On Thursday night, with the equivalent of a five-alarm siren, the Washington Post and New York Times, along with other media outlets, blared the major bullet points of an internal CDC slide presentation explaining a recent shift in mask guidance: The Delta variant was “as contagious as chicken pox,” according to the presentation, and “may be spread by vaccinated people as easily as the unvaccinated,” as the Times put it. “The war has changed,” the presentation declared, and public-health officials needed to acknowledge it.
To those who’d been following the science of Delta closely, the slides didn’t break much news. We’ve known for a while that Delta is dramatically more transmissible than the “wild” strain of SARS-CoV-2 and much more transmissible than even some of the earlier variants, also distinguished by their transmissibility. And there’d been signs for a week or so that, while vaccines were doing remarkably well protecting against severe disease, hospitalization, and death, and pretty well protecting against symptomatic disease, they were doing less well in protecting against transmission.
On this point, the CDC slides — or rather, the coverage of them — elided some very important context. There are two sides to transmission: getting infected and infecting others. And it is very clear, as even the CDC slides emphasize, that the vaccinated are much, much less likely to get infected than the unvaccinated — about eight times less. That’s very good protection, even if those who do get an infection turn out to transmit the virus at rates roughly comparable to the unvaccinated (a proposition supported by suggestive rather than definitive evidence, at this point). And while there has been a fire hose of criticism since the leak, of both the emphasis of the slides themselves and the fear-mongering tone of the press coverage, the central proposition — that breakthrough cases may be capable of prolifically spreading the disease — would deserve serious and widespread attention, if it proves out.
The most hopeful and encouraging facts about the Delta surge were even harder to find in the coverage. The first is that, thanks to widespread vaccination of the elderly, however fast this disease spreads it will ultimately inflict a much, much smaller death toll than earlier waves, because vaccination has probably eliminated 90 percent or more of the country’s total COVID-19 mortality risk. The second is that, in those countries with roughly comparable vaccination rates to the U.S., the surge has already peaked and begun a rapid decline, suggesting that such a turn here is possible — or even quite likely — within a few weeks. In the U.K., the Delta surge began in mid-May and peaked in mid-July; in the Netherlands, it began at the beginning of July and has already peaked. If the U.S. followed the British trajectory, our Delta surge, which began about a month ago, would peak by September 1; if it followed the Dutch course, even sooner, perhaps even imminently. And while there still may be some rise in deaths in both the U.K. and the Netherlands, given the lag between infection and ultimate outcomes, in neither country have deaths reached even one-fifteenth of the level of the local winter surge. In the U.K., they had almost as many new daily cases as they’d had in January; in the Netherlands, even more.
Can we count on precisely the same pattern unfolding here? The causes of the sudden case declines in those two countries are murky, so it’s not necessarily a sure bet — just a very encouraging sign. “Something strange is happening in Britain,” the Washington Post declared this week. “COVID cases are plummeting instead of soaring.” A few weeks ago, when the country’s new daily-case total was around 60,000, the prominent British epidemiologist and government adviser Neil Ferguson declared that a rise to 100,000 a day was inevitable, and that 200,000 a day was possible. The country is now at 27,000 and falling.
Ferguson looks foolish now, but predictions about the near-term course of pandemic spread have made their makers look foolish again and again over the last 18 months, in part because the disease seems to be driven by a much wider and more mysterious range of factors (weather, superspreader luck, social behavior that often moves independent of public advisories) than we tend to acknowledge (focusing instead on mask-wearing and indoor-dining policies). The challenges of forecasting were clear as early as last spring, and bedeviled both sorts of predictions, optimistic and pessimistic — at one point last summer, for instance, it was conceivable that something like “temporary herd immunity” might be achieved with only between 10 and 30 percent of the population exposed. As I wrote earlier this year, at one point in January, 26 of 28 models collected by the CDC to project the near-term future of the pandemic failed to include what proved to be the ultimate course of the disease, just two weeks later, in their range of what was considered possible.
