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]

Newer variant of COVID-19-causing virus dominates global infections

Newer variant of COVID-19

Research out today in the journal Cell shows that a specific change in the SARS-CoV-2 coronavirus virus genome, previously associated with increased viral transmission and the spread of COVID-19, is more infectious in cell culture. The variant in question, D614G, makes a small but effective change in the virus's 'Spike' protein, which the virus uses to enter human cells.

Bette Korber, a theoretical biologist at Los Alamos National Laboratory and lead author of the study, noted, "The D614G variant first came to our attention in early April, as we had observed a strikingly repetitive pattern. All over the world, even when local epidemics had many cases of the original form circulating, soon after the D614G variant was introduced into a region it became the prevalent form."

Geographic information from samples from the GISAID COVID-19 viral sequence database enabled tracking of this highly recurrent pattern, a shift in the viral population from the original form to the D614G variant. This occurred at every geographic level: country, subcountry, county, and city.

Two independent lines of experimental evidence that support these initial results are included in today's paper. These additional experiments, led by Professor Erica Ollmann Saphire, Ph.D., at the La Jolla Institute, and by Professor David Montefiori, Ph.D., at Duke University, showed that the D614G change increases the virus's infectivity in the laboratory. These new experiments, as well as more extensive sequence and clinical data and improved statistical models, are presented in the Cell paper. More in vivo work remains to be done to determine the full implications of the change.

The SARS-CoV-2 virus has a low mutation rate overall (much lower than the viruses that cause influenza and HIV-AIDS). The D614G variant appears as part of a set of four linked mutations that appear to have arisen once and then moved together around the world as a consistent set of variations.

"It's remarkable to me," commented Will Fischer of Los Alamos, an author on the study, "both that this increase in infectivity was detected by careful observation of sequence data alone, and that our experimental colleagues could confirm it with live virus in such a short time."

Fortunately, "the clinical data in this paper from Sheffield showed that even though patients with the new G virus carried more copies of the virus than patients infected with D, there wasn't a corresponding increase in the severity of illness," said Saphire, who leads the Gates Foundation-supported Coronavirus Immunotherapy Consortium (CoVIC).

Korber noted, "These findings suggest that the newer form of the virus may be even more readily transmitted than the original form -- whether or not that conclusion is ultimately confirmed, it highlights the value of what were already good ideas: to wear masks and to maintain social distancing."

Research partners from Los Alamos National Laboratory, Duke University, and the University of Sheffield initially published work on this analysis on the bioRxiv site in an April 2020 preprint. That work also included observations of COVID-19 patients from Sheffield that suggested an association of the D614G variant with higher viral loads in the upper respiratory tract.

"It is possible to track SARS-CoV-2 evolution globally because researchers worldwide are rapidly making their viral sequence data available through the GISAID viral sequence database," Korber said. Currently tens of thousands of sequences are available through this project, and this enabled Korber and the research team to identify the emergence of the D614G variant.

GISAID was established to encourage collaboration among influenza researchers, but early in the epidemic the consortium established a SARS-CoV-2 database, which soon became the de facto standard for sharing outbreak sequences among researchers worldwide.

The study, "Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus" was supported by the Medical Research Council (MRC) part of UK Research & Innovation (UKRI the National Institute of Health Research (NIHR); Genome Research Limited, operating as the Wellcome Sanger Institute; CoVIC, INV-006133 of the COVID-19 Therapeutics Accelerator, supported by the Bill and Melinda Gates Foundation, Mastercard, Wellcome; private philanthropic support, as well as the Overton family; a FastGrant, from Emergent Ventures, in aid of COVID-19 research; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Interagency Agreement No. AAI12007-001-00000, and the Los Alamos Laboratory Directed Research and Development program.

Additional study authors included S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche.

Story Source:

Materials provided by DOE/Los Alamos National Laboratory. Note: Content may be edited for style and length.

