Heading into a “third wave” of the pandemic

https://mailchi.mp/f2794551febb/the-weekly-gist-october-23-2020?e=d1e747d2d8

The US broke its record for the highest number of new coronavirus cases in  a day - Vox

In Thursday’s second and final Presidential debate, former Vice President Joe Biden warned that a “dark winter” lies ahead in the coronavirus pandemic, and with cases, hospitalizations, and deaths on the rise across the country, it now appears that we are headed into a “third wave” of infections that may prove worse than both the initial onset of COVID on the coasts and the summertime spike in the Sun Belt.

Yesterday more than 71,600 new cases were reported nationwide, nearing a late-July record. Thirteen states hit record-high hospitalizations this week, measured by weekly averages, most in the Midwest and Mountain West. Several Northeastern states, which had previously brought the spread of the virus under control, also experienced substantial increases in infections, leading schools in Boston to suspend all in-person instruction. Of particular concern is hospital capacity, which is already being strained in the more rural areas now being hit by COVID cases. With infection spikes more geographically widespread than in earlier waves, fewer medical workers are available to lend support to hospitals in other states, leading to concerns about hospital staffing as admissions rise.
 
As hospitalizations increase, so too will demand for therapeutics to help shorten the course and moderate the impact of COVID. This week, Gilead Sciences’ antiviral drug remdesivir, previously available under an Emergency Use Authorization (EUA) from the federal government, became the first drug to win full approval from the Food and Drug Administration (FDA) to treat patients hospitalized with COVID-19. The approval was based on clinical studies that showed that remdesivir can reduce recovery time, and also includes use for pediatric COVID patients under the age of 11.

Meanwhile, the FDA cleared AstraZeneca to resume US clinical trials of its coronavirus vaccine, which had been suspended for a month following an adverse patient event. It’s widely expected that one or more drug companies will submit their vaccine candidates for EUA sometime next month, although new polling data released this week indicates that the American public is growing more skeptical in their willingness to take an early vaccine against the virus, with only 58 percent of respondents saying they would get the shot when it first becomes available, down from 69 percent in August. (Only 43 percent of Black respondents say they would get the vaccine, compared to 59 percent of Whites—a racial divide that reveals deep distrust based on the history of inequities in the US healthcare system.) 

A long, dark winter': Experts worry about mental health in first full COVID  winter - NEWS 1130

In many respects, the coming month will surely prove to be a pandemic turning point, revealing the magnitude of the next wave of COVID, the direction of US public health policy, the prospects for reliable therapeutics, and the timing of a safe and effective vaccine. We’ll soon know whether we are, indeed, headed for a winter of darkness.

Where Europe’s Second Wave Is Filling Up Hospitals

Poland has turned its largest stadium into an emergency field hospital. The numbers of Covid-19 patients in Belgium and Britain have doubled in two weeks. And doctors and nurses in the Czech Republic are falling ill at an alarming rate.

As new cases of the virus began to increase again across Europe last month, hospitals were initially spared the mass influx of patients they weathered earlier this spring. Some suggested that the virus had become less deadly, or that older, more vulnerable people would be shielded.

But a second wave of serious illness is here, new data released on Thursday shows, making it clear that the pandemic is still dangerous and that adherence to control measures over the next few weeks will be crucial in preventing hospitals from becoming overrun for a second time this year.

The number of Covid-19 patients in hospitals across the continent is still less than half of the peak in March and April, but it is rising steadily each week, according to data from the European Centre for Disease Prevention and Control. People across much of Europe — including larger countries like France, Italy, Poland and Spain — are now more likely to be hospitalized with Covid-19 than those in the United States.

Bruno Ciancio, the head of disease surveillance at the center, said he was concerned that some of the worst-hit countries now — including the Czech Republic, Poland and Bulgaria — were not as affected this spring, and may not have expanded their hospital capacity or intensive care units.

“The signals were all there in September,” said Mr. Ciancio. “At this point it’s very important that all member states prepare their hospitals to deal with the increase in demand that is coming.”

Hospitalization rates are a key measure of the pandemic’s severity. The rates rise and fall days or weeks behind the tallies of new infections. But infection figures depend heavily on each country’s testing capacity, while seriously ill people tend to enter hospitals whether they have been tested for the virus or not.

Europe’s current wave of infection is due in part to the relative normalcy it experienced this summer. Unlike the United States, where the epidemic rose to a second peak in July and a third peak this month, travelers moved around Europe, college students returned to campus and many large gatherings resumed, all while the virus kept spreading.

Now hospitals are scrambling to prepare for an onrush of Covid-19 patients, at a time when bed and intensive care capacity will already be under strain during the winter flu season.

