Focal brain lesion study shows cognitive impairment better predicted by damage to white matte

 A team of researchers from Carver College of Medicine, the University of Iowa and the University of California, San Francisco, has found that doctors looking to make predictions about the degree of cognitive impairment in brain-damaged patients might do better by looking at white matter than gray matter. In their paper published in Proceedings of the National Academy of Sciences, the group describes focal brain lesion studies they conducted and what they found.

Prior research has shown that the brain has highly connected communications regions that play a critical role in network functions—such regions have come to be known as hubs. Prior research has also shown that disruptions to hubs due to brain damage can result in significant cognitive impairment. In recent years, scientists have found that white matter—pale tissue in the brain made up mostly of nerve fibers and myelin sheaths—has hubs, as well, though they play a somewhat different role than hubs in gray matter. Hubs in white matter serve as trans-brain communication centers allowing parts of the brain made up of gray matter to communicate with one another. Gray matter hubs, on the other hand, are far more localized. In this new effort, the researchers looked at the impact of brain damage on hubs in gray matter versus similar types of damage to hubs in white matter.

The work involved studying abnormal tissue in the brain called focal brain lesions. They are typically caused by trauma from illnesses. The researchers looked at two separate groups of patients with focal brain lesions in different parts of their brains. More specifically, they wanted to know if such lesions were more likely to result in cognitive impairment if they occurred in white matter versus gray matter—tissue in the brain made up mainly of nerve cells and dendrites.

In comparing cognitive outcomes for patients with lesions in white or gray matter hubs, they found that lesions in white matter tended to result in worse outcomes than those in gray matter. They suggest this is because lesions in white matter hubs can prevent messages from being sent from one region in the brain to another, whereas lesions in gray matter result in more localized disruptions.

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What lies between grey and white in the brain

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More information: Justin Reber et al. Cognitive impairment after focal brain lesions is better predicted by damage to structural than functional network hubs, Proceedings of the National Academy of Sciences (2021). DOI: 10.1073/pnas.2018784118

https://medicalxpress.com/news/2021-05-focal-brain-lesion-cognitive-impairment.html

A third of patients hospitalized with COVID-19 have lung changes after a year

 A new study has shown that most patients discharged from hospital after experiencing severe COVID-19 infection appear to return to full health, although up to a third do still have evidence of effects upon the lungs one year on.

COVID-19 has infected millions of people worldwide. People are most commonly hospitalised for COVID-19 infection when it affects the lungs -- termed COVID-19 pneumonia. Whilst significant progress has been made in understanding and treating acute COVID-19 pneumonia, very little is understood about how long it takes for patients to fully recover and whether changes within the lungs persist.

In this new study, published in The Lancet Respiratory Medicine, researchers from the University of Southampton worked with collaborators in Wuhan, China, to investigate the natural history of recovery from severe COVID-19 pneumonia up to one year after hospitalisation.

83 patients were recruited after they were discharged from hospital following severe COVID-19 pneumonia and were followed up after three, six, nine and twelve months. At each time point they underwent clinical assessment as well as measures of how well the lungs function, a CT scan of their chest to take a picture of the lungs, and a walking test.

Over 12 months in most patients there was an improvement in symptoms, exercise capacity, and COVID-19 related CT changes. By 12 months the majority of patients appeared to have fully recovered although about 5% of patients still reported breathlessness. A third of patients' measures of lung function were still reduced -- in particular how efficiently oxygen is transferred in the lungs into the blood -- and this was more frequently found in women than in men. In around a quarter of patients CT scans showed there were still small areas of change in the lungs, and this was more common in patients with more severe lung changes at time of hospitalisation.

Dr Mark Jones, Associate Professor in Respiratory Medicine at the University of Southampton and NIHR Southampton Biomedical Research Centre who co-led the study said, "the majority of patients with severe COVID-19 pneumonia appeared to fully recover, although for some patients this took many months. Women were more likely to have persistent reductions in lung function tests and further investigation is needed to understand if there is a sex specific difference in how patient's recover. We also don't yet know what happens beyond 12 months and this will need ongoing study."

