Convalescent Plasma: The Unanswered Questions

https://www.medpagetoday.com/infectiousdisease/covid19/88264?xid=fb_o&trw=no&fbclid=IwAR0F6xiRAQ7ngBz4pNozJ2VqWm0-UJqGdlQojfOeyXbPJjbAeYtGL8jbAiw

“The data don’t show anything useful”

Problems with the government’s rationale for authorizing use of convalescent plasma in COVID-19 patients go far beyond the dustup over the purported 35% survival benefit cited by top officials on Sunday, numerous researchers say.

That figure quickly came under fire, leading to an apology from Commissioner Stephen Hahn, MD — but that’s not the only criticism leveled at the FDA’s analysis of the available data.

Much of it came from the Mayo Clinic and FDA expanded access program (EAP), at this point published only as a preprint manuscript. Although a large number of patients were included, the study was observational only, with no untreated control group. That makes the findings merely hypothesis-generating, and can’t offer any firm conclusions.

That’s fine for issuing an emergency use authorization (EUA), but not so much for making claims about survival benefit, independent researchers said.

“It’s not even a question of overstating,” Adam Gaffney, MD, MPH, a critical care doctor and health policy researcher at Harvard Medical School, told MedPage Today. “You can’t state much at all when you don’t have a randomized controlled trial.”

“People have made a big deal of Hahn referring to relative versus absolute risk reduction, but I think that’s less of a big deal,” Gaffney said. “The biggest problem is that the data they are citing … is not randomized. That’s the source of all the problems.”

Hahn took heat for saying that a “35% improvement in survival is a pretty substantial clinical benefit” further explaining that of “100 people who are sick with COVID-19, 35 would have been saved because of the administration of plasma.”

Critics rapidly took to Twitter, stating that the interpretation was incorrect. Hahn was referring to relative risk reduction, not absolute risk reduction. Thus, calculating the number of lives saved — which isn’t something experts recommend doing based on observational data in the first place — would have translated to somewhere more in the ballpark of 5 out of 100.

Moreover, the “risk reduction” came from a comparison of patients treated with high-titer plasma versus those receiving lower-titer preparations. The study offered no basis for concluding how many patients may have been “saved” relative to standard care.

And the 35% reduction in that analysis was for 7-day mortality; the relative reduction at 30 days was only 23%.

Hahn’s recital of the 35% figure “was just PART of the error,” tweeted Vinay Prasad, MD, MPH, of the University of California San Francisco. “The entire comparison is flawed. It is not a suitable control. The data don’t show anything useful.”

“The much broader problem here is the lack of commitment to performing large, national randomized controlled trials,” Gaffney said. “We could have done it for convalescent plasma. Instead, we did the EAP. I understand why people wanted it, but now we don’t know [if convalescent plasma works]. We have a question mark instead of a period.”

Undermining Trust in FDA?

Critics have charged that serious mistakes like Hahn’s misstatement could undermine FDA’s credibility, especially as it faces challenging decisions about potentially approving a vaccine this fall.

“This is playing out in the context of a hyper-politicized moment,” Gaffney said. “It behooves everyone to be extremely cautious in speaking about these things to avoid the appearance of politicization.”

On CBS This Morning on Tuesday, Hahn addressed concerns about politicization by offering reassurance to the “American people that this decision was made based upon sound science and data.”

In response to questions about the timing of the EUA announcement — it came just a day after President Donald Trump tweeted allegations that the “deep state” was holding back access to COVID-19 treatments with Hahn’s Twitter handle cited, and a day before the Republican National Convention got underway — Hahn said the agency had been working on the application for 3 or 4 weeks and was waiting on additional validation data, which were received at the end of last week and over the weekend.

“We’re going to continue to get data and as we’ve done with any other authorization, we will update that decision as new data come,” Hahn said on the news program. His agency initially issued an EUA for hydroxychloroquine, for instance, but later revoked it when the negative randomized trial data became available.

Lack of Access to FDA’s Data Review

Whether the public will ever see the full convalescent plasma data underlying the EUA is another matter. The “Clinical Memorandum” issued as the evidence behind the FDA’s decision glossed over the statistical analysis conducted by the agency; in particular, it made no mention of the 35% relative reduction in deaths.

Another problem with that is the 35% figure’s source isn’t fully clear. Although the EAP preprint manuscript is the most obvious source, Gaffney noted that HHS Secretary Alex Azar said it referred to a subgroup of patients under age 80 who were not on a ventilator. That is not found in the publicly available data. He also pointed to a tweet by FDA spokesperson Emily Miller that contains an agency slide showing a 37% reduction in mortality for non-intubated patients age 80 or under treated within 72 hours who got high-titer convalescent plasma, compared with low-titer product. Neither of those figures is reflected in the EAP manuscript.

The FDA did not return a request by MedPage Today for the full summary of data reviewed by FDA and any independent statistical analysis done by the agency.

Shmuel Shoham, MD, of Johns Hopkins University in Baltimore, said during a press briefing organized by the Infectious Diseases Society of America that “enormous amounts of data have been generated” from the EAP, in which more than 70,000 patients have been treated.

“Some data have been reported in articles and at meetings, but that’s only part of what the FDA — this is their program — has access to,” he said. “The stuff in the public domain is only a fraction of the data they have collected.”

Shoham is on the scientific advisory board of the EAP and is involved in two convalescent plasma clinical trials at Johns Hopkins.

Gaffney said Mayo researchers and FDA reviewers have noted that physicians were blinded to the dose of antibody given in plasma infusions, which he described as a “pseudo-randomization effect. We could use that to make more causal inferences about the effectiveness of antibody titers.”

However, he said there were some significant differences between those who received high-titer versus low-titer antibody, including differences in P-to-F ratio (a measure of inhaled oxygen to blood oxygen) and in those with five or more severe risk factors, suggesting the low-titer group was sicker to begin with than the high-titer group.

Also, patients in the EAP received a variety of other treatments: about half got steroids and 40% were given remdesivir.

“This is why we do randomized controlled trials,” Gaffney said. “Without them it’s very difficult to ensure that the effect you see is the result of the drug, and not the result of patient characteristics.”

Is an Answer Forthcoming?

Several randomized controlled trials of convalescent plasma are underway in the U.S., but the big concern is that wider access to convalescent plasma will limit enrollment. Will clinicians recommend that their patients enroll in a trial in which they might receive placebo? Will patients agree?

For the Hopkins studies, the prevention trial has enrolled 25 people out of a goal of 500, and its outpatient trial has enrolled 50 people of its 600-patient goal.

Liise-anne Pirofski, MD, of Montefiore Medical Center in New York, started a study at the end of April, looking to enroll 300 people. She said the team enrolled the first 150 people quickly, but “then the pandemic began to wane in New York.” With subsequent funding from the NIH, the trial has managed to enroll 190 patients, and has now expanded to four additional sites: New York University, Yale, the University of Miami, and the University of Texas Houston.

Clifton Callaway, MD, PhD, of the University of Pittsburgh Medical Center and lead investigator on the C3PO trial looking at outpatient convalescent plasma, said he hopes the EUA doesn’t discourage participation.

“To the contrary, I believe it should reassure persons considering participation that the FDA feels that convalescent plasma is safe and potentially useful and that the FDA specifically comments: ‘Current data suggest the largest clinical benefit is associated with high-titer units of CCP administered early in the course of disease.’ Giving high-titer convalescent plasma earlier (before you are sick enough to be in the hospital) is exactly what C3PO is testing.”

In addition to determining whether earlier or prophylactic treatment works, Shoham said other unanswered questions include identifying whether other components in plasma are useful therapies and whether low-titer plasma can work at all.

“What everyone agrees on is that the gaps in knowledge that exist can best be addressed by high-quality randomized controlled trials,” he said.

Pirofski said the science and data should be the focus, “rather than the decision and what drove the decision…. I don’t think anyone knows what drove that decision other than the people in that room. Hopefully they know.”

