COVID-19 vaccine developed by Brazilian scientists is ready for clinical trials

The results of animal trials were published recently in Nature Communications. The researchers have received the green light from the national health surveillance authority to proceed with testing on humans.

Peer-Reviewed Publication

FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO

Testing on humans of a novel COVID-19 vaccine developed in Brazil will begin this year. It performed well in animal trials, as reported in an article published in August in Nature Communications. The scientists responsible for the vaccine have just received authorization from the National Health Surveillance Agency (ANVISA) to begin clinical trials.

“There are only some minor adjustments left to be made in the study’s protocol before we submit it once again to the approval of the National Council for Research Ethics [CONEP]. We expect to start clinical trials by late October,” Ricardo Tostes Gazzinelli, head of the Federal University of Minas Gerais’s Vaccine Technology Center (CTV-UFMG), told Agência FAPESP. Gazzinelli is also a senior researcher at Oswaldo Cruz Foundation (Fiocruz), the Ministry of Health’s research arm.

To develop the formulation for the vaccine, the group led by Gazzinelli combined two different SARS-CoV-2 proteins: N (for nucleocapsid, which contains the virus’s genetic material) and part of S (for spike, the protein used by the virus to bind to invade human cells). The resulting chimeric molecule is called SpiN. The strategy aims to trigger a cellular immune response consisting of the production of defense cells (T lymphocytes) that specialize in recognizing and killing the novel coronavirus. This type of protection should remain effective even against novel variants.

“The COVID-19 vaccines in use now are designed mainly to trigger the production of neutralizing antibodies against the S protein and prevent the virus from infecting human cells. This is what’s known as the humoral immune response. However, with the emergence of variants with many mutations in the S protein, the ability of these antibodies to recognize this antigen has weakened, whereas the N protein is better conserved in the new strains,” said PhD candidate Julia Castro, who led the preclinical trials with Gazzinelli supervising.

According to Gazzinelli, who is also a visiting professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP), the vaccine based on the chimeric protein SpiN does not itself trigger the production of neutralizing antibodies, but if given as a booster shot it can stimulate both the humoral immunity produced by prior vaccination and cellular immunity, affording double protection. 

Challenge testing

The animal trials were performed at a high-biosafety laboratory at FMRP-USP, thanks to collaboration with João Santana da Silva and Luiz Tadeu Figueiredo, both of whom are also professors there. The research was supported by FAPESP, the Ministry of Science, Technology and Innovation (MCTI) via its virus network (Rede Vírus), the Minas Gerais Research Funding Foundation (FAPEMIG), and the City of Belo Horizonte (capital of Minas Gerais).

The first step was to test the efficacy of the vaccine in mice that had been genetically modified to express ACE2, the human protein to which the virus binds via its spike (S) to infect the cells of the host. This model mimics the severe form of COVID-19.

Some of the mice were given two doses 21 days apart. The others received a placebo. A month later they were exposed intranasally to a high viral load. Different experiments were performed to test the extent to which the vaccine protected them against the wild-type strain of SARS-CoV-2 (isolated in China in 2019), the delta variant (India, 2020) and the omicron variant (South Africa, 2021).

“In the control group, which was given placebo, 100% of the animals infected with the [wild-type] Wuhan strain or delta died. The mice exposed to omicron didn’t die but developed a significant pathology in the lungs,” Castro said. “In the vaccinated group, all the animals survived infection by all three strains and lung tissue was much more preserved. In addition, viral load was between 50 and 100 times lower.”

The next step involved testing the vaccine on a moderate disease model. To do this, the scientists used hamsters, which are naturally infected by the virus but not very effectively. They were given two doses of the vaccine and after a month were exposed to the Wuhan or delta strain. Compared with the control group, the vaccinated hamsters had a viral load that was about ten times lower and fewer signs of lung damage.

Stability and safety

A platform was established at CTV-UFMG to produce the chimeric protein SpiN in genetically modified bacteria. Tests were also performed there to guarantee purity (absence of contaminants in the formulation) and stability (durability at different temperatures).

