Bivalent Vaccines Protect Even Kids Who’ve Had COVID

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I’m Dr F. Perry Wilson of the Yale School of Medicine.

It was only 3 years ago when we called the pathogen we now refer to as the coronavirus “nCOV-19.” It was, in many ways, more descriptive than what we have today. The little “n” there stood for “novel” — and it was really that little “n” that caused us all the trouble.

You see, coronaviruses themselves were not really new to us. Understudied, perhaps, but with four strains running around the globe at any time giving rise to the common cold, these were viruses our bodies understood.

But the coronavirus discovered in 2019 was novel — not just to the world, but to our own immune systems. It was different enough from its circulating relatives that our immune memory cells failed to recognize it. Instead of acting like a cold, it acted like nothing we had seen before, at least in our lifetime. The story of the pandemic is very much a bildungsroman of our immune systems — a story of how our immunity grew up.

The difference between the start of 2020 and now, when infections with the coronavirus remain common but not as deadly, can be measured in terms of immune education. Some of our immune systems were educated by infection, some by vaccination, and many by both.

When the first vaccines emerged in December 2020, the opportunity to educate our immune systems was still huge. Though, at the time, an estimated 20 million had been infected in the US and 350,000 had died, there was a large population that remained immunologically naive. I was one of them.

If 2020 into early 2021 was the era of immune education, the postvaccine period was the era of the variant. From one COVID strain to two, to five, to innumerable, our immune memory — trained on a specific version of the virus or its spike protein — became imperfect again. Not naive; these variants were not “novel” in the way COVID-19 was novel, but they were different. And different enough to cause infection.

Following the playbook of another virus that loves to come dressed up in different outfits, the flu virus, we find ourselves in the booster era — a world where yearly doses of a vaccine, ideally matched to the variants circulating when the vaccine is given, are the recommendation if not the norm.

But questions remain about the vaccination program, particularly around who should get it. And two populations with big question marks over their heads are (1) people who have already been infected and (2) kids, because their risk for bad outcomes is so much lower.

This week, we finally have some evidence that can shed light on these questions. The study under the spotlight is this one, appearing in JAMA , which tries to analyze the ability of the bivalent vaccine — that’s the second one to come out, around September  2022 — to protect kids from COVID-19.

Now, right off the bat, this was not a randomized trial. The studies that established the viability of the mRNA vaccine platform were; they happened before the vaccine was authorized. But trials of the bivalent vaccine were mostly limited to proving immune response, not protection from disease.

Nevertheless, with some good observational methods and some statistics, we can try to tease out whether bivalent vaccines in kids worked.

The study combines three prospective cohort studies. The details are in the paper, but what you need to know is that the special sauce of these studies was that the kids were tested for COVID-19 on a weekly basis, whether they had symptoms or not. This is critical because asymptomatic infections can transmit COVID-19.

Let’s do the variables of interest. First and foremost, the bivalent vaccine. Some of these kids got the bivalent vaccine, some didn’t. Other key variables include prior vaccination with the monovalent vaccine. Some had been vaccinated with the monovalent vaccine before, some hadn’t. And, of course, prior infection. Some had been infected before (based on either nasal swabs or blood tests).

Let’s focus first on the primary exposure of interest: getting that bivalent vaccine. Again, this was not randomly assigned; kids who got the bivalent vaccine were different from those who did not. In general, they lived in smaller households, they were more likely to be White, less likely to have had a prior COVID infection, and quite a bit more likely to have at least one chronic condition.

To me, this constellation of factors describes a slightly higher-risk group; it makes sense that they were more likely to get the second vaccine.

Given those factors, what were the rates of COVID infection? After nearly a year of follow-up, around 15% of the kids who hadn’t received the bivalent vaccine got infected compared with 5% of the vaccinated kids. Symptomatic infections represented roughly half of all infections in both groups.

After adjustment for factors that differed between the groups, this difference translated into a vaccine efficacy of about 50% in this population. That’s our first data point. Yes, the bivalent vaccine worked. Not amazingly, of course. But it worked.

What about the kids who had had a prior COVID infection? Somewhat surprisingly, the vaccine was just as effective in this population, despite the fact that their immune systems already had some knowledge of COVID. Ten percent of unvaccinated kids got infected, even though they had been infected before. Just 2.5% of kids who received the bivalent vaccine got infected, suggesting some synergy between prior infection and vaccination.

These data suggest that the bivalent vaccine did reduce the risk for COVID infection in kids. All good. But the piece still missing is how severe these infections were. It doesn’t appear that any of the 426 infections documented in this study resulted in hospitalization or death, fortunately. And no data are presented on the incidence of multisystem inflammatory syndrome of children, though given the rarity, I’d be surprised if any of these kids have this either.

So where are we? Well, it seems that the narrative out there that says “the vaccines don’t work” or “the vaccines don’t work if you’ve already been infected” is probably not true. They do work. This study and others in adults show that. If they work to reduce infections, as this study shows, they will also work to reduce deaths. It’s just that death is fortunately so rare in children that the number needed to vaccinate to prevent one death is very large. In that situation, the decision to vaccinate comes down to the risks associated with vaccination. So far, those risk seem very minimal.

Perhaps falling into a flu-like yearly vaccination schedule is not simply the result of old habits dying hard. Maybe it’s actually not a bad idea.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and public health and director of Yale’s Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his book, How Medicine Works and When It Doesn’t, is available now.

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