A proof-of-concept trial led by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust has identified a drug that may benefit some patients hospitalised with COVID-19 pneumonia.
An antibody already in late-stage trials to treat rheumatoid arthritis, namilumab targets a ‘cytokine’ which is naturally secreted by immune cells in the body but, in uncontrolled levels, is believed to be a key driver of the excessive and dangerous lung inflammation seen in COVID-19 patients.
The trial, carried out in collaboration with the University of Oxford and funded by the Medical Research Council and carried out between June 2020 and February 2021, involved patients aged over 16 with COVID-19 pneumonia either being treated on a ward or Intensive Care Unit (ICU) at nine NHS hospitals across the UK.
The study, published in The Lancet Respiratory Medicine, involved 54 patients receiving ‘usual care’ (steroids and oxygen or ventilation, depending on the severity of disease) and 57 patients given usual care as well as a single intravenous dose of 150mg of namilumab.
As well as COVID-19 pneumonia, all study participants had CRP levels greater than 40mg/l. The researchers compared the probability of the reduction of levels of CRP in patients. Compared to usual care alone, the researchers found there was a 97% probability of CRP being reduced over time in those given namilumab when compared with usual care alone.
The patients were monitored, and after 28 days the study also showed there were fewer deaths and more discharges from hospital or ICU in those who had been given namilumab compared to those receiving usual care alone.
By day 28, 78% (43) of the patients receiving namilumab were discharged from hospital or ICU, compared to 61% (33) of the patients given usual care. In the namilumab group, 11% (6) were still in hospital by day 28, compared to 20% (11) in the usual care group. Of those in the namilumab group, 11% (6) patients died compared to 19% (10) who died in the usual care group by day 28.
The team calculated the differences between the two cohorts in overall probability of those being discharged from ICU or a ward at 28 days. Of those on a ward, the probability of discharge at day 28 was 64% in the usual care cohort, compared to 77% in the Namilumab cohort. Of those in ICU, probability of discharge at day 28 was 47% in the usual care group, compared to 66% in the Namilumab cohort.
Release date: 17 December 2021
Source: University of Birmingham
how exercise protects against consequences of ageing
Monash University scientists have discovered an enzyme that is key to why exercise improves our health. Importantly this discovery has opened up the possibility of drugs to promote this enzyme’s activity, protecting against the consequences of ageing on metabolic health, including type 2 diabetes.
The proportion of people worldwide over 60 years old will double in the next three decades and by 2031, more than six million Australians will be over 65 years old. The incidence of type 2 diabetes increases with age so this ageing population will also result in an increased incidence of the disease globally.
One of the main reasons for the increased prevalence of type 2 diabetes with age is the development of insulin resistance or an inability for the body to respond to insulin, and this is often caused by reduced physical activity as we age.
In a paper published in the journal Science Advances, the research team show how an enzyme called NOX-4 is essential for exercise-induced ROS and the adaptive responses that drive metabolic health.
Release date: 16 December 2021
Source: Monash University
Immune memory less durable after severe COVID-19
Infection-fighting B cells retain better memory of the coronavirus spike protein in University Hospital patients who recover from less-severe cases of COVID-19 than in those recovering from severe COVID-19, a new study suggests. Findings by scientists from The University of Texas Health Science Center at San Antonio were published in the journal PLOS ONE .
The study focused on memory B cells that react against the SARS-CoV-2 spike protein. Blood samples were analyzed one month after symptom onset and five months post-onset. After one month, a significant proportion of spike-specific B cells were active.
However, samples from eight individuals who recovered from less-severe disease showed increased expression of markers associated with durable B cell memory as compared to individuals who recovered from severe disease, the authors wrote. The markers include T-bet and FcRL5.
T-bet-positive, spike-specific B cells nearly disappeared from the blood samples five months post-symptom onset, the authors noted. Overall, a more dysfunctional B cell response is seen in severe disease cases, they wrote.