The researchers acknowledged that this study only involved a small number of patients and the findings will require confirmation in additional studies, however they have identified a number of important implications.

Dr Yihua Wang, Lecturer in Biomedical Sciences at the University of Southampton and NIHR Southampton Biomedical Research Centre who co-led the study explained, "firstly, our research provides evidence that routine respiratory follow-up of patients hospitalised with COVID-19-pneumonia is required. Secondly, given the length of time it takes for some patients to recover it suggests that research into whether exercise programmes help patients recover more quickly is required. Finally, it highlights the need for treatment strategies to prevent the development of long term COVID-19 related lung changes."

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Story Source:

Materials provided by University of Southampton. Note: Content may be edited for style and length.

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Journal Reference:

1. Xiaojun Wu, Xiaofan Liu, Yilu Zhou, Hongying Yu, Ruiyun Li, Qingyuan Zhan, Fang Ni, Si Fang, Yang Lu, Xuhong Ding, Hailing Liu, Rob M Ewing, Mark G Jones, Yi Hu, Hanxiang Nie, Yihua Wang. 3-month, 6-month, 9-month, and 12-month respiratory outcomes in patients following COVID-19-related hospitalisation: a prospective study. The Lancet Respiratory Medicine, 2021; DOI: 10.1016/S2213-2600(21)00174-0

https://www.sciencedaily.com/releases/2021/05/210506105342.htm

Prediabetes: Not benign

 People with prediabetes were significantly more likely to suffer a heart attack, stroke or other major cardiovascular event when compared with those who had normal blood sugar levels, according to research being presented at the American College of Cardiology's 70th Annual Scientific Session. Researchers said the findings should serve as a wake-up call for clinicians and patients alike to try to prevent prediabetes in the first place.

"In general, we tend to treat prediabetes as no big deal. But we found that prediabetes itself can significantly boost someone's chance of having a major cardiovascular event, even if they never progress to having diabetes," said Adrian Michel, MD, internal medicine resident at Beaumont Hospital-Royal Oak, MI, and lead author of the study, which he said is one of the largest to date. "Instead of preventing diabetes, we need to shift focus and prevent prediabetes."

Prediabetes is a condition in which the average amount of sugar in the blood is high but not high enough to be diagnosed as Type 2 diabetes. While Type 2 diabetes is a well-known, leading risk factor for heart attack, stroke and blockages in the heart's arteries, the role of prediabetes has been less clear. Yet prediabetes is fairly common. The U.S. Centers for Disease Control and Prevention estimates that 34 million Americans -- just over 1 in 10 -- have diabetes, and another 88 million -- approximately 1 in 3 -- have prediabetes.

This study revealed that serious cardiovascular events occurred in 18% of people with prediabetes compared with 11% of people with normal blood sugar levels over a median of five years follow-up. The relationship between higher blood sugar levels and cardiovascular events remained significant even after taking into account other factors that could play a role, such as age, gender, body mass index, blood pressure, cholesterol, sleep apnea, smoking and peripheral artery disease.

"Based on our data, having prediabetes nearly doubled the chance of a major adverse cardiovascular event, which accounts for 1 out of 4 deaths in the U.S.," Michel said. "As clinicians, we need to spend more time educating our patients about the risk of elevated blood sugar levels and what it means for their heart health and consider starting medication much earlier or more aggressively, and advising on risk factor modification, including advice on exercise and adopting a healthy diet."

Of particular concern was the finding that even when patients in the prediabetes group were able to bring their blood sugar level back to normal, the risk of having a cardiovascular event was still fairly high. Events occurred in just over 10.5% of these patients compared with 6% of those with no diabetes or prediabetes.

"Even if blood sugar levels went back to normal range, it didn't really change their higher risk of having an event, so preventing prediabetes from the start may be the best approach," Michel said.

