Study finds tracking brain waves could reduce post-op complications

Distinctive EEG patterns indicate when a patient’s state of unconsciousness under general anesthesia is more profound than necessary

Peer-Reviewed Publication

MASSACHUSETTS INSTITUTE OF TECHNOLOGY

 

IMAGE: AS PATIENTS RECEIVE INCREASING DOSES OF PROPOFOL (PANELS A THROUGH D), THE AMPLITUDE OF ALPHA WAVES GRADUALLY FLATTENS UNTIL PATIENTS ENTER THE STATE KNOWN AS BURST SUPPRESSION (D). AS THE DOSE IS DECREASED (PANELS E-G), THE AMPLITUDE RETURNS TO NORMAL. view more 

CREDIT: MIT RESEARCHERS

CAMBRIDGE, MA -- When patients undergo general anesthesia, their brain activity often slows down as they sink into unconsciousness. Higher doses of anesthetic drugs can induce an even deeper state of unconsciousness known as burst suppression, which is associated with cognitive impairments after the patient wakes up.

A new study from MIT, in which the researchers analyzed the EEG patterns of patients under anesthesia, has revealed brain wave signatures that could help anesthesiologists determine when patients are transitioning into that deeper state of unconsciousness. This could enable them to prevent patients from falling into that state, reducing the risk of postoperative brain dysfunction.

One of these distinctive patterns emerged in the brain’s alpha waves (which have a frequency of eight to 14 cycles per second). Once patients became unconscious, these waves started to wax and wane in amplitude. As patients went deeper into unconsciousness, the pattern of this waxing and waning in amplitude, or amplitude modulation, continually changed.

“If you track this modulation as it gets deeper or shallower, you have a very principled way to track level of unconsciousness under anesthesia,” says Emery Brown, the Edward Hood Taplin Professor of Medical Engineering and Computational Neuroscience and a member of MIT’s Picower Institute for Learning and Memory and the Institute for Medical Engineering and Science.

Brown is the senior author of the new study, which appears this week in the Proceedings of the National Academy of Sciences. The lead authors of the paper are Picower Institute research scientist Elie Adam, Ohyoon Kwon ’20, and graduate student Karla Montejo.

Measuring brain waves

Brain waves, which are generated by synchronized neuronal activity, oscillate at different frequencies depending on what kind of task the brain is performing. When the brain is strongly engaged in mental activity, it produces higher-frequency beta (15-30 hertz) and gamma (greater than 30 hertz) oscillations, which are believed to help organize information and enhance communication between different brain regions.

Commonly used anesthesia drugs such as propofol have a significant effect on these oscillations. During anesthesia induced by propofol or other anesthetics that increase the effectiveness of GABAergic inhibitory receptors in the brain, the brain enters a state of unconsciousness known as slow-delta-alpha (SDA). This state is characterized by slow (0.1-1 hertz), delta (1-4 hertz) and alpha (8-14 hertz) oscillations.

With higher doses of these anesthetic drugs, the brain can fall into an even deeper state of unconsciousness. When in this state, known as burst suppression, EEG recordings from the brain show long periods of inactivity, punctuated by brief bursts of low-amplitude oscillations. When patients enter this state, they are more likely to experience postoperative confusion, delirium, and memory loss. These effects, which can last for hours, days, weeks, or months, are more common in elderly patients.

SDA and burst suppression produce distinctive EEG patterns that have been well-studied. However, they have been studied as separate brain states; what happens during the transition between the two states is less clear. That transition is what the MIT team set out to analyze in this study.

To do that, the researchers studied 10 healthy volunteers and 30 patients who were undergoing surgery. Most of the patients received propofol intravenously, and the rest received sevoflurane, a commonly used anesthetic gas. Both of these drugs act on GABA receptors in the brain, which reduce neuron excitability.

As the dosage of propofol was increased, patients showed two distinctive patterns of change in their EEGs. The first pattern was seen in the alpha waves, which started to wax and wane. As the dose increased, waxing was shortened and waning was prolonged, until the patient reached the state of burst suppression.

“You can see a very strong modulation, which is always there. As the modulation gets to be more profound, it eventually flattens out, and that's when the brain reaches the deeper state,” Brown says.

When the amount of drug was reduced, the amplitude of the alpha waves began to increase again.

