Year: 2021

C.1.2 Variant Slows in SA; Colombian Variant Named Mu

Computer image of SARS-CoV-2. From CDC at Pexels
Source: CDC on Pexels

The Network for Genomic Surveillance in South Africa (NGS-SA) has reported that the C.1.2 variant is spreading less slowly than in July, from 2.2% of all sequenced COVID cases to 1.5% in August, and is therefore unlikely to become a dominant variant.

Meanwhile, B.1.621,  another variant that first emerged in Colombia in January has been recently classified by the World Health Organization (WHO) as a variant of interest (VOI), receiving the Greek letter “Mu”. Since its first detection, it has spread across North America, South America and Europe, and has also been detected in Asia. The majority of the Mu sequences (5123) have been detected in North America (55%, n=2841) followed by South America (23%, n=1328), Europe (18%, n=948) and Asia (0.1%, n=6). As of 3 September 2021, Mu has not been detected in Africa. Thus far, it makes up less than 1% of the globally circulating viruses with Delta accounting for 88%.

NGS-SA, which includes the National Institute for Communicable Diseases (NICD), continuously and rigorously monitors SARS-CoV-2 sequences circulating in South Africa. This work is crucial in the early detection of SARS-CoV-2 variants, including Mu.

Many of the mutations within the spike protein which define the Mu variant (T95I, E484K, N501Y, D614G, P681H and D950) have been seen before in other VOIs or variants of concern (VOCs) including Beta and Delta. Some of these mutations have previously been associated with decreased antibody responses and increased transmissibility. Therefore it is likely that Mu will have similar properties to other variants with increased transmissibility and reduced sensitivity to antibodies in vaccines and those who have recovered from COVID.

The NICD advises that both COVID vaccines being used in South Africa have high levels of protection against severe disease requiring hospitalisation and death even against VOI/VOCs such as Beta and Delta and therefore will likely also protect against Mu. 

Source: NICD

Female Blood Donors Better for Very-low-birthweight Transfusions

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The sex of adult blood donors may affect the risk of common complications in transfusions of red blood cells (RBCs) to premature or very-low-birthweight infants while in the neonatal intensive care unit (NICU), according to new research.

Anaemia is common in premature or very-low-birthweight infants, often requiring an RBC transfusion. Common negative outcomes that can occur with very low birth weight infants include necrotising enterocolitis, lung damage or retinopathy of prematurity. Studies provided conflicting evidence of transfusions being a risk factor.

The study was led by Dr Ravi Patel is director of neonatal research in the Department of Pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta. Dr Patel and colleagues followed 181 very-low-birth-weight infants at three hospitals from 2010 to 2014. The infants were selected who received RBC transfusions from only male donors or only female donors.\

The study, published in JAMA Network Open, found that a typical very-low-birth-weight infant who received red blood cell transfusion from only female donors had a three times lower risk of negative outcomes than one who received red blood cells from only male donors.

Increasing donor age increased the protective effect of female donors. Some potential explanations for the protective effect could be reduced breakdown during storage of RBCs from female donors, along with less inflammation and more antioxidant capacity, the authors wrote.

RBC transfusion is common, according to Dr Patel, with about half of very low birth infants receiving at least one RBC transfusion while in the NICU. RBC transfusion is necessary to treat anaemia related to prematurity. In rare circumstances, this can lead to an infection or transfusion reaction. It is uncertain whether RBC transfusion increases the risks of some adverse clinical outcomes.
  Is it correct to say that the suspected mechanism for the difference in risk has to do with the characteristics of the RBCs, rather than immune differences, the suspected reason for the reverse effect in adults?

Future research should investigate inflammation or antioxidant capacity of red blood cells since these mechanisms may differ from adults, Dr Patel suggested.
Should their findings that age and sex have an effect on transfusion outcomes be confirmed, the next step would be transfusing blood from only males or only females, which could inform changes in practice.
Source: Emory University

Use of Nicotine-containing E-cigarettes Increases Blood Clot Formation

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A new study found the use of e-cigarettes containing nicotine has a number of immediate effects, which include increased blood clot formation, blood vessel dysfunction, as well as raised heart rate and blood pressure.

