Vitamin D levels appear to play role in COVID-19 mortality rates

Vitamin D levels appear to play role in COVID-19 mortality rates

After studying global data from the novel coronavirus (COVID-19) pandemic, researchers have discovered a strong correlation between severe vitamin D deficiency and mortality rates.

Led by Northwestern University, the research team conducted a statistical analysis of data from hospitals and clinics across China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom (UK) and the United States.

The researchers noted that patients from countries with high COVID-19 mortality rates, such as Italy, Spain and the UK, had lower levels of vitamin D compared to patients in countries that were not as severely affected.

This does not mean that everyone -- especially those without a known deficiency -- needs to start hoarding supplements, the researchers caution.

"While I think it is important for people to know that vitamin D deficiency might play a role in mortality, we don't need to push vitamin D on everybody," said Northwestern's Vadim Backman, who led the research. "This needs further study, and I hope our work will stimulate interest in this area. The data also may illuminate the mechanism of mortality, which, if proven, could lead to new therapeutic targets."

The research is available on medRxiv, a preprint server for health sciences.

Backman is the Walter Dill Scott Professor of Biomedical Engineering at Northwestern's McCormick School of Engineering. Ali Daneshkhah, a postdoctoral research associate in Backman's laboratory, is the paper's first author.

Backman and his team were inspired to examine vitamin D levels after noticing unexplained differences in COVID-19 mortality rates from country to country. Some people hypothesized that differences in healthcare quality, age distributions in population, testing rates or different strains of the coronavirus might be responsible. But Backman remained skeptical.

"None of these factors appears to play a significant role," Backman said. "The healthcare system in northern Italy is one of the best in the world. Differences in mortality exist even if one looks across the same age group. And, while the restrictions on testing do indeed vary, the disparities in mortality still exist even when we looked at countries or populations for which similar testing rates apply.

"Instead, we saw a significant correlation with vitamin D deficiency," he said.

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm -- a hyperinflammatory condition caused by an overactive immune system -- as well as a correlation between vitamin D deficiency and mortality.

"Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients," Daneshkhah said. "This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system."

This is exactly where Backman believes vitamin D plays a major role. Not only does vitamin D enhance our innate immune systems, it also prevents our immune systems from becoming dangerously overactive. This means that having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19.

"Our analysis shows that it might be as high as cutting the mortality rate in half," Backman said. "It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected."

Backman said this correlation might help explain the many mysteries surrounding COVID-19, such as why children are less likely to die. Children do not yet have a fully developed acquired immune system, which is the immune system's second line of defense and more likely to overreact.

"Children primarily rely on their innate immune system," Backman said. "This may explain why their mortality rate is lower."

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

"It is hard to say which dose is most beneficial for COVID-19," Backman said. "However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency."

Backman is the director of Northwestern's Center for Physical Genomics and Engineering and the associate director for Research Technology and Infrastructure at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.

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Story Source:

Materials provided by Northwestern University. Original written by Amanda Morris. Note: Content may be edited for style and length.

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Journal Reference:

1. Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv, Posted April 30, 2020; [link]

Vitamin D levels appear to play role in COVID-19 mortality rates

Doctor, vitamin D concept (stock image).

After studying global data from the novel coronavirus (COVID-19) pandemic, researchers have discovered a strong correlation between severe vitamin D deficiency and mortality rates.

Led by Northwestern University, the research team conducted a statistical analysis of data from hospitals and clinics across China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom (UK) and the United States.

The researchers noted that patients from countries with high COVID-19 mortality rates, such as Italy, Spain and the UK, had lower levels of vitamin D compared to patients in countries that were not as severely affected.

This does not mean that everyone -- especially those without a known deficiency -- needs to start hoarding supplements, the researchers caution.

"While I think it is important for people to know that vitamin D deficiency might play a role in mortality, we don't need to push vitamin D on everybody," said Northwestern's Vadim Backman, who led the research. "This needs further study, and I hope our work will stimulate interest in this area. The data also may illuminate the mechanism of mortality, which, if proven, could lead to new therapeutic targets."

The research is available on medRxiv, a preprint server for health sciences.

Backman is the Walter Dill Scott Professor of Biomedical Engineering at Northwestern's McCormick School of Engineering. Ali Daneshkhah, a postdoctoral research associate in Backman's laboratory, is the paper's first author.