The researchers also found a distinctive pattern in the slow and delta waves seen in the patients’ EEG readings. Slow and delta oscillations are the slowest brain waves, and as the amount of drug was increased, the frequency of these waves became slower and slower, reflecting a decrease in brain activity.

Metabolic disruption

The researchers hypothesize that propofol exerts these effects through its influence on neuron metabolism. The drug is postulated to disrupt the production of ATP, the molecules that cells use to store energy. As ATP production declines, neurons eventually become unable to fire, leading to burst suppression.

“This is consistent with the observation that burst suppression is very frequent in older patients, because their metabolic state may be less well-regulated than that of younger patients,” Brown says.

The findings could offer anesthesiologists more refined control over a patient’s state of unconsciousness during surgery, says Brown. He now hopes to develop an algorithm that could generate a warning that a patient is approaching burst suppression, which could be displayed on a monitor in the operating room. He says that anesthesiologists could also learn to make that determination by looking for these patterns in a patient’s EEG.

“One of the reasons we're excited about this is that it’s something you can actually see in the raw EEG,” Brown says. “Now that we have pointed out these patterns, they’re very easy to see.”

The researchers now plan to further explore what is happening to the brain’s metabolism during the transition to burst suppression, using animal models.

###

The research was funded in part by the Picower Institute Innovation Fund and the National Institutes of Health.

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2300058120 

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Modulatory dynamics mark the transition between anesthetic states of unconsciousness

ARTICLE PUBLICATION DATE

17-Jul-2023

 

Bacterial protein found in the urogenital tract may contribute to reduced fertility, birth defects

Study underscores significant implications for cancer and obstetrics medicine, as well as diagnostics, and preventative therapy

Peer-Reviewed Publication

UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE

 

IMAGE: THE BACTERIAL PROTEIN DNAK (GREEN) IS TAKEN UP INTO HUMAN CANCER CELLS AND MOVES TO THE CELL’S NUCLEUS (BLUE), WHERE THE DNA IS LOCATED. view more 

CREDIT: PNAS 2018 DEC 18; 115(51): E12005–E12014.

A team of researchers from the University of Maryland School of Maryland’s (UMSOM) Institute of Human Virology (IHV), a Center of Excellence of the Global Virus Network (GVN), published new findings that emphasize the crucial role of the urinary and genital tract microbiota in adverse pregnancy outcomes and genomic instability that originate in the womb during fetal development.

The study, published on July 17 in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), established a new link between genomic instability and a protein from Mycoplasma fermentans, a kind of bacterium that commonly colonizes the urogenital tract. This bacterial protein also reduced fertility in mother mice and resulted in more birth defects in their newborn pups.

This research was spearheaded by Davide Zella, PhD, Assistant Professor of Biochemistry and Molecular Biology at UMSOM’s IHV and Robert Gallo, MD, The Homer & Martha Gudelsky Distinguished Professor in Medicine, Co-Founder and Emeritus Director of UMSOM’s IHV, and Co-Founder and Chair of the Scientific Leadership Board of the Global Virus Network.

"Our results not only broaden our understanding of the interplay between the urogenital tract microbiota and human reproductive health, but also shed light on the previously unidentified contribution of the human microbiota to genetic abnormalities," said lead author on the study Francesca Benedetti, PhD, Research Associate of Biochemistry and Molecular Biology in UMSOM’s IHV.

“We aim to further explore the mechanisms underlying these findings and their potential implications for preventing and treating chromosomal abnormalities and genetic diseases,” said co-lead author Giovannino Silvestri, PhD, former Research Associate of Medicine in UMSOM’s IHV.

The human microbiota is known to affect metabolism, susceptibility to infectious diseases, immune system regulation, and more. One of these bacterial components, Mycoplasmas, have been linked to various cancers.

The research team has been studying one Mycoplasma protein, DnaK, which belongs to a family of proteins that safeguards other bacterial proteins against damage and aids in their folding when they are newly made, acting as a so-called ‘chaperone.’ However, while this protein is advantageous for bacteria, its effects on animal cells are less favorable. To this regard, the team had previously demonstrated that this DnaK is taken up by the body’s cells and it interferes with key proteins involved in preserving DNA integrity and in cancer prevention, such as the tumor suppressor protein p53.

