Every day or two a new case. No recent hospitalizations. What will the summer bring? Here is an article on the topic followed by news on ending vaccine coverage for the uninsured and possible combination vaccines.
A new Covid variant has taken over, and experts predict a small summer wave
Coney Island’s boardwalk in Brooklyn in 2021.Nina Westervelt / Bloomberg via Getty Images
Disease experts anticipate a small uptick in Covid cases this summer, as a new variant spreads.
The KP.2 variant represents 28% of Covid infections in the U.S., up from just 6% in mid-April, according to data released Friday by the Centers for Disease Control and Prevention.
KP.2 became dominant at the end of April — meaning it accounts for the largest share of new cases — outpacing the JN.1 variant, which took over in the winter.
Some scientists collectively refer to KP.2 and another variant called KP.1.1, which shares the same key mutations, as “FLiRT” — a reference to their amino acid changes.
Both are descendants of JN.1, which is part of the omicron lineage, like all versions of the coronavirus that have gained dominance in the last couple of years.
But KP.2 has three additional mutations in its spike protein compared with JN.1, which disease experts said could make it easier for the virus to bypass protection from vaccines or prior infections.
“It looks like those additional mutations make it more immune evasive, so it’s not a surprise that it would then dominate,” said Dr. Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center in Boston.
Laboratory research from Japan, which was published as a preprint and has not been peer-reviewed, suggests that the Covid vaccines currently recommended in the U.S. may be less effective against KP.2 than against JN.1.
However, KP.2 might be less efficient at infecting cells, the research suggests, which could mean that a higher dose of the virus would be needed to infect someone.
People who were infected with JN.1 should still have some protection against KP.2, experts said.
The CDC does not collect regular data on how Covid symptoms are evolving over time, so it’s hard to assess whether illnesses caused by KP.2 look any different. Covid symptoms have generally been consistent over the last two-plus years.
Experts predict a small rise in cases this summer
Covid cases have spiked every summer in the U.S. since 2020. If KP.2 continues to gain prevalence, that pattern may repeat — but not as dramatically, experts predict.
The U.S. is in a good place with Covid heading into the summer, according to Andrew Pekosz, a virologist at Johns Hopkins University. Hospitalizations reached record lows at the end of April, the last data available before the CDC stopped requiring hospitals to report Covid admissions numbers.
“We see a late summer, early fall surge of cases, and then we see a second surge of cases right around the Christmas holidays, the New Year,” Pekosz said. “That pattern has been sort of reproducing itself for a couple of years now. The important thing, though, is the magnitude of the cases has been consistently dropping.”
Several factors could help the KP.2 variant spread this summer. When the weather gets very warm, people tend to congregate indoors to escape the heat, creating new opportunities for transmission. Many people also haven’t been vaccinated recently; less than a quarter of U.S. adults have received the updated Covid shot.
“I think that there’s going to be a significantly large susceptible population out there, from that combination of waning immunity and viral evolution, that we’re going to see a number of cases this summer,” said Dr. Thomas Russo, chief of infectious diseases at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences.
But he added that since most people have some immunity to Covid, it’s possible that “the wave won’t be as great” as in previous years.
Barouch said past summer waves have coincided with the arrival of new variants, so this year could be similar.
“The increases in the summertime have often been in the context of new variants, such as the original Delta wave, for example, or the BA.5 wave,” he said. “So I wouldn’t be surprised if there is another summertime surge.”
Will KP.2 affect vaccine recommendations?
KP.2’s rise creates questions for the public health experts who decide which variants to target with new Covid vaccines.
The Food and Drug Administration on Tuesday postponed an advisory committee meeting that was meant to decide which strains to include in the updated vaccine formula for the fall.
“We have recently observed shifts in the dominant circulating strains of SARS-CoV-2,” an FDA spokesperson said. “The additional time will allow the agency to obtain more up-to-date surveillance data and other information on the circulating strains of SARS-CoV-2 to better inform the committee’s discussions and recommendations.”
The most recent vaccine-related recommendations from the CDC came in February, when it suggested that people ages 65 and up should get an additional dose and younger people could consider one.
People who haven’t received the updated shot and feel like they need it “should get the vaccine that’s currently available,” Barouch said.
But Pekosz said people who are not immunocompromised could probably hold off until the fall.
“With case numbers being relatively low right now, I think the prudent thing is to try to wait till September and get the new formulation,” he said.
Pediatric combination vaccines, which have been available for more than 70 years, have clearly been a success. Dating back to 1948 when diphtheria, tetanus, and pertussis vaccines were first combined, combination vaccines have minimized tears and improved immunization coverage among infants and young children. One vaccine alone, for children aged 6 weeks through 4 years, protects against 6 different infectious diseases.
“I think that combination vaccines have been game changers in terms of administering vaccine and getting coverage,” said Kathleen Neuzil, MD, MPH, who has served as a vaccine policy advisor to the US Centers for Disease Control and Prevention (CDC) and the World Health Organization. “In general, they’re good. But you do have to have the right combination.”
Technically, there already are combination, or multivalent, adult vaccines, but they provide single formulation coverage against multiple strains of the same pathogen, such as seasonal influenza, not multiple unrelated infectious agents.
Scientists hope that combining adult vaccines will lead to benefits similar to those seen with childhood vaccines. For one, a fear of needles is “probably a bigger issue in adults than we recognize,” said Robert Hopkins Jr, MD, an internist at the University of Arkansas for Medical Sciences.
The first step is combining 2 adult vaccines into 1. “We’re doing something that really hasn’t been done before,” Kayvon Modjarrad, MD, executive director for vaccine research and development at Pfizer, said on a panel in early April at the World Vaccine Congress in Washington, DC. “That’s why we do it in a phased approach.”
Researchers can’t simply mix any 2 vaccines. Pairing vaccines requires that the diseases they target affect the same population and that the timing and frequency of their administration match.
For example, it wouldn’t make sense to combine vaccines against human papillomavirus and shingles because the former is indicated only for people up to 45 years of age, while the latter is routinely recommended only for those 50 years or older. Neither would it be wise to combine vaccines against tetanus with those against influenza because boosters of the former are administered every 10 years, while the latter is given annually.
Combining pediatric vaccines was simpler, Neuzil said. “They’re given to the same age group on the same schedule, so they work well.”
In the Beginning
The first new combination vaccine likely will be against COVID-19 and influenza, both now recommended every year for adults and children beginning at 6 months of age.
Pfizer and BioNTech, Moderna, and Novavax, the companies that sell COVID-19 vaccines in the US, are all testing this combination. Pfizer and BioNTech and Moderna have completed enrollment in phase 3 trials of their messenger RNA (mRNA) vaccines that target both COVID-19 and influenza but have not yet reported results. If the findings are encouraging, the 2 companies say, they expect to have their combination vaccines available for use in the fall of 2025.
Novavax plans to launch a phase 3 trial of its combination vaccine—which uses viral protein fragments to stimulate the immune system—later this year and expects that it could be available in the fall of 2026, Robert Walker, MD, the company’s chief medical officer, told JAMA Medical News in an interview. On May 10, Novavax and Sanofi announced an agreement under which they would develop novel combination vaccines using Novavax’s COVID-19 vaccine and Sanofi’s flu vaccines. Under the agreement, Novavax retains the right to continue to develop its own COVID-19-plus-influenza vaccine.
But while COVID-19 and flu seem like an obvious pairing, Neuzil said, “I can think of a few issues with it.”
For example, she pointed out, “[w]e have so many different flu vaccines now. Which flu vaccine would you combine with this?” People aged 65 years or older may still need to get their high-dose flu vaccine and their COVID-19 vaccine in 2 separate shots, she noted.
And there are other practical considerations, says Neuzil, who recently left her position as director of the Center for Vaccine Development and Global Health at the University of Maryland School of Medicine to lead the National Institutes of Health’s Fogarty International Center. “If you talk to a doctor’s office or hospital, they can’t stock 6 different flu vaccines,” she said. It’s already a challenge for them to predict out how much of each available flu vaccine to purchase each year, she added.
During the vaccine congress panel, Walker acknowledged that combination adult vaccines will require physicians’ offices, hospitals, and pharmacies to expand their inventory. “Monovalents are still going to have a place,” he explained.
Timing Matters
This past fall represented the second in a row in which new COVID-19 vaccines, based on variants circulating several months earlier, became available in the US. However, whether COVID-19 follows the same seasonal schedule as influenza still isn’t clear.
“We’re changing the paradigm, and we’re changing it based on the patterns of [COVID-19] seen over the last 3 or 4 years,” said Hopkins, medical director of the National Foundation for Infectious Diseases (NFID) and the NFID liaison to the CDC’s Advisory Committee on Immunization Practices. “It’s the best we have. We’re still looking at relatively short-term information compared with our history with the flu.”
COVID-19 and flu both peak in the winter, but so far, the former hasn’t disappeared in the spring and summer the way the latter does. People can and do catch COVID-19 year-round.
“I’m not convinced it settled into the exact same schedule as flu yet,” Neuzil said of COVID-19.
Plus, she noted, although the circulating strains of influenza predictably change each year, necessitating annual vaccine updates, only time will tell if that’s the case with SARS-CoV-2. It’s possible that the virus’ evolution could eventually slow, eliminating the need for annually updated COVID-19 vaccines, Neuzil explained.
More Takers?
A 2022 systematic review and meta-analysis concluded that combining influenza and COVID-19 vaccines could potentially increase uptake of the latter “mainly because many populations have already been accustomed to taking influenza vaccines on an annual basis,” the authors wrote.
Indeed, one hoped-for benefit of administering annual fall COVID-19 vaccines along with influenza vaccines was that doing so would normalize immunization against SARS-CoV-2, increasing coverage. Plus, annual fall COVID-19 vaccines would make it convenient for people to get immunized against SARS-CoV-2 and influenza at the same office or pharmacy visit.
However, although concurrent influenza and COVID-19 vaccination has been possible for the past 2 flu seasons, immunization rates against the former have continued to far surpass those against the latter.
As of April 27, only 22.5% of US adults aged 18 years or older reported having received the 2023-2024 COVID-19 vaccine, which became available in mid-September; only 14.1% of US children aged 6 months through 17 years were reported to have received the vaccine.
For both age groups, influenza vaccine coverage was more than double that of COVID-19 vaccine coverage. As of May 3, 48.4% of adults and 52.9% of people younger than 18 years had received the 2023-2024 seasonal influenza vaccine.
“We still have to more broadly make the case about the value of immunization for all who are eligible,” said Hopkins, adding that many of his patients want either flu vaccine or COVID-19 vaccine—or neither.
Moderna is assessing how many people have received concurrent COVID-19 and influenza vaccines because they’d likely be the first in line for a shot that combines the 2, according to Francesca Ceddia, MD, chief medical officer at Moderna.
Then there are the people on the fence. “Maybe once they are well-informed on the risks associated with COVID-19 they will jump” on a vaccine for influenza plus COVID-19, Ceddia told JAMA Medical News in an interview.
The Sum of Their Parts
Although administering influenza and COVID-19 vaccines concurrently does not appear to reduce their efficacy—and might even enhance the immune response—that might not be the case when they’re combined into a single vaccine.
“I would personally be cautious about making combination vaccines,” Joshua Nealon, PhD, medical head of new influenza and COVID-19 vaccines at Sanofi, said on the vaccine congress panel. “We don’t want to have vaccines where the combination is less protective.”
Combining vaccines may cause immune interference, reducing the immunogenicity of at least 1 of them, Ceddia noted. “You don’t expect interference when you administer them separately.”
When Merck added varicella (V) to its measles, mumps, and rubella (MMR) vaccine, the company needed to use more varicella vaccine than in the monovalent version to elicit the same immune response, Walker pointed out. “There was clearly something going on in the vial or the syringe.”
