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Saturday, April 24, 2021

The surprising thing about COVID-19 breakthrough infections.

The Really Surprising Thing About Fully Vaccinated People Who Get COVID-19

Yasmin Tayag 

"Kyle Marian Viterbo had made it a point to get regularly tested for the coronavirus, even after getting vaccinated. That’s how, a little more than a month after her first Moderna jab, she discovered she had COVID-19. She traced it back to an uncomfortably crowded outdoor comedy show she’d attended the week before testing positive.

Viterbo, a science communicator, understood this was possible given that the Moderna vaccine is 94 percent effective around two weeks after the second shot and is around 80 percent after the first shot, though experts have cautioned that it’s not clear how long protection from the first shot lasts.  Still, she said,  it was “hard to think what all those percentages mean for everyday life, especially for the consequences beyond my own body. It felt like a gut punch.” Fearing for the elderly relatives she lived with, she checked into a New York City COVID isolation hotel, where she rode out her asymptomatic infection and shared her experience on TikTok.

Last week, the Centers for Disease Control and Prevention reported that more than 5,800 out of 75 million fully vaccinated people in the U.S. have been infected with COVID-19. Of these “breakthrough cases,” 396 were hospitalized and 74 people died. The CDC defines a breakthrough case as someone who gets sick, either symptomatically or asymptomatically, 14 or more days after full vaccination. A few headlines about the report implied, rather irresponsibly, that the breakthroughs happened because the vaccines didn’t work. CNN, for instance, put it this way: “So far, 5,800 fully vaccinated people have caught Covid anyway in US, CDC says.”

The reality is that breakthrough cases are normal and expected after vaccination. That’s because none of the three vaccines available in the U.S. (or, indeed, anywhere else) is 100 percent effective at preventing disease from COVID-19. The Pfizer/BioNTech vaccine, for instance, is 95 percent effective. That’s impressively high, but a few breakthrough infections, hospitalizations, and deaths are still expected to occur in people who get the vaccine. (One slightly confusing thing about investigating breakthrough infections is that research is using the term differently. There’s the CDC’s definition of an infection two weeks after full vaccination. But some studies have also investigated breakthrough infections in people who have received only one vaccine dose, like Viterbo. Other research addressing infections after vaccination doesn’t use the term breakthrough at all.)

“If it were 95 percent protection, you would expect 5 percent of the [75] million people who’ve been vaccinated not to be protected,” said Barry Bloom, a professor of public health and an immunologist at the Harvard T.H. Chan School of Public Health on a press call on Friday. (This is a little bit of a simplification—epidemiologists like to point out that 95 percent efficacy technically means that after you’re fully vaccinated, you’re 95 percent less likely to be infected compared to an unvaccinated person.) The same logic applies to the Moderna vaccine, which is 94 percent effective, and the Johnson & Johnson vaccine, which was 72 percent effective in a U.S. trial. In fact, the number of breakthrough COVID cases was “less than I expect,” said Bloom. “Far less.” Of the 75 million vaccinated people in the U.S., the 5,800 breakthrough cases represent just 0.0075 percent.

When you take these percentages into account, it’s easier to see that the proportion of breakthrough cases is very low, according to Syra Madad, an infectious disease epidemiologist and senior director of the special pathogens program at New York City Health and Hospitals.

The numbers are “not concerning to me at all,” she said. Much of the media coverage has needlessly raised alarm because it lacked this context, she added.

It’s comforting to remember that breakthrough cases regularly happen with other common vaccines. The annual flu shot, for example, is usually only 40 percent to 60 percent effective, which means that up to 40 percent to 60 percent of vaccinated people may still get the flu if exposed to it. Despite this, said Madad, the flu shot prevented an estimated 7.5 million cases of flu in the U.S. between 2019 and 2020. The COVID-19 vaccines, which are much more effective, will protect many more people.

