27 protein biomarkers predict COVID-19 severity in patients

Some patients infected with the novel coronavirus may experience only mild symptoms, while others may need medical care due to severe illness. People who are at a high risk of developing severe coronavirus disease (COVID-19) include older adults and those with underlying health conditions. However, severe disease has also been seen in young people with no underlying disease.

Now, a blood test can help predict COVID-19 severity in infected patients, as described in the journal  Cell Systems. 

A team of scientists at London, England's Francis Crick Institute and Germany's Charite Universitaetsmedizin Berlin has shown that certain chemicals present in the blood of patients infected by the novel coronavirus can predict whether they will develop severe disease.

Protein biomarkers

The team has found 27 key proteins in the blood of those infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. They used these proteins as predictive biomarkers of how ill a patient could become due to the viral infection.

To arrive at their findings, the researchers polished an analysis method known as mass spectrometry to rapidly test for the presence and level of various proteins in the blood plasma. Developed at the Francis Crick, the platform was applied to evaluate and study the serum of 31 patients with COVID-19 at the Berlin University hospital Charite.

The results were validated and confirmed in 17 COVID-19 patients at the same hospital and 15 healthy controls.

Of the 27 key proteins detected, three were tied to interleukin IL-6, a protein that triggers inflammation and a known marker for severe symptoms. The team also suggested that treatments may include drugs that can target these proteins, to alleviate some coronavirus symptoms.

Developing a protein biomarker test

The biomarkers could also help in the development of a test that can help predict how ill a might get when infected with the virus. Further, it can help provide new targets for developing potential therapeutics for the deadly disease. The results of such tests could guide clinicians in deciding what treatment to give.

Patients with COVID-19 respond differently to the illness, with some developing no symptoms at all, while others suffer a fatal infection. A test that can help doctors predict the severity of illness is vital.

"A test to help doctors predict whether a COVID-19 patient is likely to become critical or not would be invaluable. It will help them make decisions about how to best manage the disease for each patient as well as identify those most at risk. We hope the biomarkers we've identified will lead to the development of these vitally needed tests," Christoph Messner, one of the lead authors and postdoc in the Molecular Biology of Metabolism Laboratory at the Crick, said. 

The researchers also hope that the robust method they have used in the study can be applied to other diseases. Also, they added, even if the method was not explicitly developed for COVID-19, it has proven highly valuable to gain new insights into the disease.

The coronavirus pandemic has now infected more than 6.5 million people worldwide, and the death toll has topped 385,000. Of those who had been infected, more than 2.80 million have already recovered.

The United States is the hardest-hit country, with more than 1.85 million confirmed cases and at least 107,000 deaths.

Brazil follows the U.S. with more than 584,000 people infected with SARS-CoV-2, and a death toll surpassing 32,000. Russia, the United Kingdom, and Spain report high infection rates with 431,715 cases, 281,270 cases, and 240,326 cases, respectively.

Some countries report high fatality rates due to an overwhelmed health care system and the uncertainties of the viral infection. Having a simple blood test to determine who is at high risk will help reduce the number of deaths tied to COVID-19.

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Young men who are taller may have lower risk of dementia in old age: Study

In an attempt to assess specific types of individuals at the risk of developing dementia, a study has revealed that men who are relatively taller during their young adulthood are less likely to suffer from this debilitating condition in their old age.

This finding can help people take preventive measures or plan for their future care. The study indicates that young adult height might be one potential risk factor to consider. The study was published in the journal eLife.

Previous studies have suggested that height may be a risk factor for dementia, but much of this research was not able to take into account genetic, environmental, or other early-life factors that may be linked to both height and dementia.

"We wanted to see if body height in young men is associated with diagnosis of dementia while exploring whether intelligence test scores, educational level, and underlying environmental and genetic factors shared by brothers explain the relationship," says lead author Terese Sara Hoj Jorgensen, Assistant Professor at the Section of Social Medicine, Department of Public Health, University of Copenhagen, in Denmark.