For this latest study, researchers created mice that make the DnaK protein normally produced by the bacterium Mycoplasma fermentans. These mice with exposure to DnaK accrued genomic instability in which entire sections of the genome were duplicated or deleted, resulting in mice with varying numbers of copies of certain genes.

The team noticed that some of these mice from 3-5 weeks of age had problems with movement and coordination. They found that these mice have a deletion in the Grid2 gene, which in humans leads to the rare genetic disease known as spinocerebellar ataxia-18 (SCAR18) that causes delayed development of skilled movements and intellectual disabilities.

“Remarkably, this instance marks the first time a mouse model successfully recapitulated a human genetic disease de novo, showcasing this model's potential for further cancer biology research,” said Dr. Zella.

More than a third of the female mice that made the DnaK protein were unable to get pregnant. Additionally, more than 20 percent of the pups born from moms with the DnaK protein had some sort of birth defect/deformity.

“The occurrences of genomic instability, in the form of increased number of copy number variations, could explain the decreased fertility and the increased instances of abnormally developed fetuses we observed upon DnaK exposure,” said Dr. Gallo. “These data build upon our initial work which discovered the disruptive role of DnaK on key proteins involved in the proper repair of damaged DNA, which are also known to play a role in the onset of copy number variations. Our ongoing commitment is to better understand the potential implications of these findings in cellular transformation and cancer.”

UMSOM Dean Mark T. Gladwin, MD, who is also Vice President for Medical Affairs, University of Maryland, Baltimore and the John Z. and Akiko K. Bowers Distinguished Professor, commended the work. “The researchers raise a significant question regarding whether DnaK can interfere with fetal development in humans. An important next step would be to investigate whether neutralizing either the bacteria or this protein could preserve fertility and prevent certain birth defects,” he said.

About the Institute of Human Virology

Formed in 1996 as a partnership between the State of Maryland, the City of Baltimore, the University System of Maryland, and the University of Maryland Medical System, the IHV is an institute of the University of Maryland School of Medicine and is home to some of the most globally-recognized and world-renowned experts in all of virology. The IHV combines the disciplines of basic research, epidemiology, and clinical research in a concerted effort to speed the discovery of diagnostics and therapeutics for a wide variety of chronic and deadly viral and immune disorders, most notably HIV, the virus that causes AIDS. For more information, visit ihv.org and follow us on Twitter @IHVmaryland.

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world — with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (“University of Maryland Medicine”) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the 8th highest among public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies. In the latest U.S. News & World Report ranking of the Best Medical Schools, published in 2021, the UM School of Medicine is ranked #9 among the 92 public medical schools in the U.S., and in the top 15 percent (#27) of all 192 public and private U.S. medical schools. The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu

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JOURNAL

Proceedings of the National Academy of Sciences

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Animals

ARTICLE TITLE

Mycoplasma DnaK increases DNA Copy Number Variants in vivo

ARTICLE PUBLICATION DATE

17-Jul-2023

Researchers discover group of genes that influence pain and brain communication can also influence alcohol use disorder risk

Peer-Reviewed Publication

INDIANA UNIVERSITY SCHOOL OF MEDICINE

INDIANAPOLIS—An estimated 16 million people in the United States have alcohol use disorders (AUDs), according to the National Institutes on Alcohol Abuse and Alcoholism (NIAAA). Now, Indiana University researchers have made a substantial discovery in the role genes play in the development of AUDs, finding that alteration of a group of genes known to influence neuronal plasticity and pain perceptions, rather than single gene defect, is linked to AUDs.

“We know inherited genes are a major contributor to this disease, because past studies have shown family genetics to be directly associated with alcohol dependence within a family,  such as identical twins raised in different environments,” said Feng Zhou, PhD, professor emeritus of anatomy, cell biology and physiology at IU School of Medicine.

Zhou is the lead author, along with William Muir, PhD, professor emeritus of genetics at the Purdue Department of Animal Sciences, of a new publication in Alcohol: Clinical and Experimental Research which details their new findings.

Researchers used three different animal models created in the IU Alcohol Research Center to study how the genes impact desire for alcohol. The study involved statistically sorting through about 3 billion DNA base pairs containing nearly 30,000 genes, in 70 individual animals to identify the handful that were responsible for drinking behaviors. Thanks to their experimental design, the researchers could identify population differences based on drinking behaviors rather than chance genetic differences or other environmental influences.

