COVID-19 Vaccines: Ask Dean Jha Anything

In a forum on May 27th entitled, “Ask Me Anything,” Dr. Ashish K. Jha, dean of the Brown University School of Public Health, answered the Brown community’s questions on the science behind COVID-19 vaccination and its public health implications.

Community members from across campus, including alumni and parents, listened and learned about the scientific and health aspects of COVID-19 vaccines from Dean Jha and Dr. Megan Ranney, associate dean for strategy and innovation in SPH. The answers that follow address many of the questions and concerns discussed, and have been lightly edited for length. Please be aware that as research and policies continue to evolve, opinions are subject to change. For the latest information and further reading please explore these resources from the CDC, the NIH, the RI Department of Health, and Brown University

Globally, we've administered about 1.3 - 1.4 billion doses of the various vaccines. In the United States we're getting close to about 300 million doses administered to about 165 million people. About half of all Americans have gotten at least one dose, about half of all adults have gotten both doses. This is the biggest vaccination program in the history of the world.

When I look at the three American vaccines: Moderna and Pfizer’s two-dose mRNA vaccines, and Johnson & Johnson's one-dose adenovirus vaccine, all three have far exceeded our expectations on effectiveness.

From what we know about the safety of these vaccines, all three of them are exceedingly safe, by every measure that we can think of. Of course, there are short-term side effects, but now we have data from hundreds of millions of people who have gotten these vaccines which suggest safety.

The likelihood of clotting probably depends on who you are, and your demographic status. The risk may be as high as one in 100,000, and it may be as low as one in a million. But even those rates are exceedingly rare and we have not seen these cases with the Pfizer and Moderna mRNA vaccines.

We haven't yet had these vaccines for a decade, so we don't know the long-term effects. But we can ask, how do these vaccines work, and could there be a plausible mechanism by which there could be long-term effects which we do not see in short-term periods? Also, what do we know about other vaccines, and whether they have had long-term effects?

We've been making and administering vaccines for well over half a century. I am not aware of any vaccine where the first set of negative effects show up past eight weeks after immunization. The biology of how vaccines work, suggests that it would not make sense for a new side effect to show up five years later. The history of vaccines suggests that almost all of the side effects and almost all of the problems that vaccines generate, tend to show up within two to four weeks, sometimes earlier.

The FDA, when thinking about issuing an emergency use authorization, decided on 60 days of follow up in clinical trials. This gets us beyond eight weeks (which is 56 days). Now, we have more than six months of follow up in millions of people.

The BLA is a full license, while the EUA is only issued in emergencies. EUAs were issued for Pfizer, Moderna, and Johnson & Johnson because at that time we did not have enough follow up data from clinical trials. However, we were in the middle of a crisis, and it made sense to issue EUAs in the US in order to get vaccinations started.

These vaccines have been studied with more data and more evidence than any vaccine that has ever gotten full BLA licensing. There is no question they will all get full licensing. I expect over the next month, Pfizer will get the full BLA license. Moderna will follow closely behind, and Johnson & Johnson will take a little bit longer. Before applying for a BLA, you want to have six months of follow up with large populations. And so that's why these companies are just now applying for BLAs. So while these vaccines still remain under EUAs, there is much more data on these vaccines than any other, except perhaps for the polio vaccine.

Once we have enough people fully vaccinated, campus life is going to get back to normal. We can be in meetings with other people without masks, and move around the buildings without masks. There are still issues to sort out, but I feel confident on a return to normalcy once we figure out those logistics. The standard will be, if enough people are vaccinated, everybody's back on campus, life will go back to some version of normal.

If you are in the United States and have gotten your first dose of an approved vaccine, get the second dose from the same vaccine. If you got the first shot of Moderna, get the second shot of Moderna. If you got the first shot of Pfizer, get the second shot of Pfizer. Don't start mixing on your own because you decide it could be better.

I have seen no data to suggest that people are going to need a booster in less than a year from their final shots. It is possible we may not need a booster for even longer than that. My expectation is these vaccines will give very strong levels of protection for at least a year, and possibly much longer than a year. We don't know for sure and that is still being investigated. We should move forward expecting that there's a pretty good chance that at some point in 2022 we'll all be getting boosters.

