COVID-19 trial lead researcher explains why an antibiotic might work

Recently, a team of investigators affiliated with the Francis I. Proctor Foundation at the University of California, San Francisco (UCSF), decided to investigate the potential of a common antibiotic — azithromycin — in treating mild-to-moderate cases of COVID-19 that do not require hospitalization.
The trial — called Azithromycin for COVID-19 Treatment, Investigating Outpatients Nationwide, or ACTION for short — will involve human participants, and the researchers started recruiting on May 26, 2020.

To learn more about the trial, and understand why the researchers chose to study azithromycin, despite specialists typically advising against antibiotics in the treatment of COVID-19, Medical News Today spoke to one of the trial’s principal investigators, Catherine Oldenburg, Sc.D., an infectious disease epidemiologist.
We have lightly edited the interview transcript for clarity.
Why pick a ‘counterintuitive’ candidate

MNT: What is the ACTION trial? Can you tell us a little about its premise and how it will work?
Catherine Oldenburg: The ACTION trial is a nationwide trial in the United States that is designed to evaluate the efficacy of a single dose of azithromycin compared to placebo for [the] prevention of hospitalization in COVID-19 patients who are not currently hospitalized, so patients who have […] anywhere from asymptomatic to moderate disease that doesn’t require hospitalization, and the trial is designed to be flexible and scalable.
It will be open to patients nationwide in the U.S.; it’s conducted remotely out of our trial coordinating center at UCSF.
So, patients can contact the study team from anywhere in the U.S. and be screened remotely, go through all [the initial] processes, and then we ship them [the] study drug and sample collection kits.
MNT: How did you and your team zero in on azithromycin as a potential treatment for COVID-19?
Catherine Oldenburg: It’s a great question. I think that […] it’s absolutely true, the mantra that […] antibiotics don’t treat viral infections. And so, it’s a little bit counterintuitive [to use azithromycin in the treatment of COVID-19, which is the result of a viral infection].
My team has been working with azithromycin and studying [it] for a number of indications for decades. Proctor [The Francis I. Proctor Foundation at UCSF], in general, has been working with azithromycin for trachoma control, which is an infection of the eye, [for] the last 20 years.
And so, in terms of trials [for] azithromycin, that’s something that we do a lot of. I have something like eight trials going on right now with azithromycin, most of which are for trachoma, or for childhood mortality in Sub-Saharan Africa, where there’s a large burden of bacterial disease that’s [an existing issue].
But one of the interesting things about azithromycin is that it has really strong immunomodulatory effects, so it has these kind of nondirect effects on the immune system. That means it’s an interesting candidate in terms of what it does to the immune system.
So, in vitro, there have been reports showing that azithromycin has activity against RNA viruses like Zika and rhinovirus and things like that.
And then […], I don’t remember the exact date, but there was a study out that kind of created a lot of hype around azithromycin in combination with hydroxychloroquine, and that’s sort of when we got interested, [thinking]: If there’s any indication that perhaps azithromycin has an effect against COVID-19, or against SARS-CoV-2, perhaps that’s something that we should be taking a look at because our team really has a lot of expertise in terms of azithromycin trials, specifically, and in conducting large trials.
Azithromycin is very safe; it’s prescribed all the time for all kinds of things; it’s something that people are very familiar with in a Z pack in the U.S. It seemed like a good candidate for outpatients — if it had an effect — because of its safety profile. And we decided to look at it independently of hydroxychloroquine, given concerns about [the latter’s] safety.