“The results showed that the vaccine remains viable for two weeks at room temperature and for at least six months when stored at 4 °C,” told Gazzinelli, according to whom safety and toxicity tests were performed on rats.

According to Gazzinelli, clinical trials are divided into Phase I and II. Phase I is expected to immunize 80 patients to make sure the vaccine is safe for humans, while Phase II will include a group of 400 volunteers for vaccine safety tests and also for evaluation of the vaccine’s immunogenicity – or, in other words, its capacity to induce an effective immune response. Trials will be conducted at UFMG’s medical school and will be led by Helton Santiago and Jorge Pinto, both of whom are professors there. They plan to vaccinate people who have already been given any of the available COVID-19 vaccines at least six months previously. 

“It will be a booster shot. Volunteers in the control group will receive the AstraZeneca vaccine. We’ll then compare levels of neutralizing antibodies to SARS-CoV-2 and T lymphocytes. We expect our formulation to trigger an even stronger cellular immune response,” Gazzinelli said.

About São Paulo Research Foundation (FAPESP)

The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the State of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration. You can learn more about FAPESP at www.fapesp.br/en and visit FAPESP news agency at www.agencia.fapesp.br/en to keep updated with the latest scientific breakthroughs FAPESP helps achieve through its many programs, awards and research centers. You may also subscribe to FAPESP news agency at http://agencia.fapesp.br/subscribe

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JOURNAL

Nature Communications

DOI

10.1038/s41467-022-32547-y 

METHOD OF RESEARCH

Randomized controlled/clinical trial

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein

Discovery of a new function of the cerebellum

Peer-Reviewed Publication

UNIVERSITY OF BASEL

 

IMAGE: THE CEREBELLUM (ACTIVATION IN RED) COMMUNICATES WITH VARIOUS AREAS OF THE CEREBRUM (ACTIVATIONS IN GREEN) TO ENHANCE STORAGE OF EMOTIONAL INFORMATION. view more 

CREDIT: MCN, UNIVERSITY OF BASEL

The cerebellum is known primarily for regulation of movement. Researchers at the University of Basel have now discovered that the cerebellum also plays an important role in remembering emotional experiences. The study appears in the journal PNAS.

Both positive and negative emotional experiences are stored particularly well in memory. This phenomenon is important to our survival, since we need to remember dangerous situations in order to avoid them in the future. Previous studies have shown that a brain structure called the amygdala, which is important in the processing of emotions, plays a central role in this phenomenon. Emotions activate the amygdala, which in turn facilitates the storage of information in various areas of the cerebrum.

The current research, led by Professor Dominique de Quervain and Professor Andreas Papassotiropoulos at the University of Basel, investigates the role of the cerebellum in storing emotional experiences. In a large-scale study, the researchers showed 1,418 participants emotional and neutral images and recorded the subjects’ brain activity using magnetic resonance imaging.

In a memory test conducted later, the positive and negative images were remembered by the participants much better than the neutral images. The improved storage of emotional images was linked with an increase in brain activity in the areas of the cerebrum already known to play a part. However, the team also identified increased activity in the cerebellum.

The cerebellum in communication with the cerebrum

The researchers were also able to demonstrate that the cerebellum shows stronger communication with various areas of the cerebrum during the process of enhanced storage of the emotional images. It receives information from the cingulate gyrus – a region of the brain that is important in the perception and evaluation of feelings. Furthermore, the cerebellum sends out signals to various regions of the brain, including the amygdala and hippocampus. The latter plays a central role in memory storage.

“These results indicate that the cerebellum is an integral component of a network that is responsible for the improved storage of emotional information,” says de Quervain. Although an improved memory for emotional events is a crucial mechanism for survival, it does have its downsides: in the case of very negative experiences, it can lead to recurring anxiety. This means that the findings, which have now been released, may also be relevant in understanding psychiatric conditions such as post-traumatic stress disorder.

Basel research on emotions and memory

The current study forms part of a large-scale research project conducted by the Research Platform Molecular and Cognitive Neurosciences (MCN) at the University of Basel and the University Psychiatric Clinics (UPK) Basel. The aim of this project is to gain a better understanding of emotional and cognitive processes and to transfer results from basic research to clinical projects.

