- Also Messenger RNA vaccine pioneer Katalin Karikó story
For the first year of the Covid-19 pandemic, hospitalizations and deaths followed infection patterns by a few weeks, as sure as night follows day.
Vaccines promised to sever those metrics. While they might not prevent all Covid-19 infections, vaccines would, experts predicted, dramatically reduce hospitalizations and deaths. And they have.
But with the highly transmissible Delta variant now circulating — mostly among the unvaccinated — the United States is seeing spikes in infections that have turned into increases in hospitalizations in some communities.
So, how well is the country preventing hospitalizations and deaths right now?
The answer is nuanced. Vaccines are absolutely helping blunt the impact of these outbreaks — both the size and the toll in sickness and death. But vaccine uptake isn’t to the point yet where it can preclude increases in hospitalizations and deaths.
Put another way, without vaccines, the outbreaks in Nevada, Missouri, Arkansas, and elsewhere with low immunization rates would be worse, and other states would be more vulnerable to similar spikes.
“This is a new phase of the pandemic,” Jay Butler, the deputy director for infectious diseases at the Centers for Disease Control and Prevention, said at a press briefing last week. “We’re seeing positive effects of the vaccination problem, but at the same time … it ain’t over ’til it’s over. We’re continuing to see transmission occurring, and we have a significant portion of the population that is unimmunized.” Related:
The impact of vaccines is remarkable. They’re standing up to the variants nature has thrown our way. The overwhelming majority of hospitalizations and deaths — some 98% to 99% of the latter — are among people not fully vaccinated. (No vaccine prevents all severe outcomes.)
But so many people remain unvaccinated that, nationwide, cases have more than doubled in recent weeks — a jump driven not just by Delta, but also the country’s lapsing of mitigation efforts and people traveling and reconnecting socially. Even states like Massachusetts that have comparatively high vaccination rates have started seeing upticks in cases.
“This is becoming a pandemic of the unvaccinated,” CDC Director Rochelle Walensky said Friday. She added: “Our biggest concern is that we are going to continue to see preventable cases, hospitalizations, and sadly deaths among the unvaccinated.” The shape and scope of the damage of a Covid-19 outbreak isn’t just determined by how many people in a given area are protected — it’s also a question of who is protected. While 56.8% of people in the United States 12 and over who are eligible for the shots are fully vaccinated, the rate is nearly 80% for people 65 and older — the population at greatest risk of getting severely ill and dying from Covid-19.
Having so many older people protected will in turn reduce the death rate among those people still contracting the coronavirus. It also explains why younger adults — who have lower vaccination rates — are accounting for a larger portion of people hospitalized now.
In Florida, for example, while people 70 and older accounted for nearly 1 in 2 hospitalized Covid-19 patients in the pre-vaccine era, they now make up just 1 in 4, according to data analyzed by epidemiologist Jason Salemi of the University of South Florida. And with the bulk of hospitalizations among younger adults, “we should absolutely not see as many deaths related to hospitalizations, because fewer of those hospitalized will die,” Salemi said. Related:
Similar patterns are occurring in other states.
“The infection rates are highest among young people, 15 to 45,” Andrew Pavia, a pediatric infectious disease physician at the University of Utah, said about the recent increases in Utah. “The hospitalization rates are much higher in those age groups than they were earlier in the pandemic. And the rates of infection and rates of hospitalization are highest in the rural areas, and it should be no surprise to anyone that those are the same areas that have very low rates of vaccination.”
Just how many deaths will occur as a result of the recent uptick in transmission is still unclear. Even if they die at lower rates than older adults, some of the younger adults hospitalized in recent weeks will still die. But cases only started rising in the past few weeks, and it can take people with Covid-19 that long to die, and another few weeks for their deaths to be recorded. Related:
Plus, cases are still rising.
“The deaths have remained pretty flat, but given when that increase in hospitalizations and the increase in cases occurred, I’m not surprised by that,” said infectious disease epidemiologist Brian Labus of the University of Nevada, Las Vegas’ public health school, suggesting that the state, which has had one of the country’s largest recent surges, hasn’t yet seen the full impact of that transmission.
Because so many people are protected, whatever outbreaks occur now aren’t likely to create crises for health care systems nationwide. Individual hospitals are facing a deluge of patients — hospitals in Arkansas and Missouri are under particular pressure — but even as cases and hospitalizations have built up in recent weeks, they’re still drastically down from prior months in most places. Take Utah: ICUs are at capacity, Pavia said, but hospitals haven’t had to build emergency units like they did during the winter.
Overall, it’s difficult to compare metrics like hospitalization and death rates at various points in the pandemic. Testing has fallen off in many places. Doctors have gotten better at treating Covid-19, while who is getting sick has changed. The virus has also evolved. Now dominant is Delta, but experts are still trying to sort out if it causes more severe disease on average than other forms of the virus. Related:
Even how we think about what a “case” means has fragmented. People who still get infected by the coronavirus after being fully vaccinated face a minuscule risk of becoming severely sick, having to go to the hospital, or dying. It’s presumed that many asymptomatic or even mild cases among vaccinated people — which are evidence that the vaccines are working, because they’re not getting sick — are going undetected.
But those who remain unvaccinated (or who don’t have protection from an earlier infection) still face the same risks from a case.
The vaccines have had some help in bringing transmission down from the winter to the spring to the summer. Some chunk of unvaccinated people have been infected by the coronavirus already and are protected that way (though experts say that the protection provided by vaccines appears more robust and durable than that from an infection). Scientists are still trying to sort out seasonal influences on the virus, though typically respiratory viruses spread less efficiently in warmer temperatures. Plus, people can be outside more than in the winter — though the counterpoint to that is that it’s so hot in the summer in some places, like southern states, that people there spend more time indoors. STAT+:
The way to prevent and minimize outbreaks going forward, experts stress, is getting more people vaccinated. The United States has shown it can do this: In the spring, the Alpha variant drove a spike in cases in Michigan and threatened other states. But the country vaccinated itself out of feeling more severe devastation from that variant.
