Can updated boosters prevent another Covid-19 surge? Why some experts are skeptical.

Most experts agree that updated bivalent Covid-19 boosters provide additional protection against serious illness and death among vulnerable populations—but evidence suggests that increased booster uptake may not prevent a “wave of Covid” infections this winter, Apoorva Mandavilli writes for the New York Times.

Can bivalent boosters prevent another surge of infections?

While the Biden administration’s plan to prevent another surge of Covid-19 infections relies on increasing Americans’ uptake of the updated booster doses of the PfizerBioNTech and Moderna vaccines, some experts doubt the strategy.

According to John Moore, a virologist at Weill Cornell Medicine, boosters provide additional protection to vulnerable populations—including older adults, immunocompromised individuals, and pregnant people—who should get boosted to prevent severe illness and death.

However, the benefit is not as clear for healthy, younger Americans who “are rarely at risk of severe illness or death from Covid, and at this point most have built immunity through multiple vaccine doses, infections or both,” Mandavilli writes.

“If you’re at medical risk, you should get boosted, or if you’re at psychological risk and worrying yourself to death, go and get boosted,” Moore said. “But don’t believe that will give you some kind of amazing protection against infection, and then go out and party like there’s no tomorrow.”

Separately, Peter Marks, FDA‘s top vaccine regulator, noted the limited data available data for the updated boosters.

“It’s true, we’re not sure how well these vaccines will do yet against preventing symptomatic disease,” he said, especially as the newer variants spread.

However, Marks added, “even modest improvements in vaccine response to the bivalent boosters could have important positive consequences on public health. Given the downside is pretty low here, I think the answer is we really advocate people going out and consider getting that booster.”

How much additional protection do updated shots provide?

While Pfizer-BioNTech and Moderna recently reported that their bivalent boosters produced antibody levels that were four to six times higher than the original vaccine, their results were based on BA.4 and BA.5 antibodies, instead of the more prevalent BQ.1 and BQ.1.1 variants.

According to Mandavilli, “[a] spate of preliminary research suggests that the updated boosters, introduced in September, are only marginally better than the original vaccines at protecting against the newer variants — if at all.”

These small studies have not been reviewed for publication in a journal—but they all came to similar conclusions.

“It’s not likely that any of the vaccines or boosters, no matter how many you get, will provide substantial and sustained protection against acquisition of infection,” said Dan Barouch, head of Beth Israel Deaconess Center for Virology and Vaccine Research, who helped develop Johnson & Johnson‘s vaccine.

Notably, Barouch’s team recently discovered that BQ.1.1 is around seven times more resistant to the body’s immune defenses than BA.5, and 175 times more resistant than the original strain of the coronavirus. “It has the most striking immune escape, and it’s also growing the most rapidly,” he said. BQ.1 will likely follow a similar pattern.

“By now, most Americans have some degree of immunity to the coronavirus, and it does not surprise scientists that the variant that best evades the body’s immune response is likely to outrun its rivals,” Mandavilli writes.

The new vaccine increases antibodies, but the fact it is bivalent may not be significant. In August, a study by Australian immunologists suggested that any kind of booster would offer extra protection. In addition, the study noted that a variant-specific booster would likely not be more effective than the original vaccine.

“The bulk of the benefit is from the provision of a booster dose, irrespective of whether it is a monovalent or bivalent vaccine,” according to the World Health Organization.

Florian Krammer, an immunologist at the Icahn School of Medicine at Mount Sinai, noted that despite recent research, which evaluated immune response soon after vaccination, immune response may improve over time.

“We will see with larger studies and studies at a later time point if there is a good or a significant benefit, but I think it’s certainly not worse,” he added. “I don’t see much risk when you get the vaccine, so you might as well get the benefit.”

“What we need to do right now to get us through the next few months when I think we are in yet another wave of incipient wave of Covid,” Marks added. “And then we need to look forward, and lean into how we’re going to do things differently moving forward.”

Will we see an increase in vaccine uptake?

Currently, FDA allows the booster dose at least two months after a Covid-19 infection or previous does. However, some studies suggest boosting too early could have negative consequences. “Lengthening the interval between boosts to five or six months may be more effective, giving the immune system more time to refine its response,” Mandavilli writes.

Still, “adding yet another shot to the regimen seems unlikely to motivate Americans to opt for the immunization,” no matter the schedule, she adds.

“Each new booster we roll out is going to have a lower and lower uptake, and we’re already pretty close to the floor,” said Gretchen Chapman, an expert in health behavior at Carnegie Mellon University.

Ultimately, “[w]e should not spend a lot of political capital trying to get people to get this bivalent booster, because the benefits are limited,” Chapman added. “It’s more important to get folks who never got the initial vaccine series vaccinated than to get people like me to get their fifth shot.” 

Covid-19 is surging in Europe. Is America next?

https://www.advisory.com/daily-briefing/2022/10/10/covid-resurgence

While infections, hospitalizations, and deaths from Covid-19 have been steadily declining in the United States in recent months, experts warn that rising cases in Europe may be “a harbinger for what’s about to happen in the United States,” Rob Stein writes for NPR’s “Shots.”

Will the US see a ‘winter resurgence’ of Covid-19?

Currently, several models project that U.S. Covid-19 infections will continue to decline at least until the end of 2022. However, researchers caution that there are multiple variables that could change current projections, including whether more infectious strains start circulating around the nation.

According to Stein, “[t]he first hint of what could be in store is what’s happening in Europe.” Recently, many European countries, including the U.K., France, and Italy, have seen an increase in Covid-19 infections.

“In the past, what’s happened in Europe often has been a harbinger for what’s about to happen in the United States,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. “So I think the bottom line message for us in this country is: We have to be prepared for what they are beginning to see in Europe.”

“We look around the world and see countries such as Germany and France are seeing increases as we speak,” said Lauren Ancel Meyers, director of the UT COVID-19 Modeling Consortium at the University of Texas at Austin. “That gives me pause. It adds uncertainty about what we can expect in the coming weeks and the coming months.”

However, Justin Lessler, an epidemiologist at the University of North Carolina who helps run the COVID-19 Scenario Modeling Hub, noted that the United States may not have the same experience as Europe, largely because it is unclear whether Europe’s increase is related to individuals’ vulnerability to new strains.

“If it is mostly just behavioral changes and climate, we might be able to avoid similar upticks if there is broad uptake of the bivalent vaccine,” Lessler added. “If it is immune escape across several variants with convergent evolution, the outlook for the U.S. may be more concerning.”

Some researchers believe the United States is already experiencing early signs of this. “For example, the levels of virus being detected in wastewater is up in some parts of the country, such in Pennsylvania, Connecticut, Vermont and other parts of Northeast,” Stein writes. “That could an early-warning sign of what’s coming, though overall the virus is declining nationally.”

It’s really too early to say something big is happening, but it’s something that we’re keeping an eye on,” said Amy Kirby, national wastewater surveillance program lead at CDC.

According to David Rubin, the director of the PolicyLab at Children’s Hospital of Philadelphia, which tracks the pandemic, Covid-19 infections and hospitalizations are already rising in some parts of New England, and other northern regions, including the Pacific Northwest.

“We’re seeing the northern rim of the country beginning to show some evidence of increasing transmission,” Rubin said. “The winter resurgence is beginning.”

How likely is a severe Covid-19 surge?

Unless a “dramatically different new variant emerges,” it is “highly unlikely this year’s surge would get as severe as the last two years in terms of severe disease and deaths,” Stein writes.

“We have a lot more immunity in the population than we did last winter,” said Jennifer Nuzzo, who leads the Pandemic Center at the Brown University School of Public Health.

“Not only have people gotten vaccinated, but a lot of people have now gotten this virus. In fact, some people have gotten it multiple times. And that does build up [immunity] in the population and reduce overall over risk of severe illness,” Nuzzo said.

Another factor that could affect the severity of the impact of rising infections is the number of people who receive updated Covid-19 vaccines, which help boost waning immunity from previous infections or shots.

However, the United States’ booster uptake has been slow. “Nearly 50% of people who are eligible for a booster have not gotten one,” said William Hanage, an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health. “It’s wild. It’s really crazy.”

Since updated boosters became available in September, less than 8 million of the over 200 million people who are eligible have received one.

According to Nuzzo, it is critical for people to stay up to date on their vaccines, especially with the high likelihood of another Covid-19 surge. “The most important thing that we could do is to take off the table that this virus can cause severe illness and death,” Nuzzo said.

“There are a lot of people who could really benefit from getting boosted but have not done so,” she added.

BA.5 spurs new calls to fund next-generation COVID-19 vaccines

The rise of the BA.5 variant is spurring new calls for funding for an Operation Warp Speed 2.0 to accelerate development of next-generation COVID-19 vaccines that can better target new variants. 

