Workers with Hong Kong’s Agriculture, Fisheries and Conservation Department at the Little Boss pet store in Hong Kong in January. Photographer: Chan Long Hei/Bloomberg

It was a death sentence for thousands of hamsters.

A worker at the Little Boss pet shop in Hong Kong came down with COVID-19. Testing revealed that hamsters, too, were infected. Government workers in hazmat suits raided the shop and the cull began in January.

A chilling theory is that COVID-19 was transmitted to the hamsters, incubated in them for multiple generations, then jumped back to humans and spread amongst them — perhaps explaining the genesis of new variants, said Dr. George Rutherford, professor of epidemiology and biostatistics at UC San Francisco.

“The molecular epidemiology of this virus is much more complicated than I think anyone realized,” he said. “Why that is, and what role co-evolution with other species plays, is a huge open question.”

As planet Earth enters its third year of pandemic, and as “stealth omicron” — yet another new variant — comprises nearly a quarter of new cases, a key thing experts have learned about the coronavirus is how much this little, 30-kilobase strand of RNA can surprise them.

“Most viruses are much more stable, and we would have predicted this virus was more stable,” said Dr. Yvonne Maldonado, professor and chief of the Division of Pediatric Infectious Diseases at the Stanford University School of Medicine.

Pressures to mutate

Workers remove small animals from the Little Boss pet store in Hong Kong in January.  Photographer: Chan Long Hei/Bloomberg

But mutating is just what viruses do. “There is a lot of pressure driving this virus to mutate,” Maldonado said. “The world has been fully susceptible. When you get so many different people infected over time, you’re going to see more opportunities.”

While science continues to probe the mysteries of the ever-adapting virus itself, its practitioners pause to celebrate stunning progress on multiple fronts, while contemplating lessons learned and expressing deep frustration, and even anger, over missteps and inequities they say the pandemic laid bare and aggravated.

“What we learned that we didn’t fully appreciate, but should have known: Our prior ongoing scientific research enterprise is a huge truth-based system ready to be pointed in the right direction,” said Dr. David D. Lo, distinguished professor of biomedical sciences at UC Riverside and director of the Center for Health Disparities Research. To wit: Scientists isolated and fully sequenced the virus in just weeks. They created made-to-order synthetic vaccines within months. A well-oiled drug development and clinical testing system was ready to run clinical trials on hundreds of thousands of people, and the biotech manufacturing industry roared to life to produce billions of doses.

“What we learned that should have been entirely predictable: The existing anti-science, anti-authority fringe was ready to take the existing, minor anti-vaccine movement and weaponize social media and fringe cable news to stir things up in a big way that was guaranteed to cost lives, likely in the millions globally,” he said. “Governments, as usual, fail to heed decades of warnings and preparation, relying on the usual, overly cautious head-in-the-sand playbook, resulting in poor messaging, failure to act in a timely and effective manner, and confusing everybody.”

Good, bad and ugly

COVID-19 surely won’t be the last pandemic. It’s critical, then, that we learn all we can about the vulnerabilities COVID-19 exposed so we can be better prepared for future outbreaks, said Sen. Dianne Feinstein in a recent statement.

To that end, the “Prepare for and Respond to Existing Viruses, Emerging New Threats, and Pandemics Act” emerged from a Senate committee on March 15, seeking to create a 9/11-style commission to investigate the outbreak and pinpoint “lessons learned” about the nation’s preparedness, response and recovery. It would also probe disparities in infection and mortality rates among people of color, older adults and other vulnerable groups, and how those gaps impacted response.

Workers inspect the Little Boss pet store in Hong Kong in January. Photographer: Chan Long Hei/Bloomberg

The bill, by Sen. Patty Murray, D-Washington, seeks to address inequities in pandemic response.

“Good governance makes a big difference,” said Dr. John Swartzberg, clinical professor emeritus of infectious diseases and vaccinology at UC Berkeley, by email. “Individualistic societies like ours do not do well in pandemics.” Those that do better, he said, tend to be societies that trust in their governments and each other.

Swartzberg has learned much over the past year, he said, including that an RNA genome of about 30 kilobases can have enormous plasticity, and the theoretical number of variants it can spin off is nearly uncountable. He learned that vaccines work and are very safe, but “still, many people seem to have an infinite capacity for not understanding this. … Our biases can kill us.”

He learned that many mistakenly think of COVID-19 as an acute illness and ignore the very big problem of long COVID, just as many mistakenly consider it a winter virus even though we’ve had surges for two summers in a row, he said. And he wonders why so many think we’re done with variants.

As masks come off and life returns to something resembling normal, Swartzberg urges caution. “When stripping away societal and individual precautions,” he said, “hurry slowly.”

Arriving at consensus

“Follow the science” was a mantra of the pandemic’s first year, said Andrew Noymer, UC Irvine. After the second year, we have “a la carte science,” he said.