“These rat models are all uniquely qualified as criteria for human outcomes,” said Zhou.

The genes that mediate pain sensation act in concert with two other groups of neural channel and neural excitation genes which perform neural communication functions, the team found.

“The function of these three groups of genes is important for neuroadaptation and neuroplasticity, meaning that they can change brain communications,” Zhou said.

They also discovered a key cohort of genes impacted alcohol use, with some of the genes having silent mutations, meaning they did not alter the amino acid sequence translated, but influenced the rate and conformation of gene transcription, causing changes in the other genes that had an impact on alcoholism.

“This is the first time these multiple models have ever been used for this pursuit,” Muir said. “In the past, research has focused on a single gene and how it can contribute to alcohol use, but now, we can see that these large groups of genes make a difference, which can help guide future research and clinical care for those suffering from AUDs.”

“The brain must be modified over the drinking period. That kind of modification is similar to drug abuse,” Zhou said. “It is genetically prone neural plasticity or neural adaptation to a certain level that makes drinking more pleasurable and more tolerable, or pain relief.”

“The alleviation of pain appears to be one motivation to drink and continue to drink,” Muir said. “Knowing that, it’s possible that early counseling can produce drinking avoidance.”

The new findings raise the possibility of genetic testing for alcoholism. People who get tested and know that they have a high genetic tendency to become an alcoholic might take extra care to moderate their drinking.

“One future direction is how these animal findings would translate to humans,” Zhou said. “If verified, then treatment or prevention can be more focused.”

Other study authors include Chiao-Ling Lo, PhD and Richard Bell, PhD of IU School of Medicine and the Indiana Alcohol Research Center at IU School of Medicine.

About IU School of Medicine

IU School of Medicine is the largest medical school in the United States and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

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JOURNAL

Alcoholism Clinical and Experimental Research

DOI

10.1111/acer.15131 

ARTICLE TITLE

Multi-animal-model study reveals mutations in neural plasticity and nociception genes linked to excessive alcohol drinking

 

Rice engineers’ storage technology keeps nanosurfaces clean

Containers attract, trap organic molecules that frequently foul nanosurfaces

Peer-Reviewed Publication

RICE UNIVERSITY

 

IMAGE: MECHANICAL ENGINEERS IN RICE UNIVERSITY’S PRESTON INNOVATION LABORATORY HAVE CREATED CONTAINERS THAT CAN KEEP VOLATILE ORGANIC COMPOUNDS FROM ACCUMULATING ON THE SURFACES OF STORED NANOMATERIALS. view more 

CREDIT: CREDIT GUSTAVO RASKOSKY/RICE UNIVERSITY

HOUSTON – (July 17, 2023) – Rice University engineers have created containers that can keep volatile organic compounds (VOCs) from accumulating on the surfaces of stored nanomaterials.

The portable and inexpensive storage technology addresses a ubiquitous problem in nanomanufacturing and materials science laboratories and is described in a paper published this week in the American Chemical Society journal Nano Letters.

“VOCs are in the air that surrounds us every day,” said study corresponding author Daniel Preston, an assistant professor in Rice’s Department of Mechanical Engineering. “They cling to surfaces and form a coating, primarily of carbon. You can’t see these layers with the naked eye, but they form, often within minutes, on virtually any surface exposed to air.”

VOCs are carbon-based molecules that are emitted from many common products, including cleaning fluids, paints, and office and crafting supplies. They accumulate indoors in particularly high concentrations, and the thin layers of carbon gunk they deposit on surfaces can hinder industrial nanofabrication processes, limit the accuracy of microfluidic testing kits and produce confusion for scientists who conduct fundamental research on surfaces.

To address the problem, Ph.D. student and study lead author Zhen Liu, together with Preston and others from his lab, developed a new type of storage container that keeps objects clean. Experiments showed that her approach effectively prevented surface contamination for at least six weeks and could even clean VOC-deposited layers from previously contaminated surfaces.

The technology relies on an ultraclean wall inside the container. The surface of the interior wall is enhanced with tiny bumps and divots ranging in size from a few millionths to a few billionths of a meter. The microscopic and nanoscopic imperfections increase the wall’s surface area, making more of its metal atoms available to VOCs in air that’s inside the containers when they are sealed.

