Astronomers Discovered The Most X-ray Luminous Quasar SRGE J170245.3+130104 at Redshift z ≈ 5.5 (Astronomy)

Khorunzhev and colleagues reported on the discovery of the most outstanding (so far) object found in the DaLeQoprogram — the brightest X-ray and Radio distant quasar SRGE J170245.3+130104 at redshift, z > 5, identified by spectral observations on the 6th BTA optical telescope. Their study recently appeared in journal Astronomy letters.

SRGE J170245.3+130104 was discovered by the eROSITA telescope aboard the SRG space observatory on March 13-15, 2020 during the first half-year scan of its all-sky X-ray survey. The optical counterpart of the X-ray source was photometrically identified as a distant quasar candidate at z ≈ 5.5. Follow-up spectroscopic observations, done in August/September 2020 with the SCORPIO-II instrument at the BTA 6-m telescope, confirmed that SRGE J170245.3+130104 is a distant quasar at redshift zspec = 5.466. The X-ray luminosity of the quasar during the first half-year scan of the eROSITA all-sky survey was 3.6 × 1046 erg/s (in the 2–10 keV energy range), whereas its X-ray spectrum could be described by a power law with a slope of Γ = 1.8. Six months later (September 13–14, 2020), during the second half-year scan of the eROSITA all-sky survey, the quasar was detected again and its X-ray luminosity had decreased by a factor of 2 (at the ≈ 1.9σ confidence level).

Fig 1: X-ray images of the SRG/eROSITA region 100 × 100 in the energy range 0.3–2.2 keV, centered on the optical source coordinates SRGE J170245.3+130104 (white cross). Left panel — image from the first half-year scan of SRG/eROSITA All-Sky Survey, right panel — image from the second half-year scan. Aperture with a radius of 10 is shown by red circle. Images are smoothed with a Gaussian filter (σ = 800). © Khorunzhev et al.

Now, Khorunzhev and colleagues reported that X-ray quasar SRGE J170245.3+130104 at z ≈ 5.47 discovered by the SRG X-ray observatory and the BTA 6-m telescope, is the most X-ray luminous quasar among known objects in the early Universe (z > 5) and also one of the most powerful quasars in radio.

They also mentioned that large radio-loudness (R ∼ 10³) of the quasar indicated that it can be a blazar and to test this hypothesis, it is necessary to carry out interferometric radio observations of the object at several wavelengths. Note that, only a few blazars at z > 5 are currently known, and all of them have lower X-ray luminosities than the quasar SRGE J170245.3+130104.

Fig. 2: Spectral energy distribution of the SRGE J170245.3+130104 quasar. The yellow dots show measurements in the radio spectral range, red dots — in the near-infrared and visible ranges, black dots — X-ray data SRG/eROSITA. The gray area — 1σ uncertainty of the power law model (with Galactic absorption) of the X-ray spectrum. Dot-dashed line shows the average blazar template. Solid line shows the radio-loud quasar template, corrected at wavelengths λ < 1216 Å for neutral hydrogen intergalactic absorption; the continuation of the original template at wavelengths λ < 1216 Å without considering absorption is shown by the dashed line. The blue line in the inset panel shows the smoothed optical spectrum obtained on the BTA telescope. © Khorunzhev et al.

In addition, they suggested that spectroscopic measurements in the near-infrared range (λ ∼ 1.6 microns) could also significantly complement the physical picture. It is expected that a broad MgII emission line should appear in the nearIR, which could be used to measure the mass of the black hole.

“The quasar SRGE J170245.3+130104 shows significant X-ray variability in the first two scans of the eROSITA all-sky survey. We will continue to monitor its variability in the following scans.”

— wrote authors of the study

Featured image: The 2’×2’ image in the iPS Pan-STARRS filter. The arrow indicates the position of optical companion SRGE J170245.3+130104. The radius of the small circle corresponds to the 1σ localization region. The radius of the large circle (10 arcsec) determines the size of the region where optical companion of X-ray source was searched.© Khorunzhev et al.


