Tag: 26/11/21

Viral RNA Levels Can Predict COVID Mortality

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Viral RNA levels in the blood is a reliable indicator in predicting COVID mortality, according to a study published in Science Advances.

“In our study, we were able to determine which biomarkers are predictors of mortality in the 60 days following the onset of symptoms,” said Université de Montréal medical professor Dr. Daniel Kaufmann, the study’s co-lead author alongside colleagues Nicolas Chomont and Andrés Finzi.

“Thanks to our data, we have successfully developed and validated a statistical model based on one blood biomarker,” viral RNA, Prof Kaufmann said.

Despite advances in COVID management, identifying patients at greater risk of dying of the disease has been difficult. Other studies identified various biomarkers, but assessing so many parameters is not possible in a clinical setting and gets in the way of doctors’ quick clinical decision-making ability.

Using blood samples from 279 patients hospitalised for COVID of differing severity, Kaufmann’s team measured amounts of inflammatory proteins, looking for any that stood out.

At the same time, Chomont’s team measured the amounts of viral RNA and in Finzi’s the levels of antibodies targeting the virus. Samples were collected 11 days after the onset of symptoms and patients were monitored for a minimum of 60 days after that.

The goal: to test the hypothesis that immunological indicators were associated with increased mortality.

“Among all of the biomarkers we evaluated, we showed that the amount of viral RNA in the blood was directly associated with mortality and provided the best predictive response, once our model was adjusted for the age and sex of the patient,” said Elsa Brunet-Ratnasingham, a doctoral student in Kaufmann’s lab and co-first author of the study.

“We even found that including additional biomarkers did not improve predictive quality,” she added.

Prof Kaufmann and Brunet-Ratnasingham tested the model on two independent cohorts of infected patients from Montreal’s Jewish General Hospital (recruited during the first wave of the pandemic) and the CHUM (recruited during the second and third waves).

No matter which hospital the patients were treated at, nor which period of the pandemic they fell into: in all cases, the predictive model worked. Now Prof Kaufmann and his colleagues want to put it to practical use.

“It would be interesting to use the model to monitor patients,” he said, “with the following question in mind: when you administer new treatments that have proven effective, is viral load still a predictive marker of mortality?” 

Source: University of Montreal

In Dementia, De-cluttering is of Little Value

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A new study has shown that a clutter-free environment may not help people living with dementia carry out daily tasks.

Researchers studied whether people with dementia were better able to carry out tasks, such as making a cup of tea, at home amidst their normal clutter or in a clutter-free environment. Surprisingly, participants with moderate dementia performed better when surrounded by their usual clutter. But the different environments made no difference to people with mild and severe dementia, who were able to perform at the same level in both settings. The findings were published in Alzheimer Disease & Associated Disorders.

Prof Eneida Mioshi, from the University of East Anglia. said: “As dementia progresses, people gradually lose their ability to carry out daily tasks due to changes in their cognitive, perceptual and physical abilities. Participation in daily tasks could then be improved by adapting the person’s environment.

“To this end, we wanted to investigate the role of clutter in activity participation, given the potential to use de-cluttering to support people with dementia to continue to be independent.

“Environmental clutter has been defined as the presence of an excessive number of objects on a surface or the presence of items that are not required for a task. It is generally assumed that a person with dementia will be better-able to carry out daily tasks when their home space is tidy and clutter free. However there has been very little research to really test this hypothesis.

“We wanted to see whether clutter was negatively affecting people with dementia. So we studied how people at different stages of dementia coped with carrying out daily tasks at home, surrounded by their usual clutter, compared to in a clutter-free setting – a specially designed home research lab.”

Occupational therapist and PhD student Julieta Camino carried out the study with 65 participants. They were grouped into those with mild, moderate and severe dementia, and were asked to carry out daily tasks including making a cup of tea and making a simple meal, both at their own home and at UEA’s specially designed NEAT research bungalow, a fully furnished research facility that feels just like a domestic bungalow. 

The researchers evaluated performance of activities in both settings, and also measured the amount of clutter in the participants’ homes. Meanwhile the NEAT home setting was completely clutter free.

Source: University of East Anglia

Extreme Heat Health Risks Are Higher for Younger Adults

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A new study in the US has found that complications from extreme heat appear to be more pronounced among young and middle-aged adults than older adults.

Extreme heat poses an increasing threat to the public, due to the continued effects of climate change. Although the adverse health impacts of heat have been well documented among older adults, less is known about the potential impacts of heat on young and middle-aged adults.

Published in the BMJ, the study examined the relationship between extreme temperatures and emergency department (ED) visits, and found that days of extreme heat were associated with an increase risk of ED visits for any cause, heat-related illness, renal disease, and mental disorders among all adults, but the strongest association was found among adults ages 18-64.

Prior research on heat’s health impacts have mostly focused on mortality or hospital admissions among seniors. This study is the first national-scale assessment of extreme heat effects on adults of all ages, measured with ED visits.

“Many illnesses that lead to utilisation of the ED do not lead to hospitalisation because they can be treated in a short amount of time, particularly among the younger adult population,” said study senior author Gregory Wellenius, professor of environmental health and director of the Program on Climate and Health at SPH. “By looking at emergency room visits, we aimed to obtain a more comprehensive picture of the true burden of disease that might be attributed to the days of high heat.”