 

 

 

 

Top U.S. Officials Told C.D.C. to Soften Coronavirus Testing Guidelines

The Centers for Disease Control and Prevention abruptly changed its recommendations, saying people without Covid-19 symptoms should not get tested.

 Trump administration officials on Wednesday defended a new recommendation that people without Covid-19 symptoms abstain from testing, even as scientists warned that the policy could hobble an already weak federal response as schools reopen and a potential autumn wave looms.

The day after the Centers for Disease Control and Prevention issued the revised guidance, there were conflicting reports on who was responsible. Two federal health officials said the shift came as a directive to the Atlanta-based C.D.C. from higher-ups in Washington at the White House and the Department of Health and Human Services.

Adm. Brett P. Giroir, the administration’s coronavirus testing czar, called it a “C.D.C. action,” written with input from the agency’s director, Dr. Robert R. Redfield. But he acknowledged that the revision came after a vigorous debate among members of the White House coronavirus task force — including its newest member, Dr. Scott W. Atlas, a frequent Fox News guest and a special adviser to President Trump.

“We all signed off on it, the docs, before it ever got to a place where the political leadership would have, you know, even seen it, and this document was approved by the task force by consensus,” Dr. Giroir said. “There was no weight on the scales by the president or the vice president or Secretary Azar,” he added, referring to Alex M. Azar II, the secretary of health and human services.

Regardless of who is responsible, the shift is highly significant, running counter to scientific evidence that people without symptoms could be the most prolific spreaders of the coronavirus. And it comes at a very precarious moment. Hundreds of thousands of college and K-12 students are heading back to campus, and broad testing regimens are central to many of their schools’ plans. Businesses are reopening, and scientists inside and outside the administration are growing concerned about political interference in scientific decisions.

Democratic governors who were weighing how to keep the virus contained as their economies and schools come to life said limiting testing for asymptomatic citizens would make the task impossible.

“The only plausible rationale,” Gov. Andrew M. Cuomo of New York told reporters in a conference call from Albany, N.Y., “is that they want fewer people taking tests, because as the president has said, if we don’t take tests, you won’t know the number of people who are Covid-positive.”

Over the weekend, the Food and Drug Administration, under pressure from Mr. Trump, gave emergency approval to expand the use of antibody-rich blood plasma to treat Covid-19 patients. The move came just days after scientists, including Dr. Anthony S. Fauci, the nation’s top infectious disease expert, and Dr. Francis S. Collins, the director of the National Institutes of Health, intervened to stop the practice because of lack of evidence that it worked.

The move echoed a decision by the Food and Drug Administration to grant an emergency use waiver for hydroxychloroquine, a malaria drug repeatedly sold by Mr. Trump as a treatment for Covid-19. The agency revoked the waiver in June, when clinical trials suggested the drug’s risks outweighed any possible benefits.

The testing shift, experts say, was a far more puzzling reversal. Dr. Giroir said the move was “discussed extensively by” members of the White House coronavirus task force, and he named Dr. Redfield, Dr. Atlas, Dr. Fauci and Dr. Stephen M. Hahn, the commissioner of food and drugs. Notably, he did not name Dr. Deborah L. Birx, the White House coronavirus response coordinator. But he said Dr. Fauci was among those who had “signed off.”

In a brief interview, Dr. Fauci said he had seen an early iteration of the guidelines and did not object. But the final debate over the revisions took place at a task force meeting on Thursday, when Dr. Fauci was having surgery under general anesthesia to remove a polyp on his vocal cord. In retrospect, he said, he now had “some concerns” about advising people against getting tested, because the virus could be spread through asymptomatic contact.

“My concern is that it will be misinterpreted,” Dr. Fauci said.

The newest version of the C.D.C. guidelines, posted on Monday, amended the agency’s guidance to say that people who had been in close contact with an infected individual — typically defined as being within six feet of a person with the coronavirus and for at least 15 minutes — “do not necessarily need a test” if they do not have symptoms.

Exceptions might be made for “vulnerable” individuals, the agency noted, or if health care providers or state or local public health officials recommended testing.

Dr. Giroir said the new recommendation matched existing guidance for hospital workers and others in frontline jobs who have “close exposures” to people infected with the coronavirus. Such workers are advised to take proper precautions, like wearing masks, socially distancing, washing their hands frequently and monitoring themselves for symptoms.

He argued that testing those exposed to the virus was of little utility, because tests capture only a single point in time, and that the results could give people a false sense of security.

“A negative test on Day 2 doesn’t mean you’re negative. So what is the value of that?” Dr. Giroir asked, adding, “It doesn’t mean on Day 4 you can go out and visit Grandma or on Day 6 go out without a mask on in school.”

The guidelines come amid growing concern that the C.D.C., the agency charged with tracking and fighting outbreaks of infectious disease, is being sidelined by its parent agency, the Department of Health and Human Services, and the White House. Under ordinary circumstances, administering public health advice to the nation would fall squarely within the C.D.C.’s portfolio.

Experts have called the revisions alarming and dangerous, noting that the United States needs more testing, not less. And they have expressed deep concern that the C.D.C. is posting guidelines that its own officials did not author. A former C.D.C. director, Dr. Thomas R. Frieden, railed against the move on Twitter on Wednesday:

Dr. Tom Frieden
@DrTomFrieden
Two unexplained, inexplicable, probably indefensible changes, likely imposed on CDC’s website. * Dammit, if you come from a place with lots of Covid, quarantine for 14 days * If you’re a contact, get tested. If +, we can trace your contacts and stop chains of spread. A sad day.

Later, in an interview, Dr. Frieden elaborated. He noted that the C.D.C. had recently dropped its recommendation that people quarantine for 14 days after traveling from an area with a high number of cases to one where the virus was less prevalent. And he reiterated that testing the contacts of those infected was an important means of curbing the spread of the virus.

“We don’t know the best protocol for testing of contacts: Should you test all contacts? That’s the kind of study that frankly needs to get done,” Dr. Frieden said. But absent the answer to that question, he added, “I certainly wouldn’t say, ‘Don’t test contacts.’”

Democrats, including Speaker Nancy Pelosi and two governors — Mr. Cuomo and Gavin Newsom of California — were outraged by the changes. Mr. Newsom said California would not follow the new guidelines, and Mr. Cuomo blamed Mr. Trump.

Representative Frank Pallone Jr. of New Jersey, a Democrat and the chairman of the House Energy and Commerce Committee, also chimed in on Twitter: “The Trump Admin has a lot of explaining to do. #COVID19 testing is essential to stopping the spread of the pandemic. I’m concerned that CDC is once again caving to political pressure. This simply cannot stand.”

Mr. Trump has suggested that the nation should do less testing, arguing that administering more tests was driving up case numbers and making the United States look bad. But experts say the true measure of the pandemic is not case numbers but test positivity rates — the percentage of tests coming back positive.

As Dr. Giroir denied that politics was involved, he encouraged the continued testing of asymptomatic people for surveillance purposes — to determine the prevalence of the virus in a given community — and said such “baseline surveillance testing” would still be appropriate in schools and on college campuses.

“We’re trying to do appropriate testing, not less testing,” he said.

Still, the revisions left many public health officials scratching their heads. They might have made sense when the United States was experiencing a shortage of tests, some experts said, but that no longer appears to be the case. Dr. Frieden, however, said it was possible the administration was trying to conserve testing in case of another surge.

“The problem is we have too many cases, so there is basically no way to keep up the testing if you have a huge outbreak,” he said.

Jennifer Nuzzo, an epidemiologist at Johns Hopkins Bloomberg School of Public Health, said she was “not as up in arms about the content of the guidelines” as she was about the idea that the C.D.C.’s own experts did not write them — and that C.D.C. officials were referring all questions about them to the health department in Washington.

“These guidelines are clearly controversial, and many are calling on C.D.C. to explain its rationale for them, but C.D.C. is unable to comment,” she said in an email. “This is really dangerous precedent, and I fear it will erode public trust in C.D.C.”

