The coming flu season is on track to be much worse than the last cycle, according to health experts, who fear an influx of cases could further strain hospitals already overwhelmed by the Delta surge.

The season could also strike earlier and more severely than usual, doctors and researchers said, because many people haven’t been able to build up their natural immune defenses while working from home and avoiding strangers.

“The worst case scenario is a real twindemic” of Covid-19 and flu cases, said William Schaffner, professor of preventive medicine at Vanderbilt University School of Medicine.

Several factors are behind the expectations for a potentially difficult flu season, Dr. Schaffner and other health experts said, though it is notoriously hard to predict how badly the virus will hit.

Many children will be back in school where they can pick up and spread infections, the health experts said. Many adults aren’t working in their offices where they typically get flu shots, or they don’t want another vaccination after getting their Covid-19 doses. And many people will no longer be protected by masking and other Covid-19 restrictions that have been eased.

With students attending in-person classes at schools such as this one in Novi, Mich., health experts expect an increase in flu cases.

Photo: Emily Elconin/Bloomberg News

Complicating matters, researchers and industry officials said, the flu shot may be less accurate than usual because so little virus was circulating last year, giving researchers less information to pick the correct strains for the season’s shot to target. After the World Health Organization picks the annual flu strains, a Food and Drug Administration advisory panel meets to select the ones used in the U.S. shot.

“The educated predictions had a lot less data to be based on in the strain selection committee,” said Richard Zimmerman, professor at the University of Pittsburgh and a former chair of a U.S. government flu advisory panel.

Dr. Zimmerman said his model for the coming flu season predicts 102,000 more hospitalizations than last season if flu shots aren’t more effective and their use is the same as last season.

Influenza, or the flu, is a contagious respiratory illness that commonly strikes the U.S. beginning in October and lasting through May, with peaks December through February. From nine million to 45 million people in the U.S. get infected annually, leading to 140,000 to 810,000 hospitalizations and 12,000 to 61,000 deaths, most of them in adults 65 and older, according to the Centers for Disease Control and Prevention.

Adults who are 65 and older or have a chronic health condition such as asthma, heart disease and diabetes, pregnant women and members of racial and ethnic minority groups are at higher risk of developing serious flu complications, according to the CDC.

Vaccines are the best defense against the flu, according to health authorities. The CDC recommends that people six months and older should receive a flu shot, ideally before the end of October.

Despite fears of a bad flu season last year, cases fell to a record low, the CDC said, because the virus had few opportunities to spread, with schools and businesses closed and people wearing masks and distancing.

Flu cases were at an all-time low in the 2020-2021 flu season, with public health and clinical laboratories reporting only a few thousand flu cases compared with an estimated 38 million cases in the 2019-2020 season, according to the CDC.

The recent resurgence of the respiratory syncytial virus, or RSV, augurs a more intense flu season than last year in addition to the easing of precautionary measures and return of many students to classrooms.

An FDA advisory committee in March picked four flu strains to be targeted by this season’s shots. Health experts expressed confidence in the selections, but said it is too early to know since flu season isn’t under way yet.

At Ochsner Health, Louisiana’s largest hospital network, officials said they fear the flu season could further strain its ability to provide care for patients.

The hospital system is already delaying elective surgeries to contend with staffing shortages as coronavirus patients flood hospitals. If the system faces a surge in flu cases, it could be forced to cut back on clinic visits and preventive-care procedures such as mammograms.

With Covid-19 “continuing to surge, we are worried,” said Sandra Kemmerly, a medical director for the health system, who specializes in infectious diseases.

Recent studies have shown that the effectiveness of Covid-19 vaccines is decreasing, though experts say the shots still work well. WSJ explains what the numbers mean and why they don’t tell the full story. Photo illustration: Jacob Reynolds/WSJ The Wall Street Journal Interactive Edition

Health authorities expressed hope that a relatively high rate of flu vaccinations would keep case numbers manageable this season but worry people are so fatigued by Covid-19 vaccinations they will skip the flu shot. Data indicates people are behind on routine vaccinations. By February 2021, 55% of all adults received the flu vaccine, up from about 48% at the end of the previous season, according to the CDC.

Drugmakers including GlaxoSmithKline PLC, AstraZeneca PLC and Sanofi SA are supplying between 188 million and 200 million flu vaccines to the U.S. this year, according to the CDC. The supplies would be on par with last year’s shipment, which were a record high.

Several efforts are under way to encourage use of the shots.

The CDC said that flu shots and Covid-19 vaccines can be administered together, after counseling last year, during the early days of the vaccine rollout, that the doses should be taken separately.

The agency is planning a digital campaign to encourage flu vaccination, especially for people with underlying health conditions and people within racial and ethnic minority groups, and it will launch an ad campaign in mid-October, a spokeswoman said.

The CDC is also providing more than $150 million in funding to support national, state and local campaigns aimed at increasing confidence in Covid-19 and flu vaccines among adults in racial and ethnic-minority groups, the spokeswoman said.

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GlaxoSmithKline and Sanofi said they are working on flu-vaccination public-awareness campaigns to try to drive up inoculation rates. AstraZeneca said it launched its nasal spray flu vaccine in late August for people ages 2 to 49 years, a needle-free option that it said some patients prefer, and could expand access.

Sanofi developed an online tool for doctors and nurses to provide information to patients to bring them back into doctors offices after many people stayed home last year and deferred treatments and basic vaccinations, said Elaine O’Hara, head of Sanofi’s North America vaccine business.

“Influenza is a very tricky little devil, it’s very evasive,” Ms. O’Hara said. “The last thing we want is outbreaks with respect to Covid or influenza because you don’t want both of those happening at the same time.”

Len Friedland, vice president and director of scientific affairs and public health at GlaxoSmithKline, expressed hope the Covid-19 vaccination drive will persuade many people to appreciate the benefits of inoculations.

Write to Felicia Schwartz at felicia.schwartz@wsj.com