Interview by Stephanie Desmond
How is it possible that COVID-19 vaccines prevent serious illness and death but may not prevent mild infection? How effective are vaccines at preventing long-haul COVID? How soon might we see flu mRNA vaccines and would those have to go through clinical trials?
Josh Sharfstein answers a list of important questions about COVID-19 vaccines.
Most COVID vaccine information is focused on how effective they are at preventing serious disease, hospitalization, and death. How is it possible that the vaccine is more effective at preventing serious illness and death than it is preventing a mild infection?
It’s actually very common for vaccines to be much better at preventing serious illness and death than preventing infection or mild infection. For example, with the flu vaccine, people can still often get the flu, but they are much less likely to get seriously ill or die if they get the flu vaccine.
The question is why. It partly depends on how the immune system responds to vaccines. Any infection whatsoever is a certain type of immune response, and very few vaccines give what people call a “sterilizing immune response.”
What vaccines do cause is an immune response that is strong and multifaceted inside your body. So, even if you knew that the virus can replicate a bit for a mild infection, it can’t cause that huge overwhelming infection that really puts people at risk.
Early on in the pandemic, before we even had vaccines, some vaccine experts were saying the most important thing is going to be [preventing] serious illness and death, and [vaccines will] probably will be much better for that than for mild illness, just like almost every other vaccine out there. Sure enough, that proved to be the case.
How effective are vaccines at preventing long-haul COVID?
We don’t know. It’s a good question, because people can get these long-term symptoms from relatively mild infection.
There are some studies being set up to assess this, but we don’t know for sure. The safe bet would be that the chance of getting a long-haul infection is going to be much lower [for] someone who’s vaccinated compared to someone who’s not, just because that person is much less likely to get infected at all.
There’s also this related question of whether people with long-term symptoms from COVID actually might benefit from getting vaccinated. Somebody who had an infection and has been suffering some of those symptoms like fatigue and brain fog—does it get better if you get vaccinated? There’s no answer to that; however, at multiple clinical sites, some of the doctors are hearing from their patients that they’re feeling somewhat better. I think that the real answer to that, though, is going to depend on studies that will be completed, to see whether it makes a difference.
If I have no symptoms at all after receiving the Pfizer or Moderna vaccines, does this indicate that if I had gotten COVID, I would have been asymptomatic or had mild symptoms?
I do not think it means that.
What determines how sick you are from COVID-19 is a complex set of things that include how much virus your body actually took in. That’s one reason why people who get exposed to lower levels of virus are more likely to have an infection without symptoms, for example.
It also relates to different aspects of people’s immune system and probably some other factors we haven’t figured out, so I would not assume that the response to the vaccine is the same as the response to the actual virus.
Is this the first time mRNA technology has been used in a vaccine?
It is not, actually. There are several vaccines that are in development with mRNA technology. They’ve completed safety studies for them, and that includes influenza—so there could be an mRNA flu vaccine in the future—cytomegalovirus, Zika virus, and the rabies virus.
[These vaccine trials] haven’t made it all the way to the end [because] those were going through the regular vaccine process where you go one step at a time. Those companies aren’t going to invest in a big, next trial until they’ve really analyzed the data from the previous study.
In the case of [COVID-19 vaccines], we had a lot of urgency and all the money was put up, up front. The companies didn’t have to find the money for each stage—they were just able to just proceed from the safety study to the effectiveness study very quickly. This let the coronavirus vaccines go to the front of the line because of the urgency.
This is a technology that’s been well studied, not just for vaccines, but also for therapeutics.
Do you think that having successful mRNA COVID vaccines will pave the way for these other vaccines?
It’s going to be great for people’s comfort level with the vaccine, both at a level of understanding—like, “Wow, that’s going to be like the coronavirus vaccine, and it was so successful!”—and also scientifically, I think there’ll be a greater understanding of mRNA vaccines, and that will help with the development and the review of other mRNA vaccines for different different viruses.
Having said that, just because an mRNA vaccine works for coronavirus doesn’t mean it’s necessarily going to work for a rabies or influenza virus. They’re going to have to do studies to find out.
Do we know yet how soon flu vaccines may be made as mRNA vaccines, and will they have to go through clinical trials as a new vaccine?
I would expect that they would go to clinical trials … but I do know that some studies have already been done, and hopefully this will proceed and we’ll get another great vaccine.
One of the long-held goals for flu vaccination is a vaccine that lasts more than one year, and maybe a vaccine that doesn’t require a strain change every year. The mRNA vaccines may be a way to get to that goal, but there obviously has to be a lot more research.
Why are mRNA vaccines so encouraging for the future?
This is a platform that has certain advantages, among them, that you can stand it up so quickly. It doesn’t require a lot of different ingredients—it’s a very, very small number of things that go into the vaccine—and it can be updated, very quickly, so if you need to change the strain, it’s very possible to do that.
I think we’ll look back and think that mRNA kind of had its coming out party with coronavirus, but [was] around beforehand, and it will hopefully lead to some other important advances in medicine.
How are side effects from COVID-19 vaccines being monitored?
They’re being monitored in multiple ways. One thing that people who have gotten vaccinated know is that you have an opportunity to get texted about the potential side effects you’re experiencing. The Centers for Disease Control is looking at that from millions of people who are getting vaccinated to understand the profile of side effects. People also submit reports to the manufacturers and to the FDA about potential side effects, and there are studies that are done in large insurance databases or clinical databases where you can look at the people who got the vaccine compared to people who didn’t get the vaccine to see whether there’s any difference in case there’s a question about whether or not a particular side effect might be caused by the vaccine.