Journal Reference:

1. B. Korber, W.M. Fischer, S. Gnanakaran, H. Yoon, J. Theiler, W. Abfalterer, N. Hengartner, E.E. Giorgi, T. Bhattacharya, B. Foley, K.M. Hastie, M.D. Parker, D.G. Partridge, C.M. Evans, T.M. Freeman, T.I. de Silva, C. McDanal, L.G. Perez, H. Tang, A. Moon-Walker, S.P. Whelan, C.C. LaBranche, E.O. Saphire, D.C. Montefiori, on behalf of theSheffield COVID-19 Genomics Group. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell, July 2, 2020; DOI: 10.1016/j.cell.2020.06.043

Loss of smell and taste validated as COVID-19 symptoms in patients with high recovery rate

Loss of smell and taste has been anecdotally linked to COVID-19 infections. In a study published April 12, 2020 in the journal International Forum of Allergy & Rhinology, researchers at UC San Diego Health report the first empirical findings that strongly associate sensory loss with COVID-19, the respiratory disease caused by the novel coronavirus.

"Based on our study, if you have smell and taste loss, you are more than 10 times more likely to have COVID-19 infection than other causes of infection. The most common first sign of a COVID-19 infection remains fever, but fatigue and loss of smell and taste follow as other very common initial symptoms," said Carol Yan, MD, an otolaryngologist and head and neck surgeon at UC San Diego Health. "We know COVID-19 is an extremely contagious virus. This study supports the need to be aware of smell and taste loss as early signs of COVID-19."

Yan and colleagues surveyed 1,480 patients with flu-like symptoms and concerns regarding potential COVID-19 infection who underwent testing at UC San Diego Health from March 3 through March 29, 2020. Within that total, 102 patients tested positive for the virus and 1,378 tested negative. The study included responses from 59 COVID-19-positive patients and 203 COVID-19-negative patients.

Yan said the study demonstrated the high prevalence and unique presentation of certain sensory impairments in patients positive with COVID-19. Of those who reported loss of smell and taste, the loss was typically profound, not mild. But encouragingly, the rate of recovery of smell and taste was high and occurred usually within two to four weeks of infection.

"Our study not only showed that the high incidence of smell and taste is specific to COVID-19 infection, but we fortunately also found that for the majority of people sensory recovery was generally rapid," said Yan. "Among the Covid-19 patients with smell loss, more than 70 percent had reported improvement of smell at the time of survey and of those who hadn't reported improvement, many had only been diagnosed recently."

Sensory return typically matched the timing of disease recovery. Interestingly, the researchers found that persons who reported experiencing a sore throat more often tested negative for COVID-19.

In an effort to decrease risk of virus transmission, UC San Diego Health now includes loss of smell and taste as a screening requirement for visitors and staff, as well as a marker for testing patients who may be positive for the virus.

Other known symptoms of COVID-19 include fever, fatigue, cough and difficulty breathing. Respondents in Yan's study were most often persons with milder forms of COVID-19 infection who did not require hospitalization or intubation. The findings, she said, underline the importance of identifying early or subtle symptoms of COVID-19 infection in people who may be at risk of transmitting the disease as they recuperate within the community.

"It is our hope that with these findings other institutions will follow suit and not only list smell and taste loss as a symptom of COVID-19, but use it as a screening measure for the virus across the world," Yan said.

Co-authors include: Farhoud Faraji, Divya P. Prajapti, Christine E. Boone and Adam S. DeConde, all at UC San Diego.

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Story Source:

Materials provided by University of California - San Diego. Original written by Jeanna Vazquez. Note: Content may be edited for style and length.

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Journal Reference:

1. Carol H. Yan, Farhoud Faraji, Divya P. Prajapati, Christine E. Boone, Adam S DeConde. Association of chemosensory dysfunction and Covid-19 in patients presenting with influenza-like symptoms. International Forum of Allergy & Rhinology, 2020; DOI: 10.1002/alr.22579

Wearing surgical masks in public could help slow COVID-19 pandemic's advance

Surgical masks may help prevent infected people from making others sick with seasonal viruses, including coronaviruses, according to new research that could help settle a fierce debate spanning clinical and cultural norms.

