Understanding the COVID-19 Vaccines: An Interview With Dr. David Agus

On the morning of January 25, I had the distinct pleasure of interviewing David B. Agus, M.D., Professor of Medicine and Biomedical Engineering at USC’s Keck School of Medicine and USC’s Viterbi School of Engineering.

To better prepare myself for this interview, I decided to reach out on social media and ask people what questions they wanted to ask Dr. Agus about the COVID-19 vaccines. I specifically encouraged people who are on the fence or don’t plan to vaccinate to express those doubts and give Dr. Agus a chance to answer each particular point.

Boaz Hepner: Is it a realistic concern to still spread the virus after being fully vaccinated? If so, doesn’t that make it harder to achieve herd immunity?

David Agus: That’s a fantastic question. If someone gets the vaccine and waits until full immunity — which is about a week or two after the second shot — and then they are exposed to the virus, 60% of those people will have no detectable [viral load] at all. Anywhere from 30-40% may have some detectable amount of the virus, but it would be a dramatically lower [viral load] than if they hadn’t taken the vaccine. This is fantastic because we know that the amount of virus you have dictates how infectious you are.

While it would be better if there were zero virus [after inoculation], [the vaccine] will certainly lead toward herd immunity by eliminating most of the highly contagious individuals and lowering the viral level pretty dramatically… By dramatically reducing the amount of virus, we will still achieve herd immunity and stop the virus in its tracks.

BH: Do you anticipate at least some capability of transmission post-vaccination?

DA: It will certainly be much harder to be infectious after you’ve been vaccinated, but it will remain possible. When you get vaccinated, it’s not a free pass to go hug grandma and go about any behavior or activity. What we’re looking for is that the majority of the country gets vaccinated and then waits two or three months, and we will see the virus [cases and hospitalization] fall precipitously. And that will bring us back to what will be a good new normal.

If you do get exposed to the virus, you’ll have a much lower [viral load], and we already know that these four leading candidates of vaccines result in no hospitalizations or deaths from the virus. You may get a little bit sick, you may get a mild cold, but you won’t be severely ill, and that’s what we really care about — the severely ill. What we worry about is that 5-7% of the U.S. population can’t respond well to a vaccine; it’s these individuals that we have to protect, and that’s why we’re pushing for herd immunity.

BH: To clarify, the four leading vaccines you are referring to are Moderna, Pfizer, AstraZeneca and Johnson & Johnson?

DA: Correct.

BH: Is it likely that we will have a kid-friendly vaccine by the summer? Or before the next school year?

DA: There’s no reason that the vaccines won’t be just as safe and work just as well on children. In the United States, we first do clinical trials in adults. If it proves safe, we do the safety studies on children. Safety studies with children are ongoing at the present time, and those results should be available over the next several months. So probably by the beginning of the summer, we will have safety data on children and [will] start to distribute vaccines to people under the age of 16.

BH: What ages of children do you expect them to be safely released for?

DA: Every vaccine has slightly different age requirements with what they’re doing. It will probably end up averaging age five and above.

BH: How will the vaccine hold up to the different mutations of COVID-19? Do you believe it will work on the new and future strains?

DA: We predicted — science knew — that this virus would zig and zag, and science is going to zig and zag with it. The strains are slightly different shapes of the spike protein that binds these to the receptor. For example, with the U.K. variant, our current vaccines work remarkably well. With the South African and Brazil variants, they work but not as well — they’re not conferring as much immunity to those as they would to the virus before the mutation happened.

Over time there are going to be more variants — no question about it. The sooner we vaccinate everybody, the less virus there [will be], and the less variance there will be. At some point, we are going to have boosters to the vaccine, and they will include these new variants. …This was expected. This is how immunization to viruses work. This doesn’t at all negate what we are doing now. We are still going to need vaccinations for the current strains, and then we’ll augment our immunity with boosters.

BH: What about the fear from people who say, “fine, we’ll come up with boosters, but when there are variants this doesn’t work on, how does that not just put us back to step one?