There are a lot of other trials going on with hydroxychloroquine, and we didn’t really feel like we needed to get involved in that because that was outside of our area of expertise.[…] That [is why] we’re looking at azithromycin by itself.
And, we thought, given the safety profile of azithromycin, that this [drug] could be potentially valuable [in treating COVID-19], and to have that kind of evidence would be really useful.
MNT: Can you tell us more about the mechanisms through which azithromycin produces immunomodulatory effects?
In terms of [the] mechanism, there [are] anti-inflammatory type effects with azithromycin. I’m an epidemiologist; I’m not a biochemist, [so] I can’t get into the biology of it so much. But I do think that nobody really knows what the mechanism is. Like, for example, with Zika, and in vitro studies with SARS-CoV-2, as well, nobody really knows what the mechanism is.
So, you know, it could be that there’s a direct antiviral effect. If I had to guess, I would say it’s probably unlikely, but [it] also could be that you’re reducing [the need for a more complex] treatment [by administering azithromycin].
A course of azithromycin or a dose of azithromycin could reduce other bacterial loads in patients who are presenting with both [COVID-19] and a bacterial pneumonia.
If you treat the bacterial pneumonia, [it] can free up the immune system to fight COVID-19, or it could be this immunomodulatory and anti-inflammatory response, which brings down inflammatory markers, [and] in general, allows the body to more efficiently fight the virus.
ACTION is not really designed to look at mechanisms. Specifically, it’s really just designed to look at clinical and virological outcomes in patients.
MNT: Lately, there has been a lot of talk about the issue of antibiotic resistance. Do you have any concerns in this respect, seeing that the trial is for an antibiotic?
Catherine Oldenburg: Yes, definitely. You know, I think that studies have shown, trials have shown that a course of azithromycin, a course of antibiotics, in general, does select for resistance in multiple body sources, so, in the intestines and in the nasopharynx (the back of the nose). It is something that you definitely see: Short term increases in isolation of resistance, following a course of antibiotics, and for the long term, the effects of that are unknown.
I think, in terms of doing a trial of azithromycin, the resistance point is really key for doing a trial because if we know that azithromycin does not work for COVID-19, that means that providers won’t be prescribing [it] for COVID-19.
But if there’s this sort of general feeling — which I think there is right now — that’s kind of, well, maybe it might help, maybe it doesn’t hurt, then we might actually, paradoxically, see more prescribing of azithromycin.
So, from my perspective, I’d like to know whether or not it does help. And if it does help then perhaps the trade-off of the resistance is a more warranted one versus if it does not help — then, you know, we have clear evidence that we don’t need to be prescribing azithromycin for outpatients with COVID-19.
MNT: How has the pandemic impacted the practical aspects of getting this trial underway?
Catherine Oldenburg: It’s interesting how many things we took for granted before COVID-19 — you know, [like the] moving of supplies. And even just when we were designing the study, and we were trying to get a hold of swabs.
So, we’re sending patients a self-swab collection kit — it’s an opt-in, if they want to collect swabs, they can collect their own nasal swabs — and just finding a supplier for swabs was really very, very challenging.
Fortunately, we do a lot of sample collection as part of our normal trials, and we have a stock of supplies in our lab [already], but not study drugs.
Editor’s note: When MNT conducted this interview, the trial had not yet started, largely due to delays in receiving the study drug from the overseas provider.
