Life in Denmark now feels so much like it did before the pandemic that it can put visitors on edge, says Lone Simonsen, an epidemiologist at Roskilde University. The country lifted all of its remaining coronavirus restrictions on 10 September. Copenhagen clubs are buzzing, music lovers flock to festivals, and buses are packed with unmasked commuters. The government has given up its power to close schools and shut down the country. “When we have guests now, they feel uncomfortable about how normal everything is,” Simonsen says.
Denmark is a pioneer. As the second coronavirus winter approaches in the Northern Hemisphere, Denmark and a few other countries where vaccines now protect a large percentage of the population from severe disease are entering a momentous transition: from pandemic to endemic COVID-19, when the virus is still there but ceases to be an overriding public health threat. Researchers are closely watching what happens next, because it could yield valuable information about what lies ahead for the rest of the world.
There are many unknowns: how best to manage the transition out of the public health crisis, how it might go wrong, and exactly what endemicity will look like once it arrives. “Going into a pandemic is hard enough, coming out of it is even harder,” says Jeremy Farrar, an infectious disease researcher who leads the Wellcome Trust. “We don’t just go from a no-vaccine state and horror to a status quo. There’s a transition phase, and I think that will be this winter.”
Denmark has fully vaccinated more than 88% of people older than 18 and an astonishing 97% of those over age 60, the group most vulnerable to serious COVID-19. That allows the country to try to treat SARS-CoV-2 like influenza and other infectious diseases instead of a threat to the entire health system. “We’re thinking of this virus now as a sort of defanged version of the original one. It has gotten its teeth pulled out by the vaccine,” Simonsen says. “What’s left is not much worse than diseases that we’re used to and that we don’t close schools for, like seasonal flu or maybe the 2009 influenza pandemic.”
That does not mean Denmark is out of the woods. There are still susceptible people, including children, adolescents who aren’t yet fully vaccinated, and people in whom the vaccines have not elicited sufficient immunity. Since the measures were dropped, case numbers in Denmark have been slowly rising—there were 542 yesterday—ending a long summer lull. Simonsen is not alarmed. The continuing spread will result in more natural immunity in unvaccinated children and adults, and vaccine coverage will keep inching upward, she says. “All of this together makes me think Denmark will reach herd immunity in the spring.”
Four recently published projections from the Statens Serum Institute (SSI), a governmental public health and research agency, provide some idea of what might happen between now and then. In the best-case scenario, the country reaches 90% vaccination coverage among those over age 12 and there is no increase in social activities, currently still below the prepandemic level; then no surge in cases and hospitalizations is expected, says SSI modeler Camilla Holten Møller. In the worst-case scenario—no further increase in vaccine uptake and a 10% rise in social activities—Denmark could see a wave in cases and hospitalizations as bad as those in December 2020 and January. “We do not expect [that] to happen,” Holten Møller says, but if it did the government would likely bring back some restrictions. “The key is to be ready to change one’s mind as the data comes out,” says Rustom Antia, an immunologist at Emory University.
None of the models included a waning of immunity; Denmark started to give booster shots to vulnerable groups in September and has said it expects to give the entire population a third dose eventually. The models also didn’t include a key wild card: the emergence of nasty new variants of the virus.
Norway, with a similarly high vaccine uptake, followed Denmark’s lead last week. But many countries around the world do not have access to enough vaccine to vaccinate even the most vulnerable groups. And even in Europe, awash in vaccine, few countries are as ready as Denmark to attempt this transition. “If you have a lower coverage in the elderly, you should not try to do what Denmark is trying right now,” Simonsen says. Spain has vaccinated 97% of residents over age 60, for example, France 81%, and Greece 77%. Israel, which fully reopened on 1 June, has double-vaccinated about 90% of its population older than 60, meaning that per capita, it has several times as many unvaccinated people in that vulnerable group as Denmark does. It is now struggling to contain a big new wave of cases.
Countries with lower coverage will have to accept a higher level of restrictions during the transition phase to keep the virus at bay, Farrar says. “I think that politicians across the world are sort of pretending that you can have your cake and eat it: You can have zero deaths, no control measures, vaccinate if you want or not vaccinate—and it will all end. I just don’t think that’s realistic.”
Farrar has seen that happen in England, which celebrated “Freedom Day” on 19 July, when only about half the population was fully vaccinated. Cases began to trend upward in early August, to well over 30,000 per day now; deaths have risen to an average of about 150 per day. Keeping in place some public health measures such as wearing masks would have helped keep the burden of disease down, says Farrar, who is part of the U.K. government’s scientific advisory group on emergencies. The plan to abolish free testing later this year is mistaken as well, he says.
“I don’t really understand the tremendous rush to get rid of light touch things like masks,” adds David Fisman, an epidemiologist at the University of Toronto. Canadian provinces such as Saskatchewan opened up recently with only 60% of the population vaccinated, Fisman notes. “The result is that they’ve crashed their health care system into a tree,” he adds.
Sobering analogy
Meanwhile, scientists are trying to figure out how endemic COVID-19 will behave. “The models are all over the map,” Fisman says. “I know lots of smart people who are projecting very different things.” Endemic COVID-19 probably won’t be like measles, which is highly infectious but leaves people immune from infection for life. That results in a childhood disease with a wave every few years, once a large enough new cohort has been born.
With SARS-CoV-2, it’s already clear that immunity from infection wanes, Antia says. As a result, it might follow the trajectory of the four endemic coronaviruses—which all cause the common cold—in which protection from infection erodes over time, but protection from severe disease does not. That leads to a pattern of a first infection in early childhood, followed by recurring mild infections—like a case of the sniffles—later in life.
The outlook is different if immunity against severe COVID-19 declines as well. In that case, paradoxically, it might be best if the virus keeps infecting people frequently, Antia and Elizabeth Halloran of the University of Washington, Seattle, argue in a paper published in Immunity last week. With a lot of virus circulating, those vulnerable to infection but not yet to severe disease are more likely to be infected and have their immunity boosted; when there’s little transmission, the population would slowly become vulnerable again. Avoiding infection at all costs might not be the best strategy for vaccinated people, Simonsen says: “I just have this gut feeling for myself that maybe it’s not so bad if I meet that virus naturally now that my immune system is strong.”
Influenza is a more sobering analogy. It, too, causes infections throughout life, but reinfections are often more severe than those caused by the four endemic coronaviruses because the virus evolves faster and escapes host immunity. And Trevor Bedford of the Fred Hutchinson Cancer Research Center notes that so far, SARS-CoV-2 has evolved about five times faster than H3N2, one of the three influenza types circulating in humans. That rate is likely to slow over time to something comparable to flu, Bedford says. But given SARS-CoV-2’s high transmissibility and the low vaccine uptake in the United States, he thinks it might well infect one-third of the U.S. population every year, causing 50,000 to 100,000 deaths, after society fully reopens.
It’s a grim vision of endemic COVID-19. Measures like better ventilation and even continuing to test, trace, and isolate could reduce the toll, but Bedford doubts there will be any appetite for that, given that the United States routinely tallies 30,000 deaths each year from flu. “We never really did anything about it. People still show up to work sick and so forth,” he says. “I don’t know if 50,000 people dying a year of COVID would somehow be different.”