Infections with ‘U.K. Variant’ B.1.1.7 Have Greater Risk of Mortality

Since the genome sequence of SARS-CoV-2, the virus responsible for COVID-19, was first reported in January 2020, thousands of variants have been reported. In the vast majority of cases, these variants, which arise from random genomic changes as SARS-CoV-2 makes copies of itself in an infected person, haven’t raised any alarm among public health officials. But that’s now changed with the emergence of at least three variants carrying mutations that potentially make them even more dangerous.

At the top of this short list is a variant known as B.1.1.7, first detected in the United Kingdom in September 2020. This variant is considerably more contagious than the original virus. It has spread rapidly around the globe and likely accounts already for at least one-third of all cases in the United States [1]. Now comes more troubling news: emerging evidence indicates that infection with this B.1.1.7 variant also comes with an increased risk of severe illness and death [2].

The findings, reported in Nature, come from Nicholas Davies, Karla Diaz-Ordaz, and Ruth Keogh, London School of Hygiene and Tropical Medicine. The London team earlier showed that this new variant is 43 to 90 percent more transmissible than pre-existing variants that had been circulating in England [3]. But in the latest paper, the researchers followed up on conflicting reports about the virulence of B.1.1.7.

They did so with a large British dataset linking more than 2.2 million positive SARS-CoV-2 tests to 17,452 COVID-19 deaths from September 1, 2020, to February 14, 2021. In about half of the cases (accounting for nearly 5,000 deaths), it was possible to discern whether or not the infection had been caused by the B.1.1.7 variant.

Based on this evidence, the researchers calculated the risk of death associated with B.1.1.7 infection. Their estimates suggest that B.1.1.7 infection was associated with 55 percent greater mortality compared to other SARS-CoV-2 variants over this time period.

For a 55- to 69-year-old male, this translates to a 0.9-percent absolute, or personal, risk of death, up from 0.6 percent for the older variants. That means nine in every 1,000 people in this age group who test positive with the B.1.1.7 variant would be expected to die from COVID-19 a month later. For those infected with the original virus, that number would be six.

Adapted from Centers for Disease Control and Prevention

These findings are in keeping with those of another recent study reported in the British Medical Journal [4]. In that case, researchers at the University of Exeter and the University of Bristol found that the B.1.1.7 variant was associated with a 64 percent greater chance of dying compared to earlier variants. That’s based on an analysis of data from more than 100,000 COVID-19 patients in the U.K. from October 1, 2020, to January 28, 2021.

That this variant comes with increased disease severity and mortality is particularly troubling news, given the highly contagious nature of B.1.1.7. In fact, Davies’ team has concluded that the emergence of new SARS-CoV-2 variants now threaten to slow or even cancel out improvements in COVID-19 treatment that have been made over the last year. These variants include not only B1.1.7, but also B.1.351 originating in South Africa and P.1 from Brazil.

The findings are yet another reminder that, while we’re making truly remarkable progress in the fight against COVID-19 with increasing availability of safe and effective vaccines (more than 45 million Americans are now fully immunized), now is not the time to get complacent. This devastating pandemic isn’t over yet.

The best way to continue the fight against all SARS-CoV-2 variants is for each one of us to do absolutely everything we can to stop their spread. This means that taking the opportunity to get vaccinated as soon as it is offered to you, and continuing to practice those public health measures we summarize as the three Ws: Wear a mask, Watch your distance, Wash your hands often.

References:

[1] US COVID-19 Cases Caused by Variants. Centers for Disease Control and Prevention.

[2] Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7. Davies NG, Jarvis CI; CMMID COVID-19 Working Group, Edmunds WJ, Jewell NP, Diaz-Ordaz K, Keogh RH. Nature. 2021 Mar 15.

[3] Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. Davies NG, Abbott S, Barnard RC, Jarvis CI, Kucharski AJ, Munday JD, Pearson CAB, Russell TW, Tully DC, Washburne AD, Wenseleers T, Gimma A, Waites W, Wong KLM, van Zandvoort K, Silverman JD; CMMID COVID-19 Working Group; COVID-19 Genomics UK (COG-UK) Consortium, Diaz-Ordaz K, Keogh R, Eggo RM, Funk S, Jit M, Atkins KE, Edmunds WJ.Science. 2021 Mar 3:eabg3055.

[4] Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study. Challen R, Brooks-Pollock E, Read JM, Dyson L, Tsaneva-Atanasova K, Danon L. BMJ. 2021 Mar 9;372:n579.Links:

COVID-19 Research (NIH)Nicholas Davies (London School of Hygiene and Tropical Medicine, U.K.)Ruth Keogh (London School of Hygiene and Tropical Medicine, U.K.)