On a regular basis, there is a big group that comes together and looks at data from all these different sources to see what the safety profile is and, so far, it’s been very, very strong.
I was just looking at a 60-page document that’s posted on the CDC website where they went through all these different sources and they have a huge analysis of allergic reactions. I think the Pfizer vaccine had five serious allergic reactions per million doses given, and per 2.8 million for the Moderna vaccine. Almost always, those allergic reactions are in the first dose. Not always, but almost always.
It also talks about the evidence of the mild side effects people get. Seventy percent of the people get a sore arm; I think about a third got a headache, a third got fatigue, but then of course they feel better in just a couple of days.
They’ve been even doing studies in these insurance databases to compare people who are vaccinated and people who aren’t vaccinated just for things that people think “Well, maybe, could it possibly relate to this [vaccine]?” and they have not found any serious red flags coming up.
So, there’s a lot of analysis of safety data and there will continue to be. It’s a very important part of vaccination and the vaccination program to look at safety and not just in one way, but in multiple ways.
Does someone who recovered from COVID and then gets vaccinated have a higher immunity than someone who hasn’t had COVID and also gets vaccinated?
In general, people who have had COVID have some immune reaction to COVID when they recover. But it’s variable—some people may have a pretty mild immune reaction, and some people may have a very protective immune reaction—and right now, we don’t have an easy way to tell the difference between them.
That’s why vaccination is recommended for everyone, even if you’ve had COVID before. There will be studies of different types of people, their vaccination status and when they got vaccinated, and hopefully we’ll get a picture and some markers like a blood test that you could take to find out how protected you are. We have that for certain infectious diseases. You can, for example, for hepatitis B, see whether you have antibodies.
One of the things we’ll learn from some of these studies is, is there a way to test people for their ability to withstand a coronavirus infection? When we have that, I think that might be more important than these general questions because probably it will depend on the individual and having some way to test to figure that out over time is what will be helpful to people.
If I’ve had COVID, how long should I wait to get vaccinated? Is it okay to get my first dose if I no longer have symptoms?
The basic standard requirements are that if you are in that period where you’re sick and could be spreading COVID to stay home until you get better, which I think is around 10 days and no symptoms—then it’s fine to get vaccinated.
[Some] people have said you’re probably relatively protected from another infection for a couple months after that infection and, if you want to wait a couple of months to get vaccinated, you can do that. But there’s no requirement to do that. It’s perfectly fine to get vaccinated.
There are people who may get COVID right after their first shot, before there’s any protection, and they could get vaccinated for their second shot on time if they want, with one exception: If they’ve been treated for that COVID infection with antibody treatment, then there’s a recommendation to wait 90 days so that that antibody treatment doesn’t interfere with the vaccination.
What will happen if everyone gets vaccinated? Won’t the variants get tougher as their source of food gets eliminated?
The virus is constantly mutating and every time that it replicates, there’s a chance that you could develop a variant. If the virus can’t replicate, the virus can’t develop a variant. If the virus is replicating a lot, then you’re more likely to get variants.
The goal of a vaccination campaign now is to reduce the spread of the virus, which reduces the replication of the virus, which will reduce the chance that there will be more variants.
With less virus, fewer people are dying. And with less virus, fewer variants.
The CDC recently released guidance for what vaccinated people can do safely. What do you think of this?
One important principle is that vaccination is important to people both directly and indirectly.
Directly, it’s important if you’re protected, and there may be some things that are different, like you can meet up in small groups with people who are vaccinated.
There’s also the indirect benefit, which is the more people get vaccinated, the less coronavirus is spreading out there. The less coronavirus spreading out there, the easier it is to open things up again. That’s the indirect benefit, and that may not happen the day you get vaccinated or the day you’re protected from your vaccine. But, the more people in your community get vaccinated, the more likely the benefit is going to come help you.
This is exciting because we can see what the end of the pandemic might look like, but we just have to get there. We can’t trip on our way running too fast to the end of the pandemic.
Meanwhile, states like Texas and Mississippi have both rescinded their mask mandates. Is this getting a little too far ahead?
We have to push COVID as far into the end zone as it can go through good mask wearing, social distancing, and vaccination until we really are able to open things with competence. The risk of doing it too soon is that the virus keeps spreading, you get mutations, you get potential variants spreading, and we wind up taking a step back. That takes longer, in the end, to get to the place that we all want to go.
I’m also concerned about the mixed messaging. Mask wearing really does reduce infection, and we still have a lot of infections in the United States, even though it has come down. Just to hear from one level of government “Do this,” and another level of government “Do that,” it just stirs the pot again and makes it harder for people just to stick with the program long enough to put coronavirus back in a box, which I think is within reach.
Now, will what the governors do really upend that? We don’t know. But will it increase the risk of a problem? It might, and I think that’s why you hear so many people saying, “We’re headed toward the end zone, don’t blow it.”
Joshua Sharfstein, MD, is the vice dean for Public Health Practice and Community Engagement and a professor in Health Policy and Management. He is also the director of the Bloomberg American Health Initiative and a host of the Public Health On Call podcast.
Stephanie Desmon is the co-host of the Public Health On Call podcast. She is the director of public relations and marketing for the Johns Hopkins Center for Communication Programs, the largest center at the Bloomberg School of Public Health.