Now the country has to do that again in the face of an even more transmissible variant, Delta. Because of how effectively it spreads, more people have to be protected for its circulation to slow.
At the Medical University of South Carolina, hospitalized Covid-19 patients include a mix of unprotected younger adults, but also older adults from the state’s rural areas who haven’t been vaccinated either, said infectious disease physician Krutika Kuppalli. While Charleston has a relatively high vaccination rate, many people from the rural areas — where Kuppalli sees patients through telemedicine appointments — have hardened in their resistance to the vaccines.
“Trying to get people to take a vaccine, which has been so politicized, is just really hard,” she said.
Messenger RNA vaccine pioneer Katalin Karikó shares her long journey to Covid-19 vaccines
Katalin Karikó of BioNTech speaks at the STAT Breakthrough Science Summit.
In the span of the Covid-19 pandemic, and thanks to the success of two of the currently available vaccines for SARS-CoV-2, messenger RNA, or mRNA, went from being an obscure cell biology concept understood and mentioned only by scientists to being a household term.
But the technology behind the mRNA vaccines from Moderna and Pfizer and BioNTech is anything but new. Developed over an arduous 40 years, it was the result of an unlikely success story. One of the key figures behind this achievement was Katalin Karikó, senior vice president of the German biotech company BioNTech and adjunct associate professor at the University of Pennsylvania.
Speaking at the 2021 STAT Breakthrough Science Summit Wednesday, Karikó shared how despite many, many failures — including demotions, grant rejections, and more — she was clear in her focus. “I always looked to RNA [as a way] to develop therapeutics,” she said, and shared details about her journey to BioNTech as well as her unyielding faith in the technology she was developing.
Around the world for mRNA
Karikó grew up in Hungary, where at 16 she already knew she wanted to be a scientist, and her dedication to mRNA took her around the world. She wanted to go wherever the best mRNA science was, if that meant academia or biotech, Japan or Pennsylvania, where she worked at Arbutus Biopharma, previously Tekmira. “I was just so determined to go somewhere, do something” with RNA, she said. In 1990, she ended up in Philadelphia, studying the mechanisms of mRNA biology at Penn.
On persevering against the odds
Even though Karikó’s breakthrough research has brought her recognition, and with it grant money, her trajectory was not without its low points. For the first 40 years of her research career, she did not receive a single R01 grant, the main way the National Institutes of Health funds scientists. “There were low points, but every time something went wrong, I tried to focus on the things I could change,” she said. Seeing progress, no matter how gradual, kept her going. “Whether we got more protein, better delivery, or any kind of data, that gave us the push when we were deep in the problems,” she recalled.
Karikó compared the trajectory of science to rowing, the sport in which her daughter Susan Francia, won Olympic gold medals on the U.S. team in 2008 and 2012. Because rowers face away from the direction in which they’re headed, “They don’t see the finish line, they don’t see how far it is, they just kind of sense it. Science is sometimes like that,” she said. Related:
When biotech calls
Slowly, Karikó started moving into biotech, first by founding her own company, RNARx, in 2006, and then by advancing to bigger companies. Again, she knew exactly where to go: “I was focusing on companies that already had [mRNA] formulations in humans, because then maybe I could help.” She ended up at BioNTech, where she has been since 2013.
Karikó said that biotech has a lot of upsides over academia. “We have to have a product that is functional and will cure people. It was just so much better than a paper, then another paper that maybe nobody will read.”Newsletters
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A shot in the arm
When Covid-19 hit at the beginning of 2020, BioNTech and Karikó switched into overdrive to develop the elements necessary for a vaccine based on their mRNA biology. After months of work, Karikó recounted how, one Sunday night in Philadelphia — her daughter’s birthday, no less — she received a call saying that the vaccine had worked. She wasn’t all that surprised. “I was very happy but [it was] kind of expected,” she said. Seeing not only “the clinical trial data but also how well this modified RNA worked in other infectious disease vaccines was always so powerful.”
Then on Dec. 18, 2020, she got the BioNTech vaccine she had a hand in developing. When she went outside, health care workers who were also getting their vaccines started clapping for her. “They were just so happy. I’m not a very emotional person, but I just cried a little.”
On her newfound fame
When asked her thoughts on possibly being considered for the Nobel prize, Karikó instead focused on the collaborative nature of science and how so many contributions to the mRNA vaccine by others may be overlooked. “Many scientists, just like me, work for years and years and nobody knew about them. And so, I have to represent all of them,” she said.
But she is nostalgic for the days before her newfound fame and workload, she said. “Sometimes I wish I could have that [extra time] back. When I read the title of a very exciting paper, I feel that I would never have time to read that, and I want to because that’s my favorite thing to do.”
The future of mRNA
Karikó sees mRNA, either in the form of vaccines or a therapeutic, as a powerful tool to treat everything from viruses and pathogens to autoimmune diseases, she said. At the beginning of this year, her group published a mouse study showing how an mRNA vaccine could be used to prevent immune system attacks that are common in multiple sclerosis. Although this particular vaccine has a long way to reach the clinic — about two years, she predicted — she believes that her preferred molecule will continue producing new therapies: “I am very hopeful that more and more products will be reaching the market,” Karikó said
About the Author
Claudia López Lloreda is a news intern at STAT covering health care and medicine as part of the AAAS Mass Media Fellowship. She is a neuroscience graduate student at the University of Pennsylvania.