These effects are similar to smoking traditional cigarettes with heart attack or stroke risk with long-term use, according to researchers. The study was presented at the ERS International Congress by Gustaf Lyytinen, a clinician at Helsingborg Hospital and researcher at the Karolinska Institute in Stockholm, Sweden. 

Each of the 22 occasional smoker volunteers was tested before and after taking 30 puffs from an e-cigarette with nicotine, and before and after 30 puffs from an e-cigarette without nicotine. These two sets of tests were conducted on separate occasions, at least one week apart.

On each occasion, the researchers measured volunteers’ heart rate and blood pressure and took a blood sample before they used the e-cigarettes, then 15 minutes after use and again 60 minutes after use. A laser was used to measure dilation of skin blood vessels before volunteers used e-cigarettes and 30 minutes afterwards.
E-cigarettes with nicotine caused an immediate short-term change: a 23% average increase in blood clots after 15 minutes, that returned to normal levels after 60 minutes. Average heart rates also increased from 66bpm to 73bpm. as did blood pressure from 108mmHg to 117mmHg. Researchers observed temporary narrowing of blood vessels after nicotine-containing e-cigarettes use.

These effects were not observed after volunteers used e-cigarettes without nicotine. Nicotine is known to raise levels of hormones including adrenaline, which can increase blood clot formation.

Dr Lyytinen said: “Our results suggest that using e-cigarettes that contain nicotine have similar impacts on the body as smoking traditional cigarettes. This effect on blood clots is important because we know that in the long-term this can lead to clogged up and narrower blood vessels, and that of course puts people at risk of heart attacks and strokes.”

Source: European Respiratory Society

Metabolic Changes in Plasma, Immune Cells Linked to COVID Severity

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Analysing plasma from patients infected with SARS-CoV-2, researchers have uncovered underlying metabolic changes that regulate how immune cells react to COVID, these are associated with disease severity and could be used to predict patient survival. The findings were published in the journal Nature Biotechnology.

“We know that there are a range of immune responses to COVID, and the biological processes underlying those responses are not well understood,” said co-first author Jihoon Lee, a graduate student at Fred Hutchinson Cancer Research Center. “We analyzed thousands of biological markers linked to metabolic pathways that underlie the immune system and found some clues as to what immune-metabolic changes may be pivotal in severe disease. Our hope is that these observations of immune function will help others piece together the body’s response to COVID. The deeper understanding gained here may eventually lead to better therapies that can more precisely target the most problematic immune or metabolic changes.”

The researchers performed two draws on each of nearly 200 patients during the first week after being diagnosed with SARS-CoV-2 infection, and analysed their plasma and single immune cells. The analysis included 1387 genes involved in metabolic pathways and 1050 plasma metabolites.

Increased COVID severity was found to be associated with metabolite alterations, which suggests increased immune-related activity. In addition, each major immune cell type was found to have a distinct metabolic signature.

“We have found metabolic reprogramming that is highly specific to individual immune cell classes (eg “killer” CD8+ T cells, “helper” CD4+ T cells, antibody-secreting B cells, etc.) and even cell subtypes, and the complex metabolic reprogramming of the immune system is associated with the plasma global metabolome and are predictive of disease severity and even patient death,” said co-first and co-corresponding author Dr. Yapeng Su, a research scientist at Institute for Systems Biology. “Such deep and clinically relevant insights on sophisticated metabolic reprogramming within our heterogeneous immune systems are otherwise impossible to gain without advanced single-cell multi-omic analysis.”

“This work provides significant insights for developing more effective treatments against COVID. It also represents a major technological hurdle,” said Dr. Jim Heath, president and professor of ISB and co-corresponding author on the paper. “Many of the data sets that are collected from these patients tend to measure very different aspects of the disease, and are analysed in isolation. Of course, one would like these different views to contribute to an overall picture of the patient. The approach described here allows for the sum of the different data sets to be much greater than the parts, and provides for a much richer interpretation of the disease.”