To do this, Jorgensen and her colleagues analysed data on 666,333 Danish men born between 1939 and 1959, including 70,608 brothers and 7,388 twins, from Danish national registries. They found a total of 10,599 men who developed dementia later in life.

Their adjusted analysis of this group showed that there was about a 10 per cent reduction in the risk of developing dementia for about every 6cm of height in individuals above the average height. When the team took into account the potential role of intelligence or education, the unadjusted relationship between height and dementia risk was only slightly reduced.

They found that the relationship between height and dementia also existed when they looked at brothers with different heights, suggesting that genetics and family characteristics alone do not explain why shorter men had a greater dementia risk.

This was also true when they studied data concerning twins, although the results for this group were less certain.

"A key strength of our study is that it adjusted for the potential role of education and intelligence in young men's dementia risk, both of which may build up cognitive reserve and make this group less vulnerable to developing dementia," explains senior author Merete Osler, Professor at the Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, and at the University of Copenhagen.

'Cognitive reserve' refers to the brain's ability to improvise and solve problems that come up in everyday life. Osler says that adjusting for education and intelligence reduces the likelihood that the relationship between height and dementia is really explained by the cognitive reserve.

"Together, our results point to an association between taller body height in young men and a lower risk of dementia diagnosis later in life, which persists even when adjusted for educational level and intelligence test scores," Osler says. "Our analysis of the data concerning brothers confirms these findings, and suggests the association may have common roots in early-life environmental exposures that are not related to family factors shared by brothers." 

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Fluoroquinolones antibiotics associated with risk of heart problems

In a new study, researchers have established the link between one of the most commonly prescribed class of antibiotics and heart problems.

In a study published in the Journal of the American College of Cardiology, researchers found that current users of fluoroquinolone antibiotics, such as Ciprofloxacin or Cipro, face a 2.4 times greater risk of developing aortic and mitral regurgitation, where the blood back flows into the heart, compared to patients who take amoxicillin, a different type of antibiotic.

The greatest risk is within 30 days of use.

Some physicians favour fluoroquinolones over other antibiotics for their broad spectrum of antibacterial activity and high oral absorption, which is as effective as intravenous, or IV, treatment.

“You can send patients home with a once-a-day pill,” said Mahyar Etminan, lead author and associate professor of ophthalmology and visual sciences in the faculty of medicine at University of British Columbia.

“This class of antibiotics is very convenient, but for the majority of cases, especially community-related infections, they’re not really needed. The inappropriate prescribing may cause both antibiotic resistance as well as serious heart problems,” added Etminan.

“One of the key objectives of the Therapeutic Evaluation Unit is to evaluate different drugs and health technologies to determine whether they enhance the quality of care delivered by our programs or improve patient outcomes,” said Dr. Bruce Carleton, director of the unit and research investigator at BC Children’s Hospital, a program of PHSA.

For the study, researchers analyzed data from the U.S. Food and Drug Administration’s adverse reporting system. They also analyzed a massive private insurance health claims database in the U.S. that captures demographics, drug identification, dose prescribed and treatment duration.

Researchers identified 12,505 cases of valvular regurgitation with 125,020 case-control subjects in a random sample of more than nine million patients.

They defined current fluoroquinolone exposure as an active prescription or 30 days prior to the adverse event, recent exposure as within days 31 to 60, and past exposure as within 61 to 365 days prior to an incident. They compared fluoroquinolone use with amoxicillin and azithromycin.

The results showed that the risk of aortic and mitral regurgitation, blood backflow into the heart, is highest with current use, followed by recent use. They saw no increased risk aortic and mitral regurgitation with past use.

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Scientists discover how gene mutation causes autism and intellectual disability

Scientists at Northwestern University near Chicago have made a significant stride in the quest to understand autism and other intellectual disabilities. Researchers at the school published a study in Neuron outlining why a specific gene mutation causes intellectual disability and autism spectrum disorder in children. 

The study identifies a gene called Usp9x. Individuals with mutations in this gene grow fewer synapses in the brain. When fully functional, the gene protects a protein called akyrin-G that is responsible for growing an stabilyzing synapses. These synapses help cells communicate, and are especially important in developing brains in order for children to learn.