 

 

 

 

Op-Ed: American Exceptionalism or American Insanity?

https://www.medpagetoday.com/infectiousdisease/covid19/88163?xid=nl_popmed_2020-08-20&eun=g885344d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=PopMedicine_082020&utm_content=Final&utm_term=NL_Gen_Int_PopMedicine_Active

We don’t have all of the answers, but that’s not our biggest problem.

Thirty years ago, in preparation for hunting season, I went to a shooting range to practice with my bow. I felt fine. When I finished, I got in my truck and began to back out. When I pressed on the brake, I felt a sharp pain in my foot. My first instinct was to go over what I did walking back and forth to pull arrows from the target. Had I twisted my foot, did I trip on something? No, I had not injured my foot in any way.

When I got home, I took off my shoe and looked. My big toe was slightly swollen and slightly red. It looked like gout. I took ibuprofen. I was better by the next day. I never had another attack until this week.

I was at a friend’s house drinking wine. My knee suddenly began to hurt. I walk or jog 6-8 miles per day, so my first thought was that all the exercise was catching up to me. I took ibuprofen. It got better. But the next day my ankle suddenly became very painful; then my wrist hurt a bit. I remembered my experience with gout. I treated myself for gout, and got better.

I feel very fortunate to live in a time when gout can be easily treated. One hundred years ago, I would have been in big trouble. Which is not to say that I would not have taken medicine in an attempt to get relief. I would have tried a variety of products that claimed to help but did no good.

Today, we can treat so many illnesses that were brutal and deadly in the past. A long time ago, all children with type 1 diabetes died. Today, we have effective therapy — insulin. When I was a resident in the early 1980s, we had no specific way of treating a heart attack. Today, we can place a stent and reverse the pathological process.

In the past, something as simple as poison ivy could make a person’s life miserable. Today, we can knock it out in a short time. Modern medicine can do amazing things. To a large extent, it can do these amazing things because of effective biomedical science.

However, it can’t cure everything. Nor can it beat death. The amazing accomplishments of the medical profession in the last 100 years seem to have led some to believe, or want to believe, that doctors can solve all medical problems. This belief system came to bear with the COVID-19 pandemic.

Many expected the medical profession to step up and solve the problem. When it didn’t, disappointment arose. Then accusations began to fly. Some claimed that there were conspiracies involving Big Pharma and doctors. Others claimed there were cures that were being suppressed by the government.

Some doctors and scientists responded to this by trying to appease. They turned to in vitro data — such as the zinc/hydroxychloroquine (HCQ) interaction — to claim that zinc and HCQ would work wonders. When other doctors and scientists pointed out flaws in that data, they were attacked. It was another conspiracy. I even heard accusations that this was a plot by Bill Gates for population control.

Some doctors also turned to poor, anecdotal trials with HCQ that supposedly showed benefit in a few patients. This led quite a few to believe that HCQ was a wonder drug. Once the exaggerations about HCQ came out, it could no longer be found in pharmacies. The panic was just that strong.

Everyone seemed to get caught up in the panic mindset, and then work under the notion that a lack of clear medical success just can’t be possible in the 21st century. Many patients in intensive care units across the country were being put on HCQ, steroids, remdesivir, anti-IL-6 medication, vitamin C, and whatever else seemed like it might do something.

Many patients who were put on that medication cocktail died, because there was no legitimate science behind this approach — whether it helped was unclear.

However, over time, it became more clear that steroids helped. It became more clear that HCQ did not help. Such revelations led to more reasonable, though not entirely proven, therapeutic approaches. But because the less scientific approaches had so much hype in the beginning, and because the panic was so strong, getting away from them has been fraught with problems and accusations, and even physical threats.

Sadly, some of these accusations and threats were fueled by irresponsible doctors in academic medical centers. Misinformation was fed to the public, and the public, being not well-versed in biomedical research, latched onto the credentials of these doctors rather than seeing through their hysterical and misguided arguments about HCQ and such.

The internet and the free flow of information allows many who don’t really understand the ins and outs of biomedical research and clinical medicine to read something that sounds good and believe it because it satisfies psychological needs. This is a clear pattern of behavior when it comes to HCQ.

But it is not just irresponsible people in academic medical centers who contribute to this process. Doctors, many of whom post on medical blogs, accuse anyone who says we should slow down and evaluate our therapy of “wanting to do nothing” or “not caring about the thousands who are dying.” Even well-intentioned doctors get caught up in this need to seem like something is being done, and so they order all sorts of useless tests.

One such useless test being ordered more commonly in COVID patients is an MRI of the heart. One study in a few patients comes out that shows that COVID can affect the heart, and the next thing you know everybody with COVID needs a heart MRI. Whether the MRI is a reliable test for this is unclear. What we do with the information from the MRI is unclear. It just makes some doctors and some patients feel good to engage in such useless practices.

This pattern of behavior, the pattern of engaging in useless practices to give the appearance of care, is quite common in the profession of medicine. I find it interesting that it has not been challenged by progressives, like those so interested in the Green New Deal. The environmental harm done along these lines by misguided doctors might do as much or more environmental harm than fracking — but at least with fracking you get something to show for your efforts.

With out-of-control doctors, ordering useless tests, running MRI machines and CT scans, etc., day in and day out, without valid justifications, produces nothing useful — unless one believes that feeding hypochondriasis and feeding poor medical judgment is useful.

The profession of medicine accomplished great things in the 21st century. These great things came through American exceptionalism. They came through valid biomedical science. These amazing accomplishments led many to believe that the profession of medicine has all the answers.

But it doesn’t. The COVID pandemic has shown us that. I’m sorry that we can’t save everyone. It is tragic. But it will be more tragic if we let our limitations along these lines lead us into a dark place of anger, lack of reason, lack of valid science, and then on to invalid conspiracy theories.

American exceptionalism does not need to die because of COVID. Instead, what needs to die is a type of insanity that makes us think we have all the answers. What needs to die is a type of insanity that makes us think that if we don’t have all the answers, we have to turn to useless testing, unproven therapies, and futile care.

What needs to die is the turning to false prophets and conspiracy theories. The profession of medicine has proven that it can do a very good job combating illness.

Good doctors are trying hard to deal with and solve this pandemic. When a type of insanity gets in the way, it is a problem.

W. Robert Graham, MD, completed medical school and residency at UTHSC-Dallas (Parkland Hospital) and served as chief resident. Graham received a National Institutes of Health fellowship at the Salk Institute for oncogene research in 1985. He was a professor of medicine at Baylor College of Medicine from 1998 through 2016. In retirement, he enjoys writing and ranching.

 

 

 

 

2005 chloroquine study had nothing to do with COVID-19 and the drug wasn’t given to humans

https://www.politifact.com/factchecks/2020/jul/29/facebook-posts/2005-chloroquine-study-had-nothing-do-covid-19-and/?fbclid=IwAR2e4j_lb10FWa5Cyuokzo3pbjlty_ffvwsEfVT_2iQ6ki8a9z-TpzDm9DQ

PolitiFact | 2005 chloroquine study had nothing to do with COVID ...

IF YOUR TIME IS SHORT

  • The 2005 study wasn’t published by the NIH and didn’t prove chloroquine was effective against “COVID-1” because that’s not a real disease.
  • The study found that chloroquine could inhibit the spread of Severe Acute Respiratory Syndrome in animal cell culture, and the authors said more research was needed.
  • There are currently no approved medications or treatments for COVID-19.

 

Chloroquine is back.

The anti-malarial drug first showed up as a possible COVID-19 treatment around May 2020, when President Donald Trump said he had been taking its chemical cousin, hydroxychloroquine, to prevent getting infected with the virus.

Since then, some studies have found that the drugs could help alleviate symptoms associated with COVID-19, but the research is not conclusive. There are currently no FDA-approved medicines specifically for COVID-19. (Chloroquine is chemically similar to hydroxychloroquine, but it is a different drug that’s primarily used to treat malaria. Both carry a particular risk for people with heart problems, plus other possible side effects.)

Now, hydroxychloroquine and chloroquine have been thrust back into the spotlight as misinformation about the drugs’ effectiveness and safety recently reappeared online.

