ED YONG
Fifteen months after the novel coronavirus shut down much of the world, the pandemic is still raging. Few experts guessed that by this point, the world would have not one vaccine but many, with 3 billion doses already delivered. At the same time, the coronavirus has evolved into super-transmissible variants that spread more easily. The clash between these variables will define the coming months and seasons. Here, then, are three simple principles to understand how they interact. Each has caveats and nuances, but together, they can serve as a guide to our near-term future.
The vaccines have always had to contend with variants: The Alpha variant (also known as B.1.1.7) was already spreading around the world when the first COVID-19 vaccination campaigns began. And in real-world tests, they have consistently lived up to their extraordinary promise. The vaccines from Pfizer-BioNTech and Moderna reduce the risk of symptomatic infections by more than 90 percent, as does the still-unauthorized one from Novavax. Better still, the available vaccines slash the odds that infected people will spread the virus onward by at least halfand likely more. In the rare cases that the virus breaks through, infections are generally milder, shorter, and lower in viral load. As of June 21, the CDC reported just 3,907 hospitalizations among fully vaccinated people and just 750 deaths.
Could the Delta variant (also known as B.1.617.2) change that picture? Data from the U.K. suggest that it is 35 to 60 percent better at spreading than Alpha, which was already 43 to 90 percent more transmissible than the original virus. (It may also be deadlier, but that’s still unclear.) It now causes 26 percent of new infections in the U.S. and will soon cause most of them.
But even against Delta, full vaccination—with a heavy emphasis on full—is effective. Two doses of Pfizer’s vaccine are still 88 percent effective at preventing symptomatic Delta infections, according to a U.K. study, and 96 percent effective at preventing hospitalization. (A single dose, however, is only 33 percent effective at stopping symptomatic infection.) Israel, a highly vaccinated country, is experiencing a small Delta surge, but so far, none of the new cases has been severe. And while about 30 percent of those new cases have been in fully vaccinated people, this statistic reflects, in part, the country’s success at vaccination. Because Israel has fully vaccinated about 85 percent of adults, you would expect many new infections to occur in that very large group. “It does seem like the vaccines are holding their own against the variants,” Emma Hodcroft, an epidemiologist at the University of Bern, told me. “That’s something we can take some comfort from.”
But the coronavirus can cause serious problems without triggering severe infections. Because people can develop long COVID without ending up in the hospital, could Delta still cause long-term symptoms even if vaccines blunt its sting? The anecdotal reports of long-haulers whose symptoms abated after vaccination might suggest otherwise, but “we don’t know enough to say,” Bill Hanage, an epidemiologist at Harvard, told me.
Another crucial question that “we really need to understand is the nature of transmission from breakthrough cases,” Hanage said. Worryingly, a recent study documented several cases during India’s spring surge in which health-care workers who were fully vaccinated with AstraZeneca’s vaccine were infected by Delta and passed it on.
If other vaccines have similar vulnerabilities, vaccinated people might have to keep wearing masks indoors to avoid slingshotting the virus into unvaccinated communities, especially during periods of high community transmission. “That is unfortunately the direction this is headed,” says Ravindra Gupta, a clinical microbiologist at the University of Cambridge, who led the study. Israel has reimposed a mask mandate, while Los Angeles County and the World Health Organization have advised that vaccinated people should wear masks indoors. And such measures make sense because ...
Vaccinated people are safer than ever despite the variants. But unvaccinated people are in more danger than ever because of the variants. Even though they’ll gain some protection from the immunity of others, they also tend to cluster socially and geographically, seeding outbreaks even within highly vaccinated communities.
The U.K., where half the population is fully vaccinated, “can be a cautionary tale,” Hanage told me. Since Delta’s ascendancy, the country’s cases have increased sixfold. Long-COVID cases will likely follow. Hospitalizations have almost doubled. That’s not a sign that the vaccines are failing. It is a sign that even highly vaccinated countries host plenty of vulnerable people.
Delta’s presence doesn’t mean that unvaccinated people are doomed. When Alpha came to dominate continental Europe, many countries decided not to loosen their restrictions, and the variant didn’t trigger a huge jump in cases. “We do have agency,” Hodcroft said. “The variants make our lives harder, but they don’t dictate everything.”
In the U.S., most states have already fully reopened. Delta is spreading more quickly in counties with lower vaccination rates, whose immunological vulnerability reflects social vulnerability. Black and Hispanic Americans are among the most likely groups to die of COVID-19 but the least likely to be vaccinated. Immunocompromised people may not benefit from the shots. Children under 12 are still ineligible. And unlike in many other wealthy countries, the pace of vaccinations in America is stalling because of lack of access, uncertainty, and distrust. To date, 15 states, most of which are in the South, have yet to fully vaccinate half their adults. “Watch the South in the summer,” Hanage said. “That’ll give us a flavor of what we’re likely to see in the fall and winter.”