Reference: G.A. Khorunzhev, A.V. Meshcheryakov, P.S. Medvedev, V.D. Borisov, R.A. Burenin, R.A. Krivonos, R.I. Uklein, E.S. Shablovinskaya, V.L. Afanasyev, S.N. Dodonov, R.A. Sunyaev, S.Yu. Sazonov, M.R. Gilfanov, “Discovery of the most X-ray luminous quasar SRGE J170245.3+130104 at redshift z≈5.5”, Letters to Astronomical Journal, Volume: 47, Number: 3 Year: 2021 Pages: 155-173. DOI:  10.31857 / S0320010821030037


Note for editors of other websites: Copyright of this article totally belongs to our author S. Aman. One is allowed to reuse it only by giving proper credit either to him or to us

Vegetarian Diets Reduce Risk of Death from Heart Disease (Food)

Vegetarian diets reduce the risk of death from ischemic heart disease, according to a meta-analysis published in the American Journal of Preventive Cardiology. Researchers reviewed eight observational studies that compared vegetarian and nonvegetarian diets with mortality. Vegetarian diets, including vegan eating patterns, were associated with a 30% reduced risk of death from ischemic heart disease when compared to nonvegetarian diets. Vegetarian diets benefit risk factors for heart disease, including weight, cholesterol, and blood pressure levels. Vegetarian diets avoid animal products, which are often high in saturated fat, iron, and hormones. The authors recommend clinicians consider vegetarian diets as a cost-effective intervention for high-risk groups to reduce mortality from heart disease.


Reference

Jabri A, Kumar A, Verghese E, et al. Meta-analysis of Effect of Vegetarian Diet on Ischemic Heart Disease and All-cause Mortality. Am J Prev Cardiol. Published online April 9, 2021. doi: 10.1016/j.ajpc.2021.100182 


Provided by Physicians Committee for Responsible Medicine

New Research Disputes the Biggest Soy Myths (Food)

New research addresses myths surrounding soy intake in an article published in Critical Reviews in Food Science and Nutrition. The authors note that concerns over the safety of isoflavones, phytoestrogens found in soy products, were largely based on nonhuman animal studies that did not reflect human biology. Researchers reviewed 417 reports based on human data on isoflavone intake and endocrine-related health outcomes. Evidence suggests isoflavone intake does not adversely affect thyroid function, estrogen levels, ovulation in women, or semen levels in men. These publications also showed no negative effects in children. These results suggest neither isoflavones nor soy foods should be classified as endocrine disruptors associated with disease and adverse health outcomes. Soy products are actually associated with reduced risk of breast and prostate cancer.

Featured image credit: Getty images


References

Messina M, Mejia SB, Cassidy A, et al. Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data. Crit Rev Food Sci Nutr. 2021;1-57. doi: 10.1080/10408398.2021.1895054


Provided by Physicians Committee for Responsible Medicine

Duke-Led Team Finds Why Women May Be Better Equipped to Fight COVID (Medicine)

When it comes to COVID-19, women seem to be the stronger sex, suffering severe disease at about half the rate as men, but the reason for this has been elusive.

Now a chance experiment by an ophthalmology researcher at Duke Health has led to an insight: Women have more of a certain type of immune cell that fights infections in mucosal tissue, and these immune cells amass in the lungs, poised to attack the COVID virus. 

“Better armed with these specialized immune cells, women appear to be more equipped to fight some of the most severe impacts of COVID-19, notably the respiratory infections that can become life-threatening,” said Daniel Saban, Ph.D., an associate professor in Duke’s Department of Ophthalmology and in the Department of Immunology.

Saban, who led the study that appears online in the Cell Press journal Med, said the investigation began last spring as COVID first spread and he was sidelined from his normal caseload studying eye diseases. A piece of equipment in his lab – a device that can perform 36-color flow cytometry – was sitting idle, so he decided to use it to examine blood samples from COVID patients.