One such post on Facebook falsely claims that Americans have been deceived because health officials at the National Institutes of Health have known all along that chloroquine is effective against “COVID.”

The post reads:

“N.I.H. 15 years ago published a study on chloroquine. It is effective against COVID-(1). We are being lied to America!”

The post was flagged as part of Facebook’s efforts to combat false news and misinformation on its News Feed. (Read more about our partnership with Facebook.) 

 

This is flawed. 

First, there’s no such thing as “COVID-1.” COVID-19 was named for the year it was discovered, not because it’s the 19th iteration. 

Second, the 2005 study found that chloroquine was effective on primate cells infected with severe acute respiratory syndrome, known as SARS, which is caused by a coronavirus. But while the two share similarities, SARS-CoV and COVID-19 are different diseases, and primate cells are far from human patients.

Third, the study was indexed by the NIH’s National Library of Medicine, but the NIH was not involved. It was published in the peer-reviewed Virology Journal and conducted by researchers from the Centers for Disease Control and Prevention and the Montreal Clinical Research Institute.

 

What the study says

The study was published in August 2005 and found that chloroquine has “strong antiviral effects on SARS-CoV infection of primate cells” and that it was effective on cells treated with the drug before and after exposure to the virus.

The drug was not administered to actual SARS patients, and the study’s authors wrote that more research was needed on how the drug interacts with SARS in animal test subjects.

“Cell culture testing of an antiviral drug against the virus is only the first step, of many steps, necessary to develop an antiviral drug,” Kate Fowlie, a spokesperson for the CDC previously told PolitiFact in an email. “It is important to realize that most antivirals that pass this cell culture test hurdle fail at later steps in the development process.”

Dr. Alex Greninger, assistant director of clinical virology at the University of Washington School of Medicine, told us that a problem in virology is trying to determine the difference of how drugs work in cell culture in comparison to humans.

“Data on chloroquine is largely taken from these cell culture studies, but we now have trials in people on hydroxychloroquine that show it’s not as effective,” Greninger said, “and there’s new data out in the last week that suggests that some of the reasons could be because of the cell types that SARS coronaviruses grow in, and this original experiment was done on African green monkey kidney cells, which is not the tissue we are really worried about.”

 

What officials say about the drugs now

The Food and Drug Administration granted emergency use authorizations for some medicines to be used for certain patients hospitalized with COVID-19, but it revoked the authorization for hydroxychloroquine and chloroquine in mid-June due to concerns over the drugs’ serious side effects. There are currently no FDA-approved medicines for COVID-19.

“It is no longer reasonable to believe that oral formulations of HCQ and CQ may be effective in treating COVID-19, nor is it reasonable to believe that the known and potential benefits of these products outweigh their known and potential risks,” FDA Chief Scientist Denise M. Hinton wrote.

The NIH’s COVID-19 treatment guidelines, which were developed to inform clinicians on how to care for patients with COVID-19, also currently recommend against the use of chloroquine or hydroxychloroquine for COVID-19 treatment, except in a clinical trial.

But even those trials have been halted. The World Health Organization and the NIH announced in mid-June that they would stop hydroxychloroquine patient trials, citing safety concerns that include serious heart rhythm problems, blood and lymph system disorders, kidney injuries, and liver problems and failure.

 

Our ruling

A Facebook post says that the NIH published a study 15 years ago that showed chloroquine was effective against “COVID-(1)” and that health officials have been lying to the American people.

This is wrong. There’s no such thing as “COVID-1” and the study cited was not published by the NIH and had to do with animal cells infected with SARS, not COVID-19. The drug was not given to human patients and the study’s authors said more research was needed.

Health officials caution against the use of chloroquine or hydroxychloroquine to treat COVID-19 patients, citing the possibility of serious side effects. There are currently no approved treatments for the virus.

We rate this False. 

 

 

 

 

Misinformation on coronavirus is proving highly contagious

https://apnews.com/86f61f3ffb6173c29bc7db201c10f141?utm_source=Sailthru&utm_medium=email&utm_campaign=Newsletter%20Weekly%20Roundup:%20Healthcare%20Dive:%20Daily%20Dive%2008-01-2020&utm_term=Healthcare%20Dive%20Weekender

Misinformation on the coronavirus is proving highly contagious ...

As the world races to find a vaccine and a treatment for COVID-19, there is seemingly no antidote in sight for the burgeoning outbreak of coronavirus conspiracy theories, hoaxes, anti-mask myths and sham cures.

The phenomenon, unfolding largely on social media, escalated this week when President Donald Trump retweeted a false video about an anti-malaria drug being a cure for the virus and it was revealed that Russian intelligence is spreading disinformation about the crisis through English-language websites.

Experts worry the torrent of bad information is dangerously undermining efforts to slow the virus, whose death toll in the U.S. hit 150,000 Wednesday, by far the highest in the world, according to the tally kept by Johns Hopkins University. Over a half-million people have died in the rest of the world.

For most people, the virus causes only mild or moderate symptoms, such as fever and cough. For some older adults and people with existing health problems, it can cause more severe illness, including pneumonia.

Hard-hit Florida reported 216 deaths, breaking the single-day record it set a day earlier. Texas confirmed 313 additional deaths, pushing its total to 6,190, while South Carolina’s death toll passed 1,500 this week, more than doubling over the past month. In Georgia, hospitalizations have more than doubled since July 1.

“It is a real challenge in terms of trying to get the message to the public about what they can really do to protect themselves and what the facts are behind the problem,” said Michael Osterholm, head of the University of Minnesota’s Center for Infectious Disease Research and Policy.

He said the fear is that “people are putting themselves in harm’s way because they don’t believe the virus is something they have to deal with.”

Rather than fade away in the face of new evidence, the claims have flourished, fed by mixed messages from officials, transmitted by social media, amplified by leaders like Trump and mutating when confronted with contradictory facts.

“You don’t need masks. There is a cure,” Dr. Stella Immanuel promised in a video that promoted hydroxychloroquine. “You don’t need people to be locked down.”

The truth: Federal regulators last month revoked their authorization of the drug as an emergency treatment amid growing evidence it doesn’t work and can have deadly side effects. Even if it were effective, it wouldn’t negate the need for masks and other measures to contain the outbreak.

None of that stopped Trump, who has repeatedly praised the drug, from retweeting the video. Twitter and Facebook began removing the video Monday for violating policies on COVID-19 misinformation, but it had already been seen more than 20 million times.

Many of the claims in Immanuel’s video are widely disputed by medical experts. She has made even more bizarre pronouncements in the past, saying that cysts, fibroids and some other conditions can be caused by having sex with demons, that McDonald’s and Pokemon promote witchcraft, that alien DNA is used in medical treatments, and that half-human “reptilians” work in the government.

Other baseless theories and hoaxes have alleged that the virus isn’t real or that it’s a bioweapon created by the U.S. or its adversaries. One hoax from the outbreak’s early months claimed new 5G towers were spreading the virus through microwaves. Another popular story held that Microsoft founder Bill Gates plans to use COVID-19 vaccines to implant microchips in all 7 billion people on the planet.

Then there are the political theories — that doctors, journalists and federal officials are conspiring to lie about the threat of the virus to hurt Trump politically.

Social media has amplified the claims and helped believers find each other. The flood of misinformation has posed a challenge for Facebook, Twitter and other platforms, which have found themselves accused of censorship for taking down virus misinformation.

Facebook CEO Mark Zuckerberg was questioned about Immanuel’s video during an often-contentious congressional hearing Wednesday.

“We did take it down because it violates our policies,” Zuckerberg said.

U.S. Rep. David Cicilline, a Rhode Island Democrat leading the hearing, responded by noting that 20 million people saw the video before Facebook acted.

“Doesn’t that suggest that your platform is so big, that even with the right policies in place, you can’t contain deadly content?” Cicilline asked Zuckerberg.

It wasn’t the first video containing misinformation about the virus, and experts say it’s not likely to be the last.