This single-center, retrospective study included data from 25,829 patients treated within the Beaumont Health System in Michigan between 2006 and 2020. Patients were then split into either the prediabetes or control group based on at least two A1C levels five years apart; the control group included patients who maintained a normal hemoglobin A1C during the study. A total of 12,691 patients and 13,138 were included in the prediabetes and control groups, respectively. Participants ranged in age from 18 to 104 years. All patients were followed for the 14-year study period and researchers used international classification of disease codes or diagnostic codes to determine whether a major adverse cardiovascular event occurred.

The relationship between prediabetes and events were strongest among males, Blacks and people with a family history of cardiovascular disease or personal risk factors for heart disease. People who were overweight had the highest rates of cardiovascular events among all patients, even more than those who were obese, which is something Michel said needs to be studied further.

Prediabetes is thought to play a role in heart health because elevated glucose levels in the blood can damage and cause inflammation within the vessels. This causes injury to the vessels in the body and can lead to narrowing of the vessels and ultimately cardiovascular injury, Michel said.

The study findings are an important reminder for adults to know their blood sugar numbers, especially as prediabetes usually has no symptoms. As with diabetes, prediabetes is diagnosed based on results from blood sugar tests, including an A1C, which reflects someone's average blood sugar for the past two to three months; a fasting plasma glucose test, which measures your blood sugar after not eating or drinking for at least eight hours beforehand; and/or an oral glucose tolerance test, which checks how well the body processes sugar after drinking a sweet drink given by the clinician. Prediabetes is suspected with an A1C between 5.7-6.4%, fasting blood sugar of 100-125 mg/dl, or an oral glucose tolerance test of 140-199 mg/dl, according to the American Diabetes Association.

More research is needed to validate these findings.

Story Source:

Materials provided by American College of Cardiology. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2021/05/210505090240.htm

COVID-19 vaccine is associated with fewer asymptomatic SARS-CoV-2 infections

 Vaccination dramatically reduced COVID-19 symptomatic and asymptomatic infections in St. Jude Children's Research Hospital employees compared with their unvaccinated peers, according to a research letter that appears today in the Journal of the American Medical Association.

The study is among the first to show an association between COVID-19 vaccination and fewer asymptomatic infections. When the Pfizer-BioNTech BNT162b2 vaccine was authorized for use in the U.S., the vaccine was reported to be highly effective at preventing laboratory-confirmed COVID-19. Clinical trial data suggested that the two-dose regimen reduced symptomatic disease, including hospitalization and death. But an association with reduced asymptomatic infection was unclear.

"While further research is needed, by preventing infections, including in people who have no symptoms, there is a high possibility that vaccination will decrease transmission of SARS-CoV-2," said Diego Hijano, M.D., of the St. Jude Department of Infectious Diseases. He and Li Tang, Ph.D., of St. Jude Biostatistics, are the first authors of the report. Tang is also the corresponding author.

The study involved 5,217 St. Jude employees who were eligible under Tennessee state guidelines for vaccination between Dec. 17, 2020, and March 20, 2021. More than 58% of employees were vaccinated during that period. Most workers received both doses.

Overall, vaccination reduced the risk of asymptomatic and symptomatic SARS-CoV-2 infection by 79% in vaccinated employees compared with their unvaccinated colleagues. An analysis of asymptomatic infections alone found vaccination reduced the risk by 72%.

Protection was even greater for employees who completed two doses. A week or more after receiving the second dose, vaccinated employees were 96% less likely than unvaccinated workers to become infected with SARS-CoV-2. When researchers looked just at asymptomatic infections, vaccination reduced the risk by 90%.

Finding SARS-CoV-2 infections

The research stems from a program that St. Jude leaders began in March 2020 to protect patients and employees from the pandemic virus.

The effort included targeted testing for employees with COVID-19 symptoms or known exposure to the pandemic virus. The plan also involved routine, laboratory testing of asymptomatic employees. Nasal swabs were collected at least weekly from self-reported asymptomatic on-campus workers to perform polymerase chain reaction to detect asymptomatic SARS-CoV-2 infection.