“The texturing allows the internal container wall to act as a ‘sacrificial’ material,” Liu said. “VOCs are pulled onto the surface of the container wall, which allows other objects stored inside to remain clean.”

She said the idea of using a large precleaned surface to accumulate pollutants was proposed 50 years ago but went largely unnoticed. She and her colleagues improved on the idea with modern methods of cleaning and nanotexturing surfaces. They showed, through a series of experiments, that their approach did a better job of preventing VOCs from coating the surfaces of stored materials than other approaches, including sealed petri dishes and state-of-the-art vacuum desiccators.

Preston’s group built on its experiments, developing a theoretical model that accurately characterized what was happening inside the containers. Preston said the model will allow them to refine their designs and optimize system performance in the future.

The research was supported by Rice’s Shared Equipment Authority, the Rice University Academy of Fellows, the United States Coast Guard Advanced Education Program and an Innovation in Buildings fellowship from the Department of Energy (DE-SC0014664).

-30-

A scanning electron microscope image (scale bar is 500 billionths of a meter in length) reveals myriad imperfections like those that Rice University engineers created on the interior walls of materials storage containers. The imperfections keep the surfaces of stored materials clean by attracting volatile organic compounds from air that gets sealed inside the containers.

CREDIT

Credit: Preston Innovation Laboratory/Rice University

Rice University Ph.D. student Zhen Liu and colleagues in the Department of Mechanical Engineering’s Preston Innovation Laboratory developed container technology that can prevent volatile organic compounds from coating the surface of stored objects for at least six weeks.

CREDIT

Credit: Gustavo Raskosky/Rice University

Peer-reviewed paper:

“Mitigating Contamination with Nanostructure-Enabled Ultraclean Storage” | Nano Letters | DOI: 10.1021/acs.nanolett.3c00626

Authors: Zhen Liu, Te Faye Yap, Anoop Rajappan, Rachel A. Shveda, Rawand M. Rasheed  and Daniel J. Preston

https://doi.org/10.1021/acs.nanolett.3c00626

Image downloads:

https://news-network.rice.edu/news/files/2023/07/0717_CLEAN_GR03xc-lg.jpg
CAPTION: Mechanical engineers in Rice University’s Preston Innovation Laboratory have created containers that can keep volatile organic compounds from accumulating on the surfaces of stored nanomaterials. (Photo by Gustavo Raskosky/Rice University)

https://news-network.rice.edu/news/files/2023/07/0717_CLEAN_GR09-ZL-lg.jpg
CAPTION: Rice University Ph.D. student Zhen Liu and colleagues in the Department of Mechanical Engineering’s Preston Innovation Laboratory developed container technology that can prevent volatile organic compounds from coating the surface of stored objects for at least six weeks. (Photo by Gustavo Raskosky/Rice University)

https://news-network.rice.edu/news/files/2023/07/0717_CLEAN-sem3x2-lg.jpg
CAPTION: A scanning electron microscope image (scale bar is 500 billionths of a meter in length) reveals myriad imperfections like those that Rice University engineers created on the interior walls of materials storage containers. The imperfections keep the surfaces of stored materials clean by attracting volatile organic compounds from air that gets sealed inside the containers. (Image courtesy of Preston Innovation Laboratory/Rice University)

https://news-network.rice.edu/news/files/2023/07/0717_CLEAN_GR12-zldp-lg.jpg
CAPTION: Zhen Liu (left), a Ph.D. student in mechanical engineering at Rice University, and Daniel Preston, an assistant professor of mechanical engineering at Rice, teamed with others from Preston’s laboratory to create storage technology that can keep volatile organic compounds from accumulating on stored surfaces. (Photo by Gustavo Raskosky/Rice University)

Related stories:

Fluidic circuits add analog options for controlling soft robots – Sept. 28, 2022
https://news.rice.edu/news/2022/fluidic-circuits-add-analog-options-controlling-soft-robots

Wearables take ‘logical’ step toward onboard control – Aug. 30, 2022
https://news.rice.edu/news/2022/wearables-take-logical-step-toward-onboard-control

Powering an ‘arm’ with air could be mighty handy – Aug. 25, 2022
https://news.rice.edu/news/2022/powering-arm-air-could-be-mighty-handy

Rice engineers get a grip with ‘necrobotic’ spiders – July 25, 2022
https://news.rice.edu/news/2022/rice-engineers-get-grip-necrobotic-spiders

Daniel Preston wins NSF CAREER Award – May 6, 2022
https://news.rice.edu/news/2022/daniel-preston-wins-nsf-career-award

Links:

Preston Innovation Laboratory: https://pi.rice.edu

Department of Mechanical Engineering: https://mech.rice.edu

George R. Brown School of Engineering: https://engineering.rice.edu

Press release URL:
https://news.rice.edu/news/2023/rice-engineers-storage-technology-keeps-nanosurfaces-clean

Follow Rice News and Media Relations via Twitter @RiceUNews.