Catherine Oldenburg: I think the first [challenge that we encountered] is just kind of the pace of it [the pandemic]. I mean, there’s this urgent need. We have this horrible infection that’s affecting so many people all over the world, and we have no good treatment for it.
I know that there’s some signal from at least one press release about remdesivir for hospitalized patients, but, you know, in terms of preventing patients from having to be hospitalized in the first place, there’s just really no good evidence. And so, there’s really this prerogative to look at what we call repurposed drugs, the drugs that have indication for something else, and to look at it as quickly as possible.
And, for example, I keep hearing people say things like, “in the U.S. we’ve had 1.3 million cases of COVID-19.” In an ideal world, every single one of those patients could contribute to a clinical trial, because then we would be moving along the evidence.
In the scheme of things, we think we need about 2,000 patients in our trial to arrive at an answer for whether or not azithromycin works, and with 1.3 million infections that, hopefully, should be possible.
So, there’s this kind of pressure, this time pressure that you don’t normally see. Normally, to get a trial like this started, it would take a year, maybe, of planning and of getting regulatory approvals and getting ethical approvals and all that stuff.
And, you know, under this situation we went from first concept of trial idea to all of our approvals being in place in less than 6 weeks, which is […] just really, really, really fast paced. That was exciting, and sometimes a little overwhelming.
So, I think that’s the first thing, that the timelines are sort of crunched, and […] I think there’s also this [other] element: […] for the work that I do normally, we’re talking about diseases where the epidemiology is fairly well described. It may be changing over time, but it’s changing really slowly.
I work mostly in trachoma and child mortality. Both of those are declining over time [in terms of the epidemiology], but they’re declining really, really, really slowly, so I can design a trial that’s going to be implemented in a year and have a pretty good idea of what the epidemiology in a year is going to look like.
It’s completely different with COVID-19. I don’t know what the epidemiology is going to look like next week.
And, it’s so complicated with, you know, just the kind of social and political dimensions of it. So, when we’re thinking about trial design, we don’t have good epidemiology to make assumptions, for example, for sample size calculations. We don’t know exactly what the timeline of the infection is going to look like.
When we first started designing this trial, I don’t think any of us were thinking [about] second wave infections in the fall, that sort of thing. We were thinking “we need to get this done in the spring, we’re going to get it done quickly in a couple [of] months, and that’s going to be over.” And now we’re thinking, “well, maybe this is going to last longer.”
And then, [there are] the supply chain issues, just [the] logistics of getting a trial started when you have to move, for example, study drug products across the world. Normally, that’s something that takes some logistics and planning but doesn’t have [to reckon with] this global economic shutdown that we’ve been seeing, in terms of flights [being grounded], in terms of people moving.
Normally, that just wouldn’t be a consideration like this. So I think it’s [multiple] dimensions affecting this particular trial.
MNT: Finally, how can people who may be interested in joining the ACTION trial enrol in it?
Catherine Oldenburg: [Prospective] participants [who] think they might qualify for the trial can go fill out [the] screening form [on the ACTION trial website], which initiates contact with our study staff, and then someone on our study team would get back to that person via phone or [other means of contact].
https://www.medicalnewstoday.com/articles/covid-19-trial-lead-researcher-explains-why-an-antibiotic-might-work#Time-pressure-and-unexpected-challenges