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JOURNAL

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2204900119 

ARTICLE TITLE

Human cerebellum and corticocerebellar connections involved in emotional memory enhancement

Geneticists discover new wild goat subspecies via ancient DNA

Peer-Reviewed Publication

TRINITY COLLEGE DUBLIN

Geneticists from Trinity College Dublin, together with a team of international collaborators, have discovered a previously unknown lineage of wild goats over ten millennia old. The research was subject to open peer review and recommendation at PCI Genomics and has just been published in the journal eLife. 

The new goat type, discovered from genetic screening of bone remains and referred to as “the Taurasian tur”, likely survived the Last Glacial Maximum (the ice age), which stranded their ancestors in the high peaks of the Taurus Mountains in Turkey where their remains were found.

A chance discovery at Direkli Cave

Over 12,000 years ago, hunter-gatherers in the Taurus Mountains of southern Turkey relied heavily on local game for food and subsistence. Located near the present-day village of Döngel and at an elevation of ~1,100 m above sea level, Direkli Cave was used for roughly three millennia (~14,000-11,000 years ago) as a seasonal camp for these hunters and may have been inhabited year-round. 

“Among the artefacts found at Direkli Cave were large amounts of bone remains with distinct processing marks, indicating that wild goats were butchered there for consumption,” says Dr Kevin Daly, from Trinity’s School of Genetics and Microbiology, who is first author of the research article. 

“With the cave surrounded by high peaks, reaching ~2,200 m, the wild goat or bezoar ibex (Capra aegagrus) that inhabit the region today were likely the target of these Late Pleistocene hunters.” 

During genetic screening of goat bone remains from Direkli, the geneticists noticed something unusual: many of the goats carried mitochondrial genomes similar to a different species of wild goat. 

Whereas the domestic goat is derived from the bezoar ibex, other species of wild goat are still alive today and are found in relatively restricted regions. These include the East and West Caucasus tur, two sister species (or subspecies) of wild goat now found only in the Caucasus Mountains in Georgia. Many of the Direkli Cave samples carried mitochondria related to these Caucasus tur, despite Direkli Cave being around 800 km from their current habitat.

Dr Daly added: “An even greater surprise came when we examined the Direkli Cave goats’ nuclear genomes: while most looked like the bezoar ibex, as expected, one sample appeared different from the rest. This sample, Direkli4, showed more ancestral genetic variants than other Direkli goats, indicating it might have been a different species than the others.” 

To better understand this, the Trinity team collaborated with researchers from Muséum national d'Histoire naturelle of Paris to generate genetic data from other species in the Capra group. 

A new lineage of Tur

The team was surprised to see that the Direkli4 sample in fact grouped with the Caucasian tur – appearing to be a sister group to both East and West types. Intrigued, the team screened more material from Direkli Cave and found an additional two samples with a “tur-like” genome, suggesting that a population of these tur relatives lived in the Taurus Mountains close to local bezoar ibex, with both hunted by humans in pre-historic times. 

The team suggest a name for the discovered Taurasian tur: Capra taurensis or Capra caucasica taurensis; researchers still classify living tur as either subspecies or two distinct species.

As tur are larger and heavier than other wild goats, with a distinctive horn shape, it should be possible to identify a group of tur relatives in animal remains. Horn remains are absent at Direkli Cave, despite the large numbers of remains – possibly pointing to these being a valuable prize among hunters. But archaeozoologists in the team showed there were a lot of large-bodied goats at Direkli Cave – and possibly at other mountainous locations in southwest Asia. 

“We hope that this will encourage re-evaluation and analysis of faunal remains in the region as there could be some exciting discoveries still to be found,” added Dr Daly.

A victim of climatic change and human activity?

The team suggest that the ancestors of tur lived across a broader geographical area over the past 100,000 years, from the Caucasus Mountains to the Taurus Mountains by the Mediterranean - and that climate change may have caused habitat fragmentation. 

Dr Daly said: “The Last Glacial Maximum, or ice age, may have made many areas inhospitable, forcing these goats to compete with other species. The Taurasian tur may have been a leftover group, restricted to the peaks in the Taurus Mountains. Increasing human activity would have placed additional pressure on the Taurasian tur, with hunting evidenced at Direkli Cave. 