“We didn’t start with a hypothesis,” Saban said. “It was a completely unbiased approach, where we asked our colleagues to provide blood and tissue samples from COVID patients as well as healthy people. We had no idea what we would find, if anything.”

Saban and the members of his lab, including Chen Yu, Ph.D. and Sejiro Littleton, quickly saw that a white blood cell called mucosal associated invariant T cells, or MAIT cell, circulated more abundantly in the blood from healthy women compared to healthy men. MAIT cells are highly specialized white blood cells that contribute to immune defenses in mucosal organs and tissues. 

Among COVID patients, however, there were few MAIT cells circulating in the blood, even among women, where the population of MAIT cells radically fell off, leading the researchers to question where these cells had gone. 

They found their answer in tissue samples from the lungs of COVID patients. Overall, there were an abundance of MAIT cells in the lung tissue of people with COVID, but upon closer inspection, they found night-and-day differences between the sexes.

“We first found this dichotomy in healthy blood,” Saban said. “Circulating MAIT cells in women expressed genes indicative of a robust profile poised for fighting an infection, but this was not the case in males. Then we looked in the tissue and were able to find evidence of this same pattern by sex.”

Saban said there are numerous examples of sexual differences in the immune responses to infections, noting those differences have been prevalent all along with COVID-19. 

“Our findings uncover a female-specific protective profile carried out by these MAIT cells, and this could potentially help guide the development of treatments and therapies,” he said.

In addition to Saban, Yu and Littleton, study authors include Nicholas S. Giroux, Rose Mathew, Shengli Ding, Joan Kalnitsky, Yuchen Yang, Elizabeth W. Petzold, Hong A. Chung, Grecia O. Rivera, Tomer Rotstein, Rui Xi, Emily R. Ko Ephraim L. Tsalik, Gregory D. Sempowsk, Thomas N. Denny, Thomas W. Burke, Micah T. McClain, Christopher W. Woods and Xiling Shen. 

The study received support from This work was supported by the National Institute of Allergy and Infectious Diseases, which is part of the National Institute of Health (U01AI066569, UM1AI104681), the U.S. Defense Advanced Projects Agency (N66001-09-C-2082, HR0011-17-2-0069), the Veterans Affairs Health System, and Virology Quality Assurance (75N93019C00015). 


Provided by Duke Health

Genetic Variants Identified That Impact Immune Cells’ Functioning (Medicine)

Researchers have combined genome-wide sequencing and functional profiling of immune cells to understand more about the impact of genetic variants on disease.

Certain genetic variants that cause modified protein binding in immune cells, are also seen in those at high risk of some autoimmune diseases, new research has found.

Scientists from the Wellcome Sanger Institute, Josep Carreras Leukaemia Research Institute in Spain, and the MRC London Institute of Medical Sciences (LMS) found that certain genetic variants, which alter the binding ability of a protein called PU.1 in neutrophils, are also found to be associated with auto immune disease susceptibility.

This new study, published in Nature Communications (16 April 2021), builds on previous research called BLUEPRINT. BLUEPRINT revealed how variation in blood cells’ characteristics and numbers can affect a person’s risk of developing complex diseases such as heart disease, and autoimmune diseases including rheumatoid arthritis, asthma, coeliac disease and type 1 diabetes.

This new research has provided more mechanistic detail on how PU.1 and neutrophils are impacted by genetic variation and has provided researchers a list of candidate genes that would be of interest for further research to investigate if these have a causal effect on the development of autoimmune disease.

Differences in individuals, such as risk of disease, can be influenced by a number of factors. While some of this variation is influenced by the environment and external factors such as diet, there is a substantial component driven by genetics. However, most variation is not driven through the function of a single gene but rather the sum of many subtle changes in genes or regions that control gene activity.

