In early December, the end of the pandemic glimmered on the horizon. Blockbuster vaccine results suggested a clear path forward. The return to normalcy would take time, but after a year of uncertainty, the conclusion seemingly had come into focus: It was a matter of making vaccine doses and getting them into people’s arms.
Then, the euphoria dissipated. The illusion — or, as one scientist puts it, the delusion — that science had bested the virus crumbled as mutation-ridden variants with concerning new characteristics were detected. For the past two months, disease trackers’ understanding of the threat has evolved day by day, as scientists piece together meaning from fragmented clinical data, lab experiments and bits of science gleaned on Twitter. The path forward is still hopeful, but longer and more labyrinthine.
It has become clear that coronavirus variants can slip past some of the immunity generated by vaccines and prior infections. The virus is here to stay — and scientists will have to remain vigilant. Vaccines may have to be updated, perhaps regularly. And the world will have to prepare for the possibility, even the likelihood, that over the long term, the novel coronavirus will become a persistent disease threat, albeit one that could eventually end up closer to the flu or the common cold.
In December, “the measles situation was on the table, and the polio situation was on the table. If you’ve got a vaccine so good it prevents almost all cases, and it prevents transmission, you vaccinate your population, and you’re fine even though it still exists elsewhere in the world,” said Shane Crotty, a virologist at the La Jolla Institute for Immunology. “That was the perspective, which was legit. Now … that’s looking like a stretch.”
That has become increasingly clear in countries such as Brazil, South Africa and the United Kingdom, where fearsome “variants of concern” have emerged, possessing the ability to spread more efficiently or evade aspects of the immune response.
On Sunday, South Africa suspended the rollout of a vaccine developed by the University of Oxford and AstraZeneca after a trial there suggested the shots had little efficacy against the B.1.351 variant that was first identified in that nation and that has become dominant there. The news arrived as scientists were grappling with preliminary evidence that people with a previous infection were susceptible to reinfection with a variant, as well as a growing body of data that many vaccines are less efficacious against that variant.
“This has tremendous implications … in terms of what you can expect with future resurgences of the virus, in terms of how long the virus will continue — and for all intents and purposes, SARS-CoV2 virus, covid-19, is likely to be with us during the course of our lifetimes,” Shabir A. Madhi, a professor of vaccinology at the University of the Witwatersrand in Johannesburg, said as he presented data Sunday showing that the Oxford-AstraZeneca vaccine did not appear to prevent mild or moderate illness.
But that seemingly bleak fact masks what many experts think is just as likely: The crisis phase of the pandemic will recede. A world with the novel coronavirus will feel markedly different as the threat of death or hospitalization diminishes — even if the possibility of a few days of sore throat, cough and fever remains.
The threat posed by the coronavirus will attenuate as immunity builds up in the human population, chiefly through vaccinations that work best at preventing the severe outcomes that threaten to overwhelm hospitals and kill people. The most hopeful signal has come from a one-shot vaccine from Johnson & Johnson, which showed strong protection against severe disease from the variant, even though it offered less-robust protection against moderate illness. Scientists think the Oxford-AstraZeneca vaccine may also protect against severe illness caused by the variant, but they currently lack the data to draw any conclusions.
Even before the entire population is protected, the rollout of the vaccine should begin to have an effect on society. Once people at high risk of severe disease are immune, fewer people will die and hospitals will be less likely to be overwhelmed. Restrictions may begin to ease in some spots, although they may be imposed again if the virus flares up.
“What’s the endgame? When does it stop? When do we wave a checkered flag and say all this is over? It has to do with watching the ICUs return to normal and seeing the excess deaths diminish,” said Yonatan Grad, an immunology expert at the Harvard T.H. Chan School of Public Health. “I don’t think the virus will be eliminated, and there won’t be a clear moment to celebrate, because the pandemic is so hyperlocal — there will be no synchronized conclusion.”
Many experts are sanguine that scientists are equipped to respond to a changing virus, as long as surveillance of the pathogen is stepped up. The coronavirus vaccines are highly protective against the versions of the virus widely circulating in the United States and appear especially effective in preventing severe illness. Rebooting vaccines against a new variant is far less daunting than where the world found itself last year — trying to invent vaccines with no guarantees any would work. The long road ahead will require vigilance and lots of work. Pfizer executive Angela Hwang recently described coronavirus vaccines as a “durable business.”