A professionally made 26-minute video that alleges the government’s top infectious-disease expert, Dr. Anthony Fauci, manufactured the virus and shipped it to China was watched more than 8 million times before the platforms took action. The video, titled “Plandemic,” also warned that masks could make you sick — the false claim Facebook cited when it removed the video down from its site.

Judy Mikovits, the discredited doctor behind “Plandemic,” had been set to appear on the show “America This Week” on the Sinclair Broadcast Group. But the company, which operates TV stations in 81 U.S. markets, canned the segment, saying it was “not appropriate” to air.

This week, U.S. government officials speaking on condition of anonymity cited what they said was a clear link between Russian intelligence and websites with stories designed to spread disinformation on the coronavirus in the West. Russian officials rejected the accusations.

Of all the bizarre and myriad claims about the virus, those regarding masks are proving to be among the most stubborn.

New York City resident Carlos Lopez said he wears a mask when required to do so but doesn’t believe it is necessary.

“They’re politicizing it as a tool,” he said. “I think it’s more to try to get Trump to lose. It’s more a scare tactic.”

He is in the minority. A recent AP/NORC poll said 3 in 4 Americans — Democrats and Republicans alike — support a national mask mandate.

Still, mask skeptics are a vocal minority and have come together to create social media pages where many false claims about mask safety are shared. Facebook has removed some of the pages — such as the group Unmasking America!, which had nearly 10,000 members — but others remain.

Early in the pandemic, medical authorities themselves were the source of much confusion regarding masks. In February, officials like the U.S. surgeon general urged Americans not to stockpile masks because they were needed by medical personnel and might not be effective in everyday situations.

Public health officials changed their tune when it became apparent that the virus could spread among people showing no symptoms.

Yet Trump remained reluctant to use a mask, mocked his rival Joe Biden for wearing one and suggested people might be covering their faces just to hurt him politically. He did an abrupt about-face this month, claiming that he had always supported masks — then later retweeted Immanuel’s video against masks.

The mixed signals hurt, Fauci acknowledged in an interview with NPR this month.

“The message early on became confusing,” he said.

Many of the claims around masks allege harmful effects, such as blocked oxygen flow or even a greater chance of infection. The claims have been widely debunked by doctors.

Dr. Maitiu O Tuathail of Ireland grew so concerned about mask misinformation he posted an online video of himself comfortably wearing a mask while measuring his oxygen levels. The video has been viewed more than 20 million times.

“While face masks don’t lower your oxygen levels. COVID definitely does,” he warned.

Yet trusted medical authorities are often being dismissed by those who say requiring people to wear masks is a step toward authoritarianism.

“Unless you make a stand, you will be wearing a mask for the rest of your life,” tweeted Simon Dolan, a British businessman who has sued the government over its COVID-19 restrictions.

Trump’s reluctant, ambivalent and late embrace of masks hasn’t convinced some of his strongest supporters, who have concocted ever more elaborate theories to explain his change of heart. Some say he was actually speaking in code and doesn’t really support masks.

O Tuathail witnessed just how unshakable COVID-19 misinformation can be when, after broadcasting his video, he received emails from people who said he cheated or didn’t wear the mask long enough to feel the negative effects.

That’s not surprising, according to University of Central Florida psychology professor Chrysalis Wright, who studies misinformation. She said conspiracy theory believers often engage in mental gymnastics to make their beliefs conform with reality.

“People only want to hear what they already think they know,” she said. 

 

 

 

COVID-19 More Deadly Than Cancer Itself?

https://www.medpagetoday.com/hematologyoncology/othercancers/87750?xid=nl_mpt_DHE_2020-07-25&eun=g885344d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Daily%20Headlines%20Top%20Cat%20HeC%20%202020-07-25&utm_term=NL_Daily_DHE_dual-gmail-definition

During the recent months of the pandemic, cancer patients undergoing active treatment saw their risk for death increase 15-fold with a COVID-19 diagnosis, real-world data from two large healthcare systems in the Midwest found.

Among nearly 40,000 patients who had undergone treatment for their cancer at some point over the past year, 15% of those diagnosed with COVID-19 died from February to May 2020, as compared to 1% of those not diagnosed with COVID-19 during this same timeframe, reported Shirish Gadgeel, MD, of the Henry Ford Cancer Institute in Detroit.

And in more than 100,000 cancer survivors, 11% of those diagnosed with COVID-19 died compared to 1% of those not diagnosed with COVID-19, according to the findings presented at the American Association for Cancer Research (AACR) COVID-19 and Cancer meeting.

“Certain comorbidities were more commonly seen in patients with COVID-19,” said Gadgeel. “This included cardiac arrhythmias, renal failure, congestive heart failure, and pulmonary circulation disorders.”

For their study, Gadgeel and colleagues examined data on 154,585 malignant cancer patients from 2015 to the present day with active cancer or a history of cancer treated at two major Midwestern health systems. Among the 39,790 patients with active disease, 388 were diagnosed with COVID-19 from February 15 through May 13, 2020. For the 114,795 patients with a history of cancer, 412 were diagnosed with COVID-19.

After adjusting for multiple variables, older age (70-99 years) and several comorbid conditions were significantly associated with increased mortality among COVID-19 patients with active cancer:

  • Older age: OR 3.4 (95% CI 1.3-9.3)
  • Diabetes: OR 3.0 (95% CI 1.5-6.0)
  • Renal failure: OR 2.3 (95% CI 1.1-4.9)
  • Pulmonary circulation disorders: OR 3.9 (95% CI 1.4-10.5)

In COVID-19 patients with a history of cancer, an increased risk for death was seen for those ages 60 to 69 years (OR 6.3, 95% CI 1.1-35.3), 70 to 99 years (OR 18.2, 95% CI 3.9-84.3), and those with a history of coagulopathy (OR 3.0, 95% CI 1.2-7.6).

Despite Black patients consisting of less than 10% of the total study population, Gadgeel noted that 39.4% of COVID-19 diagnoses in the active cancer group were among Black patients, as were a third of diagnoses in the cancer survivor group.

And the proportion of COVID-19 patients with a median household income below $30,000 was also higher in COVID-19 patients in both groups, he added.

COVID-19 carried a far greater chance for hospitalization, both for patients with active cancer (81% vs 15% for those without COVID-19) as well as those with a history of cancer (68% vs 6%), with higher hospitalization rates among Black individuals and those with a median income below $30,000. Even younger COVID-19 patients (<50 years) saw high rates of hospitalization, at 79% for those with active cancer and 49% for those with a history of the disease.

While few cancer patients without COVID-19 required mechanical ventilation (≤1%) during the study period, 21% of patients with active disease and COVID-19 needed ventilation, as did 14% of those with a history of cancer, with higher rates among those with a history of coagulopathy (36% and 23%, respectively).

CCC-19 Data Triples in Size

Another study presented during the meeting again showed higher mortality rates for cancer patients with COVID-19, with lung cancer patients appearing to be especially vulnerable.

Among 2,749 cancer patients diagnosed with COVID-19, 60% required hospitalization, 45% needed supplemental oxygen, 16% were admitted to the intensive care unit, and 12% needed mechanical ventilation, and 16% died within 30 days, reported Brian Rini, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tennessee.

“When COVID first started there was a hypothesis that cancer patients could be at adverse outcome risk due to many factors,” said Rini, noting their typically “advanced age, presence of comorbidities, increased contact with the healthcare system, perhaps immune alterations due to their cancer and/or therapy, and decreased performance status.”

Rini was presenting an updated analysis of the COVID-19 and Cancer Consortium (CCC-19), which now includes 114 sites (includes comprehensive cancer centers and community sites) collecting data on cancer patients and their outcomes with COVID-19.

Initial data from the consortium, of about 1,000 patients, were presented earlier this year at the American Society of Clinical Oncology (ASCO) annual meeting and published in The Lancet. The early analysis showed that use of hydroxychloroquine and azithromycin to treat COVID-19 in cancer patients was associated with a nearly threefold greater risk of dying within 30 days.