In Poland, the government converted the country’s largest stadium into a temporary field hospital with room for 500 patients. Hospitals in France, especially in the Paris area, have started to postpone non-emergency surgeries, while others have called back staff on leave. More than one-fifth of Spain’s intensive care beds are occupied by Covid-19 patients, and in Madrid, that figure is closer to 40 percent.

And in the Czech Republic — where the current hospitalization rate surpasses the worst period in Britain — physicians are worried about a shortage of staff. “In some regions, about 10 percent of the medical staff is either already infected or in quarantine,” said Petr Smejkal, the chief of infectious diseases and epidemiology at the Institute of Clinical and Experimental Medicine in Prague.

Mr. Smejkal said the country also lacks specialty workers like respiratory therapists, and that most nurses are not trained to operate ventilators. “I am most worried about personnel, and keeping a safe ratio of doctors to patients and nurses to patients,” he added.

There is hope that no place will experience the level of death that Bergamo, Italy, New York City and Madrid suffered this spring. How the virus spreads is better understood now, and treatments have improved, giving sick people a better chance of survival. Testing has expanded across Europe, allowing countries to identify outbreaks earlier, when they are easier to contain.

But it is unclear how successful those control measures will be, or if political resistance and collective exhaustion over new restrictions will make it harder to get the virus under control for a second time.

Deaths in most of Europe remain at a fraction of the levels seen in the spring. But they have ticked slowly upwards over the last several weeks, and they tend to lag hospitalizations by about a month. Experts say additional increases in deaths are likely over the next couple of weeks.

How the coronavirus pandemic could end

https://www.axios.com/when-will-coronavirus-pandemic-end-ecef1ae7-33b5-474c-8a02-2471742dbe99.html

It’s still the early days of the coronavirus pandemic, but history, biology and the knowledge gained from our first nine months with COVID-19 point to how the pandemic might end.

The big picture: Pandemics don’t last forever. But when they end, it usually isn’t because a virus disappears or is eliminated. Instead, they can settle into a population, becoming a constant background presence that occasionally flares up in local outbreaks.

  • Many emerging viruses become part of the viral ecology. The four coronaviruses that cause the common cold are endemic, circulating in the population, and the influenza strains that cause seasonal flu predictably surge each year.
  • The SARS outbreak in 2003 didn’t go the same way due to biology and behavior: It was much less transmissible than the virus that causes COVID-19, countries contained it quickly, and it has pretty much disappeared.
  • One virus, smallpox, was eradicated through widespread vaccination, and polio may be close, after decades of effort and billions in funding.

What’s happening: The pandemic is deepening in the U.S., Europe and elsewhere in the world.

  • Experts — from the U.K.’s chief scientific adviser to pharmaceutical CEOs to the WHO — increasingly say SARS-CoV-2 is likely to circulate in the population on a permanent basis, mainly due to the foothold the virus has already established.
  • But what damage endemic COVID-19 causes will depend on different factors, including how often people are reinfected, vaccine effectiveness and adoption, and if the virus mutates in any significant way.

“If the vaccine is really effective, like the measles vaccine or the yellow fever vaccine, it’s just going to land like a ton of bricks and suffocate this. Maybe not quite eradicate it — yellow fever and measles are not eradicated — but it’ll be an utter game changer,” UC Irvine epidemiologist Andrew Noymer says.

  • But if the vaccines are less effective — as many experts expect for at least the first generation — COVID-19 may eventually behave more like the seasonal flu, Noymer says. (Still, the death rate of COVID-19 currently well eclipses that of the seasonal flu.)

Reinfection is “the big issue,” says Columbia University’s Jeffrey Shaman, who recently described how reinfection and other factors would affect the spread of SARS-CoV-2 if it became endemic.

  • So far, there are just a handful of documented reinfection cases, but evidence about whether people retain their antibodies after infection is mixed, and a lot of unknowns remain about the likelihood of reinfection.
  • The worst-case scenario would be that there isn’t a vaccine or long-lasting immunity and people get COVID-19 repeatedly and are just as likely to end up in the hospital as with initial infections, Shaman says.

“I would say COVID-19 is already endemic,” says Larry Brilliant, an epidemiologist who worked to eradicate smallpox and now chairs the nonprofit Ending Pandemics.

  • With about 59,000 new cases per day in the U.S. alone, Brilliant says “it is already everywhere.”
  • “It doesn’t really mean very much if it is endemic,” he adds. “The real question is: How does it all end?”

Eventually, COVID-19 could end up in “the retirement village of coronaviruses,” like HIV, which today can be treated to the point of elimination, or circulate at low levels and be kept in check with a vaccine, like measles, Brilliant says, laying out a handful of possible scenarios.

  • Noymer says he suspects that after its “cataclysmic emergence,” COVID-19 may eventually fade into a common cold after a decade or so.

What’s next: We have to work with it as a virus that we will be contending with for years possibly,” Shaman says. “It doesn’t mean an effective vaccine or treatment won’t be developed. What it means is that holding out hope that we’re going to just get a vaccine and not doing anything else is not the level of preparation we need.”

