By Helen Branswell
Winter is coming, again.
A year ago, experts warned that the United States faced a grim winter if Americans didn’t mask up and social distance to slow transmission of the SARS-CoV-2 virus before “indoor weather” — aka winter — settled in for its long stay. We all know how well that warning was heeded. In January, cases topped 300,000 a day; Covid ended the lives of about 95,000 Americans before the month was out.
Now indoor weather again looms in many parts of this country, and daily case counts are rising well into the six figures. The highly transmissible Delta variant is driving spread, even among fully vaccinated people. Children are back in classrooms that can function as germ incubators. As you walk around in public you see noses poking out of masks, masks under chins, faces that are mask free.
So what should we expect as we head into our second Covid autumn and winter?
“The bottom line is, I think, uncertainty,” said Jeffrey Duchin, health officer for the Seattle and King County public health department, who has been mired in the Covid response since the earliest days of the U.S. outbreak.
“We’re experiencing a new virus, a newly emerged pathogen, and we’re trying to fight it with new tools that we don’t have a lot of experience with,” he said. “And we’re dealing with unpredictable human behavior … which is a very important factor as well, and environmental factors that may influence the severity of Covid outbreaks and how well it transmits.”
“There’s a lot of moving parts,” said Duchin, who is also an infectious diseases professor at the University of Washington. Among them: the questions of when Covid vaccines will be approved for use in children and what percentage of parents will agree to vaccinate their kids.
While the crystal ball may be cloudy, who can resist taking a peek? Let’s talk about some things we might face in the months ahead.
Whither the Delta wave?
The high, high crests of Delta transmission are subsiding in some parts of the country, as they have in countries where Delta took off before it did in the U.S.
Cécile Viboud, an infectious diseases epidemiologist at the National Institutes of Health’s Fogarty International Center, said nine modeling efforts her group is monitoring suggest that by the end of November, the Delta wave will have waned and new cases will be down “at quite a low level.” How low? Down to where the country was in late June and early July, before Delta took off. At that point the country was reporting somewhere between 7,500 to 15,000 new cases most days.
Sounds heavenly, doesn’t it? So does what Viboud said next. “We’re probably going to stay there, because there is quite a bit of immunity in the population,” she told STAT.
That heartening prediction comes with a big but. “That assumes that no new variant comes in. Because if you get a new variant that either has a higher transmissibility or immune escape potential, then we will see a resurgence.”
Late November coincides with Thanksgiving, America’s favorite week for cross-country travel. Last year, Thanksgiving and Christmas turbo-charged Covid spread. Can transmission levels remain low if large family gatherings occur across the nation this year?
Viboud said all the models factor in events like Thanksgiving. The expectation of low transmission by around that time is predicated on the amount of immunity there will be by then in the country, antibodies generated by vaccination — 63.9% of eligible Americans are fully vaccinated — or acquired the hard way, through Covid infection.
Trevor Bedford, a computational biologist at the Fred Hutchinson Cancer Research Center in Seattle, thinks the massive summer wave the country has been experiencing will have taken some of the loft out of the balloon when it comes to fall and winter spread. By crashing over the country in the summer, Delta pulled forward in time some infections that otherwise would have occurred later, he said.
“It is likely that we’ll see some wave,” Bedford said. “I would like to think it’s very unlikely to be as big as it was last year.”
The World Health Organization’s top coronavirus expert is less hopeful in her prognostication. Maria Van Kerkhove thinks people are making the mistake of trying to interpret SARS-2’s behavior and predict its path by looking through the prism of influenza. SARS-2 may one day behave much more like that seasonal scourge, which causes a wave of illness in winter months in temperate climes — but it’s not there now, she said.
“I feel that a lot of people want it so badly to behave like flu. So that we can get into this pattern of ‘OK, in the summer everybody can relax. And then we just need to gear up for the fall. We need to get the vaccines underway. Get people vaccinated and just ride it out through that peak, that winter peak,’” Van Kerkhove said. “But I don’t see that in the data that we have.”
She believes human behavior — whether that’s wearing masks, social distancing, or getting vaccinated — has much more to do with declines of Covid transmission still than built-up immunity. The Delta variant hasn’t run through all the unprotected people, she insisted.
“Delta still has a lot more energy in it,” Van Kerkhove said. “I think we should expect more ups and downs. I think we should expect more peaks and troughs. I think the peaks could become less [lofty]. Potentially. But I think those peaks will be very sharp in specific populations like unvaccinated, unprotected populations. That should be expected.”
Deaths should subside. Some.
As people’s immune systems have acquired experience grappling with SARS-2 — again, via vaccine or infection — deaths as a percentage of overall cases have declined. That trend will hopefully continue.
It’s not clear how long immunity lasts following infection. It can be pretty transient with human coronaviruses, but so far there haven’t been huge numbers of people reporting their second or third case of Covid. We’re going to learn how long infection-induced protection lasts as time goes on — as well as how long protection lasts after vaccination. When immunity levels in communities start to subside, that could trigger a new resurgence of cases, Viboud said, but she added the expectation is that with further waves of cases, hospitalization and deaths will not resemble the earlier waves of Covid.
Bedford agreed. “You could also imagine a large Covid wave this fall-winter, but with much lower morbidity and mortality than it was last year,” he said, noting “that it seems almost certain” that the infection fatality rate — the percentage of infected people who die from the disease — will remain lower than it was earlier in the pandemic.
Alpha, Beta, Gamma, Delta — what’s next?
Early in the pandemic, coronavirus experts confidently opined that this family of viruses mutates far more slowly than, say, influenza, and major changes weren’t likely to undermine efforts to control SARS-2. But no one alive had watched a new coronavirus cycle its way through hundreds of millions of people before. (The global estimate has now passed a quarter of a billion cases.) Our baseline assumptions didn’t figure on Delta.