Notably, in the new analysis, decreased all-cause mortality at 30 days was observed among the 57 patients treated with remdesivir alone, when compared to patients that received other investigational therapies for COVID-19, including hydroxychloroquine (adjusted odds ratio [aOR] 0.41, 95% CI 0.17-0.99) and a trend toward lower mortality when compared to patients that received no other investigational therapies (aOR 0.76, 95% CI 0.31-1.85).

Cancer status was associated with a greater mortality risk. Compared to patients in remission, those with stable (aOR 1.47, 95% CI 1.07-2.02) or progressive disease (aOR 2.96, 95% CI 2.05-4.28) were both at increased risk of death at 30 days.

Mortality at 30 days reached 35% for patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher, as compared to 4% (aOR 4.22, 95% CI 2.92-6.10).

“As you start to combine these adverse risk factors you get into really high mortality rates,” said Rini, with highest risk seen among intubated patients who were either 75 and older (64%) or had poor performance status (75%).

“There are several factors that are starting to emerge as relating to COVID-19 mortality in cancer patients,” said Rini during his presentation at the AACR COVID-19 and Cancer meeting. “Some are cancer-related, such as the status of their cancer and perhaps performance status, and others are perhaps unrelated, such as age or gender.”

Other factors that were significantly associated with higher mortality included older age, male sex, Black race, and being a current or former smoker, and having a hematologic malignancy.

Findings from the study were simultaneously published in Cancer Discovery.

“Importantly, there were some factors that did not reach statistical significance,” said Rini, including obesity.

“Patients who received recent cytotoxic chemotherapy or other types of anti-cancer therapy, or who had recent surgery were not in the present analysis of almost 3,000 patients at increased risk,” he continued. “I think this provides some reassurance that cancer care can and should continue for these patients.”

For specific cancer types, mortality was highest in lung cancer patients (26%), followed by those with lymphoma (22%), colorectal cancer (19%), plasma cell dyscrasias (19%), prostate cancer (18%), breast cancer (8%), and thyroid cancer (3%).

“The COVID mortality rate in cancer patients appears to be higher than the general population,” said Rini. “Lung cancer patients appear especially vulnerable by our data, as well as TERAVOLT‘s.”

 

 

 

Coronavirus drugmakers’ latest tactics: Science by press release

https://www.politico.com/news/2020/06/05/drugmakers-media-coronavirus-303895

Coronavirus drugmakers' latest tactics: Science by press release ...

Pharmaceutical companies are using the media to tout treatments that are still under review.

Vaccine maker Moderna attracted glowing headlines and bullish investors when it revealed that eight participants in a preliminary clinical trial of its coronavirus vaccine had developed antibodies to the virus. The company’s share price jumped nearly 20 percent that day as it released a massive stock offering.

But the full results of the 45-person safety study haven’t been published, even though Moderna began a second, larger trial in late May aimed at determining whether the vaccine works. Several vaccine researchers say the scant public information on the earlier safety study is hard to evaluate because it addresses less than 20 percent of participants.

Call it science by press release — a tactic that pharmaceutical companies are increasingly relying upon to set their experimental coronavirus drugs and vaccines apart in a crowded field, shape public opinion and court regulators. Public health experts say the approach could increase political pressure on federal health officials to green-light drugs and vaccines before it is clear they are safe or effective, with potentially dangerous consequences.

“There’s a long history of pharmaceutical manufacturers putting out self-serving press releases related to clinical trial data that they’re developing that present an overly rosy picture of the data, usually with a boilerplate disclaimer at the end, which is fairly useless,” said Aaron Kesselheim, a professor of medicine at Harvard Medical School who studies drug regulation and pricing.

There are already signs of hype and political pressure influencing the U.S.’ coronavirus response. The Food and Drug Administration authorized emergency use of the malaria drug hydroxychloroquine in March without any proof that it was safe or effective for coronavirus patients — but with the backing of President Donald Trump, who had begun touting the treatment during daily White House briefings.

Subsequent studies have found that hydroxychloroquine doesn’t help those with Covid-19 and can cause potentially fatal side effects. And a top government scientist, Rick Bright, filed a whistleblower complaint in May alleging that he was ousted from his job leading the Biomedical Advanced Research Authority after he resisted political pressure to greenlight widespread use of the drug.

“The FDA has remained an unwavering, science-based voice helping to guide the all-of-government response,” agency Commissioner Stephen Hahn said in a statement. “I have never felt any pressure to make decisions, other than the urgency of the situation around COVID-19.”

But observers aren’t so sure. “From the outside looking in, there seems to be more political pressure than ever,” said Marc Scheineson, a former associate commissioner at the FDA and head of the FDA group at Alston & Bird. “The example in the White House is trickling down and there is a lot of pressure on the FDA … to color information on the optimistic side for political purposes and that is a hugely disturbing trend.”

A spokesperson for Moderna, which has received nearly a half billion dollars from the U.S. government and praise from Trump, said the company previewed its vaccine trial results by press release because it was concerned that the data might leak. The National Institutes of Health’s top infectious disease expert, Anthony Fauci, had hinted at the results in an interview with National Geographic, and data from a trial of the experimental drug remdesivir had leaked in April.

“You had this data moving widely around NIH and the remdesivir leak was also in our minds,” the Moderna spokesperson said.

But Peter Bach, director of Memorial Sloan-Kettering’s Center for Health Policy and Outcomes, said Moderna’s effort to preview its findings in the press “could be construed as an effort to make sure they are part of the conversation — and it worked on that front.”

Other groups have also previewed their hotly anticipated vaccine studies in the press. In late April, The New York Times revealed that six monkeys given a vaccine developed by researchers at the U.K.’s University of Oxford had stayed healthy for 28 days despite sustained exposure to the coronavirus. The article quoted Vincent Munster, a researcher at the NIH’s Rocky Mountain Laboratory, which conducted the monkey study at the British scientists’ behest.

The Oxford researchers, who signed a deal with AstraZeneca two days later to develop the experimental vaccine, did not publish a formal scientific analysis of the monkey data until mid-May. The study revealed that the noses of vaccinated monkeys and unvaccinated monkeys contained similar levels of coronavirus particles, suggesting that the vaccinated animals could still spread the disease — and the vaccine might not be as effective as the earlier data had hinted.

AstraZeneca has since inked a $1.2 billion deal with the U.S. government to provide 300 million vaccine doses, and a £65.5 million ($80 million) agreement with the U.K. government to supply 30 million doses.

Liz Derow, a spokesperson for Oxford’s Jenner Institute, where the vaccine researchers are based, said they did not give the monkey data to The New York Times. The NIH’s National Institute of Allergy and Infectious Disease, which operates the Rocky Mountain Laboratory, said it did not provide the data to the newspaper — but one of its researchers, Vincent Munster, spoke to a Times reporter about the monkey findings at the request of the Jenner Institute.

“I was really disturbed by not just Moderna, but the Oxford group as well, presenting a press release without data, without a scientific review, without knowing what the press release was based on,” said Barry Bloom, an immunologist at the Harvard School of Public Health. “And very positively enough to raise the stock price so two days later officials within the company sold their stock and made a whole lot of money, whether or not the vaccine works.”

Four of the pharmaceutical firm’s top executives together saw gains of $29 million from prescheduled sales of shares in the company in the two days following the vaccine announcement. The company has not yet responded to a request for comment on the stock sales.

Neither the Oxford nor Moderna vaccines are available to the public. But some drugs whose safety and efficacy are now being studied have already been repurposed or authorized for emergency use during the pandemic. The rush to release snippets of information on drug trials to the press ahead of full results has left some doctors wondering how to best treat their patients.

After leaked data from a trial of Gilead’s experimental antiviral remdesivir suggested the drug might be the first shown to help coronavirus patients, the company put out a press release in late April teasing results from a larger, government-run study. Hours later, Fauci revealed some findings of the study during an Oval Office press spray.

But the full analysis of the NIAID trial results was not published until three weeks later. Until that point, frontline physicians had no way to know that patients on ventilators did not benefit from remdesivir treatment — meaning that doctors may have inadvertently wasted some of the United States’ limited stock of the drug.