"This study was possible because St. Jude invested in resources to determine how best to control the disease and protect our patients and employees," Tang said. "Few places then or now provide such broad asymptomatic testing."

Hijano said, "Testing has been invaluable to the institutional COVID-19 mitigation plan. In the end, the testing also serves as a unique tool that helps to fill in critical knowledge gaps."

Results by the numbers

During the study, 236 of the 5,217 employees included in the analysis tested positive for SARS-CoV-2. They included 185 unvaccinated employees and 51 of the 3,052 workers who had received at least one dose of the vaccine.

Almost half of the positive cases, 108, reported no symptoms upon testing. The asymptomatic cases included 20 employees who had received one vaccine dose and three who tested positive within seven days of the second dose. "The results are a reminder of the many hidden cases in the population, which makes containing the virus a big challenge," Tang said.

The study group included a cross-section of employees in regard to race and gender. More than 80% of employees were younger than 65 years old. The vaccinated group included a higher percentage of health care staff, 47%, than the unvaccinated employees, 25.7%.

Authors and funding

The senior authors are James Hoffman, Pharm.D., and Randall Hayden, M.D., of St. Jude. The other authors are Aditya Gaur, Terrence Geiger and Ellis Neufeld, all of St. Jude.

The research was funded in part by ALSAC, the St. Jude fundraising and awareness organization.

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Story Source:

Materials provided by St. Jude Children's Research Hospital. Note: Content may be edited for style and length.

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Journal Reference:

1. Li Tang, Diego R. Hijano, Aditya H. Gaur, Terrence L. Geiger, Ellis J. Neufeld, James M. Hoffman, Randall T. Hayden. Asymptomatic and Symptomatic SARS-CoV-2 Infections After BNT162b2 Vaccination in a Routinely Screened Workforce. JAMA, May 6, 2021; DOI: 10.1001/jama.2021.6564

https://www.sciencedaily.com/releases/2021/05/210506125727.htm

More evidence backs Covid-19 shots against variants

 Especially virulent variants of the pandemic coronavirus pose a big threat to global vaccination programmes. But evidence is mounting that existing vaccines still work against new circulating strains, and that specifically designed booster shots might be even more useful. A small Moderna study has found that previously vaccinated patients given booster shots went on to produce antibodies capable of fighting off the so-called South Africa and Brazil variants. Levels were higher in those boosted with a tweaked project, mRNA-1273.351, than those given the original jab for a third time; the former was specifically designed to protect against the South Africa variant. Further data from the study are required, but these are an encouraging first glimpse; efforts against variants at Moderna and Pfizer/Biontech are closely watched because mRNA vaccines are relatively easily tweaked. Elsewhere, real-world evidence is emerging that the first wave of vaccines are pretty good at fighting off the variants. The latest study, published in NEJM today, came from Qatar’s vaccination programme with Pfizer/Biontech’s Comirnaty, where the jab provided 75% protection against B.1.351 infection and 97% of severe disease caused by any variant. Other results from work on variants from Gritstone and Curevac, expected imminently, are keenly awaited.

A table from Dr Eric Topol, who has been tracking evidence of vaccine efficacy against variants

Source: Dr Eric Topol: https://twitter.com/EricTopol/status/1390048888397074432?s=20

https://www.evaluate.com/vantage/articles/news/snippets/more-evidence-backs-covid-19-shots-against-variants

Biden patent waiver unlikely to hit vaccine sales

 President Biden’s support for the WTO's proposed temporary waiver of Covid-19 vaccine patents has certainly put the cat among the pigeons, hitting stocks of coronavirus vaccine manufacturers in early trade. But just how real a threat the waiver is to vaccine sales is debatable. On Moderna’s earnings call this morning chief executive Stéphane Bancel told investors that he was not losing sleep – and well might he slumber. In October the group said it would not enforce patents around its Covid jab; in the ensuing seven months no one has used the tech, Mr Bancel said. It is one thing to have the formulation for vaccines, but a very different one to produce them, especially mRNA shots. A shortage in manufacturing capacity and professionals with knowledge of mRNA production provide very effective barriers to entry, before considering the lengthy processes involved in building new facilities and winning regulatory approvals. Any potential sales would therefore be years away. Additionally, it is far from clear that future patents will be waived. Developers are already working on jabs for variants, and Moderna itself is studying multivalent vaccines. As such the share price reaction could well turn out to be a storm in a teacup.