To a layperson, the shape of all of these surges may seem strange — a spike that often stops short of full penetration of the population. And yet it is a quite common pattern of epidemiological “waves” long predating this disease. “However efficient the virus is, it’s not capable of reaching everyone,” Eric Topol of Scripps told me last week. “Just as the 1918 flu pandemic didn’t get to everyone. These pandemic pathogens burn through a population, but they invariably leave many behind who are vulnerable.” What is happening in Britain now seems very clear, and matches the shape of other pandemic surges elsewhere — including the Delta surge in India, where cases spiked for six weeks and then collapsed without the benefit of widespread vaccines, but primarily, it seems, through immunity acquired through infection, since the country now has an estimated 70 percent seroprevalence. The why of what’s happening in the U.K. is less clear to me, even after a week spent on the phone soliciting explanations from scientists.
“I don’t think we have the definitive explanation for the recent trends in the U.K.,” Lauren Ancel Meyers of the University of Texas told me, though she cited higher vaccination levels, seasonal school closures, rates of mask-wearing, and general social vigilance to help explain the turn. “We’ve been on this roller coaster for a while, right? Depending on where you are in the United States, you’ve experienced surges at different points in the pandemic, but, in Texas, we had our summer 2020 surge, then we had our winter surge, and now we’re in the midst of our summer 2021 surge. And you see this sort of feedback between what the virus is doing and how people are behaving — we’re sort of course-correcting as we go. You see the surges and you feel the risks personally, you hear about the hospital feeling overwhelmed, and sometimes there are policies that are guiding how you behave, as well. And people go from being more relaxed and taking greater risks to being more cautionary, and taking fewer risks.”
“In general, we’re seeing quite a shift in the dynamics of these epidemics with vaccination,” Adam Kucharski of the London School of Hygiene and Tropical Medicine told me. “Last year we were in a situation where, basically, there was widespread susceptibility in the population, and so if you wanted the numbers to come down, you needed widespread behavioral change. Whereas now, because we’ve got a lot of accumulated immunity in the U.K., particularly among older groups, that means a lot of transmission and susceptibility is really concentrated in these younger groups — and even within those groups, because you often get like with like mixing. With vaccinations, for instance, people will often hang out with other vaccinated people, which means you get these other pockets of susceptibility. What’s going on in those groups, in those pockets, really drives what’s going on in your epidemic, because we’re probably at a point where it would be quite difficult to get self-sustaining transmission now in some of these older groups, just because the vaccine coverage is so high. In those pockets of susceptibility, there could be quite large-scale flare-ups, but overall, the trend is quite striking.”
Nevertheless, he said, immunity alone probably doesn’t explain the across-the-board collapse in British cases, because the vaccine coverage is so much spottier than that trend would suggest. Instead, you’d likely need widespread behavior change within those groups, particularly among the young males who had really driven the surge. He, too, cited school closures, as well as the end of the European soccer championships, which produced so much congregating among young men. (In fact, everyone I spoke to mentioned the Euros, with one scientist suggesting it elevated the British “R” figure by as much as 0.4 — a remarkable surge, given that the R boost of last year’s Thanksgiving travel surge in the U.S. may have been only 0.09, at least according to Youyang Gu, the 2020’s best pandemic modeler.) Kucharski also credited the success of the country’s contact-tracing app. In the week ending July 21, he said, 700,000 notifications were sent out via app. As a result of additional precaution, he said, “the susceptibility network is much more fragmented,” with the behavioral changes by those groups making a much bigger difference than they would have a year ago — the effect of vaccines effectively amplifying the importance of the behavior of the unvaccinated in determining the shape and rate of spread.
The most encouraging hypothesis I heard was that the country had reached some version of herd immunity, with perhaps 80 percent of the population having attained protection against the disease through exposure or vaccination — a level that, holding factors like social behavior and weather constant, might be sufficient to permanently suppress the disease spread. Other estimates have suggested that as many as 92 percent of the U.K. has antibodies. Unfortunately, American estimates of infections are much more hodgepodge — a sign of how poorly the disease is being tracked by the country’s public-health infrastructure, which, believe it or not, recently stopped counting breakthrough cases, just before the Delta surge — but probably about one-third of the country has already gotten the disease here in the U.S. Just under half of the total population has been fully vaccinated, compared to 57 percent in the U.K., though of course there is significant overlap between the groups.