Source: Max Planck Institute

Worse Lung Function Linked to Sudden Cardiac Death

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A new study found that people with modest but measurably worse lung function are more likely to suffer sudden cardiac death (SCD).

SCD is death due to a cardiovascular cause that occurs within one hour of the onset of symptoms. A sudden cardiac arrest occurs when the heart stops beating or is not beating sufficiently to maintain perfusion and life. There are often no previous warning signs, and is thought to be responsible for around 20% of all deaths in Europe.

The study was presented at the ERS International Congress by Dr Suneela Zaigham of Lund University. She said: “Although sudden cardiac deaths are common, we don’t know enough about who is at risk in the general population. There are links between lung and heart health, so we wanted to investigate whether measurable differences in lung function could offer clues about the risk of sudden cardiac death.”

The study involved 28 584 middle-aged participants with no known heart problems. All took part in spirometry tests where they were asked to blow into a machine to measure how well their lungs were working. Over the following approximately 40 years, researchers recorded any SCDs (death on the day of a coronary event) or any non-fatal coronary events (coronary events where people survived the first 24 hours)

They found that measurably lower lung function in middle-aged people (one standard deviation lower in the amount of air they could blow out in one second, which equates to around 0.8 litres) was more strongly associated with suffering a SCD (a 23% increase in risk) than a non-fatal coronary event (an 8% increase in risk) later on in life. The pattern of risk remained even in people who had never smoked.

Dr Zaigham said: “We believe this is the first study to directly compare the risk of sudden cardiac death and non-fatal coronary events and their links with lung function in the general population.

“Our findings suggest that testing people’s lungs when they are middle-aged and healthy could help spot those who have a higher risk of sudden cardiac death. This could enable people to take steps to potentially reduce the risk of this devastating event.”

A limitation of the study is that risk questionnaires were administered at the start of the study and these factors could have changed. The researchers next seek to see whether SCD could be prevented by testing lung function as part of current cardiovascular risk assessment. They plan to explore the link between lung function and SCD further to see if heart abnormalities, variable blood pressure or genetic causes are involved.

Source: European Respiratory Society

Bisexual People Have Over Twice the Rates of Lung Diseases

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A new national study found that bisexual Americans had over two times the rates of lung diseases including asthma as heterosexual adults.

The study, published in Annals of the American Thoracic Society, analysed data from 12 209 adults in the National Longitudinal Study of Adolescent to Adult Health. Overall, 29% of bisexual adults reported experiencing lung disease compared to 14% of heterosexual adults. There is consistent evidence that bisexual individuals are at increased risk for negative health outcomes (such as mental health, substance use, and sexual health problems) compared to monosexual (heterosexual and gay/lesbian) individuals.

“Higher levels of discrimination experienced by bisexual people could lead to more stress and lead to inflammation or stress hormones which would worsen asthma,” said lead author, Jason Nagata, MD, assistant professor of paediatrics at the University of California, San Francisco. “Bisexual adults have been shown to have worse health outcomes across a number of physical and mental health domains, and we add to this literature by showing disparities in asthma and other lung diseases.”

Even people who identified as ‘mostly’ heterosexual had higher rates of asthma than those who identified as exclusively heterosexual. Mostly heterosexual individuals may also face discrimination but may not be ‘out’, with access to the social support and communities ‘out’ LGBTQ+ people have available.

“Medical professionals, social workers, and clinicians need to be aware of these sexual orientation disparities in health outcomes,” said co-author Kyle T Ganson, PhD, assistant professor at the University of Toronto’s Factor-Inwentash Faculty of Social Work. “Providing appropriate and tailored care is needed to address these disparities.”

“Some sexual minorities may be less likely to seek care due to barriers to accessing health care or experiences of discrimination at a clinician’s office. Doctors should offer materials on LGBTQ health, publicise nondiscrimination statements and have inclusive forms for sexual minorities,” Prof Nagata added, “so that they’re not discouraged from seeking care.”

Source: EurekAlert!