For Johnson & Johnson: There is an ongoing trial right now examining two doses versus one for the Johnson and Johnson vaccine. Those trial results will probably come in late summer or early fall.

With vaccines, we start with the high risk group, which is adults, then move to kids. Because not all kids are the same, we start with older kids and work our way down.

We have good data on 16 and 17 year olds from Pfizer, and now millions of 16 and 17 year olds have gotten vaccinated, and we have exquisitely good safety data on those doses. 16-17 was the first group to get vaccination because Pfizer was tested in those 16 and older, while Moderna was tested in 18+. There is now new data out on Moderna for 12 to 17 year olds, and it looks really good. So, Moderna is likely to get authorized for adolescentes as well. There is nothing about Pfizer that makes it safer for children than Moderna.

So far, clinical trials have really focused on symptomatic disease as the primary outcome. We know kids have less instances of symptomatic disease. These clinical trials were set up to go fast, get as many people enrolled as possible, and try to show outcomes reasonably quickly, because we were in the middle of a global health emergency. And so pharmaceuticals did not test the vaccines in kids at first. Kids tend to be less likely to get infected and far less likely to get seriously ill. That's why they were excluded initially.

Now the studies have been extended to these younger ages,and the next round will reduce that age down, and both Pfizer and Moderna went to 12. Younger than this, and it becomes more complicated biologically for two sets of reasons. First, physical size. A 4 year old needs a different dose than a 14 year old. Second, issues around puberty. So that's why we’ve seen the age cut offs that we have.

There are different concerns for each of these groups: lactating women, pregnant women, and women wanting to get pregnant. Before answering this, we must note that we are getting new data all the time, because clinical trials are ongoing and will be for years. Of course, we always want to be collecting more and more information.

Pregnant Women: At least 10,000 pregnant women have been vaccinated, and all have been thoroughly monitored for side effects. Larger clinical trials are also ongoing. So far, we have seen no negative safety signals for the women themselves or their babies.

But there's a flip side to this, which is what happens if you get COVID while you're pregnant? Pregnancy is a substantial risk factor for bad outcomes from COVID-19. At this point in the pandemic, if you're a pregnant person, and you're trying to decide what is safer, all the data on the vaccines look exceedingly safe, and all the data on what happens if you get COVID look really not that great. I have been saying for months now, that if I had a pregnant woman ask me, I would say very clearly that people should be vaccinated.

Lactating Women: On lactating women I think the data is less good in terms of what we know, but all of the data so far suggests that the antibodies that people generate are passed on through breast milk and may offer a level of protection to the baby. There has been no data whatsoever on adverse effects for lactating women or on the baby. So you may be offering a level of protection to your baby if you're pregnant and vaccinated, but I don't want to overstate that benefit because we don't fully know yet.

Women Wanting to Get Pregnant: No vaccine has ever been linked with infertility. There is zero evidence that any of the three vaccines will cause problems with fertility or have done so thus far. Again, we've had hundreds of millions of people get vaccinated, including lots of people of childbearing age.

I understand the concerns around fertility, but I remain unworried because there is no biological basis for this. So where does the misinformation come from? People who spread misinformation usually take some small piece of data or information out of context and then blow it up. There is a protein found in placenta that they claim looks a lot like the COVID-19 spike protein. It does share four common amino acids, but there are hundreds of proteins in your body that share more common amino acids than that. And so you can take one piece of fact—that this protein shares four common amino acids with the COVID spike protein—and that sounds bad. But if that alone could generate an autoimmune problem, these vaccines would be unbearable and intolerable, and they're not. I remain convinced that this misinformation campaign will ultimately fail, because it's not rooted in science.

While infertility has never shown up in vaccines, there are some signs that COVID itself may temporarily decrease sperm counts. So, if you're worried about fertility the best possible advice is to not get COVID-19.

Kids under 12 are not vaccinated, and they are unlikely to be vaccinated in the next few months. I'm hoping they will be able to get vaccinated by early to mid Fall. So what's the best way to protect kids under 12? The single best way to protect kids under 12, is to make sure the people around them are vaccinated. The data on this is overwhelmingly clear. What happens is essentially, you create a ring of protection around the child. Studies in Israel, the US, and the UK show if you want to protect kids in a community, get the adults vaccinated. When adults get vaccinated, infection numbers drop and then kids generally won’t get COVID-19.