  • Until we have an effective vaccine and better contact tracing and testing, Johns Hopkins University epidemiologist Justin Lessler says public health measures should continue encouraging the use of face masks and social distancing.
  • If the disease does become endemic, Lessler says it’s likely to eventually become more like a childhood infection because adults will gradually build an immunity. And since children tend to have fewer complications, “it will no longer be the same sort of burden to health that it is now.”

The good news: Viruses can sometimes become milder with time, treatments are already becoming more effective and vaccines can be improved.

  • “Right now we are frightened, depressed and on our back heels. We will be able to conquer this disease,” Brilliant says. “It will be a matter of time and science.”

A compelling link between severe COVID and immune system response

https://mailchi.mp/45f15de483b9/the-weekly-gist-october-9-2020?e=d1e747d2d8

Help for your immune system.

One of the most perplexing elements of the novel coronavirus is its variability. It’s common knowledge that while many infected people will experience mild symptoms, those who are older, male and have underlying chronic disease are at much higher risk of severe disease and death.

Two recent papers published in Science provide some of the most compelling evidence behind the impaired immune response seen in severely affected patients—and a potential link to the gender disparities in outcomes.

Both papers are centered on the role of Type I interferon, an immune protein that provides a first line of defense in viral illness.

The first study analyzed the DNA of over 650 patients with severe COVID to assess mutations in the genes that code for interferon-1. Some 3.5 percent of patients with life-threatening COVID carried mutations, but these were found in none of the control patients who only had mild disease.

The second paper evaluated the presence of antibodies to the patient’s own interferon, finding that 14 percent of patients with severe disease had these “auto-antibodies”, which are extremely rare in the general population. Interestingly, 12.5 percent of severely ill men had the antibodies, compared to just 2.6 percent of women with severe disease. Previous work linked poor interferon response to the X chromosome, highlighting the potential increased risk for men. 

Taken together, these studies indicate that impaired Type I interferon could contribute to 1 in 7 severe COVID cases. Scientists are hopeful this work could lead to new diagnostics that estimate a patient’s risk of poor outcomes. This growing body of work, with new insights published every week in Science and other journals, underscores the rapid advances being made in understanding and treating this novel and complex disease.

A high-profile reminder of the importance of therapeutics

https://mailchi.mp/45f15de483b9/the-weekly-gist-october-9-2020?e=d1e747d2d8

Stemline Therapeutics Inc (NASDAQ:STML): What's The Other Side Of The  Story? - Market Exclusive

Along with the many political and public health questions raised by President Trump’s recent and very public bout with COVID-19 is the issue of when the public might have access to the same monoclonal antibody therapy that he received from doctors last week.

Having seen the President tout the benefits of Regeneron’s experimental antibody cocktail, COVID patients have reportedly been asking physicians about participating in clinical trials of the therapy, which is only available on a “compassionate use” basis outside of ongoing studies.

On Wednesday, Regeneron announced it had submitted a request to the US Food and Drug Administration (FDA) for an Emergency Use Authorization (EUA) for the treatment, claiming that early data from ongoing trials showed promise in moderating coronavirus symptoms.

Eli Lilly, which is developing a similar antibody therapy, also announced plans to apply for an EUA, saying its drug has shown the ability to reduce hospitalizations among those infected with the virus.

The US government has already paid Regeneron $450M to access up to 300,000 doses of the therapy, and on Friday a spokesman for the Department of Health and Human Services (HHS) said the government would acquire up to a million doses from Regeneron and Eli Lilly by the end of the year, which it will allocate to hospitals in a similar approach to the way it has distributed Gilead Science’s antiviral drug remdesivir, which the President was also given last week.
 
News on the availability of potentially effective therapies to mitigate the impact of COVID-19 is welcome, particularly as the timeline for COVID vaccines appears to be lengthening.

In guidance released this week, the FDA said it would require pharmaceutical companies to submit two months’ worth of data on vaccine safety and efficacy after patients received their final dose, as part of the EUA application process. The data requirement effectively means that, despite repeated promises from the White House, none of the vaccine candidates being developed will be available before the November 3rd Presidential election.

The head of the government’s vaccine program said separately this week that he expects data on vaccines being developed by Pfizer and Moderna to be available by December. As many have predictedit will take months beyond that for a safe and effective vaccine to be distributed and administered to a majority of Americans.

Challenges will abound: ensuring sufficient manufacturing capacity, managing a complex supply chain, setting up specialized distribution and vaccination centers, and tracking those vaccinated (especially if two shots will be required). A massive public education campaign will also be needed to overcome vaccine hesitancy and ensure widespread immunization. And all of that will take time, and money. 