In Women, Avocado Consumption Reduces Abdominal Visceral Fat

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An avocado a day could help reduce abdominal visceral fat in women and result in health benefits, researchers wrote in the Journal of Nutrition.

In a randomised study, women who consumed avocado as part of their daily meal experienced a reduction in deeper visceral abdominal fat, though glucose tolerance markers were unchanged.

Study leader Naiman Khan, professor of kinesiology and community health, at University of Illinois Urbana-Champaign said:

“The goal wasn’t weight loss; we were interested in understanding what eating an avocado does to the way individuals store their body fat. The location of fat in the body plays an important role in health,” Prof Khan said.

“In the abdomen, there are two kinds of fat: fat that accumulates right underneath the skin, called subcutaneous fat, and fat that accumulates deeper in the abdomen, known as visceral fat, that surrounds the internal organs. Individuals with a higher proportion of that deeper visceral fat tend to be at a higher risk of developing diabetes. So we were interested in determining whether the ratio of subcutaneous to visceral fat changed with avocado consumption,” he said.

The participants were divided into two groups; one received meals incorporating a fresh avocado, and the other received a meal that had nearly identical ingredients and similar calories but without avocado. At the beginning and end of the trial, the researchers measured participants’ abdominal fat and their glucose tolerance, a measure of metabolism and a marker of diabetes.

Female participants who consumed an avocado a day as part of their meal had a reduction in visceral abdominal fat and experienced a reduction in the ratio of visceral fat to subcutaneous fat, indicating a redistribution of fat away from the organs. However, in males there was no change in fat distribution, and neither males nor females had improvements in glucose tolerance.

“While daily consumption of avocados did not change glucose tolerance, what we learned is that a dietary pattern that includes an avocado every day impacted the way individuals store body fat in a beneficial manner for their health, but the benefits were primarily in females,” Prof Khan said. “It’s important to demonstrate that dietary interventions can modulate fat distribution. Learning that the benefits were only evident in females tells us a little bit about the potential for sex playing a role in dietary intervention responses.”

The next step would be to provide all of the participants’ daily meals and look at additional markers of gut health and physical health for a more complete understanding of metabolic impacts and whether this sex difference persists.

Source: University of Illinois Alabama

Ridhwaan Suliman on Twitter: Graphs, Insight and Empathy

Photo by Tracy le Blanc from Pexels
Photo by Tracy le Blanc from Pexels

The Daily Maverick interviewed Dr Ridhwaan Suliman, a senior researcher at CSIR who has entered the spotlight by posting his concise, easy-to-understand COVID numbers graphs on Twitter.

Trained as a mechanical engineer and with a PhD in applied mathematics, he develops computational tools to model and simulate physical systems and processes. Equations in real-world contexts and how they govern physical systems are the relationships he translates into code. And from the code and modelling he can find solutions to make things work more optimally.

As a boy, he took apart his brothers’ old toys to see how they worked, and he took the same approach with COVID data to make sense of it. He started tracking the data in early 2020, and wanted to contribute in some way amidst all the growing uncertainty.

“When I started seeing the raw numbers that were being fed to us daily I couldn’t quite make sense of it myself because the raw numbers in isolation don’t show what’s happening, actually.”

As he tweeted his analyses, he drew attention for his concise summaries of the situation, and praise for helping people to understand the trends. However, he stresses that this is all unpaid, with nobody else’s agenda and that he is not a medical expert.

https://twitter.com/rid1tweets/status/1434570126091821062
This week’s update from Dr Ridhwaan

“I’m just comfortable with the numbers.” He gratefully turns to the science experts he engages with on Twitter because “there’s so much more to learn”, he says. That, and a lot of background reading, which he readily dives into.

Dr Suliman’s tracking of the data let him identify gaps and to add to the call for open data, better data collection and smarter analysis. This allows for the factoring in of more variables and laying out of better parameters. “Sure, data can be manipulated to fit a certain narrative, but the benefits outweigh the risks,” he says.

Even in the polarising, easily toxic world of Twitter, Dr Suliman’s interactions show a great empathy.