The BA.5 subvariant of omicron that now makes up the majority of U.S. COVID-19 cases is sparking concern because it has a greater ability to evade the protection of current vaccines than past strains of the virus did.

Pfizer and Moderna are working on updated vaccines that target BA.5 that could be ready this fall, but experts say that by the time they are ready, a new variant very well could have taken hold.  

As alternatives to vaccine makers chasing each variant, experts point to research on “pan-coronavirus” vaccines that are “variant-proof,” targeting multiple variants, as well as nasal vaccines that could drastically cut down on transmission of the virus.

There is ongoing research on these next-generation vaccines, but unlike in 2020, when the federal government’s Operation Warp Speed helped speed the development of the original vaccine, there is less funding and assistance this time around.  

COVID-19 funding that could help develop and manufacture new vaccines more quickly has been stalled in Congress for months.

“There’s no Operation Warp Speed,” said Eric Topol, professor of molecular medicine at Scripps Research. “So it’s moving very slowly. But at least it’s moving.” 

Leana Wen, a public health professor at George Washington University, wrote in a Washington Post op-ed this week that the U.S. needs “urgent investment” in next-generation vaccines and “we need an ‘Operation Warp Speed Part 2.’” 

Pfizer and Moderna are working on updated vaccines that target BA.5 that could be ready this fall, but experts say that by the time they are ready, a new variant very well could have taken hold.  

As alternatives to vaccine makers chasing each variant, experts point to research on “pan-coronavirus” vaccines that are “variant-proof,” targeting multiple variants, as well as nasal vaccines that could drastically cut down on transmission of the virus.

There is ongoing research on these next-generation vaccines, but unlike in 2020, when the federal government’s Operation Warp Speed helped speed the development of the original vaccine, there is less funding and assistance this time around.  

COVID-19 funding that could help develop and manufacture new vaccines more quickly has been stalled in Congress for months.

“There’s no Operation Warp Speed,” said Eric Topol, professor of molecular medicine at Scripps Research. “So it’s moving very slowly. But at least it’s moving.” 

Leana Wen, a public health professor at George Washington University, wrote in a Washington Post op-ed this week that the U.S. needs “urgent investment” in next-generation vaccines and “we need an ‘Operation Warp Speed Part 2.’” 

Administration health officials pointed to funding when asked about next-generation vaccines at a press briefing on Tuesday.

“We need resources to continue that effort and to accelerate that effort,” said Anthony Fauci, the government’s top infectious disease expert. “So although we’re doing a lot and the field looks promising, in order to continue it, we really do need to have a continual flow of resources to do that.” 

But COVID-19 funding has been stuck in Congress for months. Republicans have long said they do not see any urgency in approving the money. Democrats, while generally calling for the funding, have been caught up in their own internal divisions, like when a group of House Democrats objected to a way to pay for the new funding in March.

“Of course more funding would accelerate some parts of the development,” Karin Bok, acting deputy director of the National Institutes of Health’s (NIH) Vaccine Research Center, said in an interview.  

She also cautioned that development of next-generation vaccines like nasal vaccines would take longer than the original vaccines, because less groundwork has been laid over the preceding years.  

Experts stress that even for BA.5, the current vaccines still provide important protection against severe disease and hospitalization, and are urging people to get their booster shots now. But there is potential for further improvement in the vaccines as well.

Aside from funding, another obstacle is obtaining copies of the existing COVID-19 vaccines for use in research, said Pamela Bjorkman, a California Institute of Technology professor working on a next-generation vaccine. 

“I would say we’ve wasted at least six months,” with various procedural hurdles on that front, she said. “It’s just ridiculous.” 

For example, she said at one point when her team was able to get access to the AstraZeneca COVID-19 vaccine, it then took two or three months to get an import permit to send it from the United Kingdom.

“This is a hot topic,” Bok, of the NIH, said of access to existing vaccine doses for researchers. “The government is working very hard on an agreement with the companies to provide it to us and to all the investigators…that are funded by NIH.” 

Asked about providing vaccine doses for researchers and any talks with the administration on that front, a Moderna spokesperson said: “We do provide vaccine in certain investigator-initiated studies where physicians and scientists propose research they have designed and want to conduct with our support,” pointing to a South African study as an example.  

More broadly, the White House says it is working on accelerating next-generation vaccine research and will have more announcements soon.  