But this specific question is what do you do in the office environment? If everybody in the office environment is vaccinated, it’s unlikely that you will pick up the virus from another vaccinated person. Vaccinated people spreading it to other vaccinated people is exceedingly rare, and usually requires symptomatic disease. We have no evidence that asymptomatic spread of the virus, which is very common among unvaccinated people, happens among vaccinated people. So, even if you have been exposed to a vaccinated colleague who is an asymptomatic carrier of COVID-19, them spreading it to you is extremely unlikely. And you, a vaccinated individual, then spreading it to your child is even more unlikely. We have never seen a case of this. These are risk levels that get well below the risks of getting hit by lightning.

Let's do one more scenario about the workplace that doesn't require vaccines. That is far more tricky. We just have a lot less data, and I would be much more concerned. One of the reasons I have pushed for Brown to be a place that does require vaccinations, is because I want to create that ring of safety that makes it so our family members—who may be unvaccinated kids or immunocompromised adults—are protected by our fully vaccinated workplace environment. I still think you're probably pretty well protected if you're vaccinated, in terms of not spreading it to your kids, but a workplace that doesn't require vaccines is probably a higher risk.

Think of your immune system as a multi-layered defense. By the way, the vaccine is not protecting you, your immune system is. The vaccine is just priming your immune system, and getting it ready to protect you. These vaccines generate an antibody response, they generate memory B cells, and they generate T cells as well.

Again, there's a lot of complexity in immunology and I'm going to simplify a little bit. T cells are what we often think of as cellular immunity. They are a very powerful and different level of defense against severe illness. So the Johnson & Johnson vaccine, for example, produces a phenomenal T cell response, but maybe less powerful B cell and antibody response. And that's why you tend to see with J&J, a little bit more in the way of breakthrough infections. But the level of protection from severe disease is awesome in J&J, because of the T cell response.

So, there are two sets of things to think about. There are some variants that have immune escape, which might include 351 originally from South Africa, perhaps 617.2 from India, and P.1 that was originally found in Brazil. You're going to see a few more breakthrough infections with these variants. But what you really care about is one, preventing that from turning into a large outbreak, and two, making sure that you don't get very sick. The breakthrough infections are happening because the immune escape is beating the antibodies, so you get less neutralization, but your T cells are preventing you from getting really sick. So all of the data suggests so far that the vaccines train our immune system to be phenomenal at preventing you from getting very sick from all the variants, but some variants cause a few more breakthrough infections than others.

Nothing is 100% so we will still see some breakthrough infections leading to people getting very sick, but those will be exceedingly rare. So, in the big picture, variants are bad. Some of them are much more contagious. That's a real problem in terms of causing infections among unvaccinated people, but vaccines still hold up really well against those variants. That doesn't mean that we will never have a variant that causes more breakthrough infections, or even begins to cause a lot more severe illness. I'm relatively hopeful that they won't, but that’s the most reassuring statement I can give you. The best way to prevent that nightmare scenario is to get the world vaccinated.

You should not get an antibody test after your vaccination, largely because you won't know how to interpret it. There are a couple of reasons why. First, almost everybody generates some antibodies. But we don't know which antibodies matter the most for preventing infection. So you may have a lot of antibodies, but they may not be the ones that matter the most. On the other hand, you may not have many antibodies, but the ones you do have may be the most important for preventing infection. We just don't understand it. There's a lot of science happening here, so I may change my answer in three months because I think we'll know a lot more. But as of today, I wouldn't do it.

There is very good evidence that if you've been previously infected, you have some real protection. There are a couple of studies that suggest this protection may last out to a year, but most of the studies suggest it is probably just six months. There is also good data that just one shot of an mRNA vaccine is good enough, and a bunch of us have tried to lobby the FDA and NIH to think about letting people who've been previously infected (with documentation of this) to get away with one shot. So far the FDA is holding tight. So while there is good evidence that if you've been previously infected you may only need one shot, right now the current policy is what you should go with.