Previously, BLUPERINT ran large-scale genome-wide association studies (GWAS) to investigate which genetic differences are linked to changes in blood cells and if these have a link to disease. GWAS are powerful tools for identifying regions of the genome associated with human variation and diseases. However, GWAS doesn’t look at specific cell types, which makes it difficult to determine the genes that certain regions code for and the cell types they regulate.

In this new research, scientists from the Wellcome Sanger Institute, Josep Carreras Leukaemia Research Institute, Spain, and the MRC London Institute of Medical Sciences (LMS), combined previous GWAS data with in-depth functional analysis of neutrophils − a type of immune cell that make up 80 percent of the white blood cells in the body.

They found that the genetic variants that are associated with an increased risk of autoimmune disease also have an impact on binding of a certain protein in neutrophils, known as PU.1. Some genetic variants made PU.1 unable to bind to neutrophil DNA, which led to subsequent changes in gene expression and neutrophil behaviour.

While further research is needed to see if this change in the ability of PU.1 to bind directly causes certain autoimmune diseases, this research provides further understanding about the impact of these genetic variants on the cells in the body. In addition to this, the researchers suggest a list of candidate genes that could hold further information about the genetic causes of autoimmune disease.

“It is crucial to understand the mechanisms in the cell if we are to fully understand the impact of these on disease. In this case, how the genetic variants affect the ability of PU.1 binding, which goes on to modulate gene expression in neutrophils, could be vital in understanding the role that neutrophils play in certain autoimmune diseases.”

Dr Biola-Maria Javierre,co-senior author and group leader at Josep Carreras Leukaemia Research Institute, Barcelona

“Our work shows how mutations in the “molecular switch regions” on the DNA can lead to changes in the expression of disease-relevant genes by affecting the binding of regulatory proteins and a whole cascade of downstream events. Knowing the mechanisms by which these mutations affect cellular function brings us one step closer to being able to devise therapeutic approaches to mitigate their effects.”

Dr Mikhail Spivakov, co-senior author and group leader at the Functional Gene Control Group, MRC London Institute of Medical Sciences (LMS)

“Research such as this that integrates large-scale genetic research with functional analysis gives us essential data that widen our understanding of how differences in the human genome and epigenome interact to cause devastating common diseases. Building on this understanding through further research will help inform new avenues for treating these conditions.”

Stephen Watt,lead author and senior staff scientist at the Sanger Institute

More information

Neutrophils play a significant role in the innate immune system, which is the body’s first line of defence against pathogens, as well as in the adaptive immune system.

Publication:

Biola-Maria Javierre, Mikhail Spivakov, and Nicole Soranzo, et al. (2021) Genetic perturbation of PU.1 binding and chromatin looping at neutrophil enhancers associates with autoimmune disease. Nature Communications. DOI: 10.1038/s41467-021-22548-8.

Funding:

This research was funded by Wellcome, the NIHR Cambridge Biomedical Research Centre, the UK Medical Research Council, the Spanish Ministry of Science and Innovation and by LaCaixa Banking Foundation.

Featured image credit: adobestock


Provided by Wellcome Sanger Institute

How To Discover Mirror Stars? (Cosmology / Astronomy)

Curtin and Setford examine the visible signatures of Mirror Stars in observations for the first time.

Friends, many studies suggested that visible sector interact with dark sector through some kind of channels (like fields, symmetries etc.). Chacko and colleagues also suggested that there are many similarities between standard model (SM) matter and mirror matter which makes it clear that the mirror matter could cool and clump in our galaxy, leading to the formation of Mirror Stars (MS) that fuse mirror nuclei and shine in mirror photons.

The possibility that some fraction of DM could form Mirror Stars is both extremely intriguing and quite general for a complex dark sector, requiring only a massless dark photon. The idea of Mirror Stars has been discussed in the context of Mirror-DM models but their more general nature and non-gravitational observational consequences were never carefully explored.