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 4,240 undergraduates and 3,972 graduate students, Rice’s undergraduate student-to-faculty ratio is just under 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for lots of race/class interaction and No. 4 for quality of life by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger’s Personal Finance.

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JOURNAL

Nano Letters

DOI

10.1021/acs.nanolett.3c00626 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Mitigating Contamination with Nanostructure-Enabled Ultraclean Storage

THIRD WORLD U$A GOP COUNTIES

Rural mortality rose during year two of pandemic, despite vaccines, new study finds

BU research highlights how healthcare inequities between urban and rural areas, and vaccine skepticism, played a role in deaths related to COVID

Peer-Reviewed Publication

BOSTON UNIVERSITY

 

IMAGE: THE RESEARCHERS CREATED AN INTERACTIVE MAP TO VISUALIZE COUNTY-LEVEL ESTIMATES OF EXCESS DEATHS MONTH-BY-MONTH. HERE, THE SNAPSHOT SHOWS THE NATIONAL VIEW IN SEPTEMBER 2021—THE DARKER THE COLOR, THE HIGHER THE EXCESS MORTALITY RATE. view more 

CREDIT: COURTESY PAGLINO E, LUNDBERG DJ, ZHOU Z, WASSERMAN JA, RAQUIB R, LUCK AN, HEMPSTEAD K, BOR J, PRESTON SH, ELO IT, STOKES AC. “MONTHLY EXCESS MORTALITY ACROSS COUNTIES IN THE UNITED STATES DURING THE COVID-19 PANDEMIC, MARCH 2020 TO FEBRUARY 2022.” SCIENCE ADVANCES. 2023 JUN 23;9(25):EADF9742There was one striking difference between 2020, year one of the COVID-19 pandemic, and 2021, year two: in the second year, vaccines became readily available.

Presumably, vaccines created specifically to fight a new and deadly disease should have caused a dramatic reduction in deaths from that disease. And, according to new research from Boston University and the University of Pennsylvania, they did—but only in large, metropolitan counties. In rural counties across the United States—where vaccines were harder to obtain, where vaccine skepticism remained higher, and where access to good healthcare is often more challenging—excess deaths in year two of the pandemic actually increased, despite the presence of vaccines, according to the new study.

The study provides the first look at monthly estimates of what the researchers call “excess deaths” for every US county in the pandemic’s first two years. It says an estimated 1,179,024 excess deaths occurred during those first two years (first: 634,830; second: 544,194), a figure found by comparing mortality rates across all US counties for those years versus the years 2015–2019. 

“We define excess mortality as the difference between what was observed versus what we would have expected,” says Andrew Stokes, a BU School of Public Health assistant professor of global health and corresponding author on the study.

The Brink spoke with Stokes about the new study, published this month in the journal Science Advances. Among his other studies into COVID was one looking at “hidden deaths” from the disease—where he found the actual pandemic death toll could be 20 percent higher than the formal count.

The Brink: There have been so many studies examining death rates due to COVID. Can you talk about your interest and approach for this novel study?

Stokes: Many studies have estimated the impact of COVID-19 during the first year, 2020, but as the pandemic evolved, there was less information on the coming waves and the ways they affected different regions and communities. We thought comparing data from the first year to the second year would provide insight into the evolving impact of the pandemic and how mortality rates changed across the country. This was especially valuable to do using an excess mortality metric, as official COVID-19 death surveillance likely worsened over time as testing became increasingly limited in many communities.

Right. Because the second year is when vaccines were ready, so states had to figure out how they were going to make them readily available to people.

Vaccines became available right at the end of the first year, the end of 2020. This next pandemic year, which stretches from 2021 to 2022, was an important year to understand patterns of mortality. It turns out that association with vaccines and mortality was very strong.