Blue light may be the key to defeating MRSA

Bacteria are impressively adaptive. Through rapid cell division and via horizontal gene transfer— where they transfer genes with their neighbors — bacteria can quickly strengthen their defenses against threats.
One such threat is antibiotics, and pathogens, such as some bacteria, are rapidly adapting to defeat them.
As these pathogens become resistant to more and more antibiotics, visions of a world in which the drugs on which we depend no longer work have seen scientists racing to come up with some other way to stop infections.
Now, scientists from Boston University’s College of Engineering in Massachusetts have announced success at weakening pathogens by using blue light to attack them on a molecular level.
Prof. Ji-Xin Cheng, from the College of Engineering, says that the “therapy is novel because, instead of using a drug-based approach, it takes physical aim at the structure of the cell itself.”
Prof. Cheng is the senior author of a paper in Advanced Science that now describes the research.

A fortuitous accident

Prof. Cheng and his colleagues happened across blue light’s potential by accident, during experimentation with new optical microscope techniques.
They were using Staphylococcus aureus (S. aureus) as their microscopic subject but soon found it too unstable for their purposes; the microscope’s blue light was bleaching the bacterium’s staphyloxanthin (STX) molecule.
“Golden pigmentation is the universal signature of S. aureus,” says Prof. Cheng. “For imaging purposes, this is bad. But, if it’s bleached, we wondered, is it still alive?”
The team was further surprised, and excited, to learn that their photobleaching ultimately caused their entire S. aureus colony to die. Being able to kill S. aureus is no small thing.
S. aureus is arguably the clearest harbinger of an imminent postantibiotic era.
Methicillin-resistant S. aureus (MRSA) causes skin and soft tissue infections, sepsis, and pneumonia.
Methicillin was the first antibiotic to fail against MRSA, and the bacterium has since become extremely difficult to treat with other antibiotics, as well.
According to the Centers for Disease Control and Prevention (CDC), MRSA is responsible for many of the 2.8 million antibiotic resistant infections, and the 35,000 resulting deaths each year in the United States.
Confronted with the unexpected death of S. aureus, Cheng’s team found themselves wondering, “If we bleach [MRSA’s golden pigment], can we kill the [bacterium]?”
The answer to the question turned out to be: “Almost.” It may be enough.
Blue light photolysis and MRSA
Further study revealed that when the microscope’s blue light photons broke down STX, small openings appeared all over the membranes protecting the MRSA cells, and 90% of the colony died.
However, when dealing with a fast-moving bacterium like MRSA, that is not enough: Within half-an-hour, the cells were dividing again.
According to lead study author Pu-Ting Dong, “MRSA grows back very quickly, so to be effective, we need to kill 99.9% of bacteria.”
For the remaining 10%, Cheng’s team tried something new: After blue light photolysis, which refers to the breakdown of molecules through light, they dosed the cells with hydrogen peroxide, a strong oxidizer that can attack living cells.
The hydrogen peroxide entered the S. aureus cells through the holes in their membranes, causing them to implode. Finally, they had destroyed 99.9% of the S. aureus colony.
Thus, blue light photolysis looks to be the first strike in a one-two punch that can take out antibiotic resistant pathogens.
Since their initial findings in the lab, Cheng and his team have partnered with researchers from Purdue University and Massachusetts General Hospital Wellman Center for Photomedicine in Boston to confirm the effectiveness of their technique on MRSA skin wounds in mice.
Part of what makes blue light photolysis so attractive, as a therapy, is that it does not damage normal cells.
This is also true of the blue light pulse laser therapy, which Cheng’s team has learned can provide even more effective photolysis. Study co-author Jie Hui explains:

“Using a pulsing blue laser, we can significantly shorten the therapy time and increase the depth of tissues we can effectively treat. The laser light feels painless and doesn’t give off any sensation of heat, ideal for clinical applications.”
— Jie Hui

Next up for Cheng and colleagues will be the development of a trial for a treatment for people with skin ulcers that diabetes causes.
“If we can treat diabetic ulcers,” he says, “that will change people’s lives. As scientists, we don’t just want to publish papers, we also want to return the fruits of our work and research funding to society.”
https://www.medicalnewstoday.com/articles/blue-light-may-be-the-key-to-defeating-mrsa#Blue-light-photolysis-and-MRSA

COVID-19, ARDS patients face significant financial effects in recovery

It begins with shortness of breath. And for approximately one third of patients, acute respiratory distress syndrome, or ARDS, ends in death. For those who survive, their lives are often turned upside-down. Michigan Medicine researchers have been investigating the downstream effects of ARDS for years. As the COVID-19 pandemic rages on, their work has relevance for hundreds of thousands of new patients.

