Answers and even more questions on COVID-19 vaccines

When three infectious disease experts gathered virtually on March 24 for the fourth ACP and Annals of Internal Medicine forum on COVID-19 vaccines, they found a lot to be happy about.

Speakers Carlos del Rio, MD, FACP, and Paul Sax, MD, participated in a panel led by Annals deputy editor Deborah Cotton, MD, MPH, FACP, to reminisce about when they first heard the vaccines' efficacy statistics (“I just get chills,” said Dr. Sax) and ponder long-term impacts of the pandemic (“I want to see a renaissance of public health, but I also want to see more investment in public health,” said Dr. del Rio).

They also addressed some of the many ongoing questions about the vaccines and their implementation, as well as other aspects of the response to COVID-19. Excerpts are included here. Their discussion was also described in a paper published by Annals on March 26, which includes a full video of the event.

On contraindications to vaccination

Dr. Sax, clinical director of the division of infectious diseases at Brigham and Women's Hospital and professor of medicine at Harvard Medical School in Boston: People who have severe acute illness are not good immunization candidates, and people who are currently experiencing COVID-19 shouldn't get immunized. In fact, we ask them to wait, preferably at least 90 days …. Since there is a very small risk of anaphylaxis to the mRNA vaccines, if it's known that people have severe allergic reactions to the components, then they shouldn't receive those vaccines. The CDC has said that people with a history of these severe allergic reactions could potentially receive the J&J vaccine; that's a new recommendation. … People with untreated HIV, I personally think it's much more important that they go on HIV therapy first before they get their COVID vaccine because the vaccine responsiveness is so much improved by going into antiretroviral therapy.

On vaccine prioritization

Dr. del Rio, professor of infectious diseases at Emory University in Atlanta: I think lists have really been a problem and it has created a lot of competition. … I think it's much better that we just prioritize getting people in. My biggest concern continues to be people who are not savvy enough to make an appointment through the Internet, who are not digitally savvy and are still being left behind. So we ought to think about, instead of lists, how do we make vaccine access easy for people? … I'm worried that in most states, we're vaccinating primarily white and middle-class to upper-class people as opposed to those most heavily impacted by the pandemic, which are many African Americans, Latinos, and poor.

On transmission

Dr. Sax: Do the vaccines reduce the risk of transmitting the virus? They enormously do. Absolutely. We've gone from saying, we don't know how much they reduce it—people somehow hear that as we don't know if they reduce it—but they enormously reduce the risk of transmission. It's not 100%. Nothing's 100%.

Dr. del Rio: Increasingly, the evidence is that these vaccines prevent infection and likely because of that prevent transmission. … The [initial vaccine] studies were not designed to show decreased transmission. The clinical trials were designed to show a decrease in clinical disease. So in December, we're telling people, “Get vaccinated, because that's how you prevent getting really sick, but continue wearing your mask, because we don't know if this prevents transmission.” And as Paul says, people translated that as “These vaccines don't prevent transmission.” And now that we have data that says vaccines prevent infection transmission, we're trying to change the narrative. … The message changes week to week, because what we learn advances.

On treating infection after vaccination

Dr. del Rio: It's anecdotal. … I know one person, an older elderly individual who had received her first dose of vaccine, then two weeks after that developed COVID, and she actually had a pretty mild episode of COVID. I think she had a mild episode because she had been partially immunized. We decided not to give her monoclonal antibodies. She did fine. … If somebody had been sicker, I probably would have done something different.

Dr. Sax: We had a whole slew of people who got COVID-19 between their first and second vaccine doses because the incidence in Boston in December and January was incredibly high. … So we had pretty extensive experience with this very question and ended up managing them just based on clinical principles. If they weren't that sick, we just managed them. If they were sick and at high risk, we then went and got the monoclonal antibodies and remdesivir and you name it.

On SARS-CoV-2 variants

Dr. Sax: We think bad news is more newsworthy, so we're going to report more bad news about the variants. What someone will show is that the serum from a patient who has been immunized with the Moderna vaccine has a sixfold reduced likelihood of neutralizing certain variants. That's an experiment done in a test tube. But have they actually shown yet that these variants escape the protective effects of the Moderna or the Pfizer or the J&J vaccine? Not yet. What it's going to take is studies of people who have been immunized, who failed immunization, and then taking those viruses and sequencing them and seeing if they're enriched for variants before we really know whether the variants are causing a problem. And in addition, [we have to look at] the clinical features, because if [the vaccines] are not 100% protective against infection, but they're still protective against disease, that's still a win. There are all kinds of reasons why the variants are of concern, and we have to watch them. They're nicknamed “scariants.”

On the future of infection control

Dr. Sax: Mask wearing in the hospital … I think it's here to stay. And it's not just because of COVID, it's because we have seen a dramatic decline in transmission of other respiratory viruses. … This is actually really beneficial for a lot of people in the hospital, because remember, people in the hospital are elderly, they're immunocompromised, they're getting chemotherapy. Those are the people for whom viral respiratory tract infections have always been lethal. Whether it's influenza or RSV or adenovirus, dropping the incidence of those infections is beneficial for all. Now we have to work on one more thing, which is that we have to get rid of shared rooms in our hospitals.

Dr. Cotton: In nursing homes as well, there's now the understanding that the days of having three- to four-bed rooms in nursing homes needs to be over. But again, it's the financing. We have always underfinanced nursing homes in a tragic way, and we have seen that now and we can only hope that changes will come.