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'Information theory' recruited to help scientists find cancer genes

Using a widely known field of mathematics designed mainly to study how digital and other forms of information are measured, stored and shared, scientists at Johns Hopkins Medicine and Johns Hopkins Kimmel Cancer Center say they have uncovered a likely key genetic culprit in the development of acute lymphoblastic leukemia (ALL).
ALL is the most common form of childhood leukemia, striking an estimated 3,000 children and teens each year in the United States alone.
Specifically, the Johns Hopkins team used “information theory,” applying an analysis that relies on strings of zeros and ones — the binary system of symbols common to computer languages and codes — to identify variables or outcomes of a particular process. In the case of human cancer biology, the scientists focused on a chemical process in cells called DNA methylation, in which certain chemical groups attach to areas of genes that guide genes’ on/off switches.
“This study demonstrates how a mathematical language of cancer can help us understand how cells are supposed to behave and how alterations in that behavior affect our health,” says Andrew Feinberg, M.D., M.P.H., Bloomberg Distinguished Professor at the Johns Hopkins University School of Medicine, Whiting School of Engineering and Bloomberg School of Public Health. A founder of the field of cancer epigenetics, Feinberg discovered altered DNA methylation in cancer in the 1980s.
Feinberg and his team say that using information theory to find cancer driver genes may be applicable to a wide variety of cancers and other diseases.
Methylation is now recognized as one way DNA can be altered without changing a cell’s genetic code. When methylation goes awry in such epigenetic phenomena, certain genes are abnormally turned on or off, triggering uncontrolled cell growth, or cancer.

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Astronauts' mental health risks tested in the Antarctic

Astronauts who spend extended time in space face stressors such as isolation, confinement, lack of privacy, altered light-dark cycles, monotony and separation from family. Interestingly, so do people who work at international research stations in Antarctica, where the extreme environment is characterized by numerous stressors that mirror those present during long-duration space exploration.
To better understand the psychological hurdles faced by astronauts, University of Houston professor of psychology Candice Alfano and her team developed the Mental Health Checklist (MHCL), a self-reporting instrument for detecting mental health changes in isolated, confined, extreme (ICE) environments. The team used the MHCL to study psychological changes at two Antarctic stations. The findings are published in Acta Astronautica.
“We observed significant changes in psychological functioning, but patterns of change for specific aspects of mental health differed. The most marked alterations were observed for positive emotions such that we saw continuous declines from the start to the end of the mission, without evidence of a ‘bounce-back effect’ as participants were preparing to return home,” reports Alfano. “Previous research both in space and in polar environments has focused almost exclusively on negative emotional states including anxiety and depressive symptoms. But positive emotions such as satisfaction, enthusiasm and awe are essential features for thriving in high-pressure settings.”
Negative emotions also increased across the study, but changes were more variable and predicted by physical complaints. Collectively, these results might suggest that while changes in negative emotions are shaped by an interaction of individual, interpersonal and situational factors, declines in positive emotions are a more universal experience in ICE environments. “Interventions and counter measures aimed at enhancing positive emotions may, therefore, be critical in reducing psychological risk in extreme settings,” said Alfano.
At coastal and inland Antarctic stations, Alfano and her team tracked mental health symptoms across a nine-month period, including the harshest winter months, using the MHCL. A monthly assessment battery also examined changes in physical complaints, biomarkers of stress such as cortisol, and the use of different emotion regulation strategies for increasing or decreasing certain emotions.
Study results also revealed that participants tended to use fewer effective strategies for regulating (i.e., increasing) their positive emotions as their time at the stations increased.
“Both the use of savoring — purposely noticing, appreciating, and/or intensifying positive experiences and emotions — and reappraisal — changing the way one thinks about a situation — decreased during later mission months compared to baseline. These changes likely help explain observed declines in positive emotions over time,” said Alfano.
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Materials provided by University of Houston. Original written by Laurie Fickman. Note: Content may be edited for style and length.

