Eletiofe We Still Don’t Know How Well Covid Vaccines Stop...

We Still Don’t Know How Well Covid Vaccines Stop Transmission

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This week, the US passed a grim milestone in the ongoing coronavirus crisis: 500,000 deaths, more than the number of Americans killed in World War II, the Korean War, and the Vietnam War combined. And yet there is a growing sense of hope that the worst might now be behind us. With new cases declining and immunizations accelerating—45.2 million people have so far received at least one dose of a Covid-19 vaccine, including 20.6 million who have been fully vaccinated—many Americans are beginning to allow themselves to imagine what post-pandemic life might be like.

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Achieving that is likely to take a few more months—provided vaccine makers don’t hit any production snags and worrisome variants don’t derail current progress. In the interim, an increasing number of people will find themselves in a liminal state, navigating what it means to be a vaccinated person moving through an unvaccinated world. What are its rules, and what will it take to be a good citizen of it? Answering those questions means confronting an even more fundamental unknown. A vaccinated person may be well-protected from the worst ravages of Covid-19. But it’s not clear if they can still carry the coronavirus and transmit it to susceptible people around them.

This week, two new studies—neither of which have yet gone through peer review—made splashy headlines about the extent to which vaccines slash viral spread. The first, a leaked manuscript first reported by Israeli news site Ynet before being covered by MIT Technology Review, Bloomberg, The Financial Times, and Vox, found that two doses of Pfizer-BioNTech’s shot drove an 89.4 percent drop in infections—both symptomatic and asymptomatic—among vaccinated people in Israel. Though they did not directly measure transmission, the study’s authors—researchers from the Israel Ministry of Health, Hebrew University, and Pfizer—stated in the abstract that the Pfizer vaccine “was highly effective in preventing SARS-CoV-2 infections.” Subsequent news coverage hailed it as the first evidence from the real world that the vaccine could strongly suppress spread of the virus. But scientists not associated with the study say that was an overstatement. (Indeed, Bloomberg later updated its story to include such criticisms, though not the headline.)

In the report, which WIRED has obtained, the research team analyzed aggregated data from Israel’s national testing and disease surveillance system, comparing infection rates in vaccinated versus unvaccinated groups of people between January 17 and February 6. However, as the study authors noted, the ministry’s testing recommendations exempt vaccinated people from requirements like getting tested after travel or being exposed to a known Covid case. Under these protocols, unvaccinated people aren’t just required to get tested more often, they might also choose to, because they’re more worried about contracting Covid-19 than people who’ve gotten the jab. And because infections—especially asymptomatic ones—are more likely to be detected in the group that’s testing more frequently, the estimated 89.4 percent transmission-blocking effect of the vaccine is almost certainly too optimistic (a caveat the authors acknowledged, saying more research is needed to confirm their findings).

“The testing rates were such a hodgepodge, I don’t know you can make any conclusions about how much the vaccine cut transmission in Israel, let alone assigning a number as concrete as 89.4 percent,” says Eric Topol, a professor of molecular medicine at the Scripps Research Institute. The only way to do a careful study of asymptomatic spread and how well the shots curtail it, he says, is to swab both groups—vaccinated and unvaccinated people—every day, ideally for months. Though perhaps prohibitively expensive, the most rigorous version of that experiment would be to also follow each positive test up with contact tracing and genomic sequencing to confirm the route of transmission. The way the Israeli team did it is not the way to get the answer, he says: “It’s a way to get a lot of interest, because everybody wants to hear this.”

Indeed, right on cue, a few hours after the Israeli study began making the rounds in American media, one of my family members sent it to me. Just a few days prior, this person—who is vaccinated with the Pfizer shot—had asked me how safe it would be to fly and immediately join a pod of unvaccinated relatives. They did not like my answer (probably still risky, but we really don’t know just how risky just yet). They liked the Israeli study’s answer much better.

Scott Halpern, an epidemiologist and critical care physician at the University of Pennsylvania, says this is a pretty classic case of optimism bias—the general proclivity of the human species to believe that our desired outcome is likely to be the correct one. (Halpern has written about how other cognitive biases have hampered a smart and effective public health response here in the US.) It’s the same neural tick that drives people who’ve been told their loved one hooked up to a ventilator in the Covid-19 ward has a 5 percent chance of surviving. Most people believe their loved one will be in that 5 percent. Halpern knows this one from first-hand experience; he’s still seeing Covid-19 patients in the ICU most weeks.

