Omicron could have a silver lining by boosting immunity, some experts say. But don't bet on it. – The Washington Post

The idea that omicron has a silver lining is not a fully formed scientific theory. It’s conjecture, in some cases unspooled on Twitter threads and floated in television interviews. At worst, it is “arm-waving,” to use the term that serious scientists employ as a pejorative.

And even the experts promoting the idea concede that it is an educated guess — and is contingent upon the virus itself, which has repeatedly surprised experts and may generate new variants that are more dangerous than omicron.

“Every prediction about the future has to come with the parenthesis that there could be another variant that screws this up,” said Robert Wachter, the chief of medicine at the University of California at San Francisco, who has used social media to share his speculation that omicron could carry long-term benefits.

After this omicron wave subsides, he suggests, so many people would have some level of immunity to the virus that it would not subsequently deliver the same level of pain and suffering. In an interview, he said that in the past he would have submitted his thoughts to a peer-reviewed journal, a process that probably would have taken three months. In this health emergency, he went straight to Twitter.

“It’s hard to say omicron is a lucky break, but it sort of is,” Wachter said in the interview. “Because the combination of significantly lower pathogenicity, and only modest immune evasion — and tremendous infectivity — leads to what you would call the opposite of a perfect storm.”

This hypothesis has generated pushback from other scientists, who say too much remains unknown about the virus to make such a forecast. They note that every time the experts have suggested that the pandemic is nearing the endgame, the virus comes up with a new trick — in the case of omicron, packaging dozens of mutations that make the variant more infectious while also enabling it to slip past a key line of immune defense.

Any broad immunity boost comes at a known, enormously high cost — health-care systems are teetering at the brink and medical workers are burned out. World Health Organization Director General Tedros Adhanom Ghebreyesus warned Thursday that omicron infections should not be described as “mild”: “Just like previous variants, omicron is hospitalizing people, and it is killing people.”

The coronavirus continues to mutate, and its spread in much of the world is made easier by the shortage of vaccines in many developing countries. There is no scientific evidence that the virus is settling into a permanently milder state. A new variant could conceivably combine omicron’s transmissibility with the higher disease severity caused by previous variants, including the still-circulating delta variant.

Emory University biostatistician Natalie Dean said people thought the pandemic was waning last spring, and then delta came along. And then in the fall things looked better — and omicron appeared.

“There’s always this threat of curveballs,” she said.

Infectious-disease experts say the idea that widespread omicron infection will create immunity in a broad swath of the population, and a shield against future variants, is certainly plausible. But it’s unknown how durable that immunity would be or how well it would protect against a future variant.

“The idea that mild infection can lead to better antibody levels and protection in the future from other variants is intriguing, but we certainly don’t have any data on this yet,” said Matthew B. Frieman, a virologist at the University of Maryland School of Medicine.

Monica Gandhi, a physician and colleague of Wachter’s at UC-San Francisco, said in an email that the spread of omicron could signal the approach of the “endgame” of the pandemic, with the virus becoming endemic — meaning it would continue to circulate at modest levels but not cause society-disrupting outbreaks.

“Unless we have a new variant that is more virulent (which can occur if we don’t work hard on global vaccine equity), it looks like we could be approaching endemicity in the U.S. once the omicron surge is over,” she wrote.

Any discussion of long-term benefits from omicron necessarily views the situation at the 30,000-foot level, because the country and much of the world is in the middle of a health crisis. In the United States, patients are flooding hospitals, with most of the country still facing what is likely to be the worst phase of the winter surge.

Wachter acknowledges that omicron has attractive attributes for the long run but extremely bad attributes in the short run: “This is really awful for January. Our hospitals are being overrun.”

Many people appear to be resigned to being exposed to the virus. That is an understandable response to news reports saying that omicron is a milder version of the coronavirus and that there’s probably no avoiding such a contagious pathogen.

Six medical experts who advised President Biden during the transition from the Trump administration published articles Thursday in the Journal of the American Medical Association that urged the Biden administration to shift its strategy, ending the current cycle of unending emergency and adjusting to the reality of coronavirus infections as a “new normal.” One article suggested that the administration cease tracking covid deaths independently from those caused by other potentially lethal respiratory viruses, including flu.

“The ‘new normal’ requires recognizing that SARS-CoV-2 is but one of several circulating respiratory viruses that include influenza, respiratory syncytial virus (RSV), and more. COVID-19 must now be considered among the risks posed by all respiratory viral illnesses combined,” wrote Ezekiel Emanuel, Celine Gounder and Michael Osterholm, prominent disease experts who have been outspoken throughout the pandemic.