Release date: 23 December 2021
Source: University of Texas Health Science Center at San Antonio
Metabolic syndrome increases risk of respiratory distress, death for hospitalized COVID-19 patients
Patients hospitalized with COVID-19 who had a combination of high blood pressure, obesity, diabetes or other conditions associated with metabolic syndrome were at much higher risk of acute respiratory distress syndrome (ARDS) and death, according to an international study published in the medical journal JAMA Network Open.
The risk for developing ARDS, a life-threatening lung condition that causes low blood oxygen, grew progressively higher with each additional metabolic syndrome criteria present. The study, one of the largest to examine the link between metabolic syndrome and outcomes for COVID-19, examined records of more than 46,000 patients admitted in 181 hospitals across 26 countries.
Researchers from Tulane University, the Society of Critical Care Medicine and Mayo Clinic followed outcomes for patients hospitalized between mid-February 2020 to mid-February 2021 in the Discovery VIRUS: COVID-19 Registry. Researchers compared 5,069 patients (17.5%) with metabolic syndrome with 23,971 control patients (82.5%) without metabolic syndrome. They defined metabolic syndrome as having more than three of the following criteria: obesity, pre-diabetes or diabetes, hypertension and high cholesterol.
Patients with metabolic syndrome were 36% more likely to develop ARDS, almost 20% more likely to die in the hospital, more than 30% more likely to be admitted to an ICU and 45% more likely to require mechanical ventilation. Researchers calculated these risks after adjusting for race, age, sex, ethnicity, other comorbid conditions and hospital case volume.
Overall, slightly more than 20% of the patients with metabolic syndrome died in the hospital, 20% developed ARDS and almost half were admitted to the ICU. Approximately 16% of those without metabolic syndrome died, 12% developed ARDS and nearly 36% were admitted to the ICU.
Metabolic syndrome was significantly more common among patients with COVID-19 admitted to U.S. hospitals (18.8%) than those admitted to non-U.S. hospitals (8%). According to the Centers for Disease Control, more than a third of adults in the U.S. meet the criteria for metabolic syndrome, with some regions having a metabolic syndrome prevalence greater than 40%.
Release date: 22 December 2021
Source: Tulane University
Infant Immune Systems Are Stronger Than You Think
New study may help explain why infants are less affected by COVID than adults. The infant immune system has a reputation for being weak and underdeveloped when compared to the adult immune system, but the comparison isn’t quite fair.
Babies do get a lot of respiratory illnesses from viruses, like influenza and respiratory syncytial virus, compared to adults. But unlike adults, babies are seeing these viruses for the first time. “Adults don’t get sick as often because we’ve recorded memories of these viruse, and the memories protect us,” Farber says, “whereas everything the baby encounters is new to them.”
The paper, titled “Infant T cells are developmentally adapted for robust lung immune responses through enhanced T cell receptor signaling(link is external and opens in a new window),” was published in Science Immunology.
Release date: 10 December 2021
Source: Columbia University Irving Medical Center
Triggers of stroke: anger, emotional upset, and heavy physical exertion
global study co-led by NUI Galway into causes of stroke has found that one in 11 survivors experienced a period of anger or upset in the one hour leading up to it. One in 20 patients had engaged in heavy physical exertion.
The suspected triggers have been identified as part of the global INTERSTROKE study – the largest research project of its kind, which analysed 13,462 cases of acute stroke, involving patients with a range of ethnic backgrounds in 32 countries, including Ireland.
Stroke prevention is a priority for physicians, and despite advances it remains difficult to predict when a stroke will occur. Many studies have focused on medium to long-term exposures, such as hypertension, obesity or smoking. Our study aimed to look at acute exposures that may act as triggers.
The research analysed patterns in patients who suffered ischemic stroke – the most common type of stroke, which occurs when a blood clot blocks or narrows an artery leading to the brain, and also intracerebral haemorrhage – which is less common and involves bleeding within the brain tissue itself.
The research has been published in the European Heart Journal.
