Earlier in the COVID-19 pandemic, much of the discussion about when and how society would "return to normal" focused on herd immunity, the level at which enough people are immune — through vaccination or previous infection — to protect those who are susceptible.

Last spring, health experts estimated the rate at 60% to 70%. But later in 2020, Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases cited figures as high as 75% and 85%. Dr. Oliver Mayorga, chief medical officer for Lawrence + Memorial Hospital in New London, in January called herd immunity a "moving target" that is influenced by many things, such as new, more contagious variants of the coronavirus.

And when the more infectious delta variant became the dominant strain by this past summer, and increased "breakthrough infections" among vaccinated people, herd immunity became more elusive.

In August, the Infectious Diseases Society of America estimated that the delta variant pushed the level for herd immunity above 80% and potentially close to 90%. Also complicating the question is waning immunity against the coronavirus, whereas some vaccines and infections of some other diseases confer lifelong immunity.

Doctors from the Brown University Alpert Medical School and Emory University School of Medicine in July published a viewpoint in the Journal of the American Medical Association laying out four potential COVID-19 endgame scenarios: eradication, elimination, cohabitation or conflagration.

They expressed that eradication "may prove too aspirational a goal even as a thought experiment," given stringent requirements: "Both vaccine- and infection-derived immunity would have to be highly effective, long-lasting, adept at preventing secondary transmission and reinfection, and protective against all manner of present and future viral variants."

Elimination means disease prevalence being reduced to zero regionally rather than globally. Some countries, such as Australia and Singapore, previously pursued an elimination strategy but have pivoted in recent months.

The authors of the JAMA article said the United States appears to be in a state of cohabitation, meaning vaccines help limit severe illness, interrupt transmission and mostly counter variants.

While so-called breakthrough infections can occur due to "limited vaccine efficacy" due to supply or quality control issues or future virus variants, or in people with compromised immune systems, they wrote, it's possible for the U.S. to enter an endemic state. That means a virus continues to circulate for the foreseeable future but at lower and more manageable levels.

A worse outcome than cohabitation would be conflagration, meaning circulation of the coronavirus would remain robust, giving the virus more opportunities to adapt.

Dr. Richard Martinello, medical director for infection prevention for Yale New Haven Health, said earlier this month with a laugh, "It'd be great to see it disappear. Of course, I don't think that's going to happen."

"For the rest of our lives, and our kids' lives, there's always going to be COVID," he said, "but generally what I would suspect is the severity of disease is going to become less, and it's going to become less because people are developing immunity, from vaccination and from infection."

He expects to see waxing and waning of community spread but the virus settling out over time, with numbers lower than they are now.

Martinello thinks that a year from now and into the future, there won't be the need for as much testing and thinks "there's better than a 50-50 chance that our next fall will be pretty much back to normal."

Dr. Ajay Kumar, chief clinical officer of Hartford HealthCare, said earlier this month that the future is difficult to predict. "We have a bit more tools in our toolbox now than what we had one and a half years ago, and next year we'll have hopefully a lot more tools, so this pandemic becomes something like the flu over time."

Of course, optimism in the past has sometimes been followed by a rise in cases and tightening of restrictions, and past predictions have been wrong. President Joe Biden struck a victorious note in an address May 13, after the Centers for Disease Control and Prevention stopped recommending that fully vaccinated people wear a mask, but the CDC later reversed course when cases rose.

Now, two things that are giving scientists and public health experts optimism are the possibilities of vaccine approval for younger children and the approval of a pill to treat people sick with COVID-19.

Pfizer and BioNTech have asked the Food and Drug Administration to authorize emergency use of its coronavirus vaccine for kids ages 5 to 11, and an FDA advisory committee is scheduled to meet Oct. 26 to review the request.

On Oct. 1, drug company Merck said its experimental pill for people sick with COVID-19, called molnupiravir, reduced hospitalizations and deaths by half when studied in unvaccinated people. Merck has requested an emergency use authorization, and the FDA announced Thursday that its Antimicrobial Drugs Advisory Committee would meet to discuss the data on Nov. 30.

In an opinion piece in The Washington Post on Oct. 6, George Washington University Milken Institute School of Public Health professor Dr. Leana Wen cited three actions for turning COVID-19 "from an existential crisis into a manageable problem": making vaccines available for younger children, oral outpatient treatments, and free rapid tests.

"Barring the terrible circumstance of a much worse variant developing, I believe that we have already passed the darkest days of (COVID-19)," she wrote. "The virus may be here to stay, but if we are armed with the right tools, it no longer needs to dominate our lives."

Dr. Scott Gottlieb — FDA commissioner from 2017 to 2019 and Pfizer board member — told NBC Connecticut earlier this month, "Barring us getting a new variant that pierces the immunity that we've acquired, I think this delta wave of infections is the last major surge of infection that we're going to have, and this is going to become a more persistent menace, it's going to become a more endemic virus, but we're not going to be dealing with the very high prevalence of infection we're dealing with now."

Denmark, which has a vaccination rate more than 18 percentage points higher than the U.S., lifted all its remaining COVID-19 restrictions on Sept. 10, putting the country at the forefront of the transition from pandemic to endemic conditions.

"We're thinking of this virus now as a sort of defanged version of the original one. It has gotten its teeth pulled out by the vaccine," Lone Simonsen, an epidemiologist at Roskilde University in Denmark, told Science. "What's left is not much worse than diseases that we're used to and that we don't close schools for, like seasonal flu or maybe the 2009 influenza pandemic."

Yonatan Grad, a professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, said in a Q&A in August that because viruses spread when there are enough susceptible people and enough contact among them, "it's hard to anticipate what the timeline will be for the expected shift of COVID-19 to endemicity."

It depends, he said, on the strength and duration of protection from prior infection and vaccination, patterns of human contact, and transmissibility of the virus.

e.moser@theday.com