunize you against future infection.

So there are three important aspects to vaccines that utilize some of the principles that I’ve shown you about immunology. So the three important questions are about efficacy, side effects, and how long does the protection last? So efficacy is how effective is the vaccine. In the case of the Moderna vaccine, which I’ll be showing in one moment, it is about 94% effective. So that means that 94% of people who get vaccinated will be protected from being infected. That is a really excellent level of protection. Are there side effects? Side effects mean if you get the immunization, does the immunization itself cause problems? Does it give you the disease or give you some other overreaction to it? And that’s the reason why we have to do testing is extremely important with any new vaccine. It’s very important to know that it doesn’t have side effects.

So the Moderna vaccine was tested, for example, in 30,000 volunteers. They split up those 30,000 volunteers into roughly two equal groups, 15,000 each. 15,000 people got the actual vaccine. 15,000 people got a placebo. And the evidence showed that 90 people that were in the unvaccinated group got the disease, whereas only 5 people in the vaccinated group got the disease. So if you do a little bit of math there, it turns out that that shows that that vaccine effectiveness is 94%.

Now, there’s been huge efforts worldwide to make vaccines for COVID-19. To date, there are almost 100 vaccines that are under development at various stages of development. And this graph here is showing you the different types of viral vaccines they are going after. The first two are called virus-type vaccines that use either a weakened virus or inactivated virus. These are similar to the traditional [vaccines], like, for example, for polio, you have the inactivated virus with the Salk vaccine or you have the weakened virus with the oral Sabin vaccine for polio. Those are traditional viral vaccines. Then there are some new generation vaccines, particularly the nucleic acid vaccines, that are RNA based vaccines or DNA based vaccines or protein based vaccines. These are more modern approaches that are faster to develop and have fewer side effects. So I mentioned this about the Sabin polio vaccine and the Salk vaccine already, but I will say vaccines are among our most powerful public health approaches to addressing outbreaks of major diseases or pandemics.

So the new generation of vaccines, and I do want to spend a little bit of time about these. So you’ve heard a lot about the Moderna and Pfizer vaccines. They are 21st century relatively new ideas, and how do they work? Well, they take a small section of the RNA. So now that we have that sequence of the genome of the SARS-CoV-2 genome, we can take just a small part of it, that is the part that encodes the spike protein, and make the RNA just for that little part. And we can encapsulate that RNA in a little bit of a lipid coat. That lipid coat helps protect the RNA and helps it get into the cell. Once that RNA gets into the cell, then now we’re not infecting you with a whole virus, just with a single gene from the SARS-CoV-2, the spike protein, which is not the whole virus. So you’re not going to get a disease from this. It’s impossible to get the disease from these types of vaccines. And also, because it’s only one gene, it’s much less likely to have side effects.

So this gene, once it gets into your cell, it is translated into the spike protein. Which you see, just that little spike protein. Now, your immune system says, “Hey, those are not supposed to be here, those spike proteins.” And it elicits an immune response. And that immune response allows your body to have a memory so that if later on, if you are assaulted by the SARS-CoV-2 virus, the actual virus, it has the antibodies and other immune response ready to go to respond. So the Moderna and Pfizer vaccines are of this type. Super interesting.

All right, well, we don’t have time to get into all the other different types of viruses. And I have more information on some of these slides. I do want to say a little bit about something called herd immunity. So herd immunity, let’s just talk about … This is a topic that has led to a lot of misunderstandings about what is it. All right. Let’s talk about normal transmission of disease first.

If you have a few infected individuals which are shown in red here and you have many people who are not immunized and vulnerable to the disease, then what happens is the disease spreads like [crazy]. On the other hand, the more people who can become immunized to disease [, the better]. So if you have a large number of people who are these yellow people [i.e. in the figure], if they are immunized, then the chances of a person who is not immunized, these blue people here, if you’re one of these unimmunized people and you’re in a sea of population of many people who have been immunized, then it’s very unlikely or less likely that you’ll meet a person who is infected. And that is the herd immunity.