DA: Because [the vaccines] will still work somewhat against those variants. By saying there’s decreased immunity against a variant, it probably means you’ll [have] some immunity, and [it will] probably prevent you from getting really sick, but you may still get a mild cold. It’s not all or nothing. We have to deal with the viruses we have now. We have to look at it [on] a strain by strain basis. At the same time, we have to plan for the future of developing and augmenting further immunity to these new variants.

BH: How easy is it for them to keep adjusting the vaccine for new strains?

DA: Already, the four leading vaccines have developed variants to the new strains. Vaccine boosters will go through safety studies and at some point be added. It may be that when you get your flu shot in the fall, we add a couple of variants of spiked protein to them. Or we give an additional booster shot separately. Which of these ways they choose to go isn’t yet clear, but they are already under development, and safety testing will soon begin.

BH: If someone was presented with an opportunity to get vaccinated before others who are more at risk, should they decline or jump at the opportunity?

DA: It’s a really difficult question. When I was vaccinated, I felt guilt. I felt guilt my parents hadn’t been vaccinated yet. I felt guilt that many of my patients, who are older and have more risk factors, didn’t have it yet. But at the same time, by vaccinating me — a frontline provider — I couldn’t be a conduit to spread the virus as easily anymore. If you look at it in the sense that every single person who is vaccinated is one more person slowing or stopping the spread of the virus, then we all need to be vaccinated.

By setting up this hierarchy, saying [that] this person needs it more than that person, society has imposed its ethical constraints on vaccination. I don’t think anybody should be cutting the line. I think that every state is setting their hierarchy, and we all have to abide by the rules of that, and there will be an order to it all, and we can and will be able to get it in the next few months.

I don’t think anybody should be cutting the line.

If there isn’t an indication where you can be vaccinated now, I would stay back and let the people who need to be vaccinated sooner get it first. Right now, there is an advantage to those who can search on a computer and find the times. Think about who has the resources and time to do that, to keep logging in and seeing when a slot opens. That’s not equal across the board. We need to find a way to distribute this vaccine to the right people at the right time, regardless of personal resources.

BH: Some people are hearing about doses being wasted at the end of the day, and some people are told by friends “be on standby, I might call you if we have extra doses being thrown away so come and get it quickly if that happens.” I assume that’s something you’d be comfortable with?

DA: Yes, that’s playing by the rules. If the rules are that these people get it first, but at the end of the day, we don’t want to waste a dose, and so it’s available to anyone nearby [because] we don’t waste it, that’s all fine as long as you’re playing by the rules.

Unfortunately, there’s been a lot of chaos in the organization of all of this. The federal government and every single state made their own rules, and what you had was some states being really good with it, and other states weren’t. Some states wanted to give all of the doses they had and tried to immediately get more, and other states were holding back doses to have a supply prepared for each person’s second dose. I think we’re going to start to get more of a national policy on this, which makes a lot more sense. 

BH: How likely is it that people will get long-term side effects from the vaccine? People are scared of getting MS or cancer or birth defects in future children and countless other scary things.

DA: When you get the vaccine, the important thing is to realize the vaccine is no longer present in your body after a couple of days. Your immune response actually eliminates the vaccine. Regarding side effects, this is what we learn from our trials. If you look historically, we can learn the different things they observe[d] during those trials when things [did] not go as planned. In some cases, the side effects have been that when you make an immune response, it targets something else in your body instead. In other unsuccessful trials, they’ve found the immune response to be so powerful that you get sick from the vaccine itself. And in yet another example during trials, they’ve found that the immune response doesn’t really deal with the virus and instead hides it from the body, so you can get sicker from the virus. But the beauty of it is that all of those examples are consistently seen in the first four to six weeks of inoculation. So every vaccine that I’m aware of in the modern era has involved side effects that have been caught in the first four to six weeks.