This lack of understanding on how to use remdesivir was evident in a recent survey more than 250 hospitals by the American Society of Health-System Pharmacists, which found that just 15 percent planned to use their remdesivir doses as described in the FDA’s emergency authorization for the drug.

Andre Kalil, an infectious disease doctor at the University of Nebraska Medical Center who led the NIAID trial, told POLITICO that physicians could have patterned their use of remdesivir on the dosages given during the trial.

Others say doctors using experimental treatments should have as much information as possible.

“If we want doctors to make rational medical decisions based on data, then before an authorized product reaches patients, the data should be available to review in some way, not just a press release,” said Walid Gellad, director of the University of Pittsburgh’s Center for Pharmaceutical Policy and Prescribing.

Kesselheim, too, said that clinical trial data should be made public alongside any emergency authorizations to give physicians “the maximum amount of help they need in figuring out how to prescribe the drug.”

Gilead did not respond to a request for comment. But NIAID said that the urgency of the coronavirus prompted Fauci to share initial results before a full analysis was ready for publication.

Ivan Oransky, a professor of medical journalism at New York University and co-founder of the blog Retraction Watch, which monitors errors and misconduct in scientific research, told POLITICO he fears that the temptation to conduct science by press release will get “worse before it gets better.”

The world is growing more desperate for drugs and vaccines that could bring the coronavirus to heel. And many members of the public and politicians are treating every scrap of scientific information about the pandemic equally, he said — whether data comes from a peer-reviewed study or a company press release.

“There have been mechanisms to review science critically that, given the speed of Covid, have gone out the window,” said Bloom.

And interpreting results of clinical trial data can be difficult under the best of circumstances — especially when that data concerns a virus that was unknown to science until December of last year. When to end a trial and which conclusions to highlight are in many cases a matter of discretion, said Scheineson.

“It’s an art, not a science, in that respect,” he said. “I, for one, will not be the first in line to the new Moderna vaccine.”

 

 

 

 

Major study finds common steroid reduces deaths among patients with severe Covid-19

Major study finds common steroid reduces deaths among patients with severe Covid-19

What is Dexamethasone? | What Is News,The Indian Express

A cheap, readily available steroid drug reduced deaths by a third in patients hospitalized with Covid-19 in a large study, the first time a therapy has been shown to possibly improve the odds of survival with the condition in the sickest patients.

Full data from the study have not been published or subjected to scientific scrutiny. But outside experts on Tuesday immediately embraced the top-line results. The drug, dexamethasone, is widely available and is used to treat conditions including rheumatoid arthritis, asthma, and some cancers.

In a statement, Patrick Vallance, the U.K. government’s chief scientific adviser, called the result “tremendous news” and “a ground-breaking development in our fight against the disease.” Scott Gottlieb, a former commissioner of the U.S. Food and Drug Administration, called it “a very positive finding” in an interview on CNBC. “I think it needs to be validated, but it certainly suggests that this could be beneficial in this setting.”

Atul Gawande, the surgeon, writer and public health researcher, urged caution, tweeting, “after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper.”

The study randomly assigned 2,104 patients to receive six milligrams of dexamethasone once a day, by mouth or intravenous injection. These were compared to 4,321 patients assigned to receive usual care alone.

In patients who needed to be on a ventilator, dexamethasone reduced the death rate by 35%, meaning that doctors would prevent one death by treating eight ventilated patients. In those who needed oxygen but were not ventilated, the death rate was reduced 20%, meaning doctors would need to treat 25 patients to save one life. Both results were statistically significant.

There was no benefit in patients who didn’t require any oxygen. The researchers running the study, called RECOVERY, decided to stop enrolling patients on dexamethasone on June 8 because they believed they had enough data to get a clear result.

“Dexamethasone is the first drug to be shown to improve survival in COVID-19,” Peter Horby, one of the lead investigators of the study and a professor in the Nuffield Department of Medicine at the University of Oxford, said in a statement. He added that the drug should now become the standard treatment for patients with Covid-19 who need oxygen. “Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide.’”

A different arm of the same study showed on June 5 that hydroxychloroquine, widely touted as a potential Covid treatment, had no benefit in hospitalized patients. Yesterday, based in part on those results, the Food and Drug Administration revoked an Emergency Use Authorization for using hydroxychloroquine in those patients.

From the start of the pandemic in March, researchers have focused on two different stages of Covid-19, which will likely require very different interventions. Some drugs are designed to directly combat the novel coronavirus, SARS-CoV-2, that causes the disease. The first medicine shown to have a benefit, remdesivir from the biotech firm Gilead Sciences, falls into this category, even though, because it must be given intravenously, it has been tested in hospitalized patients. Remdesivir shortens the course of infection, but has not been shown to save lives.

After patients have become profoundly sick, the problem starts to become not only the virus but their own immune system, which attacks the lungs, a condition called acute respiratory distress syndrome, or ARDS. For these patients, doctors have believed, they would need to dampen patients’ immune response even as they fought the virus.

Initially, excitement in this area fell on new and expensive drugs, such as Actemra, a rheumatoid arthritis drug from Roche that is used to treat a similar condition caused by some cancer immunotherapies. But a study in patients who needed oxygen showed no benefit from a similar drug, although another arm in sicker patients is continuing. The National Institutes of Health is conducting a study of an Eli Lilly pill targeting rheumatoid arthritis, an extension of the study that showed remdesivir has a benefit.

Dexamethasone, which reached the market 59 years ago, seemed an unlikely candidate to help these patients; it was seen as too crude a way of tamping down the immune system. In guidelines for physicians treating the disease, the NIH doesn’t even mention the therapy.

Studies that are testing other medicines may now need to incorporate the use of the drug, which could complicate analyzing the results. A spokesperson for Regeneron, which is testing Covid-19 drugs focused on both attacking the virus and dampening the immune system, said the company’s studies are written so that when a new medicine becomes the standard of care, it becomes available to patients in the trial.

Some studies have shown a benefit for using dexamethasone in acute respiratory distress syndrome not related to Covid-19, although the benefit was smaller than in RECOVERY. 

The result, should it hold up to further scrutiny, shows the benefit of the strategy of Horby and Martin Landray, the Oxford researchers who designed the study, leveraging the U.K. health system to start a study of multiple inexpensive potential Covid-19 therapies — including hydroxychloroquine, dexamethasone, and also some older HIV medicines. Several months into the Covid-19 pandemic, two of the most important results come from this single study.

Neither of those results, however, have been scrutinized or published.

 

 

 

FDA ends emergency use authorization for hydroxychloroquine

https://www.axios.com/hydroxychloroquine-fda-ends-emergency-use-authorization-f5353a2c-115a-4a57-b8e2-360b735b4937.html?stream=health-care&utm_source=alert&utm_medium=email&utm_campaign=alerts_healthcare

FDA withdraws emergency use authorization for hydroxychloroquine ...

The FDA ended Monday its emergency use authorizations for two controversial drugs, hydroxychloroquine and chloroquine, as a potential coronavirus treatment.

Why it matters: Despite gaining President Trump’s adamant support and use, the drugs have failed in several clinical trials and have been found to possibly cause serious heart problems.

What they’re saying: The FDA said it believes the drugs “are unlikely to be effective in treating COVID-19” under the emergency use authorization.

  • It also said that “in light of ongoing serious cardiac adverse events and other serious side effects, the known and potential benefits of [the drugs] no longer outweigh the known and potential risks for the authorized use.”

Read the letter and memo regarding the revocation:

 

 

 

Public Health Officials Face Wave Of Threats, Pressure Amid Coronavirus Response

Public Health Officials Face Wave Of Threats, Pressure Amid Coronavirus Response

Public health officials face wave of threats, pressure amid ...

Emily Brown was director of the Rio Grande County Public Health Department in Colorado until May 22, when the county commissioners fired her after battling with her over coronavirus restrictions. “They finally were tired of me not going along the line they wanted me to go along,” she says.

Emily Brown was stretched thin.