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Newly discovered airway cells may shed light on SIDS and other conditions

Recent research links certain cells that line the human airway with different infant diseases. The work, which is published in Cell Reports and was led by investigators at Massachusetts General Hospital (MGH), could lead to new prevention and treatment strategies for these conditions.
The human airway — from the windpipe to the lungs — is lined with epithelial cells, including a type called pulmonary neuroendocrine cells (PNECs) that communicate with the nervous system and secrete different factors and hormones. Increased numbers and clusters of PNECs have been observed in various breathing-related illnesses, but the cells’ roles in health and disease are unclear. To better understand PNECs and their effects in the body, researchers analyzed lung and airway tissues from humans and mice.
The scientists were surprised to find that PNECs are much more varied than previously described. In fact, it appears that the airway harbors three distinct types of PNECs. Some PNECs express a protein called tubulin beta 3 class III (TUBB3), and this protein is required for protrusions involved in communication between the cells and their environment. Therefore, PNECs with and without TUBB3 may have different sensing mechanisms. Also, higher numbers of certain PNECs were present in autopsied tissues from children who had died from diseases such as sudden infant death syndrome and neuroendocrine hyperplasia in infancy, a rare lung disorder of unknown cause.
“We are currently studying how different subpopulations of PNECs differ in their function,” says senior author Xingbin Ai, PhD, a pulmonary disease specialist in the Department of Pediatrics at MGH. “We hope to leverage this knowledge for future development of markers and treatment strategies for infant diseases that involve abnormalities in these cells.”
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Reversal of blood droplet flight predicted, captured in experiments

Forensic science includes the analysis of blood backspatter involved in gunshot wounds, but scientific questions about the detailed role of fluids in these situations remained unresolved.
To search for answers about how blood droplets from a gunshot wound can reverse direction while in flight, University of Illinois at Chicago and Iowa State University researchers explored the influence of propellant gases on blood backspatter.
In Physics of Fluids, from AIP Publishing, the researchers report using numeric modeling to capture the behavior of gun muzzle gases and predict the reversal of blood droplet flight, which was captured experimentally. Their experiments also show the breakup of blood droplets, a future extension of their modeling efforts.
Propellant gases from gunpowder issue from the gun barrel at high speed and form turbulent vortex rings, which can be visualized by high-speed shadowgraph images, like those used to capture flow structures of supersonic aircraft or spacecraft.
A penetrating bullet tends to spatter blood droplets from the victim backward, toward the shooter, but a turbulent vortex ring of muzzle gases moving from the shooter toward the victim can reverse the flight of the droplets.
The researchers’ prior work focused on modeling the trajectories of blood droplets that lead to bloodstains that end up being analyzed by forensics experts.
“We used proper fluid dynamics models for the aerodynamic drag, which led to significant improvements, but concluded muzzle gases should also be included and can dramatically alter the formation and size of blood droplets,” said Alexander Yarin, a distinguished professor at the University of Illinois at Chicago.
In their most recent work, the researchers identified an additional feature at play beyond deflection and reversal of blood spatter back toward the victim: the secondary breakup of formed droplets in flight, identified by James Michael’s group at Iowa State University.
“We concluded that forensic analysis of formed bloodstains should account for additional uncertainty in the trajectories of droplets, if muzzle gas interactions are present for short-range shooting,” said Yarin. “And while determination of the origin of droplets is often a desirable outcome of forensic analysis, muzzle gas interactions can confound interpretation.”
The researchers’ imaging results made it clear “the size of droplets can be dramatically impacted through the secondary breakup induced by the muzzle gas wind,” said Yarin. “We’re working to analyze this behavior using bloodstain patterns with Drs. James Michael and Daniel Attinger and their team at Iowa State University.”
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Certain gut microbes make mosquitoes more prone to carry malaria parasite