“While we don’t know exactly when or how this goat lineage became extinct, additional genomic surveys in the region might show that their genomes live on in present day wild goats.” 

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JOURNAL

eLife

DOI

10.7554/eLife.82984 

 

Taking salt out of the water equation

Peer-Reviewed Publication

KING ABDULLAH UNIVERSITY OF SCIENCE & TECHNOLOGY (KAUST)

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IMAGE: KAUST RESEARCHERS HAVE DEVELOPED A MEMBRANE (PICTURED ABOVE) WITH EXCELLENT WATER DESALINATION PERFORMANCE IN FORWARD AND REVERSE OSMOSIS CONFIGURATIONS. view more 

CREDIT: © 2022 KAUST; ANASTASIA SERIN.

Ultrathin polymer-based ordered membranes that effectively remove salt from seawater and brine could provide a promising alternative to existing water desalination systems, a KAUST-led team demonstrates.

 

“Water desalination membranes should simultaneously exhibit high water flux and high salt rejection,” says Yu Han, who led the study. Carbon nanomaterials, such as carbon nanotubes and graphene, are expected to meet these requirements because of their unique surface chemistry and propensity to stack into channels with diameters smaller than one nanometer. Yet, channel alignment and stacking difficulties make their large-scale use in membranes challenging.

 

“One way to address these limitations is through two-dimensional porous carbonaceous membranes with regular and uniformly distributed subnanometer-sized molecular transport channels,” says first author Jie Shen, a postdoc in Han’s group. However, these membranes are typically synthesized in solution, which promotes the random growth of a disordered three-dimensional structure with poorly defined micropores.

 

Yu Han, Vincent Tung, Ingo Pinnau and former KAUST scientist Lance Li, who is now at the University of Hong Kong, have developed a method that helps control the growth of two-dimensional conjugated polymer frameworks into ultrathin carbon films using chemical vapor deposition.

The researchers deposited the monomer triethynylbenzene on atomically flat single-crystalline copper substrates in the presence of an organic base that acts as a catalyst. Triethynylbenzene bears three reactive groups that serve as anchor points for additional monomers. These groups show a 120-degree angle with respect to each other, generating organized arrays of well-defined cyclic structures that stack into subnanometer-sized rhombic hydrophobic channels.

 

The membrane displayed excellent water desalination performance in forward and reverse osmosis configurations, surpassing those containing advanced materials such as carbon nanotubes and graphene. It also showed strong rejection for divalent ions, as well as small charged and neutral molecules.

 

The researchers discovered that the water molecules formed a three-dimensional network inside the membrane instead of moving through the membrane along vertical triangular channels as one-dimensional chains. This explains the fast water transport through the membrane. “This unexpected result revealed that the seemingly discrete vertical channels are actually interconnected by short horizontal channels that can be easily overlooked in the projected structural model,” Han says.

 

The team is now working on improving the antifouling property, mechanical strength and long-term chemical stability of the membrane for future practical applications. They are also fine-tuning its surface-charge properties and channel sizes. “Our ultimate goal is to provide a versatile multifunctional platform that meets the needs of various applications, such as ion sieving, single-molecule sensing and neural interfaces,” Han says.

Taking salt out of the water equation (VIDEO)

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JOURNAL

Nature Materials

DOI

10.1038/s41563-022-01325-y 

ARTICLE TITLE

Fast water transport and molecular sieving through ultrathin ordered conjugated-polymer-framework membranes

ICYMI

Mouthwashes may suppress SARS-CoV-2

Peer-Reviewed Publication

HOKKAIDO UNIVERSITY

 

IMAGE: CETYLPYRIDINIUM CHLORIDE (CPC), THE CHEMICAL TESTED IN THE STUDY (PHOTO: RYO TAKEDA) view more 

CREDIT: RYO TAKEDA

SARS-CoV-2, the virus that causes COVID-19, is an airborne disease transmitted via aerosols, which are spread from the oral and nasal cavities—the mouth and the nose. In addition to the well-known division and spread of the virus in the cells of the respiratory tract, SARS-CoV-2 is also known to infect the cells of the lining of the mouth and the salivary glands.