FIG. 1: Important interactions between mirror and visible matter. Left: nucleus-nucleus scattering. Right: Thomson conversion of a mirror photon to a SM photon © Curtin and Setford

Now, Curtin and Setford in their recent paper, examined the visible signatures of mirror stars in observations for the first time. They demonstrated that, mirror stars lead to spectacular astrophysical signals if the standard model/visible and dark photons have a small kinetic mixing.

They found that when Mirror Stars capture SM matter in their cores. This “SM nugget” gets heated up to T ∼ 10⁴ K by ϵ² -suppressed interactions with the mirror matter, giving rise to an optical signal similar to but much fainter than standard white dwarfs. They also showed for the first time that “mirror Thomson conversion” allows thermal dark photons from the Mirror Star core to be converted to visible X-rays that escape the nugget, providing a direct window into the MS interior.

“This robust and highly distinctive signature is a smoking gun of mirror stars and could be discovered in optical and X-ray searches”

— told Curtin, first author of the study

FIG. 2: A Hertzsprung-Russell diagram showing the dual signatures of their Mirror Star benchmarks estimated in their paper. Each MS is represented by two points connected by a line. The solid lines show the approximate distances up to which such objects could be observed in Gaia or Chandra. © Curtin and Setford

In addition, they suggested that this could be discovered in full-sky surveys like Gaia out to the distances indicated by blue lines in fig 2. (which also provides a parallax measurement to determine absolute luminosity). The discovery of such faint Mirror Star candidates would prompt extremely detailed study with an X-ray observatory: Chandra could see the X-ray signal roughly out to distances indicated by green lines (in fig. 2 above) with an exposure equal to the Hubble Deep Field North. Detection of this black-body-like X-ray signal would be a true smoking gun of Mirror Stars and provide a direct window into their interior, allowing measurement of the core temperature and perhaps even aspects of mirror nuclear physics via detailed study of spectral features. This is also true for higher ϵ ≳ 10¯10, where Mirror Stars might appear similar to white dwarfs, providing additional motivation to study them with X-ray observations.

“We have shown that Mirror Star signals are highly distinctive and robust. They arise in well-motivated theories that may not show up in collider measurements. This makes dedicated searches for Mirror Stars a new frontier in DM detection with completely untapped discovery potential, and an opportunity we cannot afford to miss.”

— concluded authors of the study

Reference: David Curtin, Jack Setford, “How to discover Mirror Stars”, Physics Letters B, Volume 804, 2020, 135391, ISSN 0370-2693, https://doi.org/10.1016/j.physletb.2020.135391.
(https://www.sciencedirect.com/science/article/pii/S0370269320301957)


Note for editors of other websites: Copyright of this article totally belongs to our author S. Aman. One is allowed to reuse it only by giving proper credit either to him or to us

Risk Of Rare Blood Clotting Higher For COVID-19 Than For Vaccines (Medicine)

COVID-19 leads to a several-times higher risk of cerebral venous thrombosis (CVT) blood clots than current COVID-19 vaccines. 

Researchers at the University of Oxford have today reported that the risk of the rare blood clotting known as cerebral venous thrombosis (CVT) following COVID-19 infection is around 100 times greater than normal, several times higher than it is post-vaccination or following influenza.

The study authors, led by Professor Paul Harrison and Dr Maxime Taquet from Oxford University’s Department of Psychiatry and the NIHR Oxford Health Biomedical Research Centre, counted the number of CVT cases diagnosed in the two weeks following diagnosis of COVID-19, or after the first dose of a vaccine. The then compared these to calculated incidences of CVT following influenza, and the background level in the general population.

They report that CVT is more common after COVID-19 than in any of the comparison groups, with 30% of these cases occurring in the under 30s. Compared to the current COVID-19 vaccines, this risk is between 8-10 times higher, and compared to the baseline, approximately 100 times higher.