When the Usp9x gene is mutated, it can't protect the akyrin-G protein, which degrades and destabilizes. Scientists found that individuals with this specific gene mutation showed "developmental delay, difficulty learning, increased anxiety and hyperactivity."

“We have solved an important piece of the puzzle in understanding how this mutation causes intellectual disabilities and mental illness,” Peter Penzes, lead author for the study and director of Northwestern's Center for Autism and Neurodevelopment said in a statement.

The Usp9x gene also protects several other proteins that may cause intellectual disability and autism when degraded. Less severe mutations of the ankyrin-G protein have also been linked to the development of schizophrenia and bipolar disease.

According to the Centers for Disease Control and Prevention, 1 in 59 children in the U.S. is diagnosed with autism spectrum disorder (ASD). Individuals with ASD may have problems with social, emotional, and communication skills. Boys are four times more likely to be diagnosed than girls, and the disorder occurs across racial, ethnic and socioeconomic groups.

The CDC also says more people than ever are being diagnosed with ASD.  It's unclear whether the increase is due to a broadening definition of the disorder, better efforts in diagnosis or a true increase in the number of people with ASD. The organization believes the increase in diagnosis is due to a combination of the three factors.

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Fat over-spills from the liver into the pancreas trigger Type 2 diabetes

For the first time, scientists have been able to observe people developing type 2 diabetes - and confirmed that fat over-spills from the liver into the pancreas, triggering the chronic condition.
The research, led by Professor Roy Taylor at Newcastle University, UK, is published in the academic journal, Cell Metabolism.

The study involved a group of people from Tyneside who previously had Type 2 diabetes but had lost weight and successfully reversed the condition as part of the DiRECT trial, which was funded by Diabetes UK and led by Professors Roy Taylor and Mike Lean (Glasgow University).

The majority remained non-diabetic for the rest of the two year study, however, a small group went on to re-gain the weight and re-developed Type 2 diabetes.

Professor Roy Taylor, from the Newcastle University Institute of Translational and Clinical Research, explained what the advanced scanning techniques and blood monitoring revealed.

He said:We saw that when a person accumulates too much fat, which should be stored under the skin, then it has to go elsewhere in the body. The amount that can be stored under the skin varies from person to person, indicating a 'personal fat threshold' above which fat can cause mischief.

When fat cannot be safely stored under the skin, it is then stored inside the liver, and over-spills to the rest of the body including the pancreas. This 'clogs up' the pancreas, switching off the genes which direct how insulin should effectively be produced, and this causes Type 2 diabetes."

This research by Professor Taylor confirms his Twin Cycle Hypothesis - that Type 2 diabetes is caused by excess fat actually within both the liver and pancreas, and especially that this process is reversible.

Body of research

This latest paper builds on previous Newcastle studies supported by Diabetes UK showing exactly why Type 2 diabetes can be reversed back to normal glucose control. Those studies led to the large DiRECT trial which showed that Primary Care staff can achieve remission of Type 2 diabetes by using a low calorie diet with support to maintain the weight loss.

A quarter of participants achieved a staggering 15 kg or more weight loss, and of these, almost nine out of 10 people put their Type 2 diabetes into remission. After two years, more than one third of the group had been free of diabetes and off all diabetes medication for at least two years.

In 2020, this approach to management of short duration Type 2 diabetes is to be piloted in the NHS in up to 5,000 people across England, and a similar program is being rolled out in Scotland.

Professor Taylor adds:This means we can now see Type 2 diabetes as a simple condition where the individual has accumulated more fat than they can cope with. 

Importantly this means that through diet and persistence, patients are able to lose the fat and potentially reverse their diabetes. The sooner this is done after diagnosis, the more likely it is that remission can be achieved."

The team are continuing work to establish what may affect an individual's personal threshold and are supporting the roll out of the NHS Initiatives in both England and Scotland. 'Life Without Diabetes - The definitive guide to understanding and reversing your Type 2 diabetes' by Professor Roy Taylor will be published by Short Books on 26th December 2019.

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