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The rise of the Delta variant has driven new Covid-19 outbreaks, rattled markets, and reminded us that — for all the progress made in the fight against the pandemic — vulnerabilities persist.

In the United States, where the variant is estimated to be causing more than 4 out of 5 new infections, largely among the unvaccinated, the outbreaks in places like Arkansas and Missouri have once again placed health systems under stress. They’ve also led to more questions about whether Delta even poses a threat to people who are vaccinated and complicated the discussion about what precautions schools need to reopen fully in the fall.

Below, STAT runs through some of the most pressing concerns about Delta and how it’s changing the landscape of the pandemic.

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The most important takeaway: Even in the face of Delta, vaccines are still doing what they’re designed to do. That is, they’re defanging the threat of a Covid-19 infection, protecting people from getting so sick they have to be hospitalized and from death. Pretty much nothing in medicine is absolute, so a tiny fraction of vaccinated people will still wind up getting really sick, but there’s a clear reason why some 97% to 99% of current hospitalizations and deaths are occurring among those who are unvaccinated.

Why is Delta such a big deal?

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It’s important to keep in mind that Delta is a much bigger threat in places with limited vaccines access, unlike in the United States. But Delta spreads so effectively that it is fueling spikes in cases, and, in turn, increases in hospitalizations, in vulnerable U.S. communities as well.

Scientists are still trying to determine if Delta causes more severe disease on average than other variants, but in fact, experts worry more about a virus becoming more transmissible than they do about one mutating to become more dangerous. Viruses that spread more efficiently drive up cases more quickly, so the end result is an overall greater number of hospitalizations and deaths.

In this case, Delta appears to spread more voraciously than earlier forms of the coronavirus in part because people infected with it have much higher levels of virus in their airways. That means they “shed” more virus, and that if others come into contact with them, they’re more likely to get infected. Delta has underscored the argument from experts that people are either going to get vaccinated, or that at some point they’re going to get Covid-19.

At a population level, communities also need to have higher levels of protection (meaning more people who are vaccinated, or who’ve had previous infections) to gradually put a brake on the spread of more transmissible viruses. That helps explain why Delta is driving case upticks even in states with relatively high vaccination coverage, though those increases are significantly smaller than those in less vaccinated states.

I’m hearing a lot about breakthrough infections. Is Delta causing more of them? What does that mean about the vaccines? 

We’ve never really had a good estimate for how frequently breakthrough infections occur. The carefully monitored clinical trials that gave us our best estimates for vaccine effectiveness were generally designed to measure how well the shots protect against symptomatic Covid-19 cases — not any infection. And in the real world, it’s presumed that a lot of mild and asymptomatic breakthrough infections go undetected. Without that baseline, it’s hard to say how the rate is changing over time. What is clear is that the vast majority are asymptomatic or mild.

There are a couple reasons why you might be hearing more about breakthrough infections now. One is that they make news — someone contracting the coronavirus even though they’re vaccinated makes for an easy headline, even though we’ve been told from the early days of the vaccine campaign that immunized people would still sometimes get Covid-19. Also, people are coming to realize that even if vaccines broadly limit disease to “mild” illness, that can still leave them feeling pretty crappy for a few days — even as it saves them from feeling worse for longer, and from getting much sicker.

It’s also possible that breakthrough infections are happening more frequently for reasons that have nothing to do with how well vaccines are working. For one, many of us have returned to activities we had put off. Having more, unmasked contact with others — at bars, weddings, family gatherings, whatever — increases the risk that we’ll come into contact with an infectious person. (It’s no surprise that the place with the highest rate of new cases in Massachusetts is summer tourism hot spot Cape Cod.) Plus, as cases increase, there’s just more virus around, so we’re more likely to be exposed.

There’s a statistical reason that could also be playing a role. The higher the percentage of a community that’s vaccinated, generally the lower the absolute number of cases will be — which is what everyone is aiming for. But as a greater proportion of that community becomes vaccinated, breakthrough infections will actually account for a greater share of overall cases. Think about a scenario where 100% of people are vaccinated — 100% of cases would be among the vaccinated.

Then, there’s Delta’s impact on vaccines. The good news is that the vaccines are maintaining their ability to protect against hospitalization and deaths, even in the face of this evolved virus. As researchers wrote in a New England Journal of Medicine study this week that looked at the effectiveness of the Pfizer-BioNTech and AstraZeneca vaccines against Delta, “only modest differences in vaccine effectiveness were noted with the Delta variant as compared with” other forms of the virus, as long as people had both shots of the two-dose regimens.