The breakdown comparison for reported cases of CVT in COVID-19 patients in comparison to CVT cases in those who received a COVID-19 vaccine is:

  • In this study of over 500,000 COVID-19 patients, CVT occurred in 39 in a million patients.
  • In over 480,000 people receiving a COVID-19 mRNA vaccine (Pfizer or Moderna), CVT occurred in 4 in a million.
  • CVT has been reported to occur in about 5 in a million people after first dose of the AZ-Oxford COVID-19 vaccine.
  • Compared to the mRNA vaccines, the risk of a CVT from COVID-19 is about 10 times greater.
  • Compared to the AZ-Oxford vaccine, the risk of a CVT from COVID-19 is about 8 times greater.

However, all comparisons must be interpreted cautiously since data are still accruing.

Paul Harrison, Professor of Psychiatry and Head of the Translational Neurobiology Group at the University of Oxford, said: ‘There are concerns about possible associations between vaccines, and CVT, causing governments and regulators to restrict the use of certain vaccines. Yet, one key question remained unknown: ‘What is the risk of CVT following a diagnosis of COVID-19?’.

‘We’ve reached two important conclusions. Firstly, COVID-19 markedly increases the risk of CVT, adding to the list of blood clotting problems this infection causes. Secondly, the COVID-19 risk is higher than we see with the current vaccines, even for those under 30; something that should be taken into account when considering the balances between risks and benefits for vaccination.’

Dr Maxime Taquet, also from the Translational Neurobiology Group, said: ‘It’s important to note that this data should be interpreted cautiously, especially since the data on the Oxford-AstraZeneca vaccine come from EMA monitoring, whereas the other data uses the TriNetX electronic health records network. However, the signals that COVID-19 is linked to CVT, as well as portal vein thrombosis – a clotting disorder of the liver – is clear, and one we should take note of.’

An important factor that requires further research is whether COVID-19 and vaccines lead to CVT by the same or different mechanisms. There may also be under-reporting or mis-coding of CVT in medical records, and therefore uncertainty as to the precision of the results.

Full data are available from the OSF website.

Featured image: Risk of rare blood clots higher after COVID-19 than after current vaccines. © Image credit: Shutterstock


Provided by University of Oxford

Asthma Drug Budesonide Shortens Recovery Time in Non-hospitalised Patients With COVID-19 (Medicine)

Inhaled budesonide, a common corticosteroid, is the first widely available, inexpensive drug found to shorten recovery times in COVID-19 patients aged over 50 who are treated at home and in other community settings, reports the UK’s PRINCIPLE trial in 1,779 participants.

Early treatment with inhaled budesonide shortens recovery time by a median of three days in patients with COVID-19 who are at higher risk of more severe illness and are treated in the community, finds Oxford University’s Platform Randomised Trial of Interventions against COVID-19 in Older People (PRINCIPLE) trial.

PRINCIPLE is the world’s largest Phase 3 platform randomised controlled trial to find clear evidence of an effective COVID-19 treatment for use in the community that can significantly shorten recovery time. As one of the UK Government’s national priority platform trials, findings from PRINCIPLE have potential to change how COVID-19 is treated in its early stages in non-hospital, community settings in the UK and internationally.

Inhaled budesonide is a safe, relatively inexpensive and readily available corticosteroid commonly used around the world in inhalers to treat asthma and chronic obstructive pulmonary disease. It was added to the PRINCIPLE trial on 28th November 2020.

Recruitment for the inhaled budesonide arm of the trial stopped on 31st March 2021 since, in the view of the Trial Steering Committee, enough patients had been enrolled to establish whether or not the drug had any meaningful benefit on time to recovery. Obtaining further data on hospital admissions or death was unlikely due to the reducing number of cases in the UK.

For the interim report, a total of 961 patients were randomly assigned to receive inhaled budesonide at home and were compared with 1819 patients randomly assigned to the usual standard of NHS care alone. Of these, 751 people in the budesonide group and 1028 in the usual care group were SARS-CoV-2 positive and included in the primary interim analysis.