“We originally were maybe a little asleep at the wheel as to the potential of the virus,” said Larry Corey, a virologist at the Fred Hutchinson Cancer Research Center in Seattle. “Science will have to lead us out of it, again. … I do think we can keep ahead of this virus. Yes, it has shifted — I call it the virus’s gambit. But we have a countermeasure.”
As vaccination campaigns ramp up — averaging nearly 1.5 million shots a day over the past week in the United States — people will be protected against versions of the virus circulating in the near term. Even if vaccines are less protective against variants, decades of studying how viruses interact with the immune system suggests that even partial immunity is helpful in providing protection and slowing the march of pathogens.
Scientists are hesitant to make firm predictions, given how many surprises the pandemic has produced during the past year, but many believe that even the current generation of vaccines will go a long way to restoring normalcy.
“I do think society will open back up. We always have colds. We always have some diseases, but we were not dying, and hospitals were not overwhelmed,” said Moncef Slaoui, former chief science adviser to Operation Warp Speed, the Trump administration initiative to hasten development of vaccines and drugs to treat covid-19, the illness caused by the virus. “Having the virus isn’t the point — having the disease is the point.”
After the 1918 influenza pandemic, the H1N1 virus still circulated as a seasonal threat. But it did not cause the same level of devastation to society, in large part because of the immunity that had built up in the population. In the case of the coronavirus, public health officials have an additional powerful tool — vaccines — to engender immunity safely.
Marc Veldhoen, an immunologist at the University of Lisbon, painted a picture of what could happen in a world where the coronavirus is still circulating in 2035. One day, a person wakes up with a slight fever and a stuffy nose.
“If you would have been tested, you would find out you have SARS-CoV2. It’s nothing to be freaking out about, maybe you already had it twice — it’s just a minor cold. However, you might pass it on to another person,” Veldhoen said. “Once all of us have a certain level of immunity, we reduce the burden of the disease in the population. The virus will not go through the population like wildfire.”
The road to herd immunity — when outbreaks stop because so few people are susceptible — has been painted as a simple, one-way path, with constant speculation about what percent of the population needs to be in the herd to reach the finish line. But the emerging reality is far more complex. If immunity is incomplete and protection doesn’t last forever, the herd won’t be static — people who were once protected could become partially susceptible in a fluid, cyclical manner.
That could lead to a situation more analogous to how repeated exposure protects people against the common-cold coronaviruses, said Jennie Lavine, a postdoctoral fellow at Emory University. Lavine showed in a recent paper in Science how the coronavirus could become, over the course of years, a mild endemic disease — similar to a flu or common cold. If that happens, people could get sick in childhood and be periodically vulnerable to reinfection, but those reinfections would not pose a dire threat.
“What I think is a really wide-open question is how sick are you going to get when you get reinfected and you get your immunity boosted,” Lavine said.
Scientists by now know how dangerous it is to make predictions about a pandemic that has consistently humbled experts. Looking forward, there is little consensus about exactly how often immunity will need to be boosted, how often vaccines will need to be updated, or how long it will take for the interplay between the virus and the immune system to settle into a steady state in which disease is less severe.
Experts agree on this: Vaccination campaigns need to accelerate. And because supplies will be limited for years, there’s a need to prepare for what will happen as the virus spreads and acquires new mutations.
“If we could get vaccines immediately to everybody, we’d be okay,” said Ravindra Gupta, a professor of clinical microbiology at the University of Cambridge. But with “lots of transmission and [vaccines] not being delivered as fast as we like, we’re in a tricky spot.”
That’s because risk anywhere on the planet is a risk to everyone on the planet. As long as the virus is circulating, there will be immune pressure that can spark the emergence of variants that are even more deft at evading naturally acquired immunity or protection afforded by vaccines. There is good reason to hope that even then, the situation would not be a repeat of 2020, when a new virus jumped into a population with no existing immunity and wreaked havoc. Even partial immunity from previous versions of the virus would protect against severe illness, many scientists think.
“That’s the theory, that’s the hope. But it’s not a guarantee,” said Rajeev Venkayya, president of the global vaccine business at Takeda Pharmaceutical and a board member of the nonprofit Coalition for Epidemic Preparedness Innovations. “This will continue to be a risk until we get most of the world immunized.”