However, Stephen Kissler, an immunology and infectious disease expert at the Harvard T.H. Chan School of Public Health, cautioned that the vaccines’ impressive efficacy isn’t the only reason the proportion of people with breakthrough infections is so small.

For one thing, breakthrough cases can only happen when vaccinated people are exposed to COVID-19, and since most people were vaccinated recently, they haven’t had much time to be exposed. Another factor driving the number down may be that vaccinated people who have symptomatic breakthrough infections might not get tested because they assume they can’t be sick with COVID-19.

For these reasons, the proportion of breakthrough cases we’re seeing now may increase past 0.0075 percent. But Kissler doesn’t think it’ll change too much, “just because of how effective the vaccine is, both at preventing disease and reducing transmission.”

Experts still don’t know why some people aren’t completely protected by the vaccines. According to Bloom, early unpublished research suggests that some people respond to them by making the wrong kind of antibody. Instead of making antibodies against the SARS-CoV-2 spike protein—which is what’s supposed to happen—some people appear to make antibodies against the nucleocapsid protein, and those antibodies don’t have the same protective effect. Other early research, he said, shows some people don’t make antibodies in response to the vaccines at all.

Still, the proportion of these people is “infinitesimal—a thousandth of a percent—and they just have some hang-up, genetic or otherwise, where they don’t see the antigens on the spike protein,” Bloom said.

Now, the CDC is collecting data on breakthrough infections that lead to hospitalizations and deaths, looking for patterns related to age, underlying medical conditions, vaccine type, COVID-19 variant, and other factors. This data can help experts determine any instances in which deaths or hospitalizations that were chalked up to COVID-19 were actually driven by other factors, health-related or otherwise. “While they may have gotten vaccinated and they’re post two weeks out and they’ve passed away, it may not directly be related to COVID-19,” Madad said.

It’ll also help experts figure out what role variants play in breakthrough cases. Right now, it’s still not clear. “That’s the big question that even a lot of our clinicians and providers often have,” she said.

A small recent study of 149 people in Israel, which hasn’t yet been peer reviewed, suggested that the B.1.1.7 and B.1.351 variants (first identified in the U.K. and South Africa, respectively) caused more breakthrough cases in people who had received their first dose of the Pfizer/BioNTech vaccine. A week after the second dose, the B.1.351 variant was driving more cases. These findings, however, come with two big caveats: There weren’t any B.1.351-linked breakthrough cases two weeks after the second dose, which may mean that the vaccine’s reduced effectiveness is short-lived, lead author Adi Stern tweeted. Second, even though the B.1.351 variant has caused some breakthrough cases, it isn’t spreading in Israel, so these cases may not be worth worrying about.

All of the approved vaccines provide protection against the known variants circulating in the U.S. That said, it’s still important to keep your guard up even after you’re fully vaccinated, especially if there’s high community transmission where you live (right now, that’s most places in the U.S.). You’ve heard it before, but it bears repeating: Keep wearing masks, social distancing, and avoiding large gatherings—whether indoors or outdoors.

Viterbo learned that the hard way, at a backyard gathering packed with unmasked people eating and drinking. “Continue to get tested for COVID especially if you’re in contact with people who haven’t been fully vaccinated yet or haven’t contracted COVID before,” said Viterbo. “Get tested when you’ve spent time unmasked in a poorly ventilated area—and yes, that includes dining indoors.”

Breakthrough cases will happen, and they can be a nasty surprise. But take comfort in knowing that a growing body of evidence shows that most fully vaccinated people who do get infected have mild symptoms, and the real-world data on the frequency of breakthrough cases is actually quite reassuring.

“I think, overall, I am completely surprised that the breakthrough numbers of people in the States is as low as it is,” said Bloom. “And we should be grateful for that.”

Update, April 23, 2021: This article has been updated to clarify what it means for a vaccine to be 95 percent effective. 

Future Tense is a partnership of SlateNew America, and Arizona State University that examines emerging technologies, public policy, and society."

The surprising thing about COVID-19 breakthrough infections.

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