A team of researchers led by Professor Kyoko Hida at Hokkaido University have shown that low concentrations of the chemical cetylpyridinium chloride, a component of some mouthwashes, has an antiviral effect on SARS-CoV-2. Their findings were published in the journal Scientific Reports.

Commercially available mouthwashes contain a number of antibiotic and antiviral components that act against microorganisms in the mouth. One of these, cetylpyridinium chloride (CPC), has been shown to reduce the viral load of SARS-CoV-2 in the mouth, primarily by disrupting the lipid membrane surrounding the virus. While there are other chemicals with similar effects, CPC has the advantage of being tasteless and odorless.

The researchers were interested in studying the effects of CPC in Japanese mouthwashes. Mouthwashes in Japan typically contain a fraction of the CPC compared to previously tested mouthwashes. They tested the effects of CPC on cell cultures that express trans-membrane protease serine 2 (TMPRSS2), which is required for SARS-CoV-2 entry into the cell.

They found that, within 10 minutes of application, 30–50 µg/mL of CPC inhibited the infectivity and capability for cell entry of SARS-CoV-2. Interestingly, commercially available mouthwashes that contain CPC performed better than CPC alone. They also showed that saliva did not alter the effects of CPC. Most significantly, they tested four variants of SARS-CoV-2—the original, alpha, beta and gamma variants—and showed that the effects of CPC were similar across all strains.

This study shows that low concentrations of CPC in commercial mouthwash suppress the infectivity of four variants of SARS-CoV-2. The authors have already begun assessing the effect on CPC-containing mouthwashes on viral loads in saliva of COVID-19 patients. Future work will also focus on fully understanding the mechanism of effect, as lower concentrations of CPC do not disrupt lipid membranes.

 

CAPTION

Antiviral efficacy of CPC against SARS-CoV-2 in cell cultures expressing TMPRSS2. For all of the four strains tested, a concentration of 40 µg/mL of CPC significantly reduced the viral titers, the number of virus particles. Asterisks indicate significant results (Ryo Takeda, et al. Scientific Reports. August 18, 2022).

CREDIT

Ryo Takeda, et al. Scientific Reports. August 18, 2022

 

CAPTION

Ryo Takeda (back row, orange t-shirt), first author, and Kyoko Hida (front row, yellow-green jacket), corresponding author of the study, with members of the Hida Group (Photo: Kyoko Hida).

CREDIT

Kyoko Hida

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JOURNAL

Scientific Reports

DOI

10.1038/s41598-022-18367-6 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Cells

ARTICLE TITLE

Antiviral effect of cetylpyridinium chloride in mouthwash on SARS‐CoV‐2

NTU Singapore scientists develop inexpensive device that can harvest energy from a light breeze and store it as electricity

Peer-Reviewed Publication

NANYANG TECHNOLOGICAL UNIVERSITY

 

IMAGE: (L-R) MR LIU ZICHENG, PHD STUDENT FROM NTU’S SCHOOL OF CIVIL AND ENVIRONMENTAL ENGINEERING (CEE), DR HU GUOBIAO, RESEARCH FELLOW FROM NTU’S CEE, MR ZHAO CHAOYANG, RESEARCH ASSOCIATE FROM NTU’S CEE, AND PROFESSOR YANG YAOWEN, ASSOCIATE CHAIR (FACULTY) OF NTU’S CEE. view more 

CREDIT: NTU SINGAPORE

Scientists from Nanyang Technological University, Singapore (NTU Singapore) have developed a low-cost device that can harness energy from wind as gentle as a light breeze and store it as electricity.

When exposed to winds with a velocity as low as two metres per second (m/s), the device can produce a voltage of three volts and generate electricity power of up to 290 microwatts, which is sufficient to power a commercial sensor device and for it to also send the data to a mobile phone or a computer.

The light and durable device, called a wind harvester, also diverts any electricity that is not in use to a battery, where it can be stored to power devices in the absence of wind.