“Herd immunity” has been described in some strange ways during the pandemic. It is not a light switch that goes on at a certain point, completely stopping the disease, but a growing level of protection in the population at large that, as it accumulates, slows spread. But that is one reason the recent British trajectory is so striking — a rapid ascent is followed, not by a plateau or a gradual downslope, but by a just-as-rapid descent. It is almost like a light switch was flipped, all the more conspicuous for happening just two days after the country’s pandemic restrictions were, amidst much consternation, lifted.
“No one expected it to go up so quickly, and no one expected it to go down so quickly,” said Gu. “I think the short answer is just that the pandemic is unpredictable, even for scientists.”
Buried in the CDC presentation was one additional striking fact: that the Delta variant was so much more transmissible, in part, because of how quickly and prolifically it reproduces and takes root within the nose. What is most remarkable about that is that we have a suite of tools that might help precisely combat that problem, though we aren’t using them: intranasal vaccinations, which are delivered not by jabbing a needle into the muscle of your shoulder but by spraying a mist up your nostril.
This isn’t just a matter of Delta. Back in March, before India’s Delta surge had even begun, Scientific American published a sort of intranasal call to arms, by Eric Topol and Daniel P. Oran, under the headline “To Beat COVID, We May Need a Good Shot in the Nose.” As they wrote then, the current class of vaccines being rolled out, all delivered via intramuscular injection, were proving almost miraculously effective at preventing serious disease, hospitalization, and death. “But several coronavirus variants have emerged that could at least partly evade the immune response induced by the vaccines,” they wrote. “These variants should serve as a warning against complacency — and encourage us to explore a different type of vaccination, delivered as a spray in the nose.”
Today, the article reads almost like a Delta prophecy. “Although injected vaccines do reduce symptomatic COVID cases, and prevent a lot of severe illness, they may still allow for asymptomatic infection,” they wrote. “The reason is that the coronavirus can temporarily take up residence in the mucosa — the moist, mucus-secreting surfaces of the nose and throat that serve as our first line of defense against inhaled viruses.” An intranasal vaccine, they suggested, was the solution: “With a quick spritz up the nose, intranasal vaccines are designed to bolster immune defenses in the mucosa, triggering production of an antibody known as immunoglobulin A, which can block infection. This overwhelming response, called sterilizing immunity, reduces the chance that people will pass on the virus.”
Oran and Topol cited one study with animals that showed intranasal vaccines were able to almost entirely prevent infection with SARS-CoV-2 and another that showed they could completely block transmission — the point at which our intramuscular vaccines, it seems, are doing much worse with Delta. The advantages were presumably just as clear even earlier in the pandemic to Preston Estep, who, well before the FDA approved any vaccines and even before any clinical-trial data was available for them, was distributing his own DIY version to friends and colleagues around Harvard and MIT via nasal spray last summer.
A “Perspective” published last week in Science, by Frances Lund and Troy Randall, contemplates the same themes from a post-Delta vantage. “Given the respiratory tropism of the virus,” they write, “it seems surprising that only seven of the nearly 100 SARS-CoV-2 vaccines currently in clinical trials are delivered intranasally.” After walking through the scientific weeds of intranasal vaccination, they conclude, that, for best results, a shot should be followed by a spray.
Perhaps we don’t have time to roll out spray boosters in time to beat back Delta — one hopes the surge will have definitively crashed by the time any of those seven intranasal vaccines finish their clinical trials. But while we in the wealthy West may have missed the opportunity to use them, at least for this surge, there are almost inevitable booster cycles to come — and, of course, billions still in the developing world expecting now to wait until 2023 for their vaccines. The spray offers advantage there, too: It’s painless, can be done without expert training, and can be sent through the mail and stored without the refrigeration requirements that have proven such a burden to vaccine distribution thus far. That all sounds very promising, raising the same unfortunate question that could be asked of global vaccine rollout generally: What are we waiting for?