Backman and his team were inspired to examine vitamin D levels after noticing unexplained differences in COVID-19 mortality rates from country to country. Some people hypothesized that differences in healthcare quality, age distributions in population, testing rates or different strains of the coronavirus might be responsible. But Backman remained skeptical.

"None of these factors appears to play a significant role," Backman said. "The healthcare system in northern Italy is one of the best in the world. Differences in mortality exist even if one looks across the same age group. And, while the restrictions on testing do indeed vary, the disparities in mortality still exist even when we looked at countries or populations for which similar testing rates apply.

"Instead, we saw a significant correlation with vitamin D deficiency," he said.

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm -- a hyperinflammatory condition caused by an overactive immune system -- as well as a correlation between vitamin D deficiency and mortality.

"Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients," Daneshkhah said. "This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system."

This is exactly where Backman believes vitamin D plays a major role. Not only does vitamin D enhance our innate immune systems, it also prevents our immune systems from becoming dangerously overactive. This means that having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19.

"Our analysis shows that it might be as high as cutting the mortality rate in half," Backman said. "It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected."

Backman said this correlation might help explain the many mysteries surrounding COVID-19, such as why children are less likely to die. Children do not yet have a fully developed acquired immune system, which is the immune system's second line of defense and more likely to overreact.

"Children primarily rely on their innate immune system," Backman said. "This may explain why their mortality rate is lower."

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

"It is hard to say which dose is most beneficial for COVID-19," Backman said. "However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency."

Backman is the director of Northwestern's Center for Physical Genomics and Engineering and the associate director for Research Technology and Infrastructure at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University.

---

Story Source:

Materials provided by Northwestern University. Original written by Amanda Morris. Note: Content may be edited for style and length.

---

Journal Reference:

1. Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. medRxiv, Posted April 30, 2020; [link]

Baby and adult brains 'sync up' during play

Woman and baby playing (stock image).

Have you ever played with a baby and felt a sense of connection, even though they couldn't yet talk to you? New research suggests that you might quite literally be "on the same wavelength," experiencing similar brain activity in the same brain regions.

A team of Princeton researchers has conducted the first study of how baby and adult brains interact during natural play, and they found measurable similarities in their neural activity. In other words, baby and adult brain activity rose and fell together as they shared toys and eye contact. The research was conducted at the Princeton Baby Lab, where University researchers study how babies learn to see, talk and understand the world.

"Previous research has shown that adults' brains sync up when they watch movies and listen to stories, but little is known about how this 'neural synchrony' develops in the first years of life," said Elise Piazza, an associate research scholar in the Princeton Neuroscience Institute (PNI) and the first author on a paper published Dec. 17, 2019, in Psychological Science.

Piazza and her co-authors -- Liat Hasenfratz, an associate research scholar in PNI; Uri Hasson, a professor of psychology and neuroscience; and Casey Lew-Williams, an associate professor of psychology -- posited that neural synchrony has important implications for social development and language learning.

Studying real-life, face-to-face communication between babies and adults is quite difficult. Most past studies of neural coupling, many of which were conducted in Hasson's lab, involved scanning adults' brains with functional magnetic resonance imaging (fMRI), in separate sessions, while the adults lay down and watched movies or listened to stories.

But to study real-time communication, the researchers needed to create a child-friendly method of recording brain activity simultaneously from baby and adult brains. With funding from the Eric and Wendy Schmidt Transformative Technology Grant, the researchers developed a new dual-brain neuroimaging system that uses functional near-infrared spectroscopy (fNIRS), which is highly safe and records oxygenation in the blood as a proxy for neural activity. The setup allowed the researchers to record the neural coordination between babies and an adult while they played with toys, sang songs and read a book.

The same adult interacted with all 42 infants and toddlers who participated in the study. Of those, 21 had to be excluded because they "squirmed excessively," and three others flat-out refused to wear the cap, leaving 18 children, ranging in age from 9 months to 15 months.

The experiment had two portions. In one, the adult experimenter spent five minutes interacting directly with a child -- playing with toys, singing nursery rhymes or reading Goodnight Moon -- while the child sat on their parent's lap. In the other, the experimenter turned to the side and told a story to another adult while the child played quietly with their parent.

The caps collected data from 57 channels of the brain known to be involved in prediction, language processing and understanding other people's perspectives.