With these [Pfizer, Moderna and AstraZeneca] vaccines, which have been given to over 25 million people globally to date, there have yet to be any long-term side effects at all. All of the side effects are short-term and reversible. They are pain in the arm, fatigue for a day or two after the shot [and] fever the day after the shot. The wonderfully predictable thing is that these are really markers of an immune response, not side effects necessarily of targeting this spike protein of COVID-19. This is remarkable — new vaccines where there have yet to be any long-term side effects from the vaccine. And I think that’s making us all very encouraged. At the same time, these vaccines have … prevented death and hospitalizations [just about 100%] (assuming you wait a week or two after the second dose). You can’t do better in terms of a vaccine than what we have now.

BH: People have a fear that vaccines may typically show side effects in the first 4-6 weeks, but they’re also touting mRNA technology as new and revolutionary. How can you be confident that there won’t be any long-term side effects on this vaccine if the technology is so new?

DA: Because it’s not as new as people think. We’ve been using mRNA vaccines for over a decade now. They aren’t yet approved by the FDA, but they’ve been used in clinical trials and studies for many years, and we haven’t seen any long-term issues with them. So the backbone for these vaccines — Pfizer, Moderna, Johnson & Johnson and AstraZeneca — all of these have significant history and data behind them. They weren’t created from scratch. All of these vaccines were built on scientific knowledge that took decades to create. So it’s not like these vaccines were made overnight. They were tweaked overnight to be able to target COVID-19, but the foundations have a long-term science behind them.

BH: Wouldn’t it be safer to wait until millions of people have had the vaccine for years before taking it? What if it has unintended side effects that we can only find out about years later, such as birth defects or cancer?

DA: Even people who are asymptomatic can get heart and lung problems from this virus that can last a lifetime. We know that. The inflammation from this virus can cause havoc on your body throughout your life.

[Compare that to] the vaccine, which now from 25 million people has yet to show any significant issues. I look at the risk/benefits from both, and clearly it favors getting the vaccine. Can I definitively say no, there won’t ever be a side effect from the vaccines? No, obviously not; until we’ve gone long-term, we can’t know 100%. But I can tell you that if you do get the virus, the chances of something significant happening health-wise is very real, whether it be [to your] heart or lungs; it can even happen to the young, asymptomatic individuals.

We all have to be a part of this. We’re in a new era, and the era dictates that you have to look after your community. By you getting the vaccine now, you are significantly helping to prevent spread to others, especially to people who physically can’t respond to a vaccine. We have to think of ourselves as one community, and I think that’s a really powerful notion, being one community together, creating a necessary herd response.

By getting the vaccine now, you significantly help prevent the spread to others.

BH: What’s the point if doctors are saying everyone will still have to wear masks even though they are vaccinated? Has there ever been a virus that you’ve been capable of still transmitting to others after achieving immunity?

DA: Yes, it’s certainly not uncommon [with] the flu and other viruses to find the vaccine giving some immunity and protecting you from getting very ill but still being able to transmit the virus to others. For the first couple of months after herd immunity, if we all continue to wear masks, the virus will go away. That’s what we’re shooting for.

We’re not asking people to wear masks forever. But we are saying [to wear masks for] a month or two after we achieve herd immunity. And then, the new normal will be that you wear a mask when you’re sick, just as they do in most Asian countries. If you have a cough or a cold that day, you [will] wear a mask if you’re going out.

BH: What is different about “FDA Emergency Use Authorization” versus “FDA approval,” and what additional steps (trials, studies, etc.), if any, would the vaccine manufacturers have to take in order to obtain actual FDA approval?

DA: In order to get full FDA approval, they need more follow-up time on the vaccines, which should happen in the relatively near future. This is a vaccine process that’s different from almost everything we’ve ever done because classically, when a drug or vaccine is approved, we stop collecting data. That’s it. But the beauty of this vaccine is that every single person who is vaccinated is given a card with something called V-Safe on it, where they can actually submit their side effects and how they’re feeling. We’ve collected over 20 million data points after the vaccine has been administered, and that is ongoing. The exciting part is collecting real-world data, which is powerful and important as we move forward.

BH: Do mRNA-based vaccines suffer from a greater chance of becoming less functional/adaptable to viral genetic mutations than other vaccine types — such as adenovirus-based vaccines — due to the more precise nature of these mRNA vaccines?