The scientists say their invention has the potential to replace batteries in powering light emitting diode (LED) lights and structural health monitoring sensors. Those are used on urban structures, such as bridges and skyscrapers, to monitor their structural health, alerting engineers to issues such as instabilities or physical damage.

Measuring only 15 centimetres by 20 centimetres, the device can easily be mounted on the sides of buildings, and would be ideal for urban environments, such as Singaporean suburbs, where average wind speeds are less than 2.5 m/s, outside of thunderstorms[1].

The findings were published in the scientific peer-reviewed journal Mechanical Systems and Signal Processing in September.

Professor Yang Yaowen, a structural engineer from NTU’s School of Civil and Environmental Engineering (CEE), who led the project, said: “As a renewable and clean energy source, wind power generation has attracted extensive research attention. Our research aims to tackle the lack of a small-scale energy harvester for more targeted functions, such as to power smaller sensors and electronic devices. The device we developed also serves as a potential alternative to smaller lithium-ion batteries, as our wind harvester is self-sufficient and would only require occasional maintenance, and does not use heavy metals, which if not disposed of properly, could cause environmental problems.”

The innovation has received interest from the industry. The NTU research team is also working towards commercialising their invention.

The study, which presents an innovation that could help cut down on electronic waste and find alternative sources for energy, reflects NTU's commitment to mitigate our impact on the environment, which is one of four humanity’s grand challenges that the University seeks to address through its NTU 2025 strategic plan.

Riding the wind

The device was developed to harness efficient wind energy at low cost and with low wear and tear. Its body is made of fibre epoxy, a highly durable polymer, with the main attachment that interacts with the wind and is made of inexpensive materials, such as copper, aluminium foil, and polytetrafluoroethylene, a durable polymer that is also known as Teflon.

Due to the dynamic design of its structure, when the harvester is exposed to wind flow, it begins to vibrate, causing its plate to approach to and depart from the stopper. This causes charges to be formed on the film, and an electrical current is formed as they flow from the aluminium foil to the copper film.

In laboratory tests, the NTU-developed harvester could power 40 LEDs consistently at a wind speed of 4 m/s. It could also trigger a sensor device, and power it sufficiently to send the room temperature information to a mobile phone wirelessly.

This demonstrated that the harvester could not only generate electricity to consistently power a device, but that it could store excess charge that was sufficient to keep the device powered for an extended period in the absence of wind.

Prof Yang added: “Wind energy is a source of renewable energy. It does not contaminate, it is inexhaustible and reduces the use of fossil fuels, which are the origin of greenhouse gasses that cause global warming. Our invention has been shown to effectively harness this sustainable source of energy to charge batteries and light LEDs, demonstrating its potential as an energy generator to power the next generation of electronics, which are smaller in size and require less power.”

The NTU team will be conducting further research to further improve the energy storage functions of their device, as well as experiment with different materials to improve its output power. The research team is also in the process of filing for a patent with NTUitive, NTU’s innovation and enterprise company.

CAPTION

Professor Yang Yaowen demonstrating how the device can generate and store electricity when exposed to a breeze generated by a wind tunnel.

CREDIT

NTU Singapore

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[1] Meteorological Service Singapore. Climate of Singapore (2022).

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JOURNAL

Mechanical Systems and Signal Processing

DOI

10.1016/j.ymssp.2022.109185 

METHOD OF RESEARCH

Meta-analysis

ARTICLE TITLE

A cantilever-type vibro-impact triboelectric energy harvester for wind energy harvesting

Wear and tear from lifelong stress can increase cancer mortality

Peer-Reviewed Publication

MEDICAL COLLEGE OF GEORGIA AT AUGUSTA UNIVERSITY

 

IMAGE: DR. JUSTIN X. MOORE view more 

CREDIT: MIKE HOLAHAN, AUGUSTA UNIVERSITY

AUGUSTA, Ga. (Oct. 6, 2022) – The wear and tear on the body from chronic and lifelong stress can also lead to an increased risk of dying from cancer, Medical College of Georgia researchers report.