In some children, there’s a tradeoff for opting for the MMRV vaccine instead of the MMR vaccine. Although the MMRV vaccine reduces the number of shots needed, it’s associated with a higher rate of fevers or febrile seizures than MMR vaccines in children 12 months to 47 months old, according to the CDC, which recommends that the first doses of MMR and varicella vaccine in that age group be administered separately.
In Novavax’s combination influenza and COVID-19 vaccine that will be tested in a phase 3 trial, the amount of SARS-CoV-2 antigen will be 35 μg, 7 times the amount used in its stand-alone vaccine, Walker said. In addition, Novavax tested 30, 45, and 60 μg of antigens per influenza strain in combination with its COVID-19 vaccine before settling on the largest amount for the best immunogenicity, Walker said. (Novavax doesn’t yet have a flu vaccine on the market but plans to add a standalone influenza vaccine arm to the phase 3 trial of the combination vaccine it developed.)
Generally, though, vaccine interference shouldn’t be a problem with the combination vaccines for flu and COVID-19 because they don’t use live viruses, Neuzil noted. “It’s unlikely that effectiveness or immunogenicity would be compromised,” she said. “Where we usually see interference is live vaccines with other live vaccines,” as is the case with the MMRV vaccine.
RSV Plus HMPV
Another adult combination vaccine expected to enter phase 3 trials this year targets 2 other respiratory viral infections—one against respiratory syncytial virus (RSV), which, Hopkins says, some physicians still mistakenly think affects only infants, and the other against the lesser-known human metapneumovirus (HMPV).
First reported in 2001, HMPV has been circulating undetected since around 1950, serological studies found. In temperate climates, HMPV, which can cause upper and lower respiratory disease in all ages, is most active during late winter and spring. There is no vaccine against HMPV alone, but a company called Icosavax, acquired by AstraZeneca in February of this year, developed a combination RSV and HMPV vaccine, dubbed IVX-A12, using the virus-like particle (VLP) platform.
VLPs are like sheep in wolf’s clothing. The synthetic particles mimic viruses in appearance, eliciting an immune response, but they’re not infectious themselves because they contain no viral genetic material, only a protein core. Licensed VLP vaccines target such diseases as human papillomavirus infection, hepatitis B, and malaria.
“IVX-A12 is potentially the first vaccine for HMPV, the first RSV combination vaccine, and the first VLP vaccine for respiratory pathogens,” an AstraZeneca spokesperson told JAMA Medical News in an email. “We are planning to commence phase 3 trials as quickly as possible.”
Determining whether someone with respiratory symptoms has HMPV is “an ongoing challenge,” Hopkins noted. He explained that there is no rapid antigen home test for HMPV in the US, and polymerase chain reaction testing for the disease is used mainly among hospitalized patients with respiratory illnesses.
“While the burden of RSV in older adults…is now better understood, there is limited awareness of the impact of HMPV, especially in older adults, with the burden of disease likely underappreciated in the absence of systemic testing,” the AstraZeneca spokesperson wrote. The lack of systemic testing as well as published literature about the burden of HMPV may help explain why it isn’t as well-known as influenza, RSV, and SARS-CoV-2, she explained.
“As we develop the vaccine, we will put in place a comprehensive education program, working closely with health authorities, medical practitioners, and patient groups to increase awareness about the impact of HMPV on older adults and those with chronic conditions,” the AstraZeneca spokesperson wrote about IVX-A12.
In a presentation last November, Moderna said it was enrolling people in a phase 1 trial of its own RSV-plus-HMPV vaccine and had completed enrollment for phase 1 trials of flu-plus-RSV and flu-plus-RSV-plus–COVID-19 vaccines, all of which use the mRNA platform.
“I think they see it as a competitive advantage,” Neuzil said, referring to vaccine manufacturers’ interest in combination products. “We need to see the data.”
Published Online: May 17, 2024. doi:10.1001/jama.2024.7370
Conflict of Interest Disclosures: Dr Hopkins reported that besides being employed by the University of Arkansas for Medical Sciences and the National Foundation for Infectious Diseases, he is a special employee of the US Department of Health and Human Services in his role as chair of the National Vaccine Advisory Committee. No other disclosures were reported.