Many people have said, “I am not getting the shot because I've been previously infected. Why bother?” Because there's good evidence at this point that vaccines probably give you more durable immunity. That is, your immunity will last longer than if you've just been previously infected, and you will also achieve broader immunity. This is counterintuitive to how a lot of people think. How can having been exposed to the virus give you less immunity? It turns out the real virus, when it infects you, has all sorts of mechanisms that it uses to try to hide itself from your immune system. And so while your immune system is still able to manage it, it doesn't get the same degree of exposure as it would with mRNA vaccines and the Johnson & Johnson vaccine. So all of the evidence right now says you have better immunity if you've been vaccinated and if you’ve also been previously infected, the two together probably give you the best immunity. But you get fabulous immunity from just the vaccine. That's why I've been pretty clear that people should get vaccinated, and that's where the policy is as well.

Domestic travel is totally fine. I expect that we'll see policy updates around that relatively soon. Follow CDC guidelines, of course. The CDC continues to ask people to mask up during interstate travel.

International travel is tricky, because international travel includes everything from going to Toronto, to going to Delhi, to going to Hong Kong. First and foremost, there's a whole bunch of State Department policies, which are all changing, and you need to follow those.

There are also going to be some rules about coming back and getting tested. So, while I do think vaccines are relatively safe for international travel, there's a lot of complexity, and you have to decide based on how badly you need to go, where you are going, what the local circumstances are, and how easy it would be for you to get back home. But if you're fully vaccinated, from a safety point of view, international travel is probably okay.

This is a policy question at the university level. I wasn't involved in the policy, but I fully support it. These decisions should be made based on science and data. First, the chances that Pfizer is going to get full approval are well north of 99% because the data is so overwhelming. Full approvals often take six months or a year, because there's usually no rush. I think this will move faster, because we are in the middle of a national emergency. At the same time, the FDA doesn't feel a huge rush because people are getting vaccinated anyway and delays may continue for a while.

I don't think Brown wants to let FDA delays drive their decisions. If the FDA delayed their decision by three months until November, we've lost the Fall semester. My sense is we should do this based on data and science, and the data on this is overwhelmingly clear. A lot of legal scholars have said universities and private entities are well within their rights to do this and the Equal Employment Opportunity Commission has come out and said as much for the government. So, I think Brown’s policy is very reasonable.

These are deeply personal subjects for people. I have spent years talking to people about vaccines, and about medicines, and there are a few principles I abide by. First, hear people out, listen to them. Don't dismiss what they have to say. Respect and understanding goes a long way. Second, this is about finding trusted voices for your family and friends, which can often be you. When I talk about vaccines to the public, I talk about what I do for my own family. Try leading with personal experiences, and helping people understand what you've done and why you’ve done it.

Lastly, you should see these as long term projects. This is not a one-off conversation. This is a project, so we should see it as a long term engagement, where you're going to want to help people get more comfortable and more confident. Already, 62% of adults have gotten their first shot. I think we're going to get into the 70s without too much difficulty here in Rhode Island and eventually we're going to get into the 80s in the United States, but we just have to keep helping people understand the information, answer their questions, and treat people with respect. I think that goes a long way towards helping people get there.

I’m super hopeful. First, this has been a once in a century event for us but we should not assume this is going to remain a once in a century event. We are going to have more of these. A lot has gone wrong in our response, a lot of misinformation, a lot of shenanigans in the public health response, but a lot went right. The way the scientific community, not just in the United States but around the world, pulled together is nothing short of extraordinary. I think we have clearly turned the corner in the United States. We will never go back to the kinds of infections and suffering we saw in the Fall and Winter of last year.

We're not completely done. We will have to continue to manage this virus for years, but it will become part of our background. It will be something we manage and get on with our lives, and that will be much sooner than most people realize. There is a huge global problem. What I just described is true for the United States and a small number of other high income countries, but it is not true for the rest of the world. There are no simple solutions, but there are a lot of people working on this and I'm hopeful on the global front as well, that we will make a lot of progress in 2021. My hope is, by early to mid 2022, we will have a majority of the world vaccinated. That's among the most optimistic timelines that I've seen, but I remain confident.

We also need to make sure that as we pull out of this pandemic that we do two sets of things. First, think about what it will take to prevent and manage future pandemics. Second, use this public health moment to think about the underlying health challenges that this pandemic has revealed. Some of them are not inherently linked to health, but have huge health consequences, such as structural inequities and racism in our country, issues around opioid use and disorders, and many more. There are opportunities for us to begin to address some of these things in a much more concerted way, and that gives me optimism.