Prof Wellenius and colleagues analysed healthcare claims data to quantify the risk of ED visits for any cause and for heat-associated conditions during the warm season (between May and September) from 2010 to 2019.

For the study, the researchers analysed claims data among 74 million adults, including more than 22 million ED visits. They found that days of extreme heat (varying by location, but averaging about 34°C), were associated with a 66% greater risk of ED visits for heat-related illness, as well as a 30% increased risk for renal disease, compared to ED visits on cooler days. But the risk according to extreme heat varied by age. A day of extreme heat was associated with a 10.3% higher risk of ED visits among people ages 45 to 54 years old, compared to a 3.6% higher risk among those older than 75.

“Younger adults may be at greater risk of exposure to extreme heat, particularly among workers that spend substantial time outdoors,” says study lead author Shengzhi Sun, research scientist in the Department of Environmental Health at SPH. “Younger adults may also not realise that they too can be at risk on days of extreme heat.”

Prior studies had shown that people in US counties with lower warm-season temperatures still experience higher risks of heat-related complications.
“While extreme heat threatens everyone’s health, this study provides further evidence that it is especially dangerous in regions with cooler climates that may be less adapted to heat,” says study co-author Kate Weinberger, assistant professor at the University of British Columbia’s School of Population and Public Health. “As temperatures continue to rise due to climate change, the implementation of heat adaptation measures in these regions will be critically important.”

According to the researchers, many of these heat-related complications can be prevented through policy changes that reduce exposure to heat, or improve people’s susceptibility and adaptivity to heat.

“By looking at emergency department visits for different causes and for several age groups, we were able to characterise with accuracy the varying impact on health on different populations,” said study co-author, Professor Francesca Dominici. “An important goal of this study is to provide actionable information to clinicians and public health experts regarding how to prevent these emergency department visits, also considering that we can anticipate when these extreme heat events are likely to occur.”

Source: Boston University

Differences in Influenza Responses According to Genetic Ancestries

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Researchers have uncovered differences in immune pathway activation to influenza infection between individuals of European and African genetic ancestry, according to a study published in Science. Many of the genes that were associated with these immune response differences to influenza are also enriched among genes associated with COVID disease severity. 

“The lab has been interested in understanding how individuals from diverse populations respond differently to infectious diseases,” said first author Haley Randolph, a graduate student at the University of Chicago. “In this study, we wanted to look at the differences in how various cell types respond to viral infection.”

The researchers examined gene expression patterns in peripheral mononuclear blood cells, a diverse set of specialised immune cells that play important roles in the body’s response to infection. These cells were gathered from men of European and African ancestry and then exposed the cells to flu in a laboratory setting. This let the team examine the gene signatures of a variety of immune cell types, and observe how the flu virus affected each cell type’s gene expression.

The results showed that individuals of European ancestry showed an increase in type I interferon pathway activity during early influenza infection.

“Interferons are proteins that are critical for fighting viral infections,” said senior author Luis Barreiro, PhD, Associate Professor of Medicine at UChicago. “In COVID-19, for example, the type I interferon response has been associated with differences in the severity of the disease.”

This increased pathway activation hindered the replication of the virus more and limited viral replication later on. “Inducing a strong type I interferon pathway response early upon infection stops the virus from replicating and may therefore have a direct impact on the body’s ability to control the virus,” said Barreiro. “Unexpectedly, this central pathway to our defense against viruses appears to be amongst the most divergent between individuals from African and European ancestry.”

The researchers saw a variety of differences in gene expression across different cell types, suggesting a constellation of cells that work together to fight disease.

Such a difference in immune pathway activation could explain influenza outcome disparities between different racial groups; Non-Hispanic Black Americans are more likely to be hospitalised due to the flu than any other racial group.

However, these results are not evidence for genetic differences in disease susceptibility, the researchers point out. Rather, possible differences in environmental and lifestyle between racial groups could be influencing gene expression, and affecting the immune response.

“There’s a strong relationship between the interferon response and the proportion of the genome that is of African ancestry, which might make you think it’s genetic, but it’s not that simple,” said Barreiro. “Genetic ancestry also correlates with environmental differences. A lot of what we’re capturing could be the result of other disparities in our society, such as systemic racism and healthcare inequities. Although some of the differences we show in the paper can be linked to specific genetic variation, showing that genetics do play some role, such genetic differences are not enough to fully explain the differences in the interferon response.”

These differences in viral susceptibility may not be confined to just influenza. Comparing a list of genes associated with differences in COVID severity, the researchers found that many of the same genes showed significant differences in their expression after flu infection between individuals of African and European ancestry.

“We didn’t study COVID patient samples as part of this study, but the overlap between these gene sets suggests that there may be some underlying biological differences, influenced by genetic ancestry and environmental effects, that might explain the disparities we see in COVID outcomes,” said Barreiro.

As they explore this further, the researchers hope to figure out which factors contribute to the differences in the interferon response, and immune responses more broadly, to better predict individual disease risk.

Source: EurekAlert!