“Let me be very clear: We clearly need a true next-generation vaccine,” White House COVID-19 response coordinator Ashish Jha told reporters on Tuesday. 

“You’ll hear more from us in the days and weeks ahead,” he added. “This is something that we have been working quite assiduously on.” 

COVID is not done with us, part six (…seven? eight?)

https://mailchi.mp/30feb0b31ba0/the-weekly-gist-july-15-2022?e=d1e747d2d8

The rise of ubiquitous self-testing and the paucity of accurate, timely data from the CDC on COVID numbers has left us feeling our way in the dark in terms of the current state of the pandemic. Clearly there’s a new surge underway, driven by the BA.5 variant. What we can report from our experiences on the road over the past few weeks is that the wave is significant. 

We’re hearing from our health system members that inpatient COVID volumes and COVID-related ED visits are significantly up again—often double or more what they were just two months agoalthough still well below levels of past surges. Length of stay for COVID inpatients is shorter, with fewer ICU visits than during the Delta surge—about the same intensity, proportionally, as during Omicron.

But COVID-related staffing shortages are once again having a real impact on hospitals’ ability to deliver care—clinical and non-clinical staff callouts are at high levels again, as during Omicron.

One piece of good news: masking is back in vogue among many health system executive teams, likely in response to a number of “superspreader” events: gatherings of hospital staff over the past few weeks that resulted in clusters of cases. One system described an all-hands session for anesthesiologists that resulted in more than a dozen cases across the next week—forcing the hospital to cancel procedures. 

We’re worried that this BA.5 surge is just getting started, and with booster uptake stagnating and masking all but nonexistent in the general population, the late summer and early autumn situation could be significantly worse.

Be careful out there.

The summer of subvariants

As this summer heats up, so has the spread of the hot new version of COVID-19.

Why it matters: This subvariant of Omicron called BA.5 — the most transmissible subvariant yet — quickly overtook previous strains to become the dominant version circulating the U.S. and much of the world.

BA.5 is so transmissible — and different enough from previous versions — that even those with immunity from prior Omicron infections may not have to wait long before falling ill again.

What they’re saying: “I had plenty of friends and family who said: ‘I didn’t want to get it but I’m sort of glad I got it because it’s out of the way and I won’t get it again’,” Bob Wachter, chairman of the University of California, San Francisco Department of Medicine told Axios. “Unfortunately that doesn’t hold the way it once did.”

  • “Even this one bit of good news people found in the gloom, it’s like, ‘Sorry’,” Wachter said.

State of play: This week, the CDC reported BA.5 became the dominant variant in the U.S., accounting for nearly 54% of total COVID cases. Studies show extra mutations in the spike protein make the strain three or four times more resistant to antibodies, though it doesn’t appear to cause more serious illness.

  • Hospital admissions are starting to trend upward again, CDC data shows, though they’re still well below what was seen during the initial spread of Omicron.
  • It’s unclear whether that could be indicating an increase in patients in for COVID, or patients who happen to have COVID, Wachter said. “We’re up in hospitalizations around 20% but with a relatively small number of ICU patients,” Wachter said about COVID cases at UCSF.
  • In South Africa, the variant had no impact on hospitalizations while Portugal saw hospitalizations rise dramatically, Megan Ranney, academic dean at the Brown University School of Public Health told Axios.
  • “So the big unknown is what effect it’s going to have on the health care system and the numbers of folks living with long COVID,” she said.

Yes, but: “I’m certainly hearing about more reinfections and more fairly quick reinfections than at any other time in the last two and a half years,” Wachter said.

Zoom in: That is also largely the experience of the surge seen firsthand in New York City by Henry Chen, president of SOMOS Community Care, who serves as a primary care physician across three boroughs of the city.

  • With this particular variant, he said: “The symptoms are pretty much the same but a little bit more severe than the last wave. It’s more high fever, body ache, sore throat and coughing,” Chen said, adding his patient roster is mostly vaccinated.
  • But it is occurring among patients who’d gotten the virus only three or four months ago, he said.

The big picture: Another summertime wave of cases could prolong the pandemic, coming after many public health precautions were lifted and with available vaccines losing their efficacy against the ever-evolving virus.

The bottom line: The messaging isn’t to panic, but to understand the virus is likely spreading in local communities much more than individuals realize due to shrinking testing programs  and without the level of protection they might assume they have.

  • “If you don’t want to get sick, you still need to be taking at least some precautions,” Ranney said. “[COVID] is still very much among us.”