Dietary sugars and gut microbes play a key role in promoting malaria parasite infection in mosquitoes. Researchers in China have uncovered evidence that mosquitoes fed a sugar diet show an increased abundance of the bacterial species Asaia bogorensis, which enhances parasite infection by raising the gut pH level. The study appears April 20 in the journal Cell Reports.
“Our work opens a new path for investigations into the role of mosquito-microbiota metabolic interactions concerning their disease-transmitting potential,” says co-senior study author Jingwen Wang of Fudan University in Shanghai, China. “The results may also provide useful insights for the development of preventive strategies for vector control.”
Mosquitoes rely on nectar-derived sugars, such as glucose, for energy, survival, and reproduction. Similarly, glucose is the primary energy source supporting the proliferation of Plasmodium — malaria parasites that are transmitted to human hosts by female mosquitoes of the genus Anopheles. Some indirect evidence also suggests that carbohydrate metabolism influences the capability of mosquitoes to transmit malaria parasites. Although glucose metabolism is expected to play a role in regulating Plasmodium infection in mosquitoes, the underlying mechanisms have not been clear.
To address this question, Wang teamed up with co-senior study author Huiru Tang of Fudan University. They found that feeding Anopheles stephensi mosquitoes a solution containing glucose for five days increased the number of Plasmodium berghei oocytes in the midgut after infection with the parasite. But mosquitoes treated with an antibiotic cocktail did not show this effect, pointing to a critical role for gut microbes in the sugar-induced enhancement of Plasmodium infection.
The sugar diet specifically increased the abundance of A. bogorensis in the mosquito midgut. Infected mosquitoes that were fed glucose and colonized only with A. bogorensis showed an increased number of P. berghei oocytes. Taken together, the findings suggest that sugar intake promotes Plasmodium infection in mosquitoes by increasing the proliferation of A. bogorensis. Additional experiments provided evidence that this bacterial species mediates the sugar-induced enhancement of infection by raising the midgut pH level, which facilitates the sexual development of P. berghei.
“Our study provides crucial molecular insights into how the complex interplay between glucose metabolism of mosquitos and a component of their gut microbiota, A. bogorensis, influences malaria parasite infection,” Tang says. “Targeting mosquito glucose metabolism might be a promising strategy to prevent malaria parasite transmission.”
The study also provides evidence that the specific sugar composition of plant saps might influence malaria transmission by affecting the proliferation of A. bogorensis. Specifically, Parthenium hysterophorus — a plant species that mosquitoes feed on quite frequently — did not promote A. bogorensis proliferation or P. berghei infection when compared with other mosquito-preferred plants. According to the authors, planting this species might reduce malaria transmission. But further studies are needed to investigate the influence of natural plant saps on the microbiota composition of field mosquitoes and to examine the influence of A. bogorensis from field mosquitoes on malaria parasite infection.
The researchers will continue to investigate the metabolic interactions between mosquitos and their microbiota and the influence of these interactions on pathogen transmission. “Our goal is to find out the key metabolites or chemicals that could inhibit malaria parasite infection in mosquitoes,” Wang says.
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Review summarizes known links between endocrine disruptors and breast cancer risk

Exposure to certain endocrine-disrupting chemicals could elevate the risk of breast cancer, according to a new comprehensive systematic review of epidemiological research. However, for many chemicals, evidence is inconsistent or still limited. The review was carried out by researchers at the universities of Hong Kong and Eastern Finland and published in Critical Reviews in Food Science and Nutrition.
Endocrine-disrupting chemicals (EDCs) can interfere with the body’s hormonal system, also called the endocrine system, and are widely present in the environment. They originate from a variety of sources, including pesticides, plasticisers and other industrial and pharmaceutical chemicals, as well as natural sources. Humans are often exposed to EDCs through food, but other possible exposure routes include drinking water, skin contact and air.
Breast cancer accounts for the majority of women’s cancers. There has been an increasing interest in the role of estrogene-mimicking EDCs, so called xenoestrogens, in the development of breast cancer. They comprise a broad range of pesticides, synthetic chemicals, phytoestrogens and certain mycotoxins. The researchers reviewed 131 epidemiological studies evaluating the link between xenoestrogen exposure and breast cancer. Most studies assessed exposures by measuring the EDCs and their metabolites in urine, serum, plasma or adipose tissues.
Some may be genetically more vulnerable to EDCs
According to the review, the nowadays widely banned pesticide DDT is one of the most studied EDCs in relation to breast cancer risk. Out of 43 epidemiological studies, eleven reported positive associations between DDT or its metabolites in lipid, serum or plasma and breast cancer incidence. Nine reported higher DDT levels among women with breast cancer than among controls. In a few studies, DDT was linked to estrogen-positive breast cancer or the association to breast cancer risk depended on genotype.
Polychlorinated biphenyls, PCBs, are a large group of compounds earlier much used in electrical devices, surface coatings and other purposes. The review of 50 studies found the association between total PCBs and breast cancer risk to be inconsistent. However, 19 studies linked certain PCBs to a higher breast cancer incidence. Similar to DTT, PCBs accumulate in the adipose tissue and in the food chain and can be excreted in breast milk.

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Differing immune responses discovered in asymptomatic cases vs those with severe COVID-19

The largest study of its type in the UK has identified differences in the immune response to COVID-19, between people with no symptoms, compared to those suffering a more serious reaction to the virus.
Researchers from the Wellcome Sanger Institute, Newcastle University, University College London, University of Cambridge, EMBL’s European Bioinformatics Institute (EMBL-EBI) and their collaborators within the Human Cell Atlas initiative, found raised levels of specific immune cells in asymptomatic people. They also showed people with more serious symptoms had lost these protective cell types, but gained inflammatory cells. These differences in the immune response could help explain serious lung inflammation and blood clotting symptoms, and could be used to identify potential targets for developing therapies.
The research, published today (20th April 2021) in Nature Medicine, is one of the only studies to include people who were asymptomatic. This large-scale collaborative study is part of the Human Cell Atlas* initiative to map every cell type in the human body, to transform our understanding of health, infection and disease.
So far, the COVID-19 global pandemic has caused millions of deaths and many more infections worldwide. Symptoms vary widely in severity and can range from a mild cough to severe respiratory distress, blood clots and organ failure. Several previous studies have highlighted a complex immune response in the blood, but until now the full coordinated immune response and how this differs between symptomatic and asymptotic patients had not been investigated in detail.
In a new study to understand how different immune cells responded to the infection, a large team of researchers came together to analyse blood from 130 people with COVID-19. These patients came from three different UK centres (Newcastle, Cambridge and London) and ranged from asymptomatic to critically severe.
The team performed single-cell sequencing from ~800,000 individual immune cells, along with detailed analysis of cell surface proteins and antigen receptors found on immune cells in the blood. They revealed differences in multiple types of immune cells that are involved in the body’s response to COVID-19.

