In late 2021, on the heels of the deadly Delta wave of infections, a new variant came flying in out of left field—one so highly mutated, so drastically different that it changed the trajectory of the COVID-19 pandemic.
Dubbed Omicron by the World Health Organization, it contained more than 30 mutations that separated it from the original virus—alterations that gave it veritable wings. In short order, its lineage would become the only one of consequence, its progeny able to out-compete all other viral combinations evolution sent its way.
Omicron was the beginning of an era—one that, despite its outlandish success in infecting and reinfecting the public, would see the end of both global and national pandemic emergency statuses. For more than two years, COVID and Omicron were all but synonymous.
Now, as the world enters its fifth year of COVID, the calculus may have changed, experts say. The new, highly mutated COVID variant JN.1—dubbed “Pirola” by volunteer variant trackers—has achieved global dominance. And like Omicron, it came flying out of left field.
Most new variants differ from each other in just one or two small ways. But with its 30-plus additional mutations, Pirola is as genetically divergent from Omicron as Omicron was from the original COVID.
In short, JN.1 is, by all appearances, a game changer. Most—if not all—variants of consequence for the foreseeable future could very well evolve from it, experts tell Fortune—until the virus throws another black swan-style curveball, anyway.
Whether the WHO will recognize it with a Greek letter—in what would be its first designation in over two years—remains to be seen.
As of Jan. 3, it had not—and some experts say that’s a mistake.
‘A very serious evolution of the virus’
Among them: Dr. Eric Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif., and a leading authority on the virus.
When cases of JN.1 began skyrocketing this fall, “instead of side-stepping, the WHO could have easily given it a new Greek letter,” he told Fortune.
When the international health organization declared B.1.1.529 a variant of concern, or VOC, and assigned it the Greek letter Omicron in late November 2021, governments responded, ramping up sequencing and mitigation measures. Travel was restricted; testing was required before flight; masks were required on planes.
Aside from prompting governments to take action, Greek letters can—and should—serve as communication tools that “alert the public there is a serious variant” that could fuel a “wave around the world”—even if it isn’t pushing hospitals to the brink, Topol contends.
“But they’ve just called it a VOI (variant of interest), and that just doesn’t cut it, with the growth advantage this variant has demonstrated,” he said. “It’s just extraordinary.”
Ryan Gregory—a biology professor at the University of Guelph in Ontario, Canada, and a lead variant tracker—agrees with Topol. Greek letters should be used to warn the public of an impending COVID squall, he says—not to herald it after it hits shore.
Hurricanes, as he points out, aren’t named. But all preceding tropical storms are, “to facilitate communication early, with the understanding that some of them may go on to become more serious,” he said.
Waiting to assign a Greek letter to a variant until lagging indicators like hospitalizations and deaths are on a steep ascent is akin to “naming hurricanes as they blow through, or as they’re approaching shore,” he added.
Dr. Michael Osterholm—director of the University of Minnesota’s Center for Infectious Disease Research and Policy (CIDRAP) and another leading authority on COVID—says the authority to designate a new Greek letter should rest with the WHO alone, not citizen scientists or anyone else, for that matter.
But “I’m not saying they’ve done it appropriately,” he told Fortune, speaking of the international health organization’s variant-naming committee.
JN.1 represents “a very serious evolution of the virus,” he said. “And it isn’t over.”
Dr. Stuart Ray, vice chair of medicine for data integrity and analytics at Johns Hopkins’ Department of Medicine, agrees with Osterholm. Variants should only be named by the WHO, he says—and that day may still come.
“Given the trajectory of this, I wouldn’t be surprised if it gets a new Greek letter,” he told Fortune. “I also wouldn’t be judgemental if they don’t.”
‘I’m more worried about its descendants’
When Israeli variant trackers discovered JN.1 predecessor BA.2.86 in August, it was so unlikely anything they’d seen before that they, at first, assumed it was BA.6—a sixth generation of Omicron, so to speak.
In fact, it was a descendent of BA.2, the so called “stealth Omicron” strain that hit radars in early 2022—a veritable fossil, in the fast-paced world of COVID evolution.
Having alerted the scientific community, volunteer variant trackers—some professionals, others lay people with a knack for the work—dubbed it “Pirola,” after a large asteroid located near Jupiter. The reason: The name closely resembles both Pi and Rho, the next two Greek letters WHO officials are likely to choose from, if they deem a new strain worthy.
BA.2.86 never truly sprouted wings and took off like other “high flying” Omicron spawn. But neither did the original Omicron, Gregory said. While wildly different from the Delta, it lacked the ability to transmit rapidly. When it acquired mutations that allowed it to do so, it conquered the globe in quick succession.
In similar fashion, BA.2.86 itself may not take off, Gregory told Fortune this summer. But’s progeny could, he warned. “I’m more worried about its descendants,” he said at the time. “It’s a potential BA.2.86.1.5 that concerns me.”
He was speaking theoretically. But as it turned out, he wasn’t far off. The initially concerning BA.2.86—with a couple of additional mutations—became BA.2.86.1.1. Because long strings of letters, periods, and numbers eventually roll over, it was truncated to JN.1—the stealthily moving mutant sweeping the world today.
‘Pirola’ for now
The WHO first spoke publicly about JN.1 at an Oct. 19 news conference. “It is something we have to keep a close eye on,” Dr. Maria Van Kerkhove, head of its emerging diseases and zoonoses unit, said in response to a question posed by Fortune.
On Nov. 21, the organization named BA.2.86 a VOI, a category second only in alert level to VOC. A few weeks later, on Dec. 19, it broke out progeny JN.1 as its own VOI.