Masked students wait to go to their classroom at Stanford Elementary School in Garden Grove. (Photo by Paul Bersebach, Orange County Register/SCNG)

“Do you want a mask? There are tons of studies saying we should be masking. Do you not want a mask? UCSF has an expert who’ll tell you that masks are unproven,” he said. “Do you want to vaccinate your kids? The American Academy of Pediatrics says yes, vaccinate your kids, it’s FDA authorized, safe and effective. The surgeon general of the state of Florida, however, will tell you not only that your kids don’t need to be vaccinated, but that they should not be vaccinated unless they have an underlying condition.

“What we have is divergence, not convergence, over the last 12 months.”

Before scientific opinion coalesces around a consensus, there’s vitriolic debate, Noymer said. The idea that doctors should wash their hands after performing autopsies, but before delivering babies, was once hotly controversial, so we shouldn’t be surprised at the vitriol today.

But people are tired of aggressively planning their lives around the pandemic. They’re eager to get back to some semblance of normal. They know which precautions reduce the risk of serious illness and death, and they want to get on with it. Public policy is never about preventing every death — if so, tobacco and alcohol would be illegal rather than regulated, he said — but rather about finding an acceptable balance.

“The result is going to be, maybe not 500,000 COVID deaths a year, but maybe 250,000 a year for the next few years,” Noymer said.

Nurses perform timed breathing exercises on a COVID-19 patient on a ventilator in southern France in December. (AP Photo/Daniel Cole, File)

“The contours of the future are a little more mysterious. We’re at a time of great uncertainty. We already have data showing that each wave is not necessarily milder than the last. Omicron killed more people than delta. Fact. That means that I can’t tell you I’m optimistic the waves will dissipate. There will be another wave. Hopefully, the next wave will be the mildest yet. But there’s nothing as a matter of science that says it will be.”

A year ago, vaccines were on the verge of being widely available, and we were buoyed by optimism. “I’m more pessimistic going into the third year than I was going into the second year, with the small proviso that acquired immunity may be a long and painful way out of this.”

Variant factories?

The coronavirus has been found in dogs, cats, tigers, lions, gorillas, mink, hamsters and white-tailed deer. Cross-species spillover “might result in the establishment of a reservoir that can further drive the emergence of novel variants with potential for spillback to humans,” said a recent paper by researchers from Pennsylvania State University.

But billions of people haven’t been vaccinated or infected yet, and new variants can incubate in them as well. Worldwide, just 57% of people have been vaccinated, according to OurWorldInData. It’s as few as 11% in Afghanistan and less than 5% in some central African nations.

“Variants are going to have to be more transmissible, find a way to escape the immunity we’ve developed,” said Stanford’s Maldonado. “Vaccination is still the key at this point.”

Johns Hopkins University

Vaccination rates are much higher in the U.S. — nearly three-quarters — and Maldonado believes vaccine trial data for the youngest children will be out soon. America is approaching population — or herd — immunity in many parts of the country, but we know it will wane over time, she said. Spring and summer will hopefully continue the trend of declining case numbers, and, hopefully, COVID-19 will become background noise, like other cold viruses. People prone to severe disease, and people who haven’t responded to vaccinations, will need to exercise caution.

Two bucks at Cape Henlopen State Park in Delaware in 2020. (Photo by Eva Hambach / AFP) (Photo by Eva Hambach/AFP via Getty Images)

“If there’s one thing the past few years have taught us all is to have great humility when it comes to determining the next steps this virus will take,” said Dr. Elizabeth Hudson, regional chief of infectious diseases for the nearly 5-million- member Kaiser Permanente Southern California, by email.

“It’s important to not underestimate exactly how far we’ve come in terms of our knowledge around COVID-19 and all of the treatment options we now have. We’ve learned about how to counter this virus by attacking it at different points in its replication cycle, and learned how to use monoclonal antibodies to help both protect from and treat for COVID-19. Most importantly, we’ve learned that it is our COVID vaccines that have done much of the heavy-lifting around ensuring we’re all protected and truly decreasing the risk of being hospitalized or dying.”

Over the next year, medical professionals can hope to learn much more around long COVID, and develop real treatment options, she said. But predictions are premature.

This little girl volunteered for the Pfizer vaccine trial in younger children at Stanford Medicine. (Photo by Steve Fisch, Courtesy Stanford Medicine)

“The nature of viruses is that they replicate quickly, which can lead to mutations,” Hudson said. “Those mutations can be helpful or harmful to the virus, in terms of whether it makes it more able to infect people. With so many people worldwide … who are still unvaccinated/incompletely vaccinated, as well as the sudden large number of refugees moving in Europe, there’s a chance a new variant may arise. As with all things COVID related, time will tell.”

Case numbers are rising quickly in Europe, often a precursor to spiking cases at home. “The next deadly pandemic,” Riverside’s Lo said, “is always waiting around the corner.”

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