A Vaccine Can Be Bad for a Person but Awesome for All People

The safety pause in giving the Johnson & Johnson Covid-19 vaccine is up for debate again—a battle in a Secret War of Denominators and risk-benefit philosophies.

Carol Ritter had put about 200 doses of the Johnson & Johnson Covid-19 vaccine into patients’ arms before the government told her to stop. Ritter is a gynecologist in Bethesda, Maryland, and her office had gotten supplies of the vaccine in the last week of March. “I was telling my pregnant patients that if it comes out and you really feel like you need one, I’d rather you get the J&J,” Ritter says. “It was very compassionate, comfortable care. I call them, they make an appointment, they come in, they don’t have to fight the Hunger Games for it on the internet. And it was very emotional. It’s the first time there’s been some smiles behind the masks.”

She found out about the “pause” in the vaccine’s use the same way everyone else did—on the news. It was just six reports of weird, dangerous blood clots in women under the age of 50—out of nearly 7 million doses of J&J administered, so very rare. But still. That’s who Ritter treats. “And these patients trust me. So, oh, my God, my trust in myself went down,” she says. “I really felt blindsided. I didn’t know what to do. I didn’t know where to go.” Her patients were calling her, asking if they were in danger, asking what to do. Ritter spent a couple days researching what federal public health officials and J&J were saying; that helped. Now, two weeks later, none of her patients have experienced anything like those serious clots, so they’re probably in the clear.

The blood clots—cerebral venous sinus thrombosis, technically—have been vanishingly rare. So have other dangerous vaccine side effects, including allergic reactions and the 222 similar clotting events associated with a similar vaccine made by AstraZeneca in Europe. But while rare, they were significant, even deadly in some cases. That’s why the decision to pause the J&J vaccine is so vexing. It’s a battle in a War of Denominators. The number on the bottom of the fraction is the total number of people in the group you’re worried about. Maybe that’s all 7.8 billion of us humans, amid this global pandemic. Or maybe it’s just the people most likely to get Covid-19. Or the people likely to suffer the worst if they get it. Or it could just be one person. Maybe it’s you. Covid-19 has upended these calculations, because much of what you can do to fight the pandemic might actually help other people more than it keeps you from getting Covid, or dying from it.

Depending on which denominator you use, your risk-benefit calculation is very different—the good of the many, the few, or the one? “Grossly put, physicians treat the patient, and epidemiologists treat the population,” says Sam Scarpino, head of the Emergent Epidemics Lab at Northeastern University. “But for infectious diseases, the distinction between the patient and the population is often very blurry.”

Before the pause, Ritter worked with some patients who were hesitant to get vaccinated—for lots of different reasons, from logistics to concerns about the science. She touted the J&J vaccine’s ease of use and its reliance on a tried-and-true mechanism. (The vaccines from Pfizer and Moderna use a new approach, injecting a bit of genetic material called mRNA that codes for part of the Covid-19-causing virus to teach a person’s immune system how to fight it. But the J&J and AstraZeneca ones use an older vaccine-making trick, tucking a piece of the virus inside a different virus that’s been modified into a delivery van, an adenovirus “vector.” It’s like taking the cork and rubber guts out of a baseball and replacing it with candy, turning a 90-mph fastball into a cookie over the plate. You might remember this technology from such famous vaccines as the one against Ebola.) In other words, Ritter did what every physician is taught to do: talk to their patients about their individual risks and benefits.

But if you tell an epidemiologist or a public health expert that a drug given to 7 million people had just six bad outcomes, they understand the tragedy and sympathize with the families, but they kind of don’t see that as a global problem. They might even feel that way if it was 600 bad outcomes, or 6,000. That’s not just because of the obvious rarity of the blood clots—the low risk. It’s because of the benefit now being denied to millions more people, perhaps billions. People who actually get shots are protected from Covid-19, but if lots of people get shots, even the ones who don’t are protected from the pandemic tsunami by a wall of vaccine-induced herd immunity. In this construction, the benefits to an entire population far outweigh the risks to individuals.

The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices essentially sided with physicians and individuals rather than public health and populations. This Friday, ACIP meets again, and most observers think they’ll probably recommend opening the J&J spigot again. But people will almost certainly be less trusting of the vaccine itself. The global fight against Covid-19 now depends on widespread vaccination. Shut off the taps, or hint that the well itself is tainted, and you jeopardize the lives of millions.

I’ve written before about how Covid-19 has challenged people’s sense of individual freedom and safety versus their participation in a broader community. These philosophies aren’t exactly in opposition, but they don’t totally overlap, either. The pandemic challenged Americans to link arms against it, and candidly, we mostly failed. “One thing that came up at the ACIP meeting that was striking, and seemed like more the way that people think about things in individual, clinical medicine than in public health, was that people kept talking about this idea that there was a ‘Do no harm’ option,” says Govind Persad, a bioethicist at the University of Denver Sturm College of Law and coauthor of a Washington Post op-ed that criticized the pause. “In public health ethics and public health practice, people think in terms of a harm-reduction framework.”