Sales at risk? Near-term forecasts for selected Covid-19 vaccines
Product	Company	2021e sales ($bn)	2022e sales ($bn)	Early share price reaction (May 6)
Comirnaty	Pfizer	26.0*	4.7	-2% (partner Biontech down 6%)
mRNA-1273	Moderna	19.0*	12.1	-7%
NVX-CoV2373	Novavax	4.3	4.7	-4%
AZD1222	Astrazeneca	1.7	1.9	-1%
*Company guidance; all other figures sellside consensus from Evaluate Pharma. A reliable consensus has yet to emerge for Johnson & Johnson. https://www.evaluate.com/vantage/articles/news/snippets/biden-patent-waiver-unlikely-hit-vaccine-sales

iBio Details Successful COVID Vax Toxicology Study Results, Next-Gen Vax Program

  iBio, Inc. (NYSEA:IBIO) ("iBio" or the "Company"), a biotech innovator and biologics contract manufacturing organization, today provided an update on its IBIO-201 program and reported on its progress in developing a second-generation subunit vaccine candidate, IBIO-202, being designed for the prevention of SARS-CoV-2 infection.

IBIO-201, the Company's vaccine candidate combining antigens derived from the spike protein ("S protein") fused with iBio's patented LicKM™ booster molecule, recently completed IND-enabling toxicology studies. The studies identified no adverse effects at low or high doses.

"Combined with data from previous immune-response studies, these pathology results help demonstrate the potential value of LicKM as a useful tool in our vaccine development toolbox," said Tom Isett, Chairman and CEO of iBio.

The Company also reported on development of IBIO-202, a subunit vaccine candidate that targets the nucleocapsid protein ("N protein") of SARS-CoV-2. N proteins of many coronaviruses are highly immunogenic and are expressed abundantly during infection. In addition, the N protein is more highly conserved than the S protein, and therefore new viral variants may be less likely to escape vaccine protection.

"In light of the successful global roll-out of COVID-19 vaccines targeting the S protein and the emergence of variant strains of the disease, we decided to focus our efforts on the continued development of IBIO-202 as a differentiated vaccine candidate," commented Mr. Isett. "The COVID-19 vaccine space remains highly competitive, with multiple approved vaccines in use in many countries. Nevertheless, various unmet needs remain, including: vaccines that provide broader protection against variants; the potential requirement for annual vaccine boosters; vaccines that do not require significant cold chain management; vaccines with alternative routes of administration; pan-coronavirus vaccines; and wider vaccine availability in developing countries," said Mr. Isett.

Using its plant-based FastPharming^® System, iBio has successfully expressed N protein antigens and has initiated both intramuscular and intranasal preclinical studies to identify favorable antigen-adjuvant combinations. Results are expected in early Q1 FY2022. iBio recently filed four provisional patent applications with the U.S. Patent and Trademark Office in support of the IBIO-202 program.

"Immunization with more conserved sequences, such as the N protein, is expected to generate T-cells that could clear spike protein variant viruses in addition to the original virus," said Martin Brenner, DVM. Ph.D., iBio's CSO. "The N protein strategy of IBIO-202 is complementary to existing first-generation, S protein-directed vaccines and may be suitable as a more universal coronavirus vaccine."

In parallel with the development of IBIO-202, the Company continues to evaluate the potential of a multi-subunit vaccine candidate to further increase vaccine protection from variants by targeting two or more important elements of the SARS-CoV-2 virus.

https://www.benzinga.com/pressreleases/21/05/g21000391/ibio-reports-successful-covid-19-vaccine-toxicology-study-results-and-announces-next-gen-covid-19-