The administration’s pandemic guidance has shifted slightly: It still emphasizes vaccinations and booster shots, and common-sense measures including mask-wearing and avoidance of indoor crowds, but people also should live their lives and not isolate themselves. And scientists as well as government officials are generally emphatic that schools remain open for in-person learning.

“My attitude has been that I’m respectful of the virus — I’m taking reasonable precautions — but I’m not going to the end of the earth to avoid it,” said Andrew Noymer, an epidemiologist at the University of California at Irvine. “We’re all going to get this thing eventually.”

Vaccines usually prevent severe outcomes from omicron, particularly after a booster dose. And a number of treatments remain effective against omicron, though they are in short supply as demand surges. So far, there has not been a sharp increase in the number of deaths, and this is now many weeks into the omicron wave.

It remains unclear why omicron infections are typically less severe than those caused by delta. Some of it is probably attributable to widespread immunity from vaccination and previous infections. But the variant itself appears to operate differently. Laboratory experiments suggest that although omicron can multiply faster than delta and is able to sidestep key parts of immunity, its ability to invade lung cells and cause lethal pneumonia has been hobbled.

There is no guarantee that the next variant will do the same. And omicron still packs a punch.

“It’s not like omicron is running through the population and nobody is getting hospitalized,” said Michael Diamond, a virologist at Washington University in St. Louis. “People are getting sick and still dying.”

He is not ready to embrace omicron as a blessing in disguise.

“Yes, we will generate more immunity in the population, so maybe we will be poised better against a future variant — maybe. It remains to be seen,” Diamond said.

In a massive team effort, Diamond and collaborators scattered across the United States and Japan infected mice and hamsters with omicron and discovered a consistent, striking pattern: The omicron variant clearly causes less severe disease in rodents.

The results, published in a not-yet-peer-reviewed study, show that omicron is biologically different from the variants that came before. But there are limitations to such experiments. Mice are different from humans, and their milder disease was measured in weight loss. Mice infected with previous versions of the virus lost weight, but mice infected with omicron did not.

In hamsters, which develop respiratory illness analogous to what humans experience when infected, omicron is less likely to proliferate and cause damage in the lungs — instead tending to cause milder, upper-airway infections.

“Something is different about the ability to replicate in animals, and it seems to be slower and not able to infect the lung at the same level as the other variants,” Diamond said, calling that finding unexpected. But he said he is cautious about extrapolating too far from the animal data. Just because omicron is mild in rodents doesn’t mean it would be mild in people, too.

Why is omicron less adept at infecting the cells deep in the lungs? Converging lines of evidence from multiple laboratories show that omicron uses a different method from previous variants to enter cells.

At the University of Cambridge, scientists built miniature models of human lungs in a dish and found that harmless replicas of the omicron virus were less able to infect cells than delta was. They traced that trait back to its inefficient ability to enter cells by interacting with a protein called TMPRSS2, which is abundant in the cells of the lung. Omicron also shows less aptitude for fusing cells together, which creates masses that are a hallmark of severe covid-19 in autopsies.

Other scientists have used different experiments to arrive at similar conclusions. That could explain why this version of the virus appears less likely to cause lethal pneumonia and might more closely resemble an upper respiratory infection, like a cold.

This quirk of omicron may just be a bit of luck — not a sign that all future variants will follow omicron’s path.

“I’m worried about people getting the wrong idea about this, because what we have observed is something that has happened in omicron. I don’t think this is the way all viruses are going to go necessarily from now on,” said Ravindra Gupta, a virologist at the University of Cambridge.

Barney Graham, a scientist recently retired from the National Institute of Allergy and Infectious Diseases whose work laid the foundation for many coronavirus vaccines, said it is increasingly difficult to tell whether changes in disease severity can be traced to the virus itself or the presence of prior immunity.

And Graham said he is worried that a virus that is milder in adults may not also be milder in children.

“Younger children have smaller airways, so they can experience the same thing as adults in a different way. So if the virus is still infecting the airways, readily infecting the airways, then the very young children with small airways may have more trouble clearing that,” Graham said.

Graham said he is optimistic overall. His hope is that as the virus evolves, it will be boxed into a corner. The mutations that give the virus an edge against human immunity could come with an Achilles’ heel, hindering its ability to spread.

Over multiple waves of disease, the coronavirus could cease to be a pandemic contagion and instead be more of a seasonal threat. But how many waves would that take? He doesn’t know. The challenge is to minimize the threat of future surges by increasing vaccinations globally.

“Within the next three to six years, I think everyone on Earth is going to be exposed and to some level infected with the virus,” Graham said. “It’s inevitable.”