Do the Merck and Pfizer Pills Along With Children's Vaccination Finally Offer A Pandemic End?

Given the limited risk to children and the waning potency of vaccines after one year, the antiviral pill is more significant in reducing risk and may, finally, point to a pandemic end game. JL

David Wallace-Wells reports in New York Magazine:

Two developments over the last week may bring the COVID-19 endgame finally into view: the beginning of vaccination for children between the ages of 5 and 11, and the announcement by Pfizer that a trial for a drug revealing an 89% reduction in severe illness among those taking the pill. (Merck’s antiviral, just approved for use in the U.K., also showed impressive results). The new therapies promise a dramatic reduction of  risk, bringing the vulnerability of almost everyone to COVID into the range of far more familiar, quotidian diseases.

Probably we were always going to have to decide ourselves when the pandemic was over. Once it became impossible to eliminate the disease entirely, sometime in the early spring of 2020, it also became a lot harder to imagine that the course of the disease itself would tell us in any obvious way when to drop our masks and the social inhibitions that had reshaped so much of our worlds and get on with our lives. “Science” wasn’t going to do the job either, with the disease continuing to circulate, causing some amount of severe illness, and passing eventually into a confusing state of endemicity. Staring down that possibility, recently, it wasn’t clear whether we should be judging the state of the disease on case numbers or hospitalizations or deaths or vaccination rates or school closures and quarantines or some other metric. “America has lost the plot on COVID,” Sarah Zhang wrote memorably in the Atlantic. Though perhaps the point could’ve been put more sharply: America must make its own plot now — without an obvious one to follow or an intuitive statistical trigger for going back to “normalcy.” Cases and hospitalizations are falling (but not anywhere close to zero) as vaccinations creep higher (but not yet close to 100 percent). The Delta wave is waning, but the possibility of a winter peak is looming. A few weeks ago, newly minted MacArthur “genius” Trevor Bedford modeled an endemic future for COVID-19 in which between 40,000 and 100,000 Americans die every year from the disease — enough that it would be tricky to ever call the pandemic truly “over,” but not enough to really justify most of the precautions we’ve taken to this point, especially the universal ones. It was hard to think about those numbers — on the high end, a third as lethal as COVID was last year, and on the low end, still more lethal than the flu — and believe there was any intuitive exit in sight.

But two developments over the last week may shift our collective perspective enough to bring the COVID-19 endgame finally into view: the beginning of vaccination for children between the ages of 5 and 11, and the announcement by Pfizer that a trial for a therapeutic drug called ​​PF-07321332 was so successful it was halted midway, with data already revealing an 89 percent reduction in severe illness among those taking the pill. (Merck’s antiviral molnupiravir, just approved for use in the U.K., has also showed impressive results, though not quite as impressive.) Over the last eighteen months, it has been foolish, again and again, to declare the arrival of a pandemic endgame with each spark of good news or turn of the case graphs. And we are staring down what is, in theory, the scary season for respiratory viruses like this one. But perhaps with these two developments we have enough of the puzzle pieces in place that we can see the outline of a new phase—or at least enough to declare one, as grim as it may be to begin to turn the page, socially and culturally and psychologically, when more than a thousand Americans are still dying each day.

One of these developments is far more epidemiologically significant than the other. Vaccinating children does appear to meaningfully reduce their risk of serious illness, but that risk was so low to begin with that, while there would be some effect at the population level, for individual children it effectively meant dividing a zero into smaller zeroes. According to the Financial Times, vaccinating 25,000 children had the same effect on hospitalizations as vaccinating just 800 seniors. Major media outlets have taken to describing the vaccination program as much or more in terms of its effect on the anxiety levels of parents as on the health of their children, and while that may seem on first blush a bit silly, of course the effect on anxiety is also quite real, and a lot of Americans have been waiting for those shots to begin in order to breathe sighs of relief and feel safe again. Future histories will probably be written about exactly why the country obsessed so much over the safety of the least vulnerable group — and perhaps others about the strange logic by which we applied much less scrutiny and rigor to testing the vaccines on children than we had for the most vulnerable groups — but right now, what’s most significant is that the vaccines give us permission to stop panicking about the kids.

The Pfizer announcement is a much bigger deal because its effect goes well beyond the psychological: In the world of novel therapeutics, this is a monster breakthrough, capable of reducing the population-level severity of the disease as much as tenfold, at least in high-risk populations.

Taken together, the two bits of news draw a sort of escape hatch from pandemic anxiety — indeed, they may show the way out of the ongoing, post-vaccine zombie stage of the pandemic that has been dragging on since the summer. In many ways it has proven the most confusing period of our last couple of years. Yes, the country was underperforming on vaccination, and yes, the protections offered by those shots were, while significant, not perfect. But given the prevalence of vaccine protection and the degree to which the disease had spread through the population itself over the last 18 months, it was also reasonable to think, this summer, that, as a whole, the threat was at least subsiding. And yet, even as some of us turned away or tuned out the numbers, they weren’t actually looking much better, with 2,000 Americans dying every day during a period in late September. In late July, as the Delta wave was just beginning to take off, I had a long conversation with Eric Topol of Scripps about what seemed to be not just a troubling but a confusing pattern: At a time of widespread, if not universal, vaccination, the ratio of hospitalizations and deaths to confirmed cases with the new variant seemed unchanged from the ratio observed during the worst period in the American pandemic, the winter surge at the beginning of 2020. In other words, the vaccines had failed to make any difference at all at the national level in the share of new cases that ended up in the hospital or the morgue.