“Do no harm” is central to clinical medicine—the principle of non-maleficence, of not doing anything that could injure a patient. But harm reduction tends to apply more broadly: What can we do here that might not be great by itself but reduces the damage overall? Offer clean needle exchanges and safe injection sites to intravenous drug users to fight the spread of blood-borne disease; provide methadone to people addicted to opioids so they don’t have to get illegal drugs of abuse instead. In the case of a pandemic, the harm reduction aspects of mass vaccination seem clear: Get to herd immunity to protect the lives of everyone, especially the people who for whatever reason cannot themselves get vaccinated.

When physicians talk to their patients, though, they’re putting do-no-harm first. “It doesn’t just come down to evidence. It comes down to values, to people’s fears, to people’s anxiety. If their fear of getting a blood clot after the Johnson & Johnson vaccine is so profound for weeks after, is that worth it to that individual patient?” asks Peter Chin-Hong, an infectious disease physician at UC San Francisco. “That’s really the interesting clash that hasn’t been talked about. We do want societal benefit at the end of the day, but we shouldn’t avoid the aspects of talking about what it means to individual patients.”

That’s a quandary, though, because arguably the societal benefits are bigger than the individual ones—putting do-no-harm into conflict with harm reduction. Like: I’m a man over 50 years old, so as far as anyone can tell, at vanishingly small risk of blood clots. But I’m also (maybe) at low risk for dying of Covid-19. I’m cautious about exposure, with none of the comorbidities that tend to make an infection severe, living in a place with a low infection rate. I’m unlikely to get it, and unlikely to get a serious case if I do. Maybe the teensy tiny risks of vaccination don’t outweigh my risks from not getting vaccinated. Which is not to say I’m hesitant. I’m not! Gimme the juice, doc. But you see what I mean.

Except, of course, someone who gets Covid-19 can regift it to others. That’s how pandemics work. Earlier this year, a team of European researchers calculated that as of January 6, Covid-19 had caused enough premature deaths to add up to over 20.5 million years of life lost—given the statistical blurriness, that’s somewhere between two and nine times the impact of seasonal influenza. They couldn’t even begin to calculate the impact of disability, like long-haul Covid. And this was back when there were 1.3 million deaths worldwide; as of today there have been 3 million.

One might compare that to the years of life lost to complications from the vaccines—a number not yet known, but almost certainly not as large. Or you’d have to compare how many more cases of Covid-19 are going to occur when the J&J isn’t available, or because it’ll take longer overall to vaccinate everyone with just Moderna and Pfizer—versus how many blood clots may have occurred had it stayed in use. That’s super difficult. If you think that herd immunity kicks in for Covid-19 when around 40 or 50 percent of people are vaccinated—or let’s guess 50 or 60 percent for the more transmissible B.1.1.7 variant—that’s where some parts of the US already are. Infection numbers for any disease are basically either dropping to zero or doubling to very bad. So: “As vaccination ramps up and immunity builds, the doubling time of Covid will increase, but it’ll still be growing,” Scarpino says. “Once we hit herd immunity, growth will stall and we’ll see a decrease.” But in practice, herd immunity means different things in different parts of the world, different parts of the country, with different populations and different approaches. It’s another denominator problem. Overall numbers could be falling, but significant outbreaks could still occur, possibly in the places least well equipped to handle them. That means more fatalities, relatively speaking. Maybe. Lots of unknowns here.

Those numbers will certainly get worse if many people’s hesitancy to get vaccinated blooms into full-on skepticism, as it seems to be. Humanity can’t afford to have people bail out now; last week was the worst ever for Covid-19 worldwide, with 5.2 million new cases and more than 83,000 deaths.

At least in the US, people theoretically have the option to get a different vaccine, one without potential blood-clot side effects. That was an ethical release valve on the FDA’s original recommendation to deny the J&J option, even temporarily, though in practice the alternative isn’t really there for hard-to-reach populations like the homebound. And it’s not likely to be an option at all in the rest of the world. In Persad and coauthor William Parker’s Washington Post op-ed, that was a key observation—that public health folks were worried about the populations who wouldn’t get vaccinated at all versus rare side effects in people who did.

But these kinds of numbers tend not to move an individual person’s needle, as it were. “I’m sure practicing docs see it differently than epidemiologists, but I’m not sure in which direction—in fact, they may cancel out,” says Bob Wachter, chair of the Department of Medicine at UC San Francisco. “We’re totally used to giving medicines with risks of bad stuff that are far higher than this one, and mostly think nothing of it. The average physician taking care of a thousand people a year will never see a one-in-a-million complication.”

When the J&J vaccine comes back online, Ritter will go back to having some hard conversations with her patients. But here’s the weird part: She told me she’d have to talk to them about the risk of getting a specific kind of clot associated with the vaccine, a cerebral venous sinus thrombosis, with the risk of the same kind of clots from Covid-19. It can happen, but that’s not the axis an epidemiologist would use. They’d compare risk of side effects from the vaccine with the risks of the entire constellation of outcomes from Covid-19. “But that’s how I would talk to the patient about it,” Ritter says. “If they’re really specifically worried about that particular event—because that’s why they stopped it, right? They stopped it for that particular event.” Here again, everyone is working with different denominators. And just like in middle school math class, finding a common one is going to be the only way to get a real answer.

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