Archived: COVID 5 years later: Learning from a pandemic many are forgetting

AWAJI, JAPAN—The COVID-19 pandemic, as best as we can tell, took more than 20 million lives, cost $16 trillion, kept 1.6 billion children out of school, and pushed some 130 million people into poverty. And it’s not over: Figures from October 2024 showed at least 1000 people died from COVID-19 each week, 75% of them in the United States, and that’s relying only on data from the 34 countries that still report deaths to the World Health Organization (WHO). Last month, at a 4-day meeting here on preventing future pandemics, WHO epidemiologist Maria Van Kerkhove ticked off those figures with exasperation. “The world I live in right now, no one wants to talk about COVID-19,” she told the gathering. “Everyone is acting as though this pandemic didn’t really happen.”

Yet 5 years after a coronavirus dubbed SARS-CoV-2 first surfaced in Wuhan, China, scientists are still intensively trying to make sense of COVID-19. “We would each have to read over 240 papers every single day to actually keep up with all of the [COVID-19] literature that’s come out” in 2024, Cherilyn Sirois, an editor at Cell, noted.

Despite the flood of insights into the behavior of the virus and how to prevent it from causing harm, many at the meeting worried the world has turned a blind eye to the lessons learned from the pandemic. “I feel this massive gravitational pull to go back to what we were doing before,” Van Kerkhove said. “There’s no way we should be going back.”

Even more concerning to some at the conference, many countries have actually become hostile toward pandemic prevention research, much of the anger stemming from an unproven assertion that SARS-CoV-2 leaked from a lab. “There’s been massive public and political backlash against the virology community and public health in general, so we may be worse off now locally than we were prior to the pandemic,” said virologist Ralph Baric of the University of North Carolina at Chapel Hill, who was recently accused by Robert Redfield, former head of the U.S. Centers for Disease Control and Prevention, of being the “scientific mastermind” of a supposed effort to engineer the virus.

The conference, held under the auspices of Cold Spring Harbor Asia, brought together 140 researchers and health officials from 17 countries to discuss everything from the origin of the pandemic to SARS-CoV-2’s mutational patterns, new treatments, and creative vaccine strategies to fend off future threats. “One of the big reasons we wanted to hold this conference is because we couldn’t meet in person during the pandemic,” said virologist Kei Sato of the University of Tokyo, an organizer. He also hoped the location would attract infectious disease scientists from China, who have had limited interactions with the global research community since 2020.

Some 20 scientists from China attended, but two of the country’s most prominent COVID-19 researchers were notable no shows. Shi Zhengli, who studied bat coronaviruses at the Wuhan Institute of Virology (WIV) and became the focus of intense criticism by people who suspect SARS-CoV-2 leaked from her lab, only gave a prerecorded video talk—on the sequencing of other coronavirus genomes—despite being a co-organizer of the event. So did Chinese Academy of Sciences virologist George Gao, former head of China’s Center for Disease Control and Prevention. Sato suspects the Chinese government would not let either attend. Shi, now with the Guangzhou Laboratory, and Gao both declined to explain their absence to Science.

A Chinese scientist did offer one of the most provocative presentations. Immunologist Yunlong Cao of Peking University, another organizer of the meeting, noted the “extraordinary viral evolutionary speed” of SARS-CoV-2 not only means fresh variants are “continuously causing reinfections,” but that antibody treatments and vaccines can quickly lose effectiveness. None of the first approved monoclonal antibodies and vaccines work against current circulating strains.

Cao noted that only two of 140 antibodies his lab identified in early 2020 as able to neutralize the first variant of SARS-CoV-2 could protect against the virus in circulation 2 years later. “The only solution to this problem,” he said, “is if we can do accurate predictions about viral evolution” to assess which antibodies will retain their powers.

Cao’s group recently identified an antibody, dubbed SA55, he predicts will work against whatever SARS-CoV-2 variants evolve for at least two more years. His team began by drawing blood from an unusual cohort of 28 people; nearly 2 decades ago each had recovered from severe acute respiratory syndrome (SARS), a severe illness caused by another coronavirus, and then during the pandemic received vaccines against SARS-CoV-2. The researchers isolated some 13,000 memory B cells and screened the antibodies they made for the ability to neutralize both coronaviruses and several relatives found in bats and other species. SA55 stood out as a superstar.

Sinovac Biotech, one of China’s largest pharmaceutical companies, has tested a nasal spray containing SA55 as a preventive. In clinical trials, researchers gave it at least two times each day to participants who came in contact with infected people at home or work. The spray had about 80% efficacy at preventing infections, according to still unpublished work, Cao says. Under “compassionate use” regulations, some 300,000 people in China have already received this spray and Sinovac plans a large phase 3 efficacy study. “We still know very little about nasal antibodies and we are trying hard to advance the knowledge in this field,” says Cao, who licensed the antibody to Sinovac.

