Below are highlights from their conversation, edited for clarity and length.
Dr. Arefa Cassoobhoy: Over the past 18 months, all of us, consciously or subconsciously, have been thinking about how likely we are to get COVID and how likely we are to get really sick from it. What should people consider when they are making these risk assessments?
Dr. Carlos del Rio: I think the problem is that the risk has not been the same all the time. I think about January, February, even March of this year, when the vaccines first appeared, and I had to do my own risk assessment.
I still remember one day when a COVID patient was prone in an ICU bed and I had to essentially get on the floor and look up and stick a swab up the patient’s nose while gunk was falling on my face. My risk was significant, and I said, “I need to get myself vaccinated.”
I can see somebody else saying, “Well, I want to wait a little bit, I’m working at home. We still are pretty much in lockdown. I never go out. My risk is pretty low.”
Fast-forward to August, September, and all of a sudden we have two things happen. Number one, the delta wave. Delta is much more transmissible than the original virus strain.
The original strain — the Wuhan strain — has an R0 (reproductive number) of 2.5. That means that one infected person infects two and a half individuals, then each of those two and a half infect another two and a half. If you run that through 10 cycles of transmission in a totally naive [previously uninfected or unvaccinated] population, at the end of 10 cycles, you have about 9,600 people infected.
Then you go to delta, which has an R0 of about 6. So one infected person infects six, then each of the six infects six more. At the end of 10 cycles you have 60 million people infected.
The increase from two and a half to six is dramatic, right? There’s a lot more transmission out there. So it’s a lot more likely that you’re going to get exposed to the virus.
Number two, the economy has opened, everybody’s gone back to work. The restaurants are full, the bars are full. People are going to grocery stores and other places, and they may not be wearing masks. And your risk of exposure goes way up.
You will get exposed to delta; it’s going to happen. And when that happens, do you want to be vaccinated or unvaccinated? I want to be vaccinated, because vaccines may not prevent you from getting infected, but they’re really good at preventing you from getting sick and dying.
In the last delta wave, we lost about 180,000 Americans. Had they been vaccinated, 150,000 would not be dead today. Not to be vaccinated is putting yourself at risk of having significant disease and dying of delta.
Dr. Mark Mulligan: I would just say that a vaccine is sort of like an insurance policy. You do it now, you hope you never really need it, but it’s good to have it. Even if you think you’re fairly low risk now, things can change on a dime, as they did with delta.
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Cassoobhoy: A lot of people are wondering whether it’s safe to get a flu shot and a COVID-19 booster at the same time.
Del Rio: You can take your flu shot and your COVID booster at the same time. Some people I know took the shots in different arms.
My wife, when she went in for her booster, decided to take both in the same arm. She said, “If I get pain in the arm, I really don’t want to know if it’s the flu or the COVID vaccine.” And she had very little pain.
Cassoobhoy: How do you speak to someone who may be hesitant to get the vaccine because they already had COVID-19 and feel they have natural immunity?
Mulligan: There’s clinical data from a study in Kentucky that was published in the Morbidity and Mortality Weekly Report by the CDC [Centers for Disease Control and Prevention]. You have a 2.3 times higher chance of getting COVID a second time if you don’t get vaccinated relative to those who do get vaccinated. The clinical data are clear.
Also, in my lab and in many labs, we’ve looked at the antibody levels: If you have had COVID in the past, and you get the vaccine, you have a wonderful response. You’re already primed.
The other thing I’d like to say is that there is going to be a period of immunity after natural infection, but it wanes. Getting a vaccine, say, one to three months after recovery, I think is a really good thing to do to boost that immunity higher; as I just said, it goes quite high. You’ll probably do really, really well for some period of time, with less waning after that.
I don’t think people should trust their natural immunity. There are many people who’ve gotten COVID twice now. And I bet you can get it three times, too.
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Cassoobhoy: A lot of parents are excited to be able to vaccinate their kids, but many others are hesitant because of safety concerns.