When they looked at the data, the researchers found that during the face-to-face sessions, the babies' brains were synchronized with the adult's brain in several areas known to be involved in high-level understanding of the world -- perhaps helping the children decode the overall meaning of a story or analyze the motives of the adult reading to them.

When the adult and infant were turned away from each other and engaging with other people, the coupling between them disappeared.

That fit with researchers' expectations, but the data also had surprises in store. For example, the strongest coupling occurred in the prefrontal cortex, which is involved in learning, planning and executive functioning and was previously thought to be quite underdeveloped during infancy.

"We were also surprised to find that the infant brain was often 'leading' the adult brain by a few seconds, suggesting that babies do not just passively receive input but may guide adults toward the next thing they're going to focus on: which toy to pick up, which words to say," said Lew-Williams, who is a co-director of the Princeton Baby Lab.

"While communicating, the adult and child seem to form a feedback loop," Piazza added. "That is, the adult's brain seemed to predict when the infants would smile, the infants' brains anticipated when the adult would use more 'baby talk,' and both brains tracked joint eye contact and joint attention to toys. So, when a baby and adult play together, their brains influence each other in dynamic ways."

This two-brain approach to neuroscience could open doors to understanding how coupling with caregivers breaks down in atypical development -- such as in children diagnosed with autism -- as well as how educators can optimize their teaching approaches to accommodate children's diverse brains.

The researchers are continuing to investigate how this neural coupling relates to preschoolers' early language learning.

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Story Source:

Materials provided by Princeton University. Original written by Liz Fuller-Wright. Note: Content may be edited for style and length.

Little-known protein appears to play important role in obesity and metabolic disease

Obese related protein structure

With unexpected findings about a protein that's highly expressed in fat tissue, scientists at Scripps Research have opened the door to critical new understandings about obesity and metabolism. Their discovery, which appears Nov. 20 in the journal Nature, could lead to new approaches for addressing obesity and potentially many other diseases.

The signaling protein, known as PGRMC2, had not been extensively studied in the past. Short for "progesterone receptor membrane component 2," it had been detected in the uterus, liver and several areas of the body. But the lab of Enrique Saez, PhD, saw that it was most abundant in fat tissue -- particularly in brown fat, which turns food into heat to maintain body temperature -- and became interested in its function there.

An important role: heme's travel guide

The team built on their recent discovery that PGRMC2 binds to and releases an essential molecule called heme. Recently in the spotlight for its role in providing flavor to the plant-based Impossible Burger, heme holds a much more significant role in the body. The iron-containing molecule travels within cells to enable crucial life processes such as cellular respiration, cell proliferation, cell death and circadian rhythms.

Using biochemical techniques and advanced assays in cells, Saez and his team found that PGRMC2 is a "chaperone" of heme, encapsulating the molecule and transporting it from the cell's mitochondria, where heme is created, to the nucleus, where it helps carry out important functions. Without a protective chaperone, heme would react with -- and destroy -- everything in its path.

"Heme's significance to many cellular processes has been known for a long time," says Saez, associate professor in the Department of Molecular Medicine. "But we also knew that heme is toxic to the cellular materials around it and would need some sort of shuttling pathway. Until now, there were many hypotheses, but the proteins that traffic heme had not been identified."

An innovative approach for obesity?

Through studies involving mice, the scientists established PGRMC2 as the first intracellular heme chaperone to be described in mammals. However, they didn't stop there; they sought to find out what happens in the body if this protein doesn't exist to transport heme.

And that's how they made their next big discovery: Without PGRMC2 present in their fat tissues, mice that were fed a high-fat diet became intolerant to glucose and insensitive to insulin -- hallmark symptoms of diabetes and other metabolic diseases. By contrast, obese-diabetic mice that were treated with a drug to activate PGRMC2 function showed a substantial improvement of symptoms associated with diabetes.

"We saw the mice get better, becoming more glucose tolerant and less resistant to insulin," Saez says. "Our findings suggest that modulating PGRMC2 activity in fat tissue may be a useful pharmacological approach for reverting some of the serious health effects of obesity."

The team also evaluated how the protein changes other functions of brown and white fat, says the study's lead author, Andrea Galmozzi, PhD. "The first surprise finding was that the brown fat looked white," he says.

Brown fat, which is normally the highest in heme content, is often considered the "good fat." One of its key roles is to generate heat to maintain body temperature. Among mice that were unable to produce PGRMC2 in their fat tissues, temperatures dropped quickly when placed in a cold environment.

"Even though their brain was sending the right signals to turn on the heat, the mice were unable to defend their body temperature," Galmozzi says. "Without heme, you get mitochondrial dysfunction and the cell has no means to burn energy to generate heat."

Saez believes it's possible that activating the heme chaperone in other organs -- including the liver, where a large amount of heme is made -- could help mitigate the effects of other metabolic disorders such as non-alcoholic steatohepatitis (NASH), which is a major cause of liver transplantation today.

"We're curious to know whether this protein performs the same role in other tissues where we see defects in heme that result in disease" Saez says.

---

Story Source:

Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.

Little-known protein appears to play important role in obesity and metabolic disease

With unexpected findings about a protein that's highly expressed in fat tissue, scientists at Scripps Research have opened the door to critical new understandings about obesity and metabolism. Their discovery, which appears Nov. 20 in the journal Nature, could lead to new approaches for addressing obesity and potentially many other diseases.

The signaling protein, known as PGRMC2, had not been extensively studied in the past. Short for "progesterone receptor membrane component 2," it had been detected in the uterus, liver and several areas of the body. But the lab of Enrique Saez, PhD, saw that it was most abundant in fat tissue -- particularly in brown fat, which turns food into heat to maintain body temperature -- and became interested in its function there.

An important role: heme's travel guide

The team built on their recent discovery that PGRMC2 binds to and releases an essential molecule called heme. Recently in the spotlight for its role in providing flavor to the plant-based Impossible Burger, heme holds a much more significant role in the body. The iron-containing molecule travels within cells to enable crucial life processes such as cellular respiration, cell proliferation, cell death and circadian rhythms.

Using biochemical techniques and advanced assays in cells, Saez and his team found that PGRMC2 is a "chaperone" of heme, encapsulating the molecule and transporting it from the cell's mitochondria, where heme is created, to the nucleus, where it helps carry out important functions. Without a protective chaperone, heme would react with -- and destroy -- everything in its path.

"Heme's significance to many cellular processes has been known for a long time," says Saez, associate professor in the Department of Molecular Medicine. "But we also knew that heme is toxic to the cellular materials around it and would need some sort of shuttling pathway. Until now, there were many hypotheses, but the proteins that traffic heme had not been identified."

An innovative approach for obesity?

Through studies involving mice, the scientists established PGRMC2 as the first intracellular heme chaperone to be described in mammals. However, they didn't stop there; they sought to find out what happens in the body if this protein doesn't exist to transport heme.

And that's how they made their next big discovery: Without PGRMC2 present in their fat tissues, mice that were fed a high-fat diet became intolerant to glucose and insensitive to insulin -- hallmark symptoms of diabetes and other metabolic diseases. By contrast, obese-diabetic mice that were treated with a drug to activate PGRMC2 function showed a substantial improvement of symptoms associated with diabetes.

"We saw the mice get better, becoming more glucose tolerant and less resistant to insulin," Saez says. "Our findings suggest that modulating PGRMC2 activity in fat tissue may be a useful pharmacological approach for reverting some of the serious health effects of obesity."

The team also evaluated how the protein changes other functions of brown and white fat, says the study's lead author, Andrea Galmozzi, PhD. "The first surprise finding was that the brown fat looked white," he says.

Brown fat, which is normally the highest in heme content, is often considered the "good fat." One of its key roles is to generate heat to maintain body temperature. Among mice that were unable to produce PGRMC2 in their fat tissues, temperatures dropped quickly when placed in a cold environment.

"Even though their brain was sending the right signals to turn on the heat, the mice were unable to defend their body temperature," Galmozzi says. "Without heme, you get mitochondrial dysfunction and the cell has no means to burn energy to generate heat."

Saez believes it's possible that activating the heme chaperone in other organs -- including the liver, where a large amount of heme is made -- could help mitigate the effects of other metabolic disorders such as non-alcoholic steatohepatitis (NASH), which is a major cause of liver transplantation today.

"We're curious to know whether this protein performs the same role in other tissues where we see defects in heme that result in disease" Saez says.

---

Story Source:

Materials provided by Scripps Research Institute. Note: Content may be edited for style and length.