After months of social distancing, mask wearing, and, increasingly, “COVID-fatigue,” a vaccine for COVID-19 is on the horizon. Dr. Anthony Fauci recently said one could be available as soon as the end of November or early December. Governor Andrew Cuomo has speculated this "winter."

The Guardian’s COVID vaccine tracker notes 11 vaccines are in phase-three trials to determine effectiveness—including Pfizer’s vaccine, whose CEO had previously said the company could have a vaccine ready to seek approval by the end of October. On Tuesday, CEO Albert Bourla asked for patience, and pushed that timeline further out.

But developing a vaccine may ultimately be the easy part, compared to the complex challenge of injecting it into enough people.

“I think there's going to be this interesting dance that happens with the vaccine availability and prioritization,” said Rachael Piltch-Loeb, a preparedness fellow at the Harvard TH Chan School of Public Health and associate research scientist at NYU.

Healthcare workers and high-risk populations like older adults would be prioritized first, with varying layers of priority levels for other essential workers, non-essential workers, and everybody else, under frameworks laid out by Governor Andrew Cuomo and Mayor Bill de Blasio. It is unclear how many vaccines would be available for each state right away, or how allocation would work. President Donald Trump has previously claimed 100 million doses would be ready by the end of 2020.

Whether the federal government will seek uniformity between states is unknown. Vaccine hesitancy could also stoke fears or delay widespread distribution. And vaccines may not be a cure-all, in which case mask-wearing would supplement moderately effective vaccines. As the director of the Vaccine Research Group at the Mayo Clinic, Dr. Gregory Poland, told the NY Times, “chaos and confusion” can be expected. Vaccine storage requirements—some of which may call for ultra-cold storage at 80 degrees below zero Celsius—are another challenge, CBS News reported.

“Some of this is not about epidemiology,” said Dr. Jessica Justman, associate professor of medicine in epidemiology at Columbia Mailman School of Public Health. “Some of this is about what do people want.”

The Pew Research Center found the percentage of U.S. adults who would get a vaccine if it were available today dropped from 72% in May to 51% in September.

Justman is optimistic that those prioritized under NY’s early broad strokes plan will be early-adopters, and even if just half the state wants the vaccine, vaccinating 10 million people would be “daunting.”

Piltch-Loeb, who's researching vaccine hesitancy at Harvard, added: “Never before have we had such varied reasons why people are hesitant to take a vaccine.” Previously, NYC faced a measles outbreak largely concentrated in the Orthodox Jewish community, where parents were skeptical of vaccinating their children on religious grounds.

“What's fascinating this time around is that we're not necessarily talking about parents making a decision about vaccinating their child, we're talking about adults making a decision around taking a vaccine for themselves,” Piltch-Loeb said. Cuomo has created a task force that will explicitly determine safety and efficacy of a virus, but people who are fearful of vaccines may not be persuaded by scientific assurances.

Donna Hallas, the director of the Pediatrics Nurse Practitioner Program at NYU Rory Meyers College of Nursing, added vaccine hesitancy differs from vaccine refusal, which she says the governor’s plan doesn’t fully address.

“I think what's missing is they do talk about vaccine hesitancy, but they don't talk about vaccine refusers,” Hallas said. “Someone who's a refuser, no matter what, they're going to just refuse.” Messaging between informing people about how a vaccine works versus for groups that outright refuse vaccines has to be clear, she added.

Cuomo has compared the vaccine rollout to COVID-19 testing, which he described as an operational “nightmare” at a recent press conference.

New York has so far conducted about 13 million tests for COVID-19. That’s a far cry from vaccinating the entire state population of 20 million. A vaccine requiring two doses would mean 40 million doses have to be administered—ensuring each person vaccinated gets the proper vaccine as various companies race to test different vaccines each with different protocols.

"I really worry about complexity of second doses, and especially if we have more than one vaccine product out there, I just think it will be really hard to keep that straight," Justman said.

How the federal government will or will not create consistency between states remains an unanswered question.

“The states are operating a little bit in the dark,” said Piltch-Loeb.

Cuomo, on behalf of all governors, sent a list of 36 questions to the Trump administration on funding, vaccine allocation, and ultra-cold storage concerns. In an op-ed in the New York Daily News this week, Cuomo said the administration hadn’t yet answered those questions. Whether President Donald Trump or former Vice President Joe Biden wins the election could also change any future COVID response.

“Ideally, the role of the federal government would be to guide this kind of harmonization,” Justman said. “Certainly, that's the kind of thing that you'd hope for.”