We are now very much on the downslope of our Delta wave, and this confusing fact pattern, disconcertingly, still holds in the data from late summer and early fall. Confirmed cases were a bit lower than last winter’s uncontrolled spread but still, in raw terms, quite high, with about a month of running daily seven-day averages between 100,000 and 150,000 new cases (last winter, the same averages for the worst month ran between 150,000 and 200,000, with a brief, sharp spike above that). For a couple weeks in late August and early September, there were 100,000 hospitalizations, on average; last winter, there were between 120,000 and 130,000 at peak. During Delta, the death totals passed 2,000 per day; in the winter surge, the peak was just above 3,000. All told, this surge — which unfolded during months of temperate weather, when more than half of the country was fully vaccinated and a much larger share of the vulnerable elderly were — featured the fourth deadliest month of the pandemic overall and has helped make 2021 already a deadlier year for Americans than 2020 was despite all that vaccination. Presumably without vaccination, there would have been more rapid spread and much more dramatic spikes of severe illness, and the large majority of hospitalizations and deaths were among the unvaccinated, but in retrospect, at the national level, it seems that the Delta variant and mass vaccination effectively fought each other only to a disorienting draw.

This confusing, post-vaccine zombie stage is not just an American phenomenon. Elsewhere in the world, the patterns have been similarly divergent and contradictory. On November 2, the Lancet speculated that in Spain, where case numbers were falling, widespread vaccination may have delivered the country to herd immunity — a possibility that seemed genuinely and permanently out of reach just a month or two before. But in Portugal, where vaccination rates are considerably higher, new cases were almost twice as high. In late summer, as the U.S. stared down its Delta wave, the U.K. experience was an encouraging case study — higher vaccination rates there, it seemed, meant that while case numbers spiked, serious illnesses stayed almost flat, a near-total decoupling of disease spread, on the one hand, and hospitalization and death, on the other. But then cases started rising again, and this time, as Bill Hanage has pointed out, hospitalizations and deaths are not staying low but bumping up along with them (in often unpredictable patterns to boot). Some of this, presumably, has to do with vaccine waning, especially among the elderly, which suggests among other things that vaccination rates are quickly losing their monocausal explanatory power (at the very least, we need to also consider the dates of vaccine delivery and the age skew of vaccination). Now, in many well-vaccinated countries across Europe, cases are rising again — in some places with severe illness rising, too, and in some places, not. As it was before vaccinations, the pandemic has continued to unfold this year in rhythms that aren’t precisely legible, even after the fact, with future trajectories often shrouded by even more uncertainty. We know vaccination works, of course, and that it has been our best tool in combating the disease, at least to this point; but we can also conclude, looking back at the last few months in Europe and the U.S., that given some amount of continuing spread and some enduring risk of severe disease among the vaccinated old, it does not appear to be sufficient to truly end the pandemic, at least not everywhere and for good.

In which case: what could? Last year, once the country had settled into pandemic thinking for the long haul and starting imagining or even counting on the arrival of vaccines, it became fashionable to talk about the future of the world, post-pandemic, and even to rhapsodize about the possibility of a Roaring ’20s to come, along the lines of the one from the last century that followed the 1918 pandemic. But as the Delta wave receded and vaccinations ticked upward — 85 percent of American seniors are “fully vaccinated,” to use a term we should probably now discard in the age of boosters, and 98 percent have received at least one shot — it almost seemed harder to really see that post-pandemic future clearly. As much of the country has half-tried to move past the pandemic this fall, more than a thousand are still dying each day. In places without a real Delta surge, like New York City, there was nevertheless a rising tide of anxiety, a return to mask wearing and a simmering rage at the remaining unvaccinated. We weren’t really capable of beginning to move on, of starting to see COVID-19 as just another disease, but we also weren’t not moving on, either.

But the arrival of childhood vaccines and really effective post-infection treatment could change all that, clearing quite a bit of that fog, and pointing the way to a fairly intuitive path to at least a “next chapter” for the pandemic, as Topol put it on Twitter. We still need to decide to move on, more or less, because national risk of severe disease hasn’t been brought to zero. But on top of the vaccine effect itself, the new therapies do promise a quite dramatic reduction of that risk, bringing the vulnerability of almost everyone to COVID into the range of far more familiar, quotidian diseases.

Another long-neglected tool could help further: focusing very vigorously, from here, on the vulnerability of the old; indeed, treating COVID-19 as the disease of the very old it has always been (which we’ve refused to acknowledge through most of the pandemic in the interest of universalizing risk and preventing spread at all costs). In the spring of 2020, when I first wrote about the dramatic age skew, lamenting that it had shaped so little of our pandemic response, focusing on protecting the old might have meant one list of precautions: messaging focused on the age skew of risk, masks mailed out via AARP, federal support for mass testing in nursing homes and for better and more generous staffing there to limit turnover-based transmission. (And it is unconscionable that, given the federal government’s failure to act more quickly on rapid testing, it didn’t manage to deliver masks or rapid testing in targeted ways to the very old by the onset of the winter surge, nine months after the disease had arrived on our shores and almost as long since rapid tests had been shown to work well.)

Today, precautions might be similar in their broad strokes. First, worrying less about case numbers per se and much more about limiting the risk to those likely to become very sick. That could be achieved, in part, by focusing our vaccination efforts not on the population at large but on “boosting” the elderly; in fact, we should perhaps stop calling the shots boosters and instead conceive of them as an ongoing prophylactic treatment protocol. We could still distribute masks and rapid tests via the AARP, but now with guidance that seniors use the test not necessarily to screen others before socializing or interacting but as self-tests meant to quickly trigger the use of therapeutics like Pfizer’s if a test came back positive. With the arrival of quasi-miraculous therapeutics, these protocols seem a bit less necessary than they might have even a week ago, but they can still help — both in protecting people with enduring vulnerability and in encouraging the rest of us, finally, to relax a bit, too. Perhaps we can use the extra energy worrying about how to get these drugs to those parts of the world we have utterly failed to supply with vaccines.