President Trump’s recent and unfortunate illness underscores the importance of paying equal attention to the development of therapies and treatments—which are essentially a holding maneuver to get us through the coming winter and spring, and eventually to the promise of immunity that lies beyond.

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.”

 

 

 

 

FDA chief apologizes for overstating plasma effect on virus

https://abcnews.go.com/Health/wireStory/fda-commissioner-overstated-effects-virus-therapy-72595122?fbclid=IwAR3Um3rVuom9rJNCOvccmmTBDOrrRePEu1BX1VgRvAzYbpL2NATGjY2-1IY

FDA chief apologizes for overstating plasma effect on virus

Food and Drug Administration Commissioner Stephen Hahn is apologizing for overstating the life-saving benefits of using convalescent plasma to treat COVID-19 patients.

Responding to an outcry from medical experts, Food and Drug Administration Commissioner Stephen Hahn on Tuesday apologized for overstating the life-saving benefits of treating COVID-19 patients with convalescent plasma.

Scientists and medical experts have been pushing back against the claims about the treatment since President Donald Trump’s announcement on Sunday that the FDA had decided to issue emergency authorization for convalescent plasma, taken from patients who have recovered from the coronavirus and rich in disease-fighting antibodies.

Trump hailed the decision as a historic breakthrough even though the treatment’s value has not been established. The announcement on the eve of Trump’s Republican National Convention raised suspicions that it was politically motivated to offset critics of the president’s handling of the pandemic.

Hahn had echoed Trump in saying that 35 more people out of 100 would survive the coronavirus if they were treated with the plasma. That claim vastly overstated preliminary findings of Mayo Clinic observations.

Hahn’s mea culpa comes at a critical moment for the FDA which, under intense pressure from the White House, is responsible for deciding whether upcoming vaccines are safe and effective in preventing COVID-19.

The 35% figure drew condemnation from other scientists and some former FDA officials, who called on Hahn to correct the record.

“I have been criticized for remarks I made Sunday night about the benefits of convalescent plasma. The criticism is entirely justified. What I should have said better is that the data show a relative risk reduction not an absolute risk reduction,” Hahn tweeted.

The FDA made the decision based on data the Mayo Clinic collected from hospitals around the country that were using plasma on patients in wildly varying ways — and there was no comparison group of untreated patients, meaning no conclusions can be drawn about overall survival. People who received plasma with the highest levels of antibodies fared better than those given plasma with fewer antibodies, and those treated sooner after diagnosis fared better than those treated later.

Hahn and other Trump administration officials presented the difference as an absolute survival benefit, rather than a relative difference between two treatment groups. Former FDA officials said the misstatement was inexcusable, particularly for a cancer specialist like Hahn.

“It’s extraordinary to me that a person involved in clinical trials could make that mistake,” said Dr. Peter Lurie, a former FDA official under the Obama administration who now leads the nonprofit Center for Science in the Public Interest. “It’s mind-boggling.”

The 35% benefit was repeated by Health and Human Services Secretary Alex Azar at Sunday’s briefing and promoted on Twitter by the FDA’s communication staff. The number did not appear in FDA’s official letter justifying the emergency authorization.

Hahn has been working to bolster confidence in the agency’s scientific process, stating in interviews and articles that the FDA will only approve a vaccine that meets preset standards for safety and efficacy.

Lawrence Gostin of Georgetown University said Hahn’s performance Sunday undermined those efforts.

“I think the integrity of the FDA took a hit, if I were Stephen Hahn I would not have appeared at such a political show,” said Gostin, a public health attorney.

Hahn pushed back Tuesday morning against suggestions that the plasma announcement was timed to boost Trump ahead of the Republican convention.

“The professionals and the scientists at FDA independently made this decision, and I completely support them,” Hahn said, appearing on “CBS This Morning.”

Trump has recently accused some FDA staff, without evidence, of deliberately holding up new treatments “for political reasons.” And Trump’s chief of staff, Mark Meadows, said over the weekend that FDA scientists “need to feel the heat.”

The administration has sunk vast resources into the race for a vaccine, and Trump aides have been hoping that swift progress could help the president ahead of November’s election.

At Sunday’s briefing Hahn did not correct Trump’s description of the regulatory move as a “breakthrough.” He also did not contradict Trump’s unsupported claim of a “deep state” effort at the agency working to slow down approvals.

Former FDA officials said the political pressure and attacks against the FDA carry enormous risk of undermining trust in the agency just when it’s needed most. A vaccine will only be effective against the virus if it is widely taken by the U.S. population.

“I think the constant pressure, the name-calling, the perception that decisions are made under pressure is damaging,” said Dr. Jesse Goodman of Georgetown University, who previously served as FDA’s chief scientist. “We need the American people to have full confidence that medicines and vaccines are safe.”

Convalescent plasma is a century-old approach to treating the flu, measles and other viruses. But the evