It’s been three years since the novel coronavirus first emerged, and while a sense of normalcy may have returned for many people, experts say the pandemic isn’t over yet.

COVID-19 cases and hospitalizations remain ever present in the U.S., and experts warn of more powerful variants emerging as the virus continues to spread and mutate globally. At the same time, researchers are working on what they hope will be more effective vaccine methods and treatments for both the acute disease and the lingering, long-term effects of long COVID.

Here is some of what we can expect to see this year.

The number of COVID-19 cases reported in the U.S. has so far stayed relatively flat this winter compared to prior years, but cases are expected to rise due to recent indoor holiday gatherings. Case counts are also likely being underreported because more people are doing rapid testing at home, said Dr. Susan Hassig, an epidemiology professor at Tulane University whose research areas include infectious disease outbreaks.

“It’s probably 10 times or 15 times higher at the minimum than what we’re measuring right now,” she said of current national counts, which are tallied from tests performed by hospitals and other health care providers. “Rapid tests don’t get reported, so we don’t have a good view into the actual level of infection that exists in the United States.”

There are also concerns that COVID-19 hospitalizations could dramatically rise because fewer people have received the updated bivalent vaccine booster, which is specifically designed to protect against COVID-19 caused by the omicron variant and the original virus strain.

As of early January, omicron descendants made up the majority of cases in the U.S., according to the Centers for Disease Control and Prevention, though only 15% of the U.S. population has received an updated booster shot.

One of the most dominant new descendants, XBB.1.5, was last week called “the most transmissible variant” yet by the World Health Organization. Data on its severity was not immediately available, though there was no early indication that severity had changed judging by lab studies and current hospitalization rates, said the WHO’s senior epidemiologist Maria Van Kerkhove at a press conference.

“Omicron is highly transmissible and fewer people are protected against that right now. So that doesn’t bode well,” Dr. Thomas A. LaVeist, dean of the Tulane University School of Public Health and Tropical Medicine, said of current vaccination rates for bivalent COVID-19 boosters. “I think we’re likely headed for headwinds because we’ve let our guard down.”

“We in America need to remember that COVID isn’t over,” said Hassig. “We are still losing the equivalent of an airplane of people falling out of the sky every day from COVID.”

An average of 385 people died each day from the virus last month, according to CDC data.

White House officials last fall suggested that COVID-19 vaccinations may become annual for most people, similar to flu shots.

This would depend on a “dramatically different variant” not emerging and upending the current vaccines’ effectiveness, said Dr. Anthony Fauci, the White House’s then-chief medical adviser. Individuals with underlying health conditions may still need to get vaccinated more than once a year, he added.

A single combined COVID-19 and influenza vaccine is also in the works, with Moderna, Pfizer-BioNTech and Novavax all launching trials last year. Moderna has said it hopes to market its single shot, which would also include a vaccine for respiratory syncytial virus, or RSV, by the fall of 2023.

Hassig said she personally hopes “booster” shots are replaced with one annual shot, simply because it could be an easier ask for the public.

“I would rather just increase the likelihood that they would get it on an annual basis,” she said. “It just will become something that we have to factor into our kind of preventive medicine approach to keeping ourselves healthy and taking care of ourselves and our families on an annual basis.”

As for whether annual vaccines could one day no longer be needed for COVID-19, that’s looking unlikely, at least for the foreseeable future. That’s in part because of how quickly RNA viruses like SARS-CoV-2 ― the virus that causes COVID-19 ― and influenza mutate, which can lead to vaccine resistance, said Hassig.

“This virus mutates as it moves from person to person to person,” she said. “That’s the challenge with these organisms, that they’ve got a mechanistic way of reproducing and if we don’t behave in a way to make that less successful, they’re just going to keep doing what they do. Disruption of transmission is a really valuable thing.”

Though annual vaccines may not soon disappear, many researchers hope the needles will.

Nasal COVID-19 vaccine sprays remain in development, with researchers touting them as being potentially better at preventing coronavirus infection than intramuscular shots, since the virus spreads through respiratory droplets that enter the respiratory tract where the spray is administered.

“Delivering vaccines to the nose and airways is one of the most promising ways to achieve immunity within the airways, which could stop mild COVID infections and transmission of the virus more effectively than injected vaccines,” Dr. Adam Ritchie, Oxford University’s senior vaccine program manager, said in a recent press release on his university’s collaboration with pharmaceutical company AstraZeneca on a nasal spray. “It also has the advantage of avoiding use of a needle. Many parents will know that nasal sprays are already used for the flu vaccine offered to schoolchildren in some countries, including the U.K.”

Recent studies have shown that much work remains to determine their success. Though similar nasal COVID-19 vaccines have been developed and approved for use internationally in places like China, India and Russia, there has been little information available on their efficacy, according to the weekly science journal Nature.

A recent COVID-19 outbreak in China has overwhelmed hospitals and prompted international travel restrictions amid concerns that the government is underreporting cases and deaths from the virus.

A high rate of transmission creates new risks not just for people in China, but also for the global population due to the likelihood of a more powerful COVID-19 variant emerging “that will ultimately circle the globe, as these viruses will, and come for us too,” said Hassig.

“China is really scary, frankly, not just for the impact on them alone, but the likelihood that there are lots and lots and lots of infections happening, and this virus mutates as it moves from person to person to person,” she said. “There’s no way to predict what the variant is going to be like.”

LaVeist expressed similar concerns.

“My biggest concern always is that we’ll get another variant that would have the transmissibility of omicron combined with the lethality of delta,” LaVeist said, referring to the current and past dominant variants. “Put that together, that would be the Frankenstein version of the virus, and that variant would be very problematic, especially if the new multivariant booster wasn’t effective against it. There’d be some period of time where we’d have to catch up.”

China reopened its borders for international travel on Sunday, allowing its citizens to travel abroad for the first time since the pandemic began without wide restrictions under its strict “zero COVID” policy. Numerous countries, including the U.S., responded by mandating negative COVID-19 tests from travelers arriving from China, prompting backlash from Chinese officials who called the requirement excessive and unacceptable.

LaVeist believes public focus may eventually need to turn from preventing coronavirus infection and instead to COVID-19 treatment options if vaccine rates don’t go up and public education doesn’t improve. This “curative care model,” as he puts it, would focus on treatments like prescription or over-the-counter medications.

“That’s the way we manage influenza. People get the flu and then they go to the supermarket or the drugstore, they buy over-the-counter medications to try to manage the symptoms,” he said. “Well, with COVID, we will have therapeutics that should be more effective than just over-the-counter remedies that deal with symptoms.”

It’s more expensive to treat or recover from an illness than to avoid infection, of course, and people will still die like they do from the flu, he said.

“It’s not ideal,” LaVeist said. “I don’t think many health professionals would think that this would be the best way to do this. But I think that’s kind of where we’re going.”

The Food and Drug Administration has so far authorized two antivirals, Pfizer’s Paxlovid and Merck’s molnupiravir, to treat mild to moderate COVID-19 at home. There are also emergency-use treatments for hospitalized patients.

“If we can get them to the point where they’re easily accessible, I think that may be the way that we’ll have to manage COVID going forward,” he said.

Federal health officials continue to recommend wearing masks when indoors and in populated areas, especially if you’re unvaccinated or at high risk of getting sick, or if you’re in a community reporting high levels of viral transmission. A list of those locations can be found on the CDC’s website.

Those who suspect they have COVID-19 or have a confirmed case are still being advised to stay home, wear a mask around others, and isolate for at least five days.

“Wherever there are crowds, and by that I mean a dense urban population or a crowded social environment, there’s the possibility of transmission of a respiratory virus,” said Hassig. “I still don’t go anywhere in a public setting without a mask on and I would encourage people to do the same.”

LaVeist similarly advised people not to let their guard down, even if others around them have.

“I think that even people who are well informed, who have a very sophisticated understanding of this, can become complacent. I’m one where it happened with me,” he said of his own COVID-19 diagnosis last year after going maskless on a plane.

Mask use isn’t only helpful for preventing coronavirus transmission, but also for protecting against other respiratory viruses like flu and RSV.