This is a really important approach, actually. Some people cannot get vaccinated because they’re immunocompromised or their immune systems are being suppressed because they have something like cancer, for example, or they have an upper respiratory condition that prevents them from getting the vaccine. For those people who cannot get vaccinated, we want those people to be protected, and the only way to protect those people who can’t get vaccinated is for lots of other people to be vaccinated. So that is the herd immunity effect. Now, if everyone says, “Oh, I’m just going to rely on everyone else getting vaccinated.” Well, then there’s just not enough of the population vaccinated for that herd effect to actually work.

That leads to this important question. How many people need to get immunized in order for there to be this herd immunity effect? And the answer to that question is it depends on a lot of things, some of which we know about and some of which we don’t know. One of the things that matters is something called the herd immunity threshold, which depends on what’s called the basic reduction number, R-naught. The R-naught is for each infected person, how many others will they infect? Well, this is a hard number to get accurate. For the SARS-CoV-2, it looks like that number is around three or so, between one and three, this reproduction number. And you can develop this number called the herd immunity threshold just from this simple equation. And you get a number around 70% or so for the herd immunity threshold. So about 70% of people need to be [vaccinated], for SARS-CoV-2, according our best information, about 70% of people would need to be immunized.

Now, the problem is that there are some other effects that come into play. So the critical amount of vaccination needed is called the Vc. That is the amount you need to eliminate or minimize the disease. So that number is a little higher, because the effectiveness of the vaccine is not 100%. Remember, that Moderna vaccine is 94% effective. But also, there are some people who cannot get the vaccine. About 10% of our population cannot get it. So that means of the remaining population, we have to have at least 80% of the remaining population need to get vaccinated.

So it’s a community duty. I have a whole slide about that, which we’ll get into it. It really is something [most of us should get]. All of us have loved ones, so getting a vaccination is important to protect you, it’s important to protect your loved ones, it’s important to protect your community. So all of us who are able, and certainly there are some people who cannot get vaccinated, for various reasons, you should seek the advice of your doctor about that if you have a comorbidity or some other problem that would prevent you from getting a vaccine. So those of us who can get vaccinated really should get vaccinated to protect the community.

I have some nice slides here on convalescent plasma therapy and cytokine storm and some other topics, and I think maybe I’ll just leave those for a future conversation so that we can have the time to ask some questions and answer some questions. Oh, I will get to this one. I have one more topic here, about masks. This is an area where I would say it is fair to say that scientists and our public health officials have given us some mixed messages, and I don’t think anyone was intending to try to give bad information here, but I think we’re learning as we go, and there are some things that, frankly, we didn’t know about. So I wanted to give you sort of my view on this, and I’m going to say this: I am not an expert on this. But from what I can glean about the science of this, this is what we have learned.

And viral particles [are very small], [but] your respiratory droplets, they’re much larger. So viruses would go right through any typical mask that you would wear. They’re so small they would just go right through the mask and be relatively ineffective. So I think initially, there was some thought like, “Why are we wearing masks? It just isn’t going to help.” But I think a further analysis has shown that that was incorrect. That masks, in fact, are much more effective than we thought. And here’s the reason why. Just think about this. If you are a person in the presence of an infected person, and that infected person, their respiratory droplets [are spewing out and] if you are not wearing a mask, then those respiratory droplets go right into your lungs and you’re getting a substantial dose.

If you’re wearing a mask, not all of the virus gets through the mask. Some of the virus is trapped by the mask. So by wearing a mask, you’re reducing the dose of virus that you get. And so that reduction, the dose makes the poison. The reduction in the amount of virus that you get, I don’t know the exact number, but let’s say it’s approximately 50% reduction, and if you wear sort of double cloth masks, those are the most effective, they capture the respiratory droplets stick in the mask. So probably you’re cutting your chance, your risk, by about half. Now, if you wear a mask and the person who has the disease wears a mask, now then that sort of cuts it in half twice. So it cuts down your risk by 75%. If you social distance, that reduces your risk even more.

Now, if you think about reduction and risk, and I’m talking about truly here, wearing a mask will not eliminate your risk for getting this virus. That is overselling. But it does reduce your risk. And on a community level, if a lot people, if 95% of people are wearing a mask, then it is going to reduce that risk in a sort of exponential way. It multiplies through the community, and it can have a substantial effect, particularly while we are waiting for the mass production of these vaccines to come on board.