Del Rio: In the clinical trials that we’ve seen, vaccines have very good efficacy in preventing infections, hospitalization, and deaths in children, just as the vaccines do in adults.
With the mRNA vaccines [from Pfizer-BioNTech and Moderna], there is some risk of a complication called myocarditis, but it’s rare. The incidence is about 20 to 30 cases of myocarditis per million doses of vaccine administered.
Myocarditis is actually a very mild condition; it’s an inflammation of the heart, and the heart is very good at healing itself. You don’t even need to have specific medication. You give anti-inflammatory drugs like Advil, and people get better.
Vaccinating one million children prevents about 40,000 infections in kids, close to 200 hospitalizations, and about 10 deaths. So to me, while the risk is very low for children to get sick from COVID, it’s not zero. And the risk of getting COVID far outweighs the risk of getting a [vaccine] complication.
We all make risk-benefit decisions every day, whether we like it or not, right? We get in the car, we put on our seat belt, we get on the freeway, we cross the street.
I don’t have young kids, but if I did, I would get them vaccinated.
Mulligan: A couple of other quick points: One is that myocarditis also occurs because of infection with the COVID virus itself — and at a much higher rate than with the vaccine. So you could look at getting the vaccine as reducing your chance of myocarditis.
Another point I want to make is that children do die — 140 kids in this age group of 5 to 11 have died [in the United States since the start of the pandemic], and there have been 10 million infections.
My final point would be that children are known spreaders of infectious disease. We’re vaccinating kids to protect kids, but this will also result in helping us protect grandma and grandpa and other vulnerable family members who can’t respond well to vaccines.
I am going to recommend that my grandkids get vaccinated.
Editor’s note: Pfizer is furthest along in developing a vaccine for children under age 5, but authorization isn’t expected until the beginning of 2022 at the earliest.
Cassoobhoy: There are a lot of questions about mixing and matching boosters: “Can we take the Pfizer booster if we got the Moderna shot before?” and “I had the J&J vaccine, and I’ve heard that Moderna might be more effective.”
Mulligan: The CDC and the FDA [U.S. Food and Drug Administration] have done a wonderful thing to make it easier to get your booster, for those who qualify. You may have moved to an area where your original vaccine is no longer available. Companies that are going into nursing homes to give out vaccines, they only have to bring one vaccine type now, not three. So there are pragmatic reasons.
The other thing is, it’s been shown now in a study that both Carlos and I participated in, an NIH-funded study, that mixing and matching — giving a different booster than what you originally had — is safe, tolerated well, and produces antibody responses that in general are stronger than if you got the same kind of vaccine again. They’re either at least as good or stronger, and in no cases worse.
The J&J vaccine is associated, mainly in young women, with a very rare side effect, thrombosis [a blood clotting disorder] and thrombocytopenia [low blood platelet count]. There might be some reasons why young women [who got a J&J vaccine] might want to avoid a J&J booster. Plus, the antibody responses if you have an RNA boost to a J&J original series are much higher.
Del Rio: The best vaccine is a vaccine, no matter which vaccine you get. And I think the most important thing about the mix-and-match study is that we showed you can mix and match.
Yesterday, more people got boosters than got their first vaccination. So I want to use this conversation to say that the most important booster anybody can get is to get somebody else vaccinated. The booster I need is for the person that’s not vaccinated to get vaccinated. So when you go get a booster, bring a friend that hasn’t been vaccinated and start their immunizations.
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Cassoobhoy: People may know someone they care about who hasn’t gotten vaccinated — because they’re on the fence, scared, even adamantly opposed. What approach has been most successful for you at opening up that conversation?
Del Rio: One thing that we’ve done that has been really interesting and very highly effective working with minority populations, African Americans and Hispanics, is we create a place that we call “the no-shame zone.” And the reason I bring that up is because a lot of times people that are hesitant are waiting to be vaccinated, and sometimes they’re getting shamed way too much. They’re getting blamed.
We need to understand what their thinking is. One of the things is to ask, Why are you anxious, why are you hesitant? I have found that a lot of times, one of the biggest challenges is not lack of information but excessive misinformation. And sometimes you need to listen to what people have heard, and then you start talking to them.