Release date: 03 December 2021
Source: National University of Ireland Galway
ALS therapy should target brain, not just spine
The brain is indeed a target for treating ALS (amyotrophic lateral sclerosis), Northwestern Medicine scientists have discovered. This flips a long-standing belief that the disease starts in the spinal motor neurons and any therapy would need to target the spine as the key focus.
A new Northwestern study shows the degeneration of brain motor neurons (the nerve cells in the brain that control movement of the limbs) is not merely a byproduct of the spinal motor neuron degeneration, as had been previously thought. The study was conducted in two mouse models of ALS that represent 90% of all ALS pathologies.
ALS is a swift and fatal neurodegenerative disease that paralyzes its victims.
Upper motor neuron diseases, such as ALS, hereditary spastic paraplegia and primary lateral sclerosis affect more than 250,000 people a year in the U.S. alone. There is no cure and no effective long-term treatment strategy.
This is the first study to clearly reveal the brain motor neuron degeneration is not a consequence of spinal motor neuron degeneration but is independent of the spinal motor neuron degeneration.
The research also is the first to show that the gene UCHL1 is important for maintaining the health of brain motor neurons that are diseased due to two independent underlying causes. One is the accumulation of badly folded proteins and the other is the accumulation of sticky protein clumps inside the cells. These problems are observed in more than 90% of all ALS cases and also in other cases of upper motor neuron diseases.
Northwestern University scientists have previously identified NU-9, the first experimental compound that eliminates the ongoing degeneration of upper motor neurons that become diseased and are a key contributor to ALS. Now, this study reveals the importance and significance of treating upper motor neurons in ALS and identifies the first genetic target.
The next step is to determine the best dose and the best site of injection with respect to improvement of movement and reduction of disease conditions in at least two different ALS disease models. After preclinical toxicology studies, scientists will move to translate these results into a clinical trial, a process that likely will take several years.
The paper was published Dec. 2 in Nature Gene Therapy.
Release date: 03 December 2021
Source: Northwestern University
HOW REGULAR EXERCISE CAN PROTECT AGAINST FATTY LIVER ASSOCIATED DISEASES
Worldwide one in four persons suffers from non-alcoholic liver disease (NAFLD, also called metabolic liver disease MAFLD). Those affected often have type 2 diabetes as well as an increased risk of liver cirrhosis and cardiovascular diseases. In addition, NAFLD is associated with increased mortality. An imbalance between energy intake and consumption is discussed as a cause for the disease. This leads to fat deposits in the liver and over time impairs the function of the mitochondria * – both risk factors for the development of hepatic insulin resistance and liver inflammation.
How exercise modifies the adaptation of the liver to increased energy intake
To prevent and treat NAFLD, lifestyle modification with increased physical activity is recommended. To what extent regular exercise alters the adaptation of the liver to increased energy intake and what role skeletal muscle plays in this process was investigated by scientists at the Institute of Clinical Chemistry and Pathobiochemistry at Tübingen University Hospital and at the Institute of Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Munich at the University of Tübingen. The researchers collaborated with the Institute of Experimental Genetics (IEG) at Helmholtz Munich, the Leibniz Institute for Analytical Sciences in Dortmund, and the Dalian Institute of Chemical Physics in China.
Original publication:
Hoene, M. et al.: Exercise prevents fatty liver by modifying the compensatory response of mitochondrial metabolism to excess substrate availability. Molecular Metabolism.
Release date: 20 December 2021
Source: Deutsches Zentrum fuer Diabetesforschung DZD
Ultrasound could be used to treat psychiatric disorders
Imagine passing an exam, and thinking your success was down to the socks you wore or the number of biscuits you’d eaten, rather than the hours of study you’d put in.
This is an issue of ‘credit assignment’, where a person or animal attributes the wrong outcome to an event, exists in a variety of psychiatric disorders, like addiction or OCD where people still believe that drug consumption on engaging in certain rituals will lead to positive outcomes.