What jumped out at you through the data?

One major finding of the study, monitoring at the county level, is that yes, there was inequity across rural and urban lines, across the urban-rural continuum. While the pandemic slowed down after the first year in large metropolitan areas, rural areas continued to experience a significant burden of excess deaths throughout the second year of the pandemic.

Inequalities in mortality outcomes in the second year of the pandemic were fundamentally shaped by patterns of vaccine uptake at the community level. We observed increasingly divergent outcomes across states and across the urban-rural continuum as gaps in vaccine uptake widened.

So, what conclusions do you draw from that?

It’s a combination of factors. There was less vaccination happening in rural areas and that gap between urban and rural areas grew as the second year progressed. There was momentum for vaccine access in urban areas, with vaccine distribution clinics and mass vaccination sites. But those things were not widely implemented in rural America. Then there are the long-standing gaps in rural healthcare related to funding gaps and workforce shortages, making it much harder to be cared for and to get high-quality care. There was also a lack of COVID-19 testing.

So, the pandemic really hit rural America in the second year, when vaccines were available, harder than it hit urban areas.

Rural America was being affected disproportionately and had fewer safeguards to combat the whole of COVID-19. This was especially pronounced among blue-collar workers who suffered economic losses when they had to stay home, but could not work from home. The economic consequences those communities suffered shaped their responses to COVID-19 policies. The emergence of partisanship and misinformation further disadvantaged small metropolitan and rural areas during the second year of the pandemic. This partisanship even went as far as deteriorating the quality of surveillance data by affecting the certification of COVID-19 deaths, which were systematically undercounted in rural communities.

Can you talk more specifically about how different states responded to COVID and its impact on them?

The high excess death rates that burdened large cities in the Northeast and Mid-Atlantic regions in the first months of the pandemic began to shift to more rural areas in the South and West as early as August 2020, with the sharpest increases occurring during the wave of the highly contagious Delta variant in the spring and summer of 2021. In our maps, you see that these later waves of Delta and Omicron, when widespread vaccination was largely available, were much more pronounced in southern states and rural counties. If you compare Massachusetts to Tennessee, Massachusetts had very little impact from Delta, where Tennessee had a profound Delta surge. In Massachusetts, a large fraction of the population was vaccinated. But southern states like Tennessee or Mississippi, with lower vaccination rates, with many rural counties, really suffered during that second wave.

What about Florida? Republican Governor Ron DeSantis has proudly proclaimed that Florida did not shut down because of COVID and was better for it. Is he right?

What happened in Florida is quite heterogeneous. Highly affluent areas in south Florida, Democratic-leaning counties in certain parts that were highly vaccinated, did well. But rural Florida looks more like the rest of the South. It had very high excess mortality during Delta, and those were largely preventable deaths. And it occurred at a time when Florida had very few mitigation measures in place to protect their rural residents.

OK, then take a different big state: California.

Even states like California, with its more progressive public health policies, were not completely insulated from the widening chasm between rural and urban areas that became increasingly stark over the second year of the pandemic. This highlights the limits of states’ policy responses in reaching rural America. Even as large metro areas in those same states experienced declines in COVID-19-related mortality as the pandemic progressed, rural counties were heavily burdened with deaths from COVID-19.

Taking the data from a 30,000-foot view, what do you see?

The really striking finding is that despite the strong efficacy of vaccines and high uptake in many large metropolitan areas, the number of excess deaths in the second year was not substantially lower than in the first year. The many deaths in rural, nonmetropolitan areas likely contributed to the high excess mortality we saw in the second year. Many of the deaths in the second year were preventable, through wider vaccination.

For the vaccine skeptics out there—and we know there are many of them—what does your study say to them?

This study simply compares what happened to what should have happened. It’s hard to argue with excess mortality.

 

This interview has been edited for clarity; additional detail was also added after initial publication.

This research was supported by the Robert Wood Johnson Foundation, the National Institute on Aging, the W. K. Kellogg Foundation, the BU Center for Emerging Infectious Diseases Policy & Research, and the National Science Foundation.

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JOURNAL

Science Advances

DOI

10.1126/sciadv.adf9742 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Monthly excess mortality across counties in the United States during the COVID-19 pandemic, March 2020 to February 2022