As we close in on nearly two years of pandemic life—and COVID-19 cases in Colorado continue climbing to record levels, with many fully vaccinated and boosted people contracting breakthrough cases of the Omicron variant—it’s only natural to wonder: When will this all be over? And what will it take to get us there?

Thirteen months ago, we posed those questions to two local experts: Dr. Jonathan Samet, dean of the Colorado School of Public Health, and Dr. James Neid, infectious disease specialist at the Medical Center of Aurora. At the time, Colorado had just begun its vaccine rollout in the wake of record-breaking hospitalizations. Both Samet and Neid predicted the pandemic would end when we achieved “herd immunity”—essentially, when enough people became immune to the virus, either through natural infection or vaccination, so that it could no longer spread widely.

It sounded simple, almost soothingly straightforward. Then 2021 arrived like a wrecking ball and upended much of what we thought we knew about the virus. Now, as we enter 2022 with Omicron spreading at a breakneck pace and U.S. COVID hospitalizations reaching all-time highs, we asked Samet and Neid the same questions. This time, their answers were, well, more complicated.

“In a way, much of what has happened in 2021 was a surprise,” says Samet, citing the unexpected magnitude of vaccine hesitancy (just 62.6 percent of Americans are fully vaccinated to date, according to a Mayo Clinic tracker) and the emergence of two powerful mutant strains: Delta and Omicron.

Samet says Omicron is “illustrative of how the pandemic will be very difficult to quote end.” The variant, he explains, is very transmissible and has some ability to evade the protection afforded by the current vaccines, as evidenced in the rising number of breakthrough cases.

Right now, it looks like the virus will not go away, but instead become endemic, meaning it will live with us, says Samet. “It’s not by any means the only coronavirus that is endemic,” he adds, pointing to long-circulating strains of coronavirus that contribute to the common cold. The difference with SARS-COV-2 (the virus that causes COVID-19), however, is its “incredible transmissibility,” he says.

The pandemic will be over, says Samet, when we see just sporadic cases of COVID-19 and not epidemic waves. Suppressing these epidemic waves will require most of the world’s population to be immune to SARS-COV-2, either through vaccination or natural infection. That reality, however, is complicated by the fact that Delta and Omicron are highly transmissible and that immunity to the virus is not permanent.

Natural acquired immunity probably starts to wane after about six months, says Samet. And the proportion of people who are not vaccinated—which is high enough to sustain the pandemic—also complicates the efforts, as does waning vaccine efficacy. Another problematic factor, adds Samet, is how interconnected the world is. When a more transmissible strain emerges, as is believed to have happened in South Africa with Omicron, “it can quickly move around the world and start new waves of the epidemic,” he explains.

After Omicron peaks, Samet predicts a “lull” in the pandemic. This will be fueled by the fact that people who were infected with Omicron will have temporary immunity to the virus, as well as the hope that more people will have gotten vaccinated and the likelihood that transmission will decline in warmer months, as it has done the past two summers. But that lull may soon be followed by another wave and many more waves after that. “I think maybe we’ll get to a point with our vaccines that we will do better and have longer lasting vaccines, but we have to be prepared for further waves as the virus mutates,” Samet says.

For now, Samet stresses the importance of both national and global vaccination efforts. Looking ahead, he hopes testing will become more widely available as a tool to curb viral spread. He also predicts we may see societal changes surrounding what people can do if they’re vaccinated versus unvaccinated. For example, perhaps air travel will be limited to only vaccinated people as a way to limit viral transmission.

Vaccinating the entire world is “going to be key” to effectively curbing the virus, says Samet. And it’s “very likely” that for the near-term future, we will have annual vaccinations against SARS-COV-2 that will target whatever strain of the virus is circulating at that time, says Samet. In the short term, however, we may need to continue to rely on “non-pharmaceutical interventions”—like mask wearing and distancing—to help protect hospital capacity and accelerate the end of the pandemic, he says.

If you haven’t yet gotten boosted (or vaccinated in general), do so now, encourages Samet. And if you want to optimize your respiratory protection, use an N95 or KN95 respirator mask, he adds.

As for whether vaccinated and boosted Coloradans should frequent restaurants, bars, or other indoor public spaces right now, Samet says such decisions depend on how much personal risk you’re willing to take. During a January 12 press conference, state epidemiologist Rachel Herilhy said the current seven-day average test positivity rate of nearly 30 percent is the highest it’s ever been and “reflects the high levels of disease transmission that we are seeing in the state right now.”

Still, there is cause for optimism amid the current surge. People who are fully vaccinated and boosted against COVID-19 have a “quite low chance” of severe illness, says Samet. Moreover, the tools we have to beat back the virus—including therapeutics, vaccines, and masks—are “ever-improving,” says Neid. “For that reason,” he says, “I would be very hopeful.”

Like Samet, Neid believes SARS-COV-2 will become endemic. Going forward, the public will have to become “increasingly comfortable with getting an uncomplicated respiratory infection or a cold,” he says. (That is, as long as they’re fully vaccinated; the risks of contracting severe illness from COVID-19 are still significant for the unvaccinated.)

If cases dramatically outpace rates of severe illness and hospitalizations, and if society can tamp down its “hysteria” over COVID-19 (which Neid describes as an “emotional response” to the virus that’s bigger than the severity of the disease among vaccinated and boosted people), then Neid believes we will be “past the annoying part of the pandemic.” Instead, we’ll simply accept it as one of many circulating respiratory viruses, akin to influenza, parainfluenza, and metapneumovirus, he says.

With all unknowns and ever-shifting variables surrounding the virus, Neid can’t put a timeline on the end of the pandemic. “But,” he says, “we’re way better off than we were a year ago.”