Now a new study in macaque monkeys has shed light on which parts of the brain support credit assignment processes and, for the first time, how low-intensity transcranial ultrasound stimulation (TUS) can modulate both brain activity and behaviours related to these credit assignment processes.
While currently developed in an animal model, this line of research and the use of TUS could one day be applied to clinical research to tackle psychiatric conditions where maladaptive decisions are observed.
After stimulating this brain area, the animals in the study became more exploratory in their decisions. As a consequence of the ultrasound neuromodulation, behaviour was no longer guided by choice value – meaning that they could not understand that some choices would cause better outcomes – and decision-making was less adaptive in the task.
The study also showed that this process remained intact if another brain region (also part of the prefrontal cortex) was stimulated; showing for the first time how task-related brain modulation is specific to stimulation of areas that mediate a certain cognitive process.
The full study, entitled Ultrasound modulation of macaque prefrontal cortex selectively alters credit assignment–related activity and behaviour is available to view in the journal Science Advances.
Release date: 16 December 2021
Source: University of Plymouth
Greater Exposure to Nitrogen Dioxide Linked to Higher Levels of Biomarkers of Alzheimer Disease in the Brain
A study has found an association between air pollution and higher levels of deposition of beta-amyloid protein in the brain and of neurofilament light (NfL) in cerebrospinal fluid.
Investigators from the Barcelonaβeta Brain Research Center (BBRC), the research arm of the Pasqual Maragall Foundation, in collaboration with ISGlobal, have found an association between exposure to air pollution and higher levels of biomarkers of Alzheimer’s disease, particularly in individuals with elevated beta-amyloid deposition in the brain. The results of the study, which was supported by the ”la Caixa” Foundation, have been published in Environment International.
Release date: 16 December 2021
Source: Barcelona Institute for Global Health (ISGlobal)
Drug could more effectively treat patients hospitalised with COVID-19 pneumonia
A proof-of-concept trial led by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust has identified a drug that may benefit some patients hospitalised with COVID-19 pneumonia.
An antibody already in late-stage trials to treat rheumatoid arthritis, namilumab targets a ‘cytokine’ which is naturally secreted by immune cells in the body but, in uncontrolled levels, is believed to be a key driver of the excessive and dangerous lung inflammation seen in COVID-19 patients.
The trial, carried out in collaboration with the University of Oxford and funded by the Medical Research Council and carried out between June 2020 and February 2021, involved patients aged over 16 with COVID-19 pneumonia either being treated on a ward or Intensive Care Unit (ICU) at nine NHS hospitals across the UK.
The study, published in The Lancet Respiratory Medicine, involved 54 patients receiving ‘usual care’ (steroids and oxygen or ventilation, depending on the severity of disease) and 57 patients given usual care as well as a single intravenous dose of 150mg of namilumab.
As well as COVID-19 pneumonia, all study participants had CRP levels greater than 40mg/l. The researchers compared the probability of the reduction of levels of CRP in patients. Compared to usual care alone, the researchers found there was a 97% probability of CRP being reduced over time in those given namilumab when compared with usual care alone.
The patients were monitored, and after 28 days the study also showed there were fewer deaths and more discharges from hospital or ICU in those who had been given namilumab compared to those receiving usual care alone.
By day 28, 78% (43) of the patients receiving namilumab were discharged from hospital or ICU, compared to 61% (33) of the patients given usual care. In the namilumab group, 11% (6) were still in hospital by day 28, compared to 20% (11) in the usual care group. Of those in the namilumab group, 11% (6) patients died compared to 19% (10) who died in the usual care group by day 28.
The team calculated the differences between the two cohorts in overall probability of those being discharged from ICU or a ward at 28 days. Of those on a ward, the probability of discharge at day 28 was 64% in the usual care cohort, compared to 77% in the Namilumab cohort. Of those in ICU, probability of discharge at day 28 was 47% in the usual care group, compared to 66% in the Namilumab cohort.
Release date: 17 December 2021
Source: University of Birmingham