Mix that optimism bias with pandemic fatigue, and you have a recipe for some under-baked science getting slung around as rationale for people doing the things they really want to do. “Once you’ve been bombarded with bad news long enough, any glimmer of good news is something we just emotionally latch onto,” says Halpern. “That’s just human nature.”

The Israeli team did not respond to WIRED’s emailed questions. A Pfizer spokesperson declined to comment on the 22-page report, which was first described last week by Israeli journalist Nadav Eyal, who published screenshots of the text on Twitter.

The second report, a preprint posted on The Lancet Monday, blew that glimmer of good news into a bigger flame. It described a Public Health England study of health care workers in the United Kingdom who’d received the Pfizer-BioNTech vaccine, and who were tested every 14 days for Covid-19. The study found that in addition to making people less likely to get sick from the coronavirus—no surprise there—the vaccine sliced the risk of the recipient getting infected, period. By how much? Vaccinated health care workers were 72 percent less likely at 21 days after the first dose, and 86 percent 7 days after the second dose. The logical jump here is that a vaccinated person has far fewer chances to spread the virus, since the shot reduces the odds they’ll ever be carrying it around. “We provide strong evidence that vaccinating working age adults will substantially reduce asymptomatic and symptomatic SARS-CoV-2 infection and therefore reduce transmission of infection in the population,” the study authors concluded.

While this study was better controlled, Topol says testing every two weeks still isn’t frequent enough to catch new infections. “It’s really got to be daily,” he says. Those kinds of experiments are much harder and costlier to do. But both Pfizer and Moderna are reportedly working on them right now, with data rumored to drop sometime in the next few weeks. (A Pfizer spokesperson declined to confirm that timeline or provide any details until data from a study has been published. Moderna did not respond to an emailed request for more information.)

WIRED’s questions did not immediately receive a response from the research team or Public Health England.

For now, that leaves the public without a lot of firm answers. “We’re going to be sitting with incomplete knowledge on this topic for some time still,” says Topol—even though he and other scientists say they’re confident vaccination against Covid-19 will eventually be shown to reduce the chance of transmitting the virus. The question is: By how much?

“I think it is highly likely that there is some transmission-blocking effect to these vaccines,” says Kawsar Talaat, an infectious disease physician and vaccine safety researcher at the Johns Hopkins Bloomberg School of Public Health. She also led the Johns Hopkins Center for Immunization Research’s clinical trial of the Pfizer vaccine. But, she says, putting a number on the size of that effect is really tricky.

For one thing, scientists have yet to determine how many copies of the virus need to be in an infected person’s nose to make them contagious to others. “There’s not a clear threshold yet for the amount of viral load at which transmission happens,” says Talaat. Which means you can’t look at someone’s PCR result and know with certainty that the amount of virus the test is detecting is enough to make other people sick.

In general, researchers have found that less virus means milder symptoms and a lower risk of passing it on. But not always. People’s bodies and immune systems behave differently. We all breathe at different rates, exhaling particle plumes of varying size and density. Researchers also haven’t pinpointed exactly how much SARS-CoV-2 has to get into your nose to cause an infection. And that number is also subject to similar biological variables, as well as environmental ones, like which strains are circulating in your area. More transmissible variants, like B.1.1.7, which is currently spreading across much of the US, might need to take fewer cracks at the ACE2 receptor. So being able to say that X amount of virus in the nose equals Y risk of spreading to other people is just beyond the scope of the current science.

Even so, several research groups in Israel are measuring viral load in vaccinated people who later test positive for SARS-CoV-2. One team from the Israel Institute of Technology and Tel-Aviv University recently observed that people who caught the virus two to four weeks after receiving their first dose of the Pfizer vaccine had up to 4 times smaller viral loads than people who got infected in the first two weeks after getting the shot. The results suggest the vaccine reduces the risks of transmission, while not erasing them entirely.

That’s an expected result, says Talaat. No vaccine out there right now, no matter how good (and the Pfizer and Moderna shots are very good), will stop the coronavirus from causing infections in at least some people who’ve gotten the shots. Here’s why.

The two FDA-authorized vaccines in the US are first-in-their-generation genetic vaccines. What comes out the tip of that needle and into the muscles of your arm are microscopic, fat-encapsulated strands of mRNA. These strings of genetic letters carry the instructions for making bits of the coronavirus spike protein, which the live virus uses to infect human cells. Capillaries that run through the muscle whisk the mRNA molecules into the bloodstream and carry them to the nearest lymph node. Once there, the vaccine components encounter dendritic cells and macrophages—two types of immune cells that can sense when something foreign is sneaking around in the body. They grab the mRNA and use it to produce pieces of the spike protein, which they then display on their surfaces to flag down other immune cells. These begin churning out antibodies and activating T-cells to fight off what the body perceives as an infection.