Globally, vaccine inequities are even starker. Of the 3 billion vaccine doses administered worldwide, about 70 percent have gone to just six countries; Delta has already been detected in at least 85. While America worries about the fate of states where around 40 percent of people are fully vaccinated, barely 10 percent of the world’s population has achieved that status, including just 1 percent of Africa’s. The coronavirus is now tearing through southern Africa, South America, and Central and Southeast Asia. The year is only half over, but more people have already been infected and killed by the coronavirus in 2021 than in 2020. And new variants are still emerging. Lambda, the latest to be recognized by the WHO, is dominant in Peru and spreading rapidly in South America.
Many nations that excelled at protecting their citizens are now facing a triple threat: They controlled COVID-19 so well that they have little natural immunity; they don’t have access to vaccines; and they’re besieged by Delta. At the start of this year, Vietnam had recorded just 1,500 COVID-19 cases—fewer than many individual American prisons. But it is now facing a huge Delta-induced surge when just 0.19 percent of its people have been fully vaccinated. If even Vietnam, which so steadfastly held the line against COVID-19, is now buckling under the weight of Delta, “it’s a sign that the world may not have that much time,” Dylan Morris, an evolutionary biologist at UCLA, told me.
With Delta and other variants spreading so quickly, “my great fear is that in not very long, everyone globally will either have been vaccinated or infected,” Morris said. He didn’t want to pinpoint a time frame, but “I don’t want to bet that we have more than a year,” he said. And richer nations would be wrong to think that the variants will spare them, because ...
Whenever a virus infects a new host, it makes copies of itself, with small genetic differences—mutations—that distinguish the new viruses from their parents. As an epidemic widens, so does the range of mutations, and viruses that carry advantageous ones that allow them to, for example, spread more easily or slip past the immune system to outcompete their standard predecessors. That’s how we got super-transmissible variants like Alpha and Delta. And it’s how we might eventually face variants that can truly infect even vaccinated people.
None of the scientists I talked with knows when that might occur, but they agree that the odds shorten as the pandemic lengthens. “We have to assume that’s going to happen,” Gupta told me. “The more infections are permitted, the more probable immune escape becomes.”
If that does happen, when would we know? This is the first pandemic in history in which scientists are sequencing the genes of a new virus, and tracking its evolution, in real time—that’s why we know about the variants at all. Genomic surveillance can tell which mutations are rising to the fore, and lab experiments can show how these mutations change the virus—that’s how we know which variants are concerning. But even with such work “happening at incredible speed,” Hodcroft told me, “we can’t test every variant that we see.”
Many countries lack sequencing facilities, and those that have them can be easily swamped. “Again and again, we have seen variants pop up in places that are under extraordinary strain because those variants are causing large surges,” Hanage said. Delta ripped its way through India, “but we only understood it when it started causing infections in the U.K.—a country that had plenty of scientists with sequencers and less to do.” So the first sign of a vaccine-beating variant will likely be an uptick in disease. “If vaccinated folks start getting sick and enter hospitals with symptoms, we’ll have a pretty good picture of what’s going on,” Maia Majumder, an epidemiologist at Harvard Medical School and Boston Children's Hospital, told me.
We’re unlikely to be as vulnerable as we were at the beginning of the pandemic. The vaccines induce a variety of protective antibodies and immune cells, so it’s hard for a variant virus to evade them all. These defenses also vary from person to person, so even if a virus eludes one person’s set, it might be stymied when it jumps into a new host. “I don’t think there’ll suddenly be a variant that pops up and evades everything, and suddenly our vaccines are useless,” Gupta told me. “It’ll be incremental: With every stepwise change in the virus, a chunk of protection is lost in individuals. And people on the edges—the vulnerable who haven’t mounted a full response—will end up bearing the cost.”
If that happens, vaccinated people might need booster shots. Those should be possible: The mRNA vaccines produced by Moderna and Pfizer should be especially easy to revise against changing viruses. But “if we need boosters, I worry that countries that are able to produce vaccines will do so for their own populations, and the division around the world will become even greater,” Maria van Kerkhove, an infectious-disease epidemiologist at the WHO, told me.
The discussion about vaccine-beating variants echoes the early debates about whether SARS-CoV-2 would go pandemic. “We don’t think too well as a society about low-probability events that have far-reaching consequences,” Majumder told me. “We need to prepare for a future where we are doing vaccine rollout again, and we need to figure out how to do that better.” In the meantime, even highly vaccinated nations should continue investing in other measures that can control COVID-19 but have been inadequately used—improved ventilation, widespread rapid tests, smarter contact tracing, better masks, places in which sick people can isolate, and policies like paid sick leave. Such measures will also reduce the spread of the virus among unvaccinated communities, creating fewer opportunities for an immune-escape variant to arise. “I find myself the broken record who always emphasizes all the other tools we have,” van Kerkhove said. “It’s not vaccines only. We’re not using what we have at hand.”
The WHO’s decision to name variants after the Greek alphabet means that at some point, we’ll probably be dealing with an Omega variant. Our decisions now will determine whether that sinister name is accompanied by equally sinister properties, or whether Omega will be just an unremarkable scene during the pandemic’s closing act.
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