Based on the interim analysis using the latest data from 25th March 2021, the results showed the estimated median time to self-reported recovery for inhaled budesonide was 3.011 days shorter compared to usual care (95% Bayesian credible interval 1.134 to 5.410 days), with a high probability (0.999) of being superior to the usual standard of care. 32% of those taking inhaled budesonide, compared to 22% in the usual care group, recovered within the first 14 days since being randomised into the trial and subsequently have remained well until 28 days (relative risk 1.46, 95% CI 1.23 – 1.74). Participants in the budesonide group also reported greater wellbeing after two weeks (mean difference in WHO-5 Wellbeing score + 3.37 ,95% CI 0.97 – 5.76, p = 0.006).

Among patients who had completed all 28 days of study follow up by 25th March 2021, 8.5% (59/692) in the budesonide group were hospitalised with COVID-19 compared with 10.3% (100/968) in the usual care group (estimated percentage benefit, 2.1% [95% BCI -0.7% – 4.8%], probability of superiority 0.928). Since fewer than expected people were admitted to hospital in the trial, and with COVID-19 cases and hospitalisations continuing to drop in the UK, it is not clear from this interim analysis whether budesonide reduces hospitalisations.

Patients with COVID-19 symptoms that started within 14 days and who are at higher risk of a poor outcome from the illness could join the trial and those with a positive SARS-CoV-2 result were included in the main analysis. Patients treated with inhaled budesonide were asked to inhale 800 micrograms twice a day for 14 days and were followed-up for 28 days. All patients were aged over 50 with an underlying health condition that put them at more risk of serious COVID-19 illness, or aged over 65.

Joint Chief Investigator, Professor Chris Butler, a South Wales GP and Professor of Primary Care from the University of Oxford’s Nuffield Department of Primary Care Health Sciences, said, ‘PRINCIPLE, the world’s largest platform trial of community-based treatments for COVID-19, has found evidence that a relatively cheap, widely available drug with very few side effects helps people at higher risk of worse outcomes from COVID-19 recover quicker, stay better once they feel recovered, and improves their wellbeing. We therefore anticipate that medical practitioners around the world caring for people with COVID-19 in the community may wish to consider this evidence when making treatment decisions, as it should help people with COVID-19 recover quicker.

‘This exciting finding about the beneficial effects of inhaled budesonide would not have been possible without the contribution of those patients who volunteered to participate: your gift of taking part will help doctors and nurses provide better evidence-based care for people with COVID-19 worldwide. It also stands as a monument to the far-sighted funders of PRINCIPLE, the UK-wide clinical research networks who have been absolutely key to the successful implementation of the trial, all the general practices and clinicians who support PRINCIPLE, NHS Digital, HDRUK, the Therapeutics Task Force and the hard work and dedication of our study team and oversight committees in the Primary Care Clinical Trials Unit.’

Joint Chief Investigator, Professor Richard Hobbs, Head of Oxford University’s Nuffield Department of Primary Care Health Sciences, said, ‘For the first time we have high-quality evidence of an effective treatment that can be rolled out across the community for people who are at most risk of developing more severe illness from COVID-19. Unlike other proven treatments, budesonide is effective as a treatment at home and during the early stages of the illness. This is a significant milestone for this pandemic and a major achievement for community-based research.’

Professor Mona Bafadhel, from Oxford University’s Nuffield Department of Medicine, and a Consultant Respiratory Physician, led the earlier STOIC Phase 2 efficacy study of inhaled budesonide for early COVID-19 and led the development of the budesonide study arm for PRINCIPLE. She said, ‘The news that the findings of the earlier-phase STOIC trial, which reported at the beginning of the year, have been replicated at scale here in the PRINCIPLE trial is outstanding. We are now sure that we have a treatment that will benefit patients with early COVID-19 worldwide Inhaled budesonide is readily available worldwide and commonly used to treat asthma and chronic obstructive pulmonary disease.’