Mulligan: I really think many of the folks who haven’t taken the vaccine are hesitant more than hardcore anti-vaccine — that’s been my experience. And really I think many of them are thirsty for expert knowledge from a trusted healthcare provider.
So the first thing is to establish empathy and credibility, to say: “Hey, I know you just want what’s best for your family. You want your kids to be safe. That’s what we all want.”
We have to turn on those skills first, and then find out what the specific concerns are. Some are pretty easy to comment on — “I’ve heard that the vaccine makes you magnetic,” “The vaccine has microchips in it” — all those things that are certainly not true.
And then quickly pivot to the really serious risk of disease, and the good news, that vaccines are safe and are highly protective.
And then I close by saying, “I want you to know, I really believe in and recommend the vaccine for you, for your children. I think it’s the right thing to do.”
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Cassoobhoy: Is there real data showing that the COVID vaccine is safe during pregnancy, or is it a “take it and pray” situation?
Del Rio: Last time I checked on the data, there were thousands of pregnant women that have been vaccinated who have been followed to delivery, and everything has been fine.
Maybe part of the problem that people have is that quite frankly, there’s too much information out there. And even for us scientists, it’s really hard to keep up with the data. So what I told you yesterday may be very different from what I tell you today, because new data’s appearing, but that the vaccines are safe in pregnancy is a fact.
And there’s increasing data about how unsafe it is to be unvaccinated and pregnant and get COVID. The number of women who are pregnant and who have become hospitalized and died during this last delta wave because they were not vaccinated is simply unacceptable. And the reason for that is that only about 35 percent of women who are pregnant in this country are vaccinated.
So if you’re pregnant, get vaccinated, and if you have a friend who’s pregnant, get her vaccinated.
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Cassoobhoy: With the holidays approaching and so many people planning multigenerational gatherings at home, how can people stay safe? Can rapid home tests help? Are they accurate enough?
Mulligan: I think that the CDC guidance here is pretty good: If everybody’s vaccinated and being careful, no problem. You can be unmasked at an indoor gathering, and of course, you can be unmasked at an outdoor gathering.
If you have a mixed group, with some vaccinated and some not, it’s a more difficult situation. I think you have to remember that people may be asymptomatic and infected and that people are able to transmit the virus whether they’re vaccinated or not. So in that setting, I think you’ve got to use your judgment.
But what the CDC would say, I think, if it is a large gathering that’s mixed and not everybody’s vaccinated, that mask wearing may be an appropriate thing, or move it outdoors.
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Del Rio: I agree. I think, honestly: Have everybody vaccinated. But there may be kids ages 5 to 11 who are still unvaccinated. I think there are three important rules. Number one, if the kid is sick, don’t come. Or if anybody’s sick, don’t come. It’s better not to show up than to come in with sniffles or a headache, or having had a fever yesterday or something like that.
And number two, yes, testing. I’m a big fan of testing in those circumstances. And my family now considers me pretty famous because whenever we have a gathering like that, I bring my big box of rapid tests and I make them available. I say, “I’m not telling you that everybody needs to be tested, but if somebody wants to be tested, the test is here.” And if you have an unvaccinated person in the group, it may not be a bad idea for that person to get tested before they come.
So with those rapid home tests, if you are symptomatic, those tests are actually pretty good. If you are asymptomatic, they may have false positives and false negatives. There tends to be more false positives than false negatives. So if you test positive on a rapid test, getting a PCR test afterward is recommended.
If you test negative, could you still be positive? You could be, but the chances diminish significantly. I want to talk about one brand, which is the one I know the most, the BinaxNOW test. If you go buy a box, you’ll see that it contains two tests, for you to be tested twice. You test today and you test 24 hours later. If you do back-to-back testing, you significantly increase the predictive value of the test.
So if I’m going to a family gathering on Thanksgiving, I’ll test Tuesday and then again Wednesday. And if I’m negative both times, I’m fine for Thursday.