On pregnant women and COVID-19

Dr. Sax: [COVID-19] is like influenza, in that there is a risk for severe disease [during pregnancy]. That said, do I feel like a woman who's just found out that she's pregnant and she's in her first trimester needs to have her COVID vaccine given stat? I do not feel that way at all. … If you want to wait until the second trimester, I think that's totally reasonable. These are new vaccines. There's no theoretical reason why they'd be harmful, but you might just want to wait a bit, because they can sometimes trigger fevers and other things.

Dr. del Rio: That's exactly what I'm telling friends that asked me … Part of the problem is how we do research. I was one of the investigators in the Moderna study, and it makes me upset. “No, we're not enrolling pregnant women because we want to protect them.” And then once you get to the real world, “No, we don't know about pregnant women, because we didn't do research.” We need to change this. By “protecting vulnerable populations,” we may in fact harm vulnerable populations. We're excluding people that actually should be included in studies.

On equity

Dr. del Rio: Achieving health equity, that's a really big goal. But let's start with achieving immunological equity in our population. And I think the COVID vaccine offers us an opportunity to really try. … Some cities have done some really interesting strategies. For example, in D.C., they said, if you don't live in this ZIP code area, you cannot get the vaccine. … It's a matter of really working with trusted voices in the community and getting them to do the work. At the end of the day, I think we as physicians have a really big role to play because many patients, African American, Hispanic, otherwise, ask me, “Would you take the vaccine?” And when I say, “Yes, I would. I recommend it. I took it myself. I recommended it to my family,” then that is the trigger that changes their perception.

On the AstraZeneca vaccine

Dr. Sax: It looks like a clinical trial process that has been, unfortunately, peppered with unforced errors right from the start when, remember, they gave the wrong dose of the vaccine to some of the participants and found that it worked better in that group. … [Now we have] this thing where they reported a higher efficacy than the most recent data show. Does it matter that much, whether it's 75% or 65% effective? Probably not, if it protects against severe disease, but it's not a good look, especially in the background story of all the mistakes that have been made all along.

Dr. del Rio: The one other thing that has been just so frustrating throughout this pandemic is science by press release. I really hope that a lesson out of this is if you're going to do a press release, you should do your regulatory package at the same time. … We like to read journals, we like to go to meetings and hear abstracts and look at the total data and analyze it. … When you get press releases written by marketing people, you're going to get hype … I think we're going to have to learn to live in this world of skepticism until we see real data.

On rapid testing

Dr. Sax: When you look at the rapid tests compared to PCR, just solely based on sensitivity and even specificity, they actually come up short, and so the FDA [has] been slow to approve them. And then the companies have been more eager to get tests approved that have a medical prescription behind them, because then they're more readily reimbursed. … These tests are scientifically available and they're being sold internationally, and we ironically can't get them in the United States. If you go to Europe or Latin America, you can buy decent, rapid home COVID tests. I know of colleagues of mine overseas who use them regularly, and they should be coming to the United States. The FDA is starting to move on this issue.

Dr. del Rio: In 1996 when I came back to the U.S. from Mexico, and I wanted to do my first HIV testing study, I wanted to do it using rapid tests. And to my surprise, I discovered that rapid tests were not available in the U.S. back then and I had been using them in Mexico for years. … Repeating the same thing over and over, we don't seem to learn from the past. … [During the pandemic] I have personal experience working with, for example, Tyler Perry. He came to me and said, “How can I keep my business going? I don't want to stop my filming.” And we set up this testing system using rapid testing and other testing and he was able to keep his business running throughout the pandemic and continue filming.

On COVID-19 therapeutics

Dr. Cotton: People are still going to get COVID. Apart from dexamethasone, we haven't made much progress in terms of therapy. … Are there any promising candidates out there?

Dr. Sax: The monoclonal antibodies are effective, when given early, in preventing disease progression. I think that's pretty clear. They are enormously cumbersome to give. And I'm glad that the Regeneron product at least is going to be given subcutaneously. That seems to be a clear direction. I think molnupiravir as an antiviral looks promising. … As far as the repurposed drugs, I actually have a soft spot in my heart for fluvoxamine because it's an antidepressant. … It has off-target effects that are both antiviral and anti-inflammatory. In a randomized controlled trial—it was small—it actually was really effective in preventing disease progression.

On preventing the next pandemic

Dr. Cotton: One of my fears is we don't really know what's going to happen next and when, and we are very vulnerable right now. Do you think we're doing everything we can do to increase international recognition of emerging diseases?

Dr. del Rio: The U.S. retracted from global health … We need to recover that leadership role. I'm hoping that the Biden administration actually does that and helps us again regain that position. But that void we created has been filled by China, has been filled by Russia, has been filled by other countries that are now in fact distributing their vaccines very effectively to many countries. … We need to do almost a postmortem examination of what failed this year, and in fact the WHO is doing that.

Dr. Sax: It's fascinating to think back to what happened in China, and of course, I wasn't there, but initially, they went from not acknowledging the severity of the problem … to then suddenly sharing everything. That moment where they shared everything really was a warning signal to us, but in hindsight, it really was very generous … a model of how going forward, when we have global threats arise internationally, we have to be open and sharing with the scientific community.