An estimated 13,000 people have died from the flu so far this season, a significant drop from prior years that saw death tolls as high as 52,000 just five years ago. RSV each year kills 6,000-10,000 adults ages 65 and older, and 100-300 children younger than 5, according to CDC estimates.

The CDC has warned that flu vaccine coverage has been lower among some age groups than in past seasons and there have been more hospitalizations due to the virus than in the past decade. Most of these hospitalizations have involved those ages 65 and older and children under 5.

“Flu is very well transmitted by children, and they suffer some pretty severe consequences from flu as well. COVID is not as impactful on children but still has some very serious consequences for some of them,” said Hassig, who credited mask use and remote learning for the significant drop in flu cases in the midst of the pandemic.

Plenty of unknowns remain about the coronavirus’s lingering effects, which for some people can last months or even years. But there are encouraging developments toward longer-term treatment.

“We have a lot more tools now than we had three years ago,” said Dr. Andrew Schamess, an internal medicine physician who has been treating long-COVID patients at the Post COVID Recovery Program at Ohio State University’s Wexner Medical Center in Columbus. “I wouldn’t be surprised if in the next two to three years we really start to understand this at the level that we understand other immunologic conditions and we may be able to treat it with really disease-specific drugs.”

Despite not fully understanding the cause of long-COVID, doctors say they have found some successes in treating it, including with certain rehabilitations and the repurposing of other medicines to treat long-COVID symptoms, such as administering medications used for brain injury to treat brain fog.

“We know that there is kind of a dormancy of some areas of the brain, which causes brain fog and confusion and word-finding difficulty and fatigue,” said Schamess. “We have both rehabilitation techniques and medicines to treat that.”

There are also more case studies and clinical trials taking place than ever before, further fueling optimism.

“We are getting a better sense on the basic-science level about some of the physiologic abnormalities in long-COVID, but there is more work still to do in this area to truly have a unified understanding of the causes of symptoms, although it probably won’t be the same for everyone with long-COVID,” said Dr. Benjamin Abramoff, director of the Post COVID Assessment and Recovery Clinic at the University of Pennsylvania in Philadelphia. He added that a cure is likely nowhere near on the horizon.

Like Schamess, Abramoff said his clinic has seen a steady flow of long-COVID patients, with spikes that generally follow spikes in acute COVID-19 cases by a few months. At the Wexner Medical Center, Schamess said there’s a waiting list of 60 to 70 people seeking treatment.

“There’s just more demand than we can meet,” he said, expressing frustration that there aren’t more physicians who are knowledgeable about the condition or who are taking it seriously. “A lot of the patients I see have already been to many physicians who’ve told them ‘It’s all in your head’ or ‘It’s not for real,’ ‘Maybe it is for real, but we don’t know what to do about it,’ or giving them kind of off-the-cuff advice, which doesn’t really help them.”

Delaying care prolongs recovery, he said, raising some concerns about long-term impacts on the workforce, which Hassig likened to “a ticking time bomb of disability.”

“I think people should be paying a lot more attention to that as a possible outcome if they become infected. It’s not necessarily all about the acute disease experience with this virus,” she said. “People can get long-COVID from a relatively mild COVID infection.”

This is enough reason to avoid catching the virus whether you have a strong immune system or not, she said.

Abramoff said one of the most common things he sees among his most severely affected patients is difficulty returning to work for days or more, though he said he’s seen success with structured and incremental plans that use accommodations like working from home.

Schamess also said that most patients just need rest.

“It may be Victorian medicine, but sometimes that’s what people need to hear, and other times it’s medications and other times it’s more sophisticated things,” he said, while imploring employers to be more accommodating to their employees.

“Apart from what doctors and scientists can do, it’s important for employers to understand how disabling this condition is,” he said. “If you’re an employer, if you simply allow your [employee] to get the rest they need and have some accommodations and go back to work slowly and pursue a course of therapy, you’re going to have that worker back.”

The alternative is the employee possibly losing their job, losing their health insurance when they need it most, and for the employer, “you’ve lost a potentially very good employee,” he said.