“We’ve all had numerous moments in this pandemic when things have been depressing and that’s probably something that doesn’t come out on Twitter because you’re generally only sharing things when things are hunky-dory, you don’t share when you’re not okay. There have been many times when I’ve just wanted to stop tweeting, but I get drawn back by people who reach out and say ‘you’re helping me’ – and that’s good enough reason to continue.”

Since he first started on Twitter, he has since appeared numerous times on television to explain the data behind COVID numbers.

Despite his newfound fame however, he looks forward to the time when he can travel again.  “I’ll trade the followers any day for our lives to go back to some sense of normality,” he says.

Source: Daily Maverick

Novel Nasal Spray for Migraines Approved by FDA

Impel NeuroPharma announced that the US Food and Drug Administration (FDA) approved TRUDHESA™ (dihydroergotamine mesylate) nasal spray (0.725 mg per spray) for the acute treatment of migraine with or without aura in adults.

The innovative system delivers dihydroergotamine mesylate (DHE) through the vascular-rich upper nasal space, bypasses the gut and potential absorption issues, offering rapid, sustained, and consistent symptom relief without injection or infusion, even when administered hours after a migraine attack starts. 

During the Phase 3, open-label, pivotal safety study, STOP 301, more than 5,650 migraine attacks were treated over 24 or 52 weeks during the study. The primary objective of the study was to assess the safety and tolerability of TRUDHESA. TRUDHESA was generally well tolerated and exploratory efficacy findings showed it provided rapid, sustained, and consistent symptom relief. STOP 301 reported TRUDHESA offered consistent efficacy even when taken late into a migraine attack.

“Many of my patients need more from their migraine treatment, and TRUDHESA offers a non-oral, fast-acting, reliable option that overcomes many current medication challenges,” said Stephanie J. Nahas-Geiger, MD, MSEd, Associate Professor in the Department of Neurology, and Program Director of the Headache Medicine Fellowship Program, Thomas Jefferson University. “Its upper nasal delivery circumvents the GI tract and common phenomena associated with migraine, such as nausea and gastroparesis, that can impact the effectiveness of oral treatments. And, importantly, it is a self-administered, single dose that can be taken anytime during a migraine attack, so patients don’t need to worry about missing the opportunity to benefit from using TRUDHESA within a certain timeframe. I think patients will be very receptive to this treatment, because it pairs the long-proven benefits of DHE with a patient-friendly delivery system.”

There were no serious adverse events were observed in the study, and most adverse events were mild and transient in nature.

In the STOP 301 study, patient-reported efficacy showed that 38% of patients had pain freedom, 66% had pain relief, and 52% had freedom from their most bothersome migraine symptom at two hours after their first dose of TRUDHESA. In 16% of patients, pain relief started as early as 15 minutes. Of patients who were pain free at two hours, 93 percent were still pain free at 24 hours, and 86 percent were still pain free through two days. The great majority of patients (84%) reported that TRUDHESA was easy to use10 and preferred it over their current therapy.

Source: Impel NeuroPharma

Physical Activity, Less Sitting Reduces Risk of Sleep Apnoea

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Higher levels of physical activity and fewer hours sitting still have been linked with a lower risk of sleep apnoea in a new study.

Researchers studied information from three different databases. These databases had collected health information on men and women using tests and questionnaires over several years. In this study, researchers looked at cases of sleep apnoea that had been diagnosed by a doctor, the amount of physical activity a person completed each week and how much time a person sat still while watching TV or working.

Drawing on the database, the study found 8733 cases of sleep apnoea (6652 women, 2081 men). Across all three databases, it was found that higher levels of physical activity were linked to lower levels of sleep apnoea. Fewer hours of sitting while watching TV or while working was also linked with lower levels of sleep apnoea.
The study also noted that there was a strong link between low levels of activity and long hours sitting in women, as well as those who were overweight or obese.

According to its authors, this is the largest study of its kind that looks at the link between sleep apnoea and physical activity and the number of hours sitting down. The findings support the benefits of maintaining an active lifestyle, and avoiding sitting for long periods of time, to help to reduce the risk of sleep apnoea.

Source: European Lung Foundation