“The way COVID-19 kills patients is by depriving them from oxygen,” says Theodore (Jack) Iwashyna, M.D., professor of critical care medicine. “But only a third or fewer of COVID-19 patients who develop respiratory failure die. Most survive, and we need research that helps them not just survive but really heal.”
A team led by Iwashyna wanted to look more closely at how being hospitalized for ARDS affected people months after they were discharged. They interviewed dozens of patients from around the nation. “As we knew from past research, people had new disabilities ranging from general fatigue and weakness to where they couldn’t remember things,” says Katrina Hauschildt of the U-M department of sociology and first author on the study. “A lot of people had emotional difficulties coming to terms with just how sick they had been — a kind of PTSD from being in the ICU.”
“What I didn’t expect,” says Iwashyna, “was the lasting chaos into which surviving respiratory failure threw some of our patients and their families. Patients described problems coming not just from medical bills — although there were plenty of those — but also from losing their jobs and losing their insurance.” Given the magnitude of recession hitting at the same time as patients are trying to recover from COVID-19, Iwashyna and Hauschildt are worried this could be devastating for many families.
One 55-year old man described having to give up his small business because he could not work after getting out of the intensive care unit (ICU). “I had to sell my business. I’m on disability now…I owned a fire prevention company…We used to clean the kitchen exhaust systems in restaurants throughout the state. Degreased the restaurants, like their exhaust hoods in the kitchen and on the roof…Yeah, I sold everything.”
The team found that many respiratory failure patients experience what is known as financial toxicity, defined as the financial burdens and related distress of medical care. In turn, this financial toxicity led to additional negative effects on their physical and emotional recovery.
With hospitalization for ARDS often resulting in weeks of high intensity care, patients end up with medical bills ranging from tens of thousands to, in some cases, millions of dollars, and the proportion covered by insurance varied substantially.
One 49-year old male survivor of ARDS told the study team “I barely make it, or my bills are pending like electricity, things and other stuff.” Said another 55-year old woman “I had to pay my rent, my food and medicines and all that so I was a little bit short … They were kind of difficult to pay after the hospital … Because I had to get more medicines and all that.”
The team reported several consequences of hospitalization including emotional distress related to insurance issues and unpaid bills, reduced physical well-being due to the inability to receive follow-up care due to cost, an increased reliance on family and friends to help cover expenses and other material hardships. Said one patient: “In the next couple of months, I may end up being homeless because of the financial aspect of it.”
While these cases may seem extreme, they were not rare. And many patients described having to make hard choices about whether they could afford rehabilitation — and stopping early when their coverage ran out, even though they were not yet recovered. A 51-year old man told the study team “[Physical therapy] was very short, a couple weeks maybe; then it was over, and I just laid around basically. My insurance did not cover any more, so they had to cut me.”
Another patient, a 61-year-old woman, described not having the equipment when she tried to go home: “I could pick one item that I wanted,” of the hospital bed, wheelchair, and walker she needed, “because the insurance would only pay for one item.”
Hauschildt says the study outlines the need for doctors to be more aware of the financial toxicity faced by survivors of ARDS, including those recovering from COVID-19. “One of the biggest things any doctor involved in follow up care can do is anticipate that patients might have real financial burdens and know what resources are available so they can help,” she adds.
However, she notes, what’s available is really up to policy makers. For example, the study found that patients who were already on public insurance before their illness reported less of an out-of-pocket financial impact. “Communities that put a safety net in place for ARDS and COVID-19 survivors will ultimately have better healing and recovery. People who heal are able to return to work and care for others and their communities; people who don’t aren’t.”
This work was supported by the National Institutes of Health, National Heart, Lung and Blood Institute as part of the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network. The patients who participated in these interviews gave their consent for their words to be quoted, and were all about nine months after having had moderate to severe ARDS.

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Story Source:
Materials provided by Michigan Medicine – University of Michigan. Original written by Kelly Malcom. Note: Content may be edited for style and length.

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Journal Reference:

1. Katrina E. Hauschildt, Claire Seigworth, Lee A. Kamphuis, Catherine L. Hough, Marc Moss, Joanne M. McPeake, Theodore J. Iwashyna. Financial Toxicity After Acute Respiratory Distress Syndrome. Critical Care Medicine, 2020; Publish Ahead of Print DOI: 10.1097/CCM.0000000000004378

https://www.sciencedaily.com/releases/2020/06/200603132559.htm

New identification of genetic basis of COVID-19 susceptibility will aid treatment

The clinical presentation of Covid-19 varies from patient to patient and understanding individual genetic susceptibility to the disease is therefore vital to prognosis, prevention, and the development of new treatments. For the first time, Italian scientists have been able to identify the genetic and molecular basis of this susceptibility to infection as well as to the possibility of contracting a more severe form of the disease. The research will be presented to the 53rd annual conference of the European Society of Human Genetics, being held entirely on-line due to the Covid-19 pandemic, today [Saturday].