In laboratory experiments, the masks significantly reduced the amounts of various airborne viruses coming from infected patients, measured using the breath-capturing "Gesundheit II machine" developed by Dr. Don Milton, a professor of applied environmental health and a senior author of the study published April 3 in the journal Nature Medicine.

Milton has already conferred with federal and White House health officials on the findings, which closely follow statements this week from the head of the Centers for Disease Control and Prevention saying the agency was reconsidering oft-stated advice that surgical masks aren't a useful precaution outside of medical settings. (The debate takes place at a time when clinicians themselves face dangerously inadequate supplies of masks -- a shortfall other UMD researchers are scrambling to help solve.)

The question of masks has roiled society as well, with some retailers refusing to let employees wear them for fear of sending negative signals to customers, and cases of slurs and even physical attacks in the United States and elsewhere against Asians or Asian Americans who were wearing masks, a measure some consider a necessity during a disease outbreak.

The study, conducted prior to the current pandemic with a student of Milton's colleagues on the Faculty of Medicine at the University of Hong Kong, does not address the question of whether surgical masks protect wearers from infection. It does suggest that masks may limit how much the infected -- who in the case of the novel coronavirus often don't have symptoms -- spread diseases including influenza, rhinoviruses and coronaviruses.

Milton, who runs the Public Health Aerobiology, Virology, and Exhaled Biomarker Laboratory in the School of Public Health, demonstrated in a 2013 study that surgical masks could help limit flu transmission. However, he cautions that the effect may not be as great outside of controlled settings.

Nevertheless, he said, the chance they could help justifies taking a new look at whether all people should be encouraged to wear them when they venture out of their houses to stores or other populated locations during the current COVID-19 lockdown.

"In normal times we'd say that if it wasn't shown statistically significant or the effective in real-world studies, we don't recommend it," he said. "But in the middle of a pandemic, we're desperate. The thinking is that even if it cuts down transmission a little bit, it's worth trying."

Previous studies have shown that coronavirus and other respiratory infections are mostly spread during close contact, which has been interpreted by some infectious disease specialists to mean that the disease could spread only through contact and large droplets, such as from a cough or sneeze -- a message that has often been shared with the public.

"What they don't understand is that is merely a hypothesis," Milton said. The current study (along with earlier ones) shows, by contrast, that tiny, aerosolized droplets can indeed diffuse through the air. That means it may be possible to contract COVID-19 not only by being coughed on, but by simply inhaling the breath of someone nearby who has it, whether they have symptoms or not. Surgical masks, however, catch a lot of the aerosolized virus as it's exhaled, he said.

The study was conducted at the University of Hong Kong as part of the dissertation research of the lead author, Dr. Nancy Leung, who, under the supervision of the co-senior authors Drs. Cowling and Milton, recruited 246 people with suspected respiratory viral infections. Milton's Gesundheit machine compared how much virus they exhaled with and without a surgical mask.

"In 111 people infected by either coronavirus, influenza virus or rhinovirus, masks reduced detectable virus in respiratory droplets and aerosols for seasonal coronaviruses, and in respiratory droplets for influenza virus," Leung said. "In contrast, masks did not reduce the emission of rhinoviruses."

Although the experiment took place before the current pandemic, COVID-19 and seasonal coronaviruses are closely related and may be of similar particle size. The report's other senior author, Professor Benjamin Cowling, division head of epidemiology and biostatistics, School of Public Health, HKUMed, and co-director of the World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, said, "The ability of surgical masks to reduce seasonal coronavirus in respiratory droplets and aerosols implies that such masks can contribute to slowing the spread of (COVID-19) when worn by infected people."

Milton pointed to other measures his research has found is even more effective than masks, such as improving ventilation in public places like grocery stores, or installing UV-C lights near the ceiling that works in conjunction with ceiling fans to pull air upwards and destroy viruses and bacteria.

"Personal protective equipment like N95 masks are not our first line of defense," Milton said. "They are our last desperate thing that we do."

Hong Kong University contributed to this report.

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Story Source:

Materials provided by University of Maryland. Original written by Chris Carroll. Note: Content may be edited for style and length.

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Journal Reference:

1. Nancy H. L. Leung, Daniel K. W. Chu, Eunice Y. C. Shiu, Kwok-Hung Chan, James J. McDevitt, Benien J. P. Hau, Hui-Ling Yen, Yuguo Li, Dennis K. M. Ip, J. S. Malik Peiris, Wing-Hong Seto, Gabriel M. Leung, Donald K. Milton, Benjamin J. Cowling. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nature Medicine, 2020; DOI: 10.1038/s41591-020-0843-2

New AI diagnostic can predict COVID-19 without testing

New AI diagnostic can predict COVID-19 without testing

Researchers at King's College London, Massachusetts General Hospital and health science company ZOE have developed an artificial intelligence diagnostic that can predict whether someone is likely to have COVID-19 based on their symptoms. Their findings are published today in Nature Medicine.

The AI model uses data from the COVID Symptom Study app to predict COVID-19 infection, by comparing people's symptoms and the results of traditional COVID tests. Researchers say this may provide help for populations where access to testing is limited. Two clinical trials in the UK and the US are due to start shortly.

More than 3.3 million people globally have downloaded the app and are using it to report daily on their health status, whether they feel well or have any new symptoms such as persistent cough, fever, fatigue and loss of taste or smell (anosmia).

In this study, the researchers analysed data gathered from just under 2.5 million people in the UK and US who had been regularly logging their health status in the app, around a third of whom had logged symptoms associated with COVID-19. Of these, 18,374 reported having had a test for coronavirus, with 7,178 people testing positive.

The research team investigated which symptoms known to be associated with COVID-19 were most likely to be associated with a positive test. They found a wide range of symptoms compared to cold and flu, and warn against focusing only on fever and cough. Indeed, they found loss of taste and smell (anosmia) was particularly striking, with two thirds of users testing positive for coronavirus infection reporting this symptom compared with just over a fifth of the participants who tested negative. The findings suggest that anosmia is a stronger predictor of COVID-19 than fever, supporting anecdotal reports of loss of smell and taste as a common symptom of the disease.

The researchers then created a mathematical model that predicted with nearly 80% accuracy whether an individual is likely to have COVID-19 based on their age, sex and a combination of four key symptoms: loss of smell or taste, severe or persistent cough, fatigue and skipping meals. Applying this model to the entire group of over 800,000 app users experiencing symptoms predicted that just under a fifth of those who were unwell (17.42%) were likely to have COVID-19 at that time.

Researchers suggest that combining this AI prediction with widespread adoption of the app could help to identify those who are likely to be infectious as soon as the earliest symptoms start to appear, focusing tracking and testing efforts where they are most needed.

Professor Tim Spector from King's College London said: "Our results suggest that loss of taste or smell is a key early warning sign of COVID-19 infection and should be included in routine screening for the disease. We strongly urge governments and health authorities everywhere to make this information more widely known, and advise anyone experiencing sudden loss of smell or taste to assume that they are infected and follow local self-isolation guidelines."

Story Source:

Materials provided by King's College London. Note: Content may be edited for style and length.

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Journal Reference:

1. Cristina Menni, Ana M. Valdes, Maxim B. Freidin, Carole H. Sudre, Long H. Nguyen, David A. Drew, Sajaysurya Ganesh, Thomas Varsavsky, M. Jorge Cardoso, Julia S. El-Sayed Moustafa, Alessia Visconti, Pirro Hysi, Ruth C. E. Bowyer, Massimo Mangino, Mario Falchi, Jonathan Wolf, Sebastien Ourselin, Andrew T. Chan, Claire J. Steves, Tim D. Spector. Real-time tracking of self-reported symptoms to predict potential COVID-19. Nature Medicine, 2020; DOI: 10.1038/s41591-020-0916-2

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.

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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.

---

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]