Dr Anthony Fauci, the top US infectious-disease doctor, said he was “strongly in favour” of speeding booster shots to people with weakened immune systems.
His comments were a further sign of how the Delta variant continues to shift the strategies for curbing the pandemic.
“We need to look at them in a different light,” Dr Fauci told CNN on Sunday.
“We will almost certainly be boosting those people before we boost the general population that’s been vaccinated, and we should be doing that reasonably soon.”
Debate has grown over “breakthrough” infections among fully vaccinated people and whether official approval should be given for booster shots.
Dr Fauci said most people with compromised immune systems, including those with organ transplants or who are on chemotherapy, “never did get an adequate response” from their Covid-19 vaccination.
Across the US, the Delta variant has fuelled a rebound to more than 100,000 new infections a day, in levels last seen six months ago.
While the daily average number of deaths remains far below the levels of last winter, the pressure on hospitals is mounting.
The seven-day moving average for new admissions has consistently increased since June 25, according to official data.
In New York and New Jersey, urgent care chain CityMD is resuming its online line system and adjusting operating hours to accommodate for the “recent surge in Covid-19 testing".
In San Francisco, anyone who received the Johnson & Johnson vaccine can receive a supplemental dose of the vaccines from Pfizer-BioNTech or Moderna at city-run sites after consulting their doctor, the city’s Department of Public Health said.
Health officials do not take breakthrough infections lightly and more testing is needed to understand the exact scope of such cases, Dr Fauci told CBS.
When asked if other groups should get booster shots, he said the US Centres for Disease Control and Prevention was ready to give a recommendation as soon as it saw clear evidence.
The CDC has been tracking various groups including the elderly, those in nursing homes, and young people month by month, Dr Fauci said.
“As soon as they see that level of durability of protection goes down, then you will see the recommendation to vaccinate those individuals,” he said.
But Dr Fauci stressed: “The vaccines are still doing what you originally want them to do, to keep you out of the hospital, to prevent you from getting seriously ill.”
He said he supported mandatory vaccines at local levels, such as schools and universities, after full approval by the Food and Drug Administration.
“You’re going to see the empowerment of local enterprises giving mandates,” Dr Fauci said.
“That could be colleges, universities, places of business, a whole variety, and I strongly support that.”
A full approval could arrive “within the next few weeks", he said. “I hope it’s within the month of August.”
Vaccines in the US have so far been given under approval for emergency use, which some people have used as a reason for refusing to be vaccinated.
Dr Fauci said that with the Delta variant, vaccinated people could still transmit the virus to someone else.
That has led to the CDC revising its mask guidelines recently.