Still, JN.1 officially remains categorized under Omicron. For more than two years, the WHO has maintained that all new variants are similar enough to share the same Greek letter. The variant trackers disagree. To fill in what they perceive as a gap, the team has been assigning “street names” to particularly successful strains for nearly two years, in a bid to communicate to the public the evolving nature of the threat.
In the summer of 2022, a Twitter user dubbed the Omicron strain BA.2.75 “Centaurus,” a tag that was quickly picked up by the media. Inspired, Gregory and his team have since assigned 30 memorable monikers for Omicron spawn, from “Kraken” for XBB.1.5 and “Eris” for EG.5.1, to “Fornax” for FL.1.5.1.
On the same day the WHO designated JN.1 as its own VOI, variant trackers Gregory, Raj Rajnarayanan, and Jay Weiland told Fortune they had wrestled with whether to assign a new name to JN.1 or to simply stick with “Pirola.”
On the one hand, JN.1 was on a clear path to global dominance and would soon make even more headlines. On the other hand, it wasn’t wildly different from “Pirola” BA.2.86 and was simply an extension of that threat.
“We’ve had many discussions about whether to give JN.1 its own nickname, given its rate of growth, and we keep going back to settling on no, we’re going to stick with Pirola,” Gregory said at the time. “What matters is not individual variants and whether they’re going to cause a wave as big as the first Omicron, but the idea of evolving lineages.”
In an exclusive interview with Fortune on Dec. 30, Van Kerkhove said the WHO is ready to assign a new Greek letter on a moment’s notice, if necessary. But the organization is holding out for a variant that is “truly different," she said—one that impacts public health.
“If we were to see any change in severity, for example, we wouldn’t hesitate to call this a VOC, or the next one a VOC,” she said. “But phenotypically, we’re really seeing similar behavior to the other circulating variants.”
As for the efforts of the variant trackers, Van Kerkhove expressed appreciation, calling them "clever minds" and noting that some are professors.
"I think it's also really important they also see what we are trying to do," she added. "When we use that Greek letter is to warn the public about something different, especially a change in severity. There is a reason for our classification system."
Still, "we're all learning," she noted.
The WHO’s Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE) is devising a new variant classification system it hopes to debut later this year, Van Kerkhove said. It’s discussing various ways to group variants, taking into account how genetically similar they are, which key mutations they possess, and the symptoms they cause.
But for now, labeling variants the WHO deems concerning as VOCs—something the organization hasn’t done since November 2021—works “really well, should there be something that is really, really different, really severe,” she said.
“If we were to see a variant that fell within our classification of a VOC, we would call it in a day,” she added. “We would do that immediately, no hesitation whatsoever. ... Just because we're not giving it a name does not mean it's not a threat."
If the WHO's TAG-VE declared a new VOC—Greek letter and all—it wouldn't mean an automatic renewal of the organization's "public health emergency of international concern" status, she noted. WHO Director General Tedros Adhanom Ghebreyesus could choose to summon an emergency committee at any time, for any reason. That committee—not the TAG-VE—would make the decision as to whether or not to renew COVID-19's official pandemic status, which ended in May.
A new viral era, semantics aside
At the end of the day, whether or not JN.1 becomes Pi or Rho in the eyes of the WHO is a matter of semantics. Regardless, JN.1 very likely represents a new chapter in pandemic evolution, experts contend.
The highly mutated variant has ushered in “a new era,” Gregory told Fortune, and is “on track to become the lineage from which most variants are descended for the foreseeable future.”
Other circulating lineages will struggle to compete, Jay Weiland, a top variant forecaster, told Fortune. “Evolution is hard to predict,” he said, “but JN.1 has a big head-start with its immune evasion.”
Ryan Hisner—a top citizen variant tracker who discovered the second and third known cases of BA.2.86—says "Pirola" has brought about a startling realization: Omicron wasn't a "one-off anomaly."
"Ever since BA.1 emerged, people have asked whether the original Omicron event was essentially a freak accident or something we could expect to occur repeatedly in the future," he said. "JN.1/BA.2.86 has really changed the outlook on this front. I think it's now much more widely accepted that these extreme [evolutionary] events will be a semi-regular occurrence with SARS-CoV-2."
Van Kerkhove agrees. "We could have the next sub-lineages come from JN.1," she said. "But we could also see something quite different. We could see something like an Omicron again."
For years now, Osterholm has predicted that COVID would proceed as a play in three acts. The initial strains, through Delta, served as the first. Omicron comprised the second. And JN.1 might very well be somewhere in the third, he says, in which the virus is still a larger threat than a routine respiratory disease like the flu and hasn’t yet found seasonality.
One day, he hopes, the play will end, with COVID joining the majority of other human coronaviruses in what usually presents as a common cold.
Today is not that day.
As for Topol, he still views the pandemic in terms of waves. “It’s something like the ninth major one,” he remarked in late December. He’s not so sure about COVID being confined to three acts, mimicking the three major waves of the 1918 Spanish flu pandemic.
“Whether it’s a 20-act play or 22 waves or whatever, we have to do everything possible to improve our defenses,” he said. “We all want to be able to go on about our lives and not have to worry about infections and long COVID.”
Even before JN.1, a new chapter of the pandemic had already begun, Van Kerkhove maintains—one in which interest in vaccines is lost, thousands continue to die each month, and untold others develop disabling cases of long COVID.
“The biggest concern is complacency,” she said. “People think it’s over and gone, and that’s really scary.”
