Science

Do Delta ‘breakthroughs’ really mean vaccine protection is waning, and are boosters the answer?

Israel has started to administer COVID-19 booster shots to people ages 40 and older. 

MENAHEM KAHANA/AFP via Getty Images

Even as the United States made the controversial announcement this week that it would begin to offer COVID-19 vaccine booster shots in September, scientists and public officials were scrambling to assess the rationale officials offered: that the vaccines’ protection against the Delta variant of SARS-CoV-2 is waning.

As vaccines rolled out early this year, the pandemic coronavirus seemed to almost magically melt away in some countries. But now, as Delta infections surge in highly vaccinated countries that once seemed to have COVID-19 on the run, including Israel and the United Kingdom, many fully vaccinated people are wondering how protected they really are. Although most data still show the vaccines are very effective at preventing severe disease and death, the initial hopes that they could also squelch transmission and completely prevent “breakthrough” infections in vaccinated people have evaporated. What is uncertain is how much the trends reflect a possible decline in vaccine-induced immunity versus the extraordinarily infectious nature of the Delta variant, and whether widespread use of boosters is now warranted.

Below we address some of the key vaccine questions at this new Delta-dominated stage of the pandemic.

How is Delta affecting vaccine protection?

“[Vaccine] efficacy drops with Delta. That is indisputable,” says Leif Erik Sander, an infectious disease expert at the Charité University Hospital in Berlin. But exactly how much it drops differs across studies. In a report this week analyzing weekly reports on nursing home residents across the United States, researchers found that the messenger RNA (mRNA) vaccines made by Pfizer and Moderna had an efficacy against all infections that went from 75% pre-Delta to 53% after it took over. (The variant accounts for more than 90% of U.S. cases now.)  

A large study from the United Kingdom, posted as a preprint yesterday, used the Office for National Statistics COVID-19 Infection Survey, which regularly tests more than 300,000 randomly selected people across the United Kingdom. The study compared the numbers of fully vaccinated and unvaccinated survey participants who tested positive for SARS-CoV-2 during two time periods: December 2020 until 16 May, when the Alpha variant dominated, and 17 May to 1 August, when Delta was dominant. The researchers found that for the two main vaccines in use in the United Kingdom—the Pfizer mRNA vaccine and the adenovirus-based shot developed by the University of Oxford and AstraZeneca—protection against symptomatic infection decreased significantly for the Delta period, to 84% for Pfizer and 71% for AstraZeneca. They also found, consistent with other studies, that compared with breakthrough cases due to the Alpha variant, people with Delta breakthroughs had, on average, much higher viral loads in the nose or throat, suggesting they are more likely to spread the virus to others.

A large study of patient health records in New York released this week told a similar story: The efficacy of the three U.S.-authorized vaccines against all SARS-CoV-2 infections dropped from 91.7% to 79.8% between May and July, as Delta took over in the region.

So, is immunity waning?

Although there is still some debate, lab tests suggest the Delta variant is not particularly good at evading the antibodies produced by vaccines or previous infection. That leaves two more probable explanations for the rise in breakthrough cases: Delta’s ferocious infectiousness or a gradual waning in vaccine-induced immunity. The U.S. nursing home residents who were studied are older and frail, and their response to the vaccine might drop faster than other populations. They were also among the first to get the vaccine—some back in December 2020.

The U.K. study attempted to resolve this issue by focusing on the time period after Delta became dominant and comparing the infection rate with the time since a person received their second vaccine dose. The research team found that breakthroughs did increase slightly with more time. People who received the Oxford-AstraZeneca vaccine had 68% protection against infection 2 weeks after their second shot, and 61% after 90 days. The drop-off was sharper in those who received the Pfizer mRNA vaccine: Fourteen days after the second dose, it seemed to provide 85% protection against all Delta infections, symptomatic or not, but that fell to 75% after 90 days.