Professor Fiona Watt, Executive Chair of the Medical Research Council, which co-funded the study, said, ‘Researchers involved in the PRINCIPLE trial have overcome considerable logistical hurdles to set up a world-leading rigorous drug trial in people’s homes. We are now rewarded with the first inexpensive and widely available drug that can shorten recovery times for COVID-19 patients in the community. People around the world will be helped to recover faster thanks to these exciting new results.’

As soon as all remaining patients in the trial have completed their follow-up and a full analysis has been completed, detailed results on time to recovery and hospitalisations will be published. For this preliminary report, 92.8% of people randomised to the budesonide arm had the opportunity to complete 28 days of follow-up. To read the full pre-print, visit the MedRxiv server

PRINCIPLE is funded by a grant to the University of Oxford from UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research as part of the UK Government’s rapid research response fund.

Featured image: Asthma drug budesonide shortens recovery time in non-hospitalised patients with COVID-19 © Shutterstock


Reference: PRINCIPLE Collaborative Group, Ly-Mee Yu, Mona Bafadhel, Jienchi Dorward, Gail Hayward, Benjamin R Saville, Oghenekome Gbinigie, Oliver Van Hecke, Emma Ogburn, Philip H Evans, Nicholas PB Thomas, Mahendra G Patel, Nicholas Berry, Michelle A. Detry, Christina T. Saunders, Mark Fitzgerald, Victoria Harris, Simon de Lusignan, Monique I Andersson, Peter J Barnes, Richard EK Russell, Dan V Nicolau Jr., Sanjay Ramakrishnan, FD Richard Hobbs, Christopher C Butler, “Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial”, medRxiv 2021.04.10.21254672; doi: https://doi.org/10.1101/2021.04.10.21254672


Provided by University of Oxford

Hypoxia Drugs Join the Fight Against COVID-19 (Medicine)

Oxygen is essential to all life forms, even viruses. 

Oxygen is fundamental to all cells, impacting key functions such as metabolism and growth. Our cellular response to oxygen levels is tightly regulated and one important pathway is controlled by the Hypoxia Inducible Factors (HIFs), that activate certain genes under low oxygen conditions (hypoxia) to promote cell survival. Drugs that activate HIF are currently in use to treat anaemia caused by kidney disease.

The novel coronavirus SARS-CoV-2 needs no introduction and literally stopped the world in 2020, with more than 2 million fatalities to date. A defining feature of severe COVID-19 disease is low oxygen levels throughout the body, which may lead to organ failure and death. A cure for this virus is urgently needed.

Dr Peter Wing and Dr Tom Keeley, working in the laboratories of Prof Jane McKeating, Prof Peter Ratcliffe and Dr Tammie Bishop in the Nuffield Department of Clinical Medicine, discovered that a low oxygen environment supressed SARS-CoV-2 entry into cells that line the lungs and reduced viral propagation and shedding.

Importantly, drugs that activate HIF such as Roxadustat had a similar effect on the virus. This study provides the first evidence for repurposing HIF mimetics that could reduce SARS-CoV-2 transmission and disease development. The oxygen dependency of this virus is a new vulnerability that we could exploit. 

Research continues to expand our understanding of the interplay between oxygen sensing and COVID-19 and is published in Cell Reports.


Reference: Peter A.C. Wing, Thomas P. Keeley, Xiaodong Zhuang, Jeffrey Y. Lee, Maria Prange-Barczynska, Senko Tsukuda, Sophie B. Morgan, Adam C. Harding, Isobel L.A. Argles, Samvid Kurlekar, Marko Noerenberg, Craig P. Thompson, Kuan-Ying A. Huang, Peter Balfe, Koichi Watashi, Alfredo Castello, Timothy S.C. Hinks, William James, Peter J. Ratcliffe, Ilan Davis, Emma J. Hodson, Tammie Bishop, Jane A. McKeating, Hypoxic and pharmacological activation of HIF inhibits SARS-CoV-2 infection of lung epithelial cells, Cell Reports, 2021, 109020, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2021.109020. (https://www.sciencedirect.com/science/article/pii/S221112472100334X)


Provided by University of Oxford