Whatever comes next will almost certainly be some new twist of this now-dominant variant, Bedford said. That’s because Delta has so effectively swept the globe it has crowded out almost all the other lineages of viruses; about 88% of recent viruses that have been sequenced belong to the Delta family. “Basically everything that is circulating is Delta, so then the only avenue for evolution becomes mutations on top of Delta,” he said.
As effective as the Delta variant is, Bedford assumes it could acquire more tricks. “It seems unlikely that Delta is the ceiling, but there is going to be some ceiling,” he said.
Barney Graham, who led the vaccine design work that laid the foundation for many of the current Covid vaccines, is hopeful, though, that in Delta the virus has hit a sweet spot that will eventually undermine it.
“I’m hoping the virus has gotten itself to a point where it’s basically trapped now,” said Graham, who was deputy director of the NIH’s Vaccine Research Center until his retirement at the end of August. “That it can’t get any better at transmission, and any adaptation it makes in the immune response is going to make it less transmissible.”
If the virus effectively stands still, the increase in the rollout of vaccines worldwide that is projected to take place over the next half year or so could start to hem the virus in.
“I’m hoping now that we’re going to level out on the nature and the amount of change that’s going to be happening, especially if we can get people immunized and as the number of new infections diminishes, the less the chance that new mutations will occur,” Graham said.
Fingers crossed, everyone.
There are other complications ahead
One of the amazing things about the control measures countries used to slow Covid transmission is the effect they had on the swarm of other viruses that cause colds and flu-like illnesses every fall and winter. Rhinoviruses, the most common cause of the common cold, continued to spread. But respiratory syncytial virus (RSV), human coronaviruses, adenoviruses, and mother of all influenza-like illnesses, influenza itself, all but disappeared.
With kids back in school, mask-wearing more sporadic, and people abandoning Covid controls because they’re frankly just sick of them, these bugs are coming back. They may hit us especially hard when they do, because our immune systems are out of shape from the 20-month hiatus.
Last fall Hong Kong, which has had much more success controlling Covid than the U.S. has, resumed in-person teaching for children. Schools were quickly hit with large outbreaks of rhinoviruses. These ubiquitous viruses are generally just pests, but some of the infected children became so sick they needed to be admitted to hospitals.
We could see similar outbreaks here. And when kids, parents, and teachers start to get sick, there will be a lot of scrambling to figure out what’s the cause.
Before Covid, people rarely got tested if they came down with a respiratory infection, unless they got really sick. But now, much more is at stake. Is this a cold or the early stages of Covid? There are ramifications, depending on the answer to that question.
“How do you distinguish between Covid and flu or Covid and RSV in a child? You can’t — without a diagnostic,” said Van Kerkhove, whose youngest son had a series of three severe respiratory illnesses in the spring. He was so sick she and her husband took him to the hospital, but Switzerland doesn’t test children for Covid and they still don’t know what made him so ill.
“Kids will get sick, and I think that these other viruses that are circulating will complicate these matters,” she said.
Duchin worries we’re not ready for what’s coming when influenza-like illnesses and Covid collide. “It’s going to put a lot of stress on the health care system to help people figure out whether they have Covid-19 or not and what they need to do next,” he said. Cheap and easy-to-access Covid rapid tests could fill this gap, but tests are still too expensive and haven’t yet been adopted widely enough, he and others argue. “It’s a huge gap, I think, in our national preparedness still,” Duchin said.
A Covid season + a flu season = a whole lot of bad news
Influenza activity hasn’t yet rebounded globally from the coma induced by Covid control measures. But flu will be back. Whether that happens this season isn’t in the realm of knowable things.
Respiratory viruses each have their own patterns and there may be interactions among them — spread of one, for instance, may delay spread of another. What happens to that ballet when a new prima ballerina takes center stage? No one knows.
“I wonder what the role of the co-circulation of other pathogens will be in the dynamics of Covid transmission and/or the manifestations of Covid-19 illness,” Duchin said. “Will influenza facilitate the spread of Covid? Will RSV or parainfluenza viruses or adenoviruses … facilitate Covid or will they possibly crowd it out?”
“These are things somebody smarter than me needs to figure out,” he said.
Viboud doesn’t have answers either, but sees an enormous opportunity ahead. “It’s going to be a really interesting season to watch. We’ll learn a lot.’’
Nicole Lurie fears that what we’re about to learn is that flu plus Covid is going to make winters miserable and deadly.
Lurie, who was the assistant secretary for preparedness and response in the Department of Health and Human Services during the Obama administration, notes that in pre-Covid times, between 20,000 and 60,000 Americans died each winter from influenza. Covid’s toll could be higher than that still, because people have largely given up on changing their lifestyles to avoid becoming infected, and a substantial portion of people remain unvaccinated.
“I feel like we have to be giving this some thought and preparing the public for some kind of a steady state that minimizes morbidity and mortality and has a set of actions that you can take to mitigate the bad consequences,” said Lurie, who is now the U.S. director for the Coalition for Epidemic Preparedness Innovations.
Bedford shares her concerns.
“My expectation would be that it will become a seasonal respiratory disease, but it will be the worst of our seasonal respiratory diseases,” he said. “I’m imagining something that circulates at three times the level of flu and has a similar [infection fatality rate] to flu. So maybe causing three times flu’s deaths every year.”
But Ben Cowling of Hong Kong University voiced some optimism. People may be fed up with Covid restrictions, but they have learned that respiratory illnesses don’t have to be inevitable features of winter. In the face of surges of virus, they may choose to protect themselves, he said. “Certainly Covid has changed the perception of respiratory infections. People are much more concerned about them than they used to be.”