The relentless evolution of the coronavirus, which has spawned new variants to fuel fresh surges of disease every four to six months, could in the not-distant future propel the virus to overtake measles as the most contagious of all known infections.
Increasing infectiousness does not necessarily make the virus deadlier, but it could make it harder to control, and leave communities vulnerable to the repeated waves of illness that have defined the pandemic.
The variants now dominating around the world may be five to 10 times more infectious than the original virus that sparked the pandemic in China in late 2019, health experts believe. Lately each variant has outpaced its parent — omicron, with its massive evolutionary jump, was about three times more infectious than delta. Its subvariants — BA.2 and BA.2.12.1, which are driving the latest surge in the Bay Area — are each more infectious still, by 20% to 30%.
The basic reproduction value — a number meant to represent how many people could be infected from a single case — for these subvariants may be approaching 15, an astonishingly high score that would put the coronavirus on par with measles.
"There isn't a theoretical wall to how infectious it could get," said Dr. Robert Siegel, an infectious disease expert at Stanford. "In everyone's mind, measles is the Michael Jordan of viruses, but this guy is knocking at the door. And we're giving this virus immense opportunity to train for that goal."
New infectious are still exploding across much of the world, including in the United States, allowing the virus to develop new mutations that potentially make it faster and more efficient at infecting human cells. Some scientists believe that process has sped up in recent months, with new variants supplanting their predecessors faster than at any other moment in the pandemic.
At the same time, in an environment of increased immunity due to vaccination or prior infection, the virus is adopting other mutations that allow it to partially evade that hard-won protection. Though vaccinated individuals remain strongly shielded from severe illness, they are increasingly vulnerable to infection. And prior infection doesn't always confer much protection either — many people have now been infected two or even three times, likely by different variants.
Many scientists still believe that the virus is also evolving to become less virulent, to make people less seriously ill even as it moves faster. But there's no guarantee it will follow that path, and it may take years for the virus to mutate to a place where it's no more severe than a common cold for almost everyone who gets it.
"My own feeling is it's going to be less and less virulent, and it will take on characteristics of the other coronaviruses that cause the common cold," said Dr. Jay Levy, an infectious disease expert at UCSF. "But it could take five years to get there, and we can't sit around in the meantime."
Many experts in viral evolution say the coronavirus isn't actually mutating faster now than it was before. What has changed is the fitness of those mutations — whether they give the virus a biological advantage. Earlier in the pandemic, new variants would appear in various places around the world, triggering local surges and sparking fear of another global wave of infection, but few of them gained much traction beyond their country of origin.
"We saw lots of variants, thousands and thousands of variants as it evolved, but the functional significance was pared down to very few," said Dr. Eric Topol, executive vice president of Scripps Research in La Jolla (San Diego County). "What we're seeing now is variants that have functional impact."
The mutations alone aren't all new, Topol added. In fact, many of the defining mutations in the currently circulating variants were identified well over a year ago. But variants are adopting and shuffling those mutations in such a way that they offer new advantages. "It's their interactions that create these functional consequences," Topol said.
Viral mutations generally fall into one of three broad categories: They help the virus spread more efficiently, they help it evade immunity, or they make it cause more or less severe illness.
Sometimes a mutation can affect two or more characteristics. For example, scientists believe that a mutation in omicron made it more inclined to replicate in the upper respiratory tract instead of the lungs. That meant it caused less severe disease, because it didn't necessarily go deep into the lungs, but also made it more transmissible because it hung around in the nose and throat, where it produced more copies to be spread around.
"It's only when a collection of mutations come in at the right place and right time that we see evolution," Siegel said. "Most of them are failures, they can't even replicate. But the more times we allow the virus to replicate, the more likely it is that we're going to get significant variants."
Understanding how the virus evolves — under what conditions it picks up the most mutations, for example — would help scientists better predict future waves and potentially improve efforts to control spread. It might even prevent new variants from getting a foothold, said Stacia Wyman, senior genomics scientist at the Innovative Genomics Institute at UC Berkeley.
But that type of study has largely been pushed aside, she said, partly because because the virus is mutating so quickly that it's hard to keep up. Wyman has started some of that work, in a collaboration with Kaiser Permanente, to study the genomic sequence of the virus, including how it has shifted over time; she doesn't expect to publish results for many months.
"It appears that there are certain conditions under which it's right for it to have these bursts of evolution," Wyman said, pointing to omicron as the most obvious example. Omicron picked up dozens of mutations that set it apart from delta, the variant it supplanted.
While scientists study how the virus is mutating and why, slowing down its evolutionary journey likely will take tremendous global effort, health experts said. It will require renewed focus on vaccinating the world, and possibly a new array of vaccines that are better able to block infection.
Mitigation efforts — such as delivering vaccines and boosters and recommending widespread masking — will remain the best tools for containing surges and preventing widespread severe illness and death in the interim.
"I don't know how long this is going to continue, how many new variants there will be. It's an unsatisfying answer, but it's the truth where we are right now," said Dr. Susan Philip, the San Francisco health officer. "There's always going to be a chance that there will be new and more infectious subvariants."
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