DA: No. They are equivalent in that regard. An mRNA vaccine is basically a code to make the spike protein. And the adenovirus vaccines use the same translation of the code that the mRNA vaccines use or vice versa. There could be a one to one mapping. The conventional vaccines are also basically a code for the spike protein. So we’re describing the same spike protein in all of this. If that spike protein changes like it did… in the U.K. or South Africa or Brazil [variants], then we would have to sufficiently change the code. All of these technologies are amenable to changing the code with the new booster shot.

BH: Many are unsure whether to get vaccinated, as they’ve heard it can cause infertility in both men and women. Is there any truth or possibility of that?

DA: The fertility thing is an internet rumor. There is no effect on fertility at all with any of these vaccines. There is no way scientifically that it could affect fertility. We also know that we have over 20,000 pregnant women in the database now, and they have done fine. Mothers nursing their babies — those moms and babies all have done fine. All of that is very encouraging. We have to be cautious [about] what’s real and what’s basically an internet rumor. And in this case, the fertility accusations are entirely an internet rumor not based on science.

BH: Some vaccines can cause worse reactions than getting the virus without being vaccinated in the first place, what is called Antibody Dependent Enhancement (ADE). Is that a possibility for COVID-19?

DA: It has been disproven for all of the four vaccine candidates that we’ve been talking about.

BH: Why not just inject a bunch of spike proteins instead of injecting a fragment of RNA or DNA?

DA: In order to get good immune responses, we need carriers to basically turn on their immune systems. So with every vaccine we use, it’s a little piece of the virus that has to be given in another context. We have to basically prime the immune system. Each of these vaccines is meant to do that. You saw today, for example, Merck’s vaccine failed because it didn’t turn on the immune system enough. So it’s really critical that we not just have the spike protein, but also other components [to] activate the immune system so that the response is robust enough to provide adequate protection.

BH: After the elderly, at-risk members of a family get both doses of the vaccine and wait a few weeks after the second dose for full immunity to kick in, what does a safe family get-together look like with the younger family members who are lower risk but still not immunized?

DA: Vaccinated people can still get the virus and spread it to others. It’s really critical that we continue to have get-togethers the same way we’ve been — with wearing masks and social distancing — and not having large get-togethers until we achieve herd immunity and go past it by a few months. We’re talking this summer, probably.

Getting the vaccine is not a pass. We have to be cautious about that. We’ve seen this in the world already, where after the first shot, people have started to think it was a free pass to change behavior, and we saw a rise in the number of cases. We have to be very helpful here. If we do this together and do it right, we’ll be back to a fall where we can have children going to school; we can have businesses open; we can have the economy rebound and get back to our new normal. 

BH: How will this focused effort on COVID-19 translate into other biomedical advances?

DA: There’s no question that what COVID-19 taught us is that data matters. It taught us that we have to start to be able to use every patient’s experience to benefit others. What I think COVID-19 will do for our future is two things:

1. This horrible experience will enable us to start to use medical data in a privacy-protected way to help each other and better target disease.
2. It also shows us what the roadblocks are — how we should do things better and quicker. Being prepared for a future pandemic but also developing drugs faster for cancer, Alzheimer’s and heart disease.

We learned a lot here, and I think there are going to be ramifications for early research and clinical care of every disease in a positive way because of what we’ve gone through.

Dr. Agus invites and welcomes anyone who has questions about this or any medical topic to text him at 310-299-9322, be patient, and he’ll get back to you as soon as he can.

Dr. David B. Agus is a professor of medicine and engineering at the University of Southern California Keck School of Medicine and Viterbi School of Engineering. He is the founding director of USC’s Lawrence J. Ellison Institute for Transformative Medicine. Dr. Agus specializes in treating patients with advanced cancer. His clinical responsibilities include the development of clinical trials for new drugs and treatments for cancer, supported by the National Cancer Institute and other private foundations. He serves in leadership roles at the World Economic Forum, among other prestigious organizations.  

Boaz Hepner works as Registered Nurse in Santa Monica and lives in Pico/Robertson with his wife and daughter.