That wear and tear, called allostatic load, refers to the cumulative effects of stress over time. “As a response to external stressors, your body releases a stress hormone called cortisol, and then once the stress is over, these levels should go back down,” says Dr. Justin Xavier Moore, epidemiologist at the Medical College of Georgia and Georgia Cancer Center. “However, if you have chronic, ongoing psychosocial stressors, that never allow you to ‘come down,’ then that can cause wear and tear on your body at a biological level.”

Investigators, led by Moore, performed a retrospective analysis of more than 41,000 people from the National Health and Nutrition Examination Survey, or NHANES, collected between 1988-2019. That database includes baseline biological measures of participants — body mass index, diastolic and systolic blood pressure, total cholesterol, hemoglobin A1C (higher levels indicate a risk for diabetes), albumin and creatinine (both measures of kidney function) and C-reactive protein (a measure of inflammation) — that the researchers used to determine allostatic load. Those with a score of more than 3 were categorized as having high allostatic load.

Then they cross referenced those participants with the National Death Index, maintained by the National Center for Health Statistics and the Centers for Disease Control and Prevention, to determine which people died from cancer and when, Moore explains.

“To date, there has been limited research on the relationship between allostatic load and cancer among a current, nationally representative sample of US adults,” Moore and his colleagues write in the journal SSM Population Health. “Examining the association of allostatic load on cancer outcomes, and whether these associations vary by race may give insight to novel approaches in mitigating cancer disparities.”

The researchers found that, even without adjusting for any potential confounders like age, social demographics like race and sex, poverty to income ratio and educational level, those with a high allostatic load were 2.4 times more likely to die from cancer than those with low allostatic loads.

“But you have to adjust for confounding factors,” Moore explains. “We know there are differences in allostatic loads based on age, race and gender.”

In fact, in previous research he and his colleagues observed that when looking at trends in allostatic load over 30 years among 50,671 individuals, adults aged 40 and older had greater than a 100% increased risk of high allostatic load when compared to adults under 30. Further, regardless of the time period, Black and Latino adults had an increased risk of high allostatic load when compared with their white counterparts. Much of that, Moore says, can be attributed to structural racism — things like difficulty navigating better educational opportunities or fair and equitable home loans.

“If you’re born into an environment where your opportunities are much different than your white male counterparts, for example being a black female, your life course trajectory involves dealing with more adversity,” he says.

Even when controlling for age, the researchers found that people with high allostatic load still have even 28% increased risk of dying from cancer. “That means that if you were to have two people of the same age, if one of those people had high allostatic load, they are 28% more likely to die from cancer,” Moore says.

Adjusting for sociodemographic factors including sex and race and educational level, high allostatic load led to a 21% increase; and further adjusting the model for other risk factors like whether participants smoked, previously had a heart attack, or been previously diagnosed with cancer or congestive heart failure, led to a 14% increase.

Moore and colleagues further examined the relationship between allostatic load and cancer mortality specifically among each racial/ethnic group (e.g., non-Hispanic Black, non-Hispanic white, and Hispanic adults). However, allostatic load was not as strongly related when broken down by race categories. These findings could be explained by the sheer size of the original sample.

“Epidemiologically, when looking at 41,000 people, there are many cancer related-death events,” Moore explains. “However, it is more difficult to ascertain a relationship between x (allostatic load) and y (cancer death) when you essentially have less datapoints to measure.” For example, limiting the sample to just non-Hispanic Blacks would mean analyzing a sample of just 11,000 people, so the relationship may look diminished or attenuated.

“The reason race even matters, is because there are systemic factors that disproportionately affect people of color,” he says. “But even if you take race out, the bottom line is that the environments in which we live, work and play, where you are rewarded for working more and sometimes seen as weak for taking time for yourself, is conducive to high stress which in turn may lead to cancer development and increased morbidity and mortality.”

In the United States, cancer is the second leading cause of death and it was responsible for an estimated 1.9 million cases and nearly 609,000 deaths in 2021.

Read the full study.

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JOURNAL

SSM - Population Health

ARTICLE TITLE

Exploring racial disparities on the association between allostatic load and cancer mortality: A retrospective cohort analysis of NHANES, 1988 through 2019