Professor Alessandra Renieri, Director of the Medical Genetics Unit at the University Hospital of Siena, Italy, will describe her team’s GEN-COVID project to collect genomic samples from Covid patients across the whole of Italy in order to try to identify the genetic bases of the high level of clinical variability they showed. Using whole exome sequencing (WES) to study the first data from 130 Covid patients from Siena and other Tuscan institutions, they were able to uncover a number of common susceptibility genes that were linked to a favourable or unfavourable outcome of infection. “We believe that variations in these genes may determine disease progression,” says Prof Renieri. “To our knowledge, this is the first report on the results of WES in Covid-19.”
Searching for common genes in affected patients against a control group did not give statistically significant results with the exception of a few genes. So the researchers decided to treat each patient as an independent case, following the example of autism spectrum disorder. “In this way we were able to identify for each patient an average of three pathogenic (disease-causing) mutations involved in susceptibility to Covid infection,” says Prof Renieri. “This result was not unexpected, since we already knew from studies of twins that Covid-19 has a strong genetic basis.”
Although presentation of Covid is different in each individual, this does not rule out the possibility of the same treatment being effective in many cases. “The model we are proposing includes common genes and our results point to some of them. For example, ACE2 remains one of the major targets. All our Covid patients have an intact ACE2 protein, and the biological pathway involving this gene remains a major focus for drug development,” says Prof Renieri. ACE2 is an enzyme attached to the outer surface of several organs, including the lungs, that lowers blood pressure. It serves as an entry point for some coronaviruses, including Covid-19.
These results will have significant implications for health and healthcare policy. Understanding the genetic profile of patients may allow the repurposing of existing medicines for specific therapeutic approaches against Covid-19 as well as speeding the development of new antiviral drugs. Being able to identify patients susceptible to severe pneumonia and their responsiveness to specific drugs will allow rapid public health treatment interventions. And future research will be aided, too, by the development of a Covid Biobank accessible to academic and industry partners.
The researchers will now analyze a further 2000 samples from other Italian regions, specifically from 35 Italian Hospitals belonging to the GEN-COVID project.
“Our data, although preliminary, are promising, and now we plan to validate them in a wider population,” says Prof Renieri. “Going beyond our specific results, the outcome of our study underlines the need for a new method to fully assess the basis of one of the more complex genetic traits, with an environmental causation (the virus), but a high rate of heritability. We need to develop new mathematical models using artificial intelligence in order to be able to understand the complexity of this trait, which is derived from a combination of common and rare genetic factors.
“We have developed this approach in collaboration with the Siena Artificial Intelligence Lab, and now intend to compare it with classical genome-wide association studies in the context of the Covid-19 Host Genetics Initiative, which brings together the human genetics community to generate, share, and analyse data to learn the genetic determinants of COVID-19 susceptibility, severity, and outcomes. As a research community, we need to do everything we can to help public health interventions move forward at this time.”
Chair of the ESHG conference, Professor Joris Veltman, Dean of the Biosciences Institute at Newcastle University, Newcastle upon Tyne, UK, said: “We are very excited to have this work on the genetics of COVID19 susceptibility presented as one of our late-breaking abstract talks at the ESHG. Our Italian colleagues present the first insight into the role of genetic susceptibility influencing the severity of the response to a COVID19 infection. It needs to be expanded to encompass much larger populations, but it is impressive to see the speed at which research on this virus has proceeded in just a few months’ time.”

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Story Source:
Materials provided by European Society of Human Genetics. Note: Content may be edited for style and length.
https://www.sciencedaily.com/releases/2020/06/200605182332.htm

Stewart Health Care buys back control from Cerberus

Steward Health Care has reached an agreement to buy back control of the company from Cerberus Capital Management, L.P., a New York-based private equity firm.
Cerberus agreed Tuesday to sell control of the Dallas-based physician-owned company to a group of Steward physicians led by CEO Dr. Ralph de la Torre.
“This is a transformational moment for the healthcare industry, with new realities in a COVID-19 world that must be addressed with an equally transformational, patient-first approach,” de la Torre said in a statement. “The COVID-19 global pandemic has exposed serious deficiencies in the world’s healthcare systems, with a disproportionate impact on underserved communities and populations. We believe that future healthcare management must completely integrate long-term clinical needs with investments. As physicians first, we will focus on creating structures and timelines that meet the long-term needs of our communities and the short-term needs of our patients.”
Steward, which has been owned by Cerberus for a decade, manages 35 community hospitals across nine states.
“For nearly a decade, we have partnered with Steward Health Care to build an industry-leading company that provides access to affordable, high-quality, community-based care across the United States,” Brett Ingersoll, senior managing director and chairman of the private equity investment committee at Cerberus, said in a statement. “We believe this transaction will ensure that Steward Health Care’s transformative, accountable care model will continue to drive innovation as a physician-owned and integrated healthcare system.”
The move comes amid an economic downturn spurred by the coronavirus disease 2019 (COVID-19) outbreak.
In late March, Steward issued a statement to WBUR that described the impact of the coronavirus pandemic on the company as a “seismic financial shock.”
Additionally, according to a report released by the Massachusetts Center for Health Information and Analysis last September, Steward had the lowest total margin and operating margin in fiscal year 2018 among 11 multi-acute health systems.
Amid the outbreak, Steward has reportedly been eyeing a deal with St. Luke’s University Health Network to sell Easton Hospital, an acute care facility based in Wilson, Pennsylvania.
However, there are concerns that if the transaction falls and the hospital closes its doors on June 30 that nearly 700 people will lose their jobs.
https://www.healthleadersmedia.com/finance/steward-health-care-buys-back-control-cerberus