There isn’t one, of course. But this fire drill prepares the immune system to quickly kick into action should the vaccinated person encounter the real coronavirus in the future. The Pfizer-BioNTech and Moderna vaccines are especially good at it. But to an antibody or a T-cell, the body is a big place, and the nose is a battlefront far-removed from the initial action in the arm. “If you give a shot in the arm, you’re likely to get immunity in the body,” says Talaat. “But it’s hard to create immunity in the mucosal surfaces where the virus colonizes.”

SARS-CoV-2 might cause its deadliest damage in the lungs, heart, and blood vessels. But its first stop in the human body is usually the nose, because that’s where inhaled viral particles first encounter cells they can invade and hijack in order to make copies of themselves. From there, the swarm of new viruses can expand into other organs—if the immune system doesn’t shut them down. And it’s from the nose that infected people can send out new clouds of contagion.

So in order for a vaccine to block transmission completely, it would have to recruit a cast of SARS-CoV-2-targeted antibodies and immune cells specifically to patrol the nasal passages, where they could glom onto any coronaviruses just after they get inhaled, and before they start their self-replication spree. This is how the nasal spray versions of flu vaccines work. But that’s just not what Pfizer or Moderna’s shots were designed to do. They were designed to create a sparser crew of wider-roaming immune defenders that can jump-start a bigger response wherever they encounter the virus, giving an infected person a better chance of beating back full-blown symptoms. “The goal of these vaccines has always been to prevent people getting hospitalized and dying, because that has the biggest public health impact,” says Talaat.

The good news about the Israeli and UK studies, even with their methodological flaws regarding transmission, Talaat says, is that they show that out in the real world, away from the controlled parameters of a clinical trial, the vaccines are working fabulously at preventing people from getting seriously ill. In the leaked Israeli report, the vaccines led to a 95 percent drop in hospitalizations and 92 percent dip in deaths. And newer, better-vetted data is already starting to back that up.

A study published Wednesday in the New England Journal of Medicine that analyzed 600,000 pairs of vaccinated and unvaccinated Israeli individuals found that two doses of the Pfizer’s shot was 92 percent protective against severe disease and 87 percent effective at preventing hospitalization. Though the study did not have data on deaths following the second dose, just a single shot lowered death rates by 72 percent. So from a public health standpoint, that makes the question of whether or not the Pfizer vaccine, or any other, stops viral spread really a secondary concern, says Talaat. “If you vaccinate enough people, then you don’t need a vaccine that stops carriage in the nose and potential transmission,” she says.

But that number does matter for answering questions like these: Is it safe to eat inside a restaurant? Or get on an airplane? Or hug your grandkids?

Say the vaccine you get is 80 percent effective at blocking viral spread. That means that should you contract the virus, you may not get seriously ill or even have a single symptom—but there’s still a 20 percent chance you’ll pass it on to someone else. And what if the vaccine you get is only 50 percent effective at blocking spread? Now it’s a coin flip.

“This is exactly the type of gray area where reasonable people might reasonably arrive at different answers,” says Halpern. “It all comes down to the fact that we don’t all have the same risk tolerance.”

Talaat’s version of this calculus involves navigating family get-togethers with her parents (vaccinated) and her siblings (unvaccinated). Since she herself is vaccinated, Talaat still wears a mask when she’s visiting her siblings. And she’ll continue to do so until they get their shots. But she feels more relaxed around her parents. “If you are in a household or pod with someone who’s not vaccinated, you should still be as careful as you can to prevent potential transmission, especially if that person is high-risk,” she says.

That doesn’t mean your post-shot life has to look exactly the same as pre-jab. But it does mean continuing to wear masks and socially distancing. Both of those further reduce the risk of spread—how much exactly, no one can say, so public health experts say better to do them all. At least for now.

That’s because whatever the “real” transmission rate for vaccinated people may turn out to be, that number doesn’t exist in a vacuum. A 50 percent reduction in risk of transmission isn’t (or shouldn’t be) particularly liberating if the virus is still running rampant in your area. But it might be if local case prevalence shrinks to the point where your odds of exposure to the coronavirus are virtually zero. The calculation can’t just be about the level of protection of the vaccine against viral spread, but also about the risks in your particular community, says Halpern.

“So where we are today is that you have to keep your mask on after getting vaccinated—not because the vaccine doesn’t work, but because there’s still too much virus in pretty much every neighborhood in America,” he says. “If everyone keeps doing it, we’re going to get to a point where the masks can come off. But we’re not there yet.”


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