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SARS-CoV-2: British variant is 45 percent more contagious than the original virus, study finds

A new study at Tel Aviv University found that the British variant (termed: B.1.1.7) of Covid-19 is 45% more contagious than the original virus. The researchers relied on data from about 300,000 PCR tests for Covid-19 obtained from the COVID-19 testing lab, which was established in collaboration with the Electra Group.
The new study was conducted by Prof. Ariel Munitz and Prof. Moti Gerlitz of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine, together with Dr. Dan Yamin and PhD student Matan Yechezkel from the Laboratory for Epidemic Modeling and Analysis (LEMA) at the Department of Industrial Engineering, all at Tel Aviv University. The study’s results were published in the prominent scientific journal Cell Reports Medicine.
The Electra-TAU laboratory was established in March 2020, right after the outbreak of the first wave of the pandemic in Israel. To date, it has analyzed hundreds of thousands of tests from all over the country – from public drive-in test facilities, as well as programs targeting specific populations – such as ‘Shield for Fathers and Mothers’ which routinely ran tests in at-risk hotspots like retirement homes.
Prof. Ariel Munitz explains: “We use a kit that tests for three different viral genes. In the British variant, also known as B.1.1.7, one of these genes, the S gene, has been erased by the mutation. Consequently, we were able to track the spread of the variant even without genetic sequencing.”
According to Prof. Munitz, the data from the lab shows that the spread of the British variant was very rapid: On December 24, 2020 only 5% of the positive results were attributed to the British variant. Just six weeks later, in January 2021, this variant was responsible for 90% of Covid-19 cases in Israel. The current figure is about 99.5%.
“To explain this dramatic increase, we compared the R number of the SARS-CoV-2 virus with the R of the British variant. In other words, we posed the question: How many people, on the average, contract the disease from every person who has either variant? We found that the British variant is 45% – almost 1.5 times – more contagious.”
In the second stage of the study, the researchers segmented contagion by age groups. The results indicated that the turning point for the 60+ population compared to other age groups occurred two weeks after 50% of Israel’s 60+ population received their first vaccine shot.
“Until January we saw a linear dependence of almost 100% between the different age groups in new cases per 1,000 people,” says Dr. Dan Yamin. “Two weeks after 50% of the 60+ population received the first dose of the vaccine this graph broke sharply and significantly. During January a dramatic drop was observed in the number of new cases in the 60+ group, alongside a continued rise in the rest of the population. Simply put, since more than 90% of those who died from Covid-19 were over 60, we can say that the vaccine saved hundreds of lives – even in the short run.”
Moreover, the new study proves that active monitoring of at-risk populations works. “There is a threshold value for determining whether a specific test is positive or negative for the virus – with a lower value indicating a higher viral load,” says Prof. Munitz. “When we compared the threshold values of the different genes in 60+ residents of retirement homes with the values measured in 60+ persons in the general population, we saw significantly higher values in the retirement homes. This means that the viral load in retirement homes was lower compared to the rest of the population.
Since the residents of retirement homes are tested routinely, while other people are usually tested only when they don’t feel well or have been in contact with someone who had tested positive for the virus, we conclude that constant monitoring of at-risk populations is a method that works. It is important to emphasize: the relatively low viral load was found in retirement homes despite the fact that the British variant had already begun to spread in all populations. Consequently, we show that monitoring retirement homes, together with vaccination that gives precedence to vulnerable populations, prevent illness and mortality.”
Dr. Yemin concludes: “Due to crowded conditions, large households and age distribution in the Israeli population, the coronavirus had a more favorable environment for spreading in Israel compared to most Western countries. Our message to the world is that if with our problematic starting point a distinct decline was identified, other Western countries can certainly expect the curve to break – despite the high contagion of the British variant – with a dramatic drop in severe cases following the vaccination of 50% of the older population, alongside targeted testing at risk epicenters.”###
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