AstraZeneca approached Gilead about potential merger

AstraZeneca Plc (AZN.L) has approached rival drugmaker Gilead Sciences Inc (GILD.O) about a potential merger, Bloomberg News reported on Sunday, citing people familiar with the matter.
Any deal would bring together two of the companies leading the drug industry’s efforts to fight the coronavirus pandemic.
AstraZeneca contacted Gilead last month and it did not provide the terms of any transaction, the report bloom.bg/3h2GU9e added.

A spokeswoman for AstraZeneca said the company does comment on rumors or speculation. Gilead did not immediately respond to a request for comment.
Gilead, AstraZeneca and several other drugmakers, including Eli Lilly and Co (LLY.N), Pfizer Inc (PFE.N) and Merck & Co Inc (MRK.N), are racing to develop vaccines or treatments for COVID-19, the respiratory illness caused by the novel coronavirus.
More than 6.90 million people have been reported infected with the coronavirus globally and 399,025 have died, a Reuters tally showed on Sunday.

While Gilead has discussed the merger idea with advisors, no decision has been made on how to proceed and the companies are not in formal talks, Bloomberg News said.
Gilead is not interested in selling to or merging with another big pharmaceutical company, and prefers instead to focus its deal strategy on partnerships and smaller acquisitions, the report said.
AstraZeneca said on June 4 it had doubled manufacturing capacity for its potential coronavirus vaccine to 2 billion doses in two deals involving Microsoft billionaire Bill Gates that guarantee early supply to lower income countries. It is unclear if a vaccine will work, but AstraZeneca’s partnership with Oxford University to develop one is among a handful of initiatives U.S. President Donald Trump’s COVID task force has backed. Gilead has also been at the forefront. Its Remdesivir antiviral is the first drug to lead to improvement in COVID-19 patients in formal clinical trials.
https://www.reuters.com/article/us-gilead-sciences-m-a-astrazeneca/astrazeneca-approached-gilead-about-potential-merger-bloomberg-news-idUSKBN23E09O

ENDO Online 2020 Program, Week of June 8

ENDO Online 2020’s comprehensive program offers attendees the opportunity to learn about the latest developments in hormone science and medicine from renowned investigators, expert clinicians, and educators from all over the world. Join us for a mixture of live and on-demand content and stay at the forefront of scientific discovery and high-quality patient care.

Daily Event Schedule

(all times are listed in EDT)

Monday, June 8

Time	Session
10:00 – 11:00 AM	The Impact of COVID-19 on Endocrinology Developed in collaboration with the European Society of Endocrinology Chairs: John Newell-Price, MD, PhD, FRCP and Andrea Giustina, MD Impact of Diabetes/Obesity on Adverse Outcomes from COVID-19 Manuel Puig-Domingo, MD, PhD Practical Management of Diabetes in Patients with COVID-19 Daniel J. Drucker, MD Clinical Guidance for Patients with Adrenal Insufficiency During COVID-19 Pandemic Wiebke Arlt, MD, DSc, FRCP, FMedSci Panel Discussion with Faculty Drs. Arlt, Drucker, Guistina, Newell-Price, and Puig-Domingo
12:00 – 1:30 PM	Improving Outcomes in Acromegaly: Let Patients Be Your Guide