Accurately predicting how viruses will evolve could also allow vaccinemakers to design more durable products. Computational biologist David Robertson of the University of Glasgow is part of a growing effort to peer into the future of SARS-CoV-2 with artificial intelligence (AI). Specifically, they’re using protein language models—which convert genetic sequences of the virus into predicted protein structures—to map “evolutionary landscapes” that indicate how viral proteins might mutate and still retain their ability to infect new hosts and copy themselves. Ultimately, Robertson says, the models present the “exciting” possibility that they could guide design of vaccines that produce antibodies able to thwart a wide range of potential variants.

Many speakers emphasized that Omicron and other SARS-CoV-2 “variants of concern” have evolved in people who have weakened immune systems and cannot quickly clear infections. “A compromised host comes along and a weirdo virus comes out,” said University of Sydney evolutionary biologist Edward Holmes. He calls AI prediction of virus evolution an “amazing tool,” but cautions it has “a good way to go” in forecasting the variants that will emerge during ever changing pandemic environments.

Presenters also explored how to protect against other threatening coronaviruses. Molecular pharmacologist Gurpreet Brar of the Coalition for Epidemic Preparedness Innovations (CEPI) described how the nonprofit is funding development of vaccines for nine coronaviruses that have been found in mink, pigs, cattle, dogs, camels, and bats. “These are ones that have a high risk of spillover, and if they were to jump into humans we’d have a big problem,” Brar said. The project adds to ongoing efforts by CEPI and others to develop pancoronavirus vaccines that potentially work against all SARS-CoV-2 variants as well as unknown relatives in the same viral family.

Major mysteries remain about what SARS-CoV-2 is doing today, and where it came from. There’s no consensus on how the virus produces Long Covid, the debilitating symptoms that have afflicted millions after their infections have seemingly been cleared, or how to treat or prevent the condition. And efforts to unravel the pandemic’s origin have largely stalled.

Meeting organizers, concerned that people angered by the idea SARS-CoV-2 leaked from a lab would crash the gathering and might harm invited scientists, hired extra security guards. But only one scientist, Jonathan Latham, a virologist with the Bioscience Resource Project, made the case publicly for a lab leak, with a poster contending that SARS-CoV-2 came from WIV, which analyzed body samples from copper miners who mysteriously became ill in 2012. Virologist Angela Rasmussen from the University of Saskatchewan challenged Latham during a heated confrontation at his poster, arguing that no evidence supports his theory. She later gave a talk that described her own attempt to find new information in a much-studied set of “environmental samples” collected between January and March 2020 from the Huanan Seafood Wholesale Market in Wuhan, which has been linked to many of the first COVID-19 cases in December 2019. “I’m slicing the salami ever thinner,” Rasmussen said.

She is among a large contingent of researchers at the meeting who contend those samples and other evidence supports the theory that animals at the market carried SARS-CoV-2—and sparked the pandemic.

She reported that the market samples held animal genes that had been turned on by interferon, which occurs during viral infections. Rasmussen ultimately concluded that raccoon dogs and greater hog badgers were the two most likely wild animals at the market to have been infected with SARS-CoV-2. But she acknowledged the limits of this analysis: “Spoiler alert: I have not found an infected animal.”

Virologist Jesse Bloom of the Fred Hutchinson Cancer Center, who is not convinced the pandemic began at the market and has urged colleagues to remain open to the possibility of a lab leak, wasn’t swayed by Rasmussen’s new work. “There’s still little actual information about the first human cases,” Bloom says. “There’s just not a lot of knowledge about what was really going on in Wuhan in late 2019.”

Christian Drosten, a coronavirus researcher from the Charité Institute of Virology in Berlin who thinks the evidence strongly supports the market theory, decried the politicization of the origin debate. He was particularly exercised by a recent report from a Republican-led House of Representatives panel arguing that U.S. funding may have helped create SARS-CoV-2 at WIV before it leaked. “It’s very clear that they are not only ignoring existing evidence, but they are falsifying the evidence that’s on the table,” Drosten said. “It’s really surprising and puzzling that people at this meeting aren’t speaking up. Why don’t they go public immediately? We will be quiet until we don’t have a chance to speak anymore.”

WHO’s Scientific Advisory Group for the Origins of Novel Pathogens is expected to issue its own report in the next few weeks. But no one at the meeting anticipated major revelations. “I fully believe there’s much more data that’s out there that we don’t have access to,” says Van Kerkhove, who oversees the group. She knows of a Chinese database that has some 500 viral sequences from January and February 2020 that WHO cannot access. “The biggest question I have are the farms,” she says, referring to the possibility that SARS-CoV-2 came from animals being bred to sell at markets for their meat.

As for the future, Van Kerkhove warns that the world is dropping its guard against novel pathogens. Infectious disease is “not a safe space to really be working in,” she told Science. “Labs have been threatened. People have been threatened. Governments don’t necessarily want to be the ones to say, ‘Hey, we found something new.’”