But it is possible — though not confirmed — that the mutations in Delta give it some room to wriggle around the vaccine’s full defenses. The result could be that Delta is more likely to establish a breakthrough infection and possibly cause some symptoms, though the bulk of the protection still kicks in and guards against the worst outcomes. Health officials, however, say they’re not seeing signs that Delta or some other variant is causing a disproportionate number of breakthrough cases.

Some places are once again encouraging masks in indoor settings, even for vaccinated people. Are people infected with Delta more likely to transmit the virus even if they’ve been vaccinated? 

If vaccines achieved their main purpose in preventing severe disease and death, a huge added bonus was how much they cut transmission. They did this by preventing many infections entirely, and likely making those who still got infected less infectious for shorter periods of time — meaning they were less likely to pass the virus to others. (Though whether or to what extent vaccinated people have been spreading the virus at all is still unsettled.)

It’s possible that the shots’ impact on transmission is slightly lessened in the face of Delta, though we don’t know that for sure, either. That’s not to say that vaccines have no impact on Delta’s transmission, of course, but it might be dented.

In recent days, communities worried about rising case numbers have reupped their encouragement of masks in certain areas. Los Angeles County officials mandated them in indoor public settings. Masks, after all, are the least disruptive mitigation measure, compared to capacity limits or other restrictions. The new local recommendations could help if vaccinated people are in fact playing a significant role in transmission, but it could also help increase mask usage overall. It’s been recommended that those who remain unvaccinated keep up with masking, but when there are different recommendations for different groups, it’s hard to know for sure that the unmasked customers at the grocery store indeed got their shots.

On Thursday, Centers for Disease Control and Prevention Director Rochelle Walensky said the guidance that vaccinated people can go unmasked hasn’t changed, but allowed that local communities should make their own recommendations. It’s a reminder that the Covid-19 landscape varies dramatically across the United States, with the risk situation in, say, Vermont being quite different than in Texas.

Just how effective are vaccines against Delta? Will I need a booster?

The best measures we have of the effectiveness of authorized vaccines come from clinical trials, but they were completed before Delta emerged. Without trials, we rely on a mix of real-world studies and lab experiments, which each have their own limitations.

The real-world studies have come up with a range of effectiveness estimates, but the clear takeaway has been that full vaccine regimens protect against the worst outcomes no matter the variant they face. Delta seems to be less of a threat to immune protection than another, less common variant, Beta. (A full regimen means both of the shots in the two-dose courses.)

One key question in the United States has centered on whether people who received the one-dose Johnson & Johnson shot should get a booster of one of the mRNA vaccines, those made by Pfizer-BioNTech and Moderna. Some lab experiments have indicated the antibody levels from the one J&J shot are sufficient to stand up against Delta, though another study that garnered headlines this week suggested those antibodies weren’t all that protective against Delta. Perhaps, one hypothesis went, two doses of J&J or a combo of J&J and another shot would be needed to build up protection levels to guard against Delta — akin to how studies have shown that just one shot of some of the other vaccines is not all that effective against the variant.

But the conflicting results highlight the limitations of what can be extrapolated from these lab studies (for one, they just look at one of several components of immune protection). There will certainly be more research into this question, such as whether Delta is breaking through J&J shots more frequently than other vaccines or is more likely to cause breakthrough disease in those people. But federal officials reiterated Thursday that right now, they do not recommend that people who got the J&J shot get an mRNA booster.

Does Delta mean we’re not going to eradicate Covid-19?

Covid-19 isn’t going to be eradicated, but that was the reality before Delta came around.

Remember, the long game with the virus is that our bodies become so used to recognizing it and warding it off that, over time, it becomes little more than a nuisance. With each exposure to the virus, either through an infection or an exposure-mimicking vaccine, our bodies get retrained to fight it. Eventually, SARS-CoV-2 is likely to join the ranks of respiratory viruses that cause occasional colds, with rare exceptions of serious illness.

In a way, we’ve started the journey to making the coronavirus less of a big deal. Given how many people remain unprotected, we’ve still got a long way to go. But in areas where lots of people are protected — including the vast majority of older adults, who are most likely to die from Covid-19 — even if infections are going up, deaths are not. It’s the first step toward putting the pandemic behind us. 

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