Tuesday, June 9: Basic Science Day

Time	Session
10:00 – 11:00 AM	Basic Mechanisms in Reproduction: From Beginning to End Chair: Genevieve Scott Neal-Perry, PhD, MD Regulation of Mouse Uterine Contractility by Regulator of G-Protein Signalling 2 Daniela Urrego, BHSc Kisspeptin as a Biomarker for Pregnancy Complications Maria Phylactou, MBBS Ovarian Follicle Survival Is Determined by Follicle-Stimulating Hormone Receptor (FSHR) and Estrogen Receptor (GPER) Heteromers Livio Casarini, PhD The Expression of the Homeodomain Transcription Factor SIX3 within Kisspeptin Neurons Is Necessary for Reproduction in Mice Shanna Newton Lavalle, BS
11:00 AM – 12:00 PM	The Many Faces of Diabetes, Obesity, and Metabolism Chair: Kevin Y Lee, PhD Circadian Regulation of Chromatin State Mediates Pancreatic Islet Incretin Response Benjamin John Weidemann, BS Hepatocyte Peroxisome Proliferator-Activated Receptor Gamma (PPARG) Offsets the Anti-Steatogenic Effects of Thiazolidinediones in Obese Male Mice Jose T Muratalla, Biochemistry Undergrad The Transcriptional Coactivation Function of EHMT2 Restricts Chronic Glucocorticoid Exposure Induced Insulin Resistance Rebecca Arwyn Lee, MS Epinephrine Is Essential for Normal Renal Glucose Reabsorption via the Glucose Transporter GLUT2 Arwa Mahmoud Elsheikh, MBBS
12:00 – 1:00 PM	Keynote: If We Knew Then What We Know Now, Would We Have Approached The Development of Endocrine Therapies Differently Donald McDonnell, PhD
1:00 – 2:00 PM	The Many Faces of Nuclear Receptor Biology Chair: Patricia Virginia Elizalde, PhD Kruppel-Like Factors 9 and 13 Cooperate to Maintain Mammalian Neuronal Differentiation Jose Avila-Mendoza, PhD Expression of SLC35F1 in the Plasma Membrane of Cells of Aldosterone Producing Cell Clusters (APCCs) and Its Possible Role in Aldosterone Synthesis Emily Goodchild, BMBS, BSc Nuclear Receptor CAR Protects Female Mice from the Development of Diet-Induced Nonalcoholic Fatty Liver Disease Fabiana Oliviero, Master’s Degree When the Glucocorticoid Receptor Meets the Mineralocorticoid Receptor in the Nucleus of Human Cells Maria G. Petrillo, PhD
2:00 – 3:00 PM	From the Brain to the Belly – Insights into Pituitary and Adrenal Physiology Chair: Lori Therese Raetzman, PhD OTX2 Mutations in Congenital Hypopituitarism Patients Louise Cheryl Gregory, PhD Single-Cell Sequencing Identifies Novel Regulators of Thyrotrope Populations and POU1F1-Independent Thyroid-Stimulating Hormone Expression Leonard Cheung, PhD Glucocorticoid Production in the Nervous and Immune Systems: Evidence for a Local HPA Axis Homolog Melody Salehzadeh, BSc Sepsis-Induced Critical Illness in Mice Alters Key Regulators of ACTH Production and Secretion Within the Anterior Pituitary Gland Arno Téblick, MD

Wednesday, June 10

Time	Session
10:00 AM – 12:00 PM	Exhibit Hall Hours
12:00 – 1:30 PM	Breaking Bad: Reducing Glucose Variability and Increasing Time in Range in Patients with Diabetes

Thursday, June 11

Time	Session
10:00 AM – 12:00 PM	Exhibit Hall Hours
12:00 – 1:30 PM	Breaking the Cycle: Approaches to Long-Term Weight Loss and Obesity Care

Friday, June 12

Time	Session
10:00 AM – 12:00 PM	Exhibit Hall Hours
1:00 PM – 1:45 PM	What’s New with ABIM’s Maintenance of Certification? Susan J. Mandel, MD, MPH

https://www.endocrine.org/meetings-and-events/endo-online-2020/schedule-at-a-glance