“It could be that Pfizer’s protection drops from its initially very high levels and then stabilizes, or it could be that people who have had two doses of Pfizer will need a third,” says Sarah Walker, an epidemiologist at Oxford who led the U.K. study. In Israel, which used only the Pfizer vaccines, researchers also found that people fully immunized in January had twice the risk of being infected with SARS-CoV-2 during June and July as people who were vaccinated in April.

But David Dowdy, an infectious disease epidemiologist at Johns Hopkins University, notes that the apparent decline in protection could have other causes, including changes in individual behavior and the rate of transmission in the community. Dowdy notes that in the New York study, the efficacy of COVID-19 vaccines dropped most in the 18- to 49-year-olds and least in those older than 65. That suggests an increase in risky behavior among younger people—such as visits to restaurants, bars, and concerts—may also account for the trend. “People’s behavior has changed substantially” since the last wave, he says, with fewer masks and more large gatherings. “The potential for more frequent—and more intense—exposure over time” plays a role alongside Delta or possible waning vaccine immunity.

Do vaccines still protect against severe disease?

Here the latest data are more reassuring. “Protection against hospitalization looks quite stable,” Sander says. In the New York study, for example, vaccine efficacy against hospitalization for COVID-19 stayed close to 95%. Data from the Israeli Ministry of Health suggests protection against severe disease is still nearly 92% for people 50 and younger and 85% for those older than 50. Public Health England estimates that two doses of vaccine provide 96% protection against hospitalization.

Why are boosters controversial?

The U.S. decision to launch a booster campaign for the general population drew fire as both unnecessary, given that vaccinated people are still largely protected against serious disease, and unethical given the shortage of vaccine doses around the world. But a handful of other rich countries have also taken the step, or plan to. Israel, for example, has begun to roll out booster shots for all people over the age of 50—and is considering expanding the offer to everyone 40 and older. Germany has said it will start to offer boosters to high-risk people next month. In the United Kingdom, some officials have said third doses may begin next month, although no formal decision has been made.

There is broad agreement that for people with weakened immune systems, whether because of age or disease, boosters can offer important protection. “There’s a proportion of the population for whom two shots is not sufficient. For certain groups of people a three-dose regimen is required,” says Sander, who has studied the effects of boosters in immune-compromised patients. He has advised the German government to offer boosters to everyone over age 60. Boosters for health care workers and close contacts of people with weaker immune systems are also likely to be important, he says, to prevent transmission to vulnerable groups and to keep health care workers on the job when hospitals are stretched thin.

But the benefits of boosters for the wider population may not outweigh concerns about vaccine equity, especially for young people at low risk of severe disease, Sander says. Still, he notes, personal choices and the wisest public policy don’t always align: “I’d still rather have a third shot than catch the virus.”

Is there actual evidence that a COVID-19 vaccine boost helps?

Not much yet, but it’s likely they will to some extent. For other vaccines, another dose given months—or years—after initial doses can provide longer lasting protection. A COVID-19 vaccine study in June reported that organ transplant recipients who had responded poorly to two mRNA doses, likely because of the immune suppressant they rely on, responded better to a third dose. (Eight of 24 patients who had no antibodies after two doses developed antibodies after a third dose, and six patients who had low antibody levels all developed high levels after a booster.) Very preliminary data released this week by a health care company in Israel suggested a third dose was “86% effective” in preventing infections in people 60 and older, 1 week after receiving a booster—but no other details were provided making the figure almost impossible to assess.

“A third dose is a good idea,” says Aikiko Iwasaki, an immunologist at Yale University. Although at-risk groups should receive them first, she adds, “If there are enough doses, I think the general public will benefit.” She notes that the higher viral loads observed in breakthrough infections are independent of age, so even for people in their 20s, a higher level of immunity could help keep the virus in check, helping to prevent transmission.

Aside from severe disease, Iwasaki says, lingering symptoms from mild SARS-CoV-2 infections are a serious public health issue. “We know Long Covid can happen after breakthrough infections. And even if it’s just 1% of infections, enough people are potentially at risk that I think we need to do everything we can to prevent that from happening.”

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