As the director of the Rio Grande County Public Health Department in rural Colorado, she was working 12- and 14-hour days, struggling to respond to the pandemic with only five full-time employees for more than 11,000 residents. Case counts were rising.

She was already at odds with county commissioners, who were pushing to loosen public health restrictions in late May, against her advice. She had previously clashed with them over data releases and had haggled over a variance regarding reopening businesses.

But she reasoned that standing up for public health principles was worth it, even if she risked losing the job that allowed her to live close to her hometown and help her parents with their farm.

Then came the Facebook post: a photo of her and other health officials with comments about their weight and references to “armed citizens” and “bodies swinging from trees.”

The commissioners had asked her to meet with them the next day. She intended to ask them for more support. Instead, she was fired.

“They finally were tired of me not going along the line they wanted me to go along,” she said.

In the battle against COVID-19, public health workers spread across states, cities and small towns make up an invisible army on the front lines. But that army, which has suffered neglect for decades, is under assault when it’s needed most.

Officials who usually work behind the scenes managing everything from immunizations to water quality inspections have found themselves center stage. Elected officials and members of the public who are frustrated with the lockdowns and safety restrictions have at times turned public health workers into politicized punching bags, battering them with countless angry calls and even physical threats.

On Thursday, Ohio’s state health director, who had armed protesters come to her house, resigned. The health officer for Orange County, California, quit Monday after weeks of criticism and personal threats from residents and other public officials over an order requiring face coverings in public.

As the pressure and scrutiny rise, many more health officials have chosen to leave or been pushed out of their jobs. A review by KHN and The Associated Press finds at least 27 state and local health leaders have resigned, retired or been fired since April across 13 states.

In California, senior health officials from seven counties, including the Orange County officer, have resigned or retired since March 15. Dr. Charity Dean, the second in command at the state Department of Public Health, submitted her resignation June 4.

These officials have left their posts due to a mix of backlash and stressful, nonstop working conditions, all while dealing with chronic staffing and funding shortages.

Some health officials have not been up to the job during the biggest health crisis in a century. Others previously had plans to leave or cited their own health issues.

But Lori Tremmel Freeman, CEO of the National Association of County and City Health Officials, said the majority of what she calls an “alarming” exodus resulted from increasing pressure as states reopen. Three of those 27 were members of her board and well known in the public health community — Rio Grande County’s Brown; Detroit’s senior public health adviser, Dr. Kanzoni Asabigi; and the head of North Carolina’s Gaston County Department of Health and Human Services, Chris Dobbins.

Asabigi’s sudden retirement, considering his stature in the public health community, shocked Freeman. She also was upset to hear about the departure of Dobbins, who was chosen as health director of the year for North Carolina in 2017. Asabigi and Dobbins did not reply to requests for comment.

“They just don’t leave like that,” Freeman said.

Public health officials are “really getting tired of the ongoing pressures and the blame game,” Freeman said. She warned that more departures could be expected in the coming days and weeks as political pressure trickles down from the federal to the state to the local level.

From the beginning of the coronavirus pandemic, federal public health officials have complained of being sidelined or politicized. The Centers for Disease Control and Prevention has been marginalized; a government whistleblower said he faced retaliation because he opposed a White House directive to allow widespread access to the malaria drug hydroxychloroquine as a COVID-19 treatment.

In Hawaii, U.S. Rep. Tulsi Gabbard called on the governor to fire his top public health officials, saying she believed they were too slow on testing, contact tracing and travel restrictions. In Wisconsin, several Republican lawmakers have repeatedly demanded that the state’s health services secretary resign, and the state’s conservative Supreme Court ruled 4-3 that she had exceeded her authority by extending a stay-at-home order.

With the increased public scrutiny, security details — like those seen on a federal level for Dr. Anthony Fauci, the top infectious disease expert — have been assigned to state health leaders, including Georgia’s Dr. Kathleen Toomey after she was threatened. Ohio’s Dr. Amy Acton, who also had a security detail assigned after armed protesters showed up at her home, resigned Thursday.

In Orange County, in late May, nearly a hundred people attended a county supervisors meeting, waiting hours to speak against an order requiring face coverings. One person suggested that the order might make it necessary to invoke Second Amendment rights to bear arms, while another read aloud the home address of the order’s author — the county’s chief health officer, Dr. Nichole Quick — as well as the name of her boyfriend.

Quick, attending by phone, left the meeting. In a statement, the sheriff’s office later said Quick had expressed concern for her safety following “several threatening statements both in public comment and online.” She was given personal protection by the sheriff.

But Monday, after yet another public meeting that included criticism from members of the board of supervisors, Quick resigned. She could not be reached for comment. Earlier, the county’s deputy director of public health services, David Souleles, retired abruptly.

An official in another California county also has been given a security detail, said Kat DeBurgh, the executive director of the Health Officers Association of California, declining to name the county or official because the threats have not been made public.

DeBurgh is worried about the impact these events will have on recruiting people into public health leadership.

“It’s disheartening to see people who disagree with the order go from attacking the order to attacking the officer to questioning their motivation, expertise and patriotism,” said DeBurgh. “That’s not something that should ever happen.”

Many local health leaders, accustomed to relative anonymity as they work to protect the public’s health, have been shocked by the growing threats, said Theresa Anselmo, the executive director of the Colorado Association of Local Public Health Officials.

After polling local health directors across the state at a meeting last month, Anselmo found about 80% said they or their personal property had been threatened since the pandemic began. About 80% also said they’d encountered threats to pull funding from their department or other forms of political pressure.

To Anselmo, the ugly politics and threats are a result of the politicization of the pandemic from the start. So far in Colorado, six top local health officials have retired, resigned or been fired. A handful of state and local health department staff members have left as well, she said.

“It’s just appalling that in this country that spends as much as we do on health care that we’re facing these really difficult ethical dilemmas: Do I stay in my job and risk threats, or do I leave because it’s not worth it?” Anselmo asked.

Some of the online abuse has been going on for years, said Bill Snook, a spokesperson for the health department in Kansas City, Missouri. He has seen instances in which people took a health inspector’s name and made a meme out of it, or said a health worker should be strung up or killed. He said opponents of vaccinations, known as anti-vaxxers, have called staffers “baby killers.”

The pandemic, though, has brought such behavior to another level.

In Ohio, the Delaware General Health District has had two lockdowns since the pandemic began — one after an angry individual came to the health department. Fortunately, the doors were locked, said Dustin Kent, program manager for the department’s residential services unit.

Angry calls over contact tracing continue to pour in, Kent said.

In Colorado, the Tri-County Health Department, which serves Adams, Arapahoe and Douglas counties near Denver, has also been getting hundreds of calls and emails from frustrated citizens, deputy director Jennifer Ludwig said.

Some have been angry their businesses could not open and blamed the health department for depriving them of their livelihood. Others were furious with neighbors who were not wearing masks outside. It’s a constant wave of “confusion and angst and anxiety and anger,” she said.

Then in April and May, rocks were thrown at one of their office’s windows — three separate times. The office was tagged with obscene graffiti. The department also received an email calling members of the department “tyrants,” adding “you’re about to start a hot-shooting … civil war.”  Health department workers decamped to another office.

Although the police determined there was no imminent threat, Ludwig stressed how proud she was of her staff, who weathered the pressure while working round-the-clock.

“It does wear on you, but at the same time we know what we need to do to keep moving to keep our community safe,” she said. “Despite the complaints, the grievances, the threats, the vandalism — the staff have really excelled and stood up.”

The threats didn’t end there, however: Someone asked on the health department’s Facebook page how many people would like to know the home addresses of the Tri-County Health Department leadership. “You want to make this a war??? No problem,” the poster wrote.

Back in Colorado’s Rio Grande County, some members of the community have rallied in support of Brown with public comments and a letter to the editor of a local paper. Meanwhile, COVID-19 case counts have jumped from 14 to 49 as of Wednesday.

Brown is grappling with what she should do next: dive back into another strenuous public health job in a pandemic, or take a moment to recoup?

When she told her 6-year-old son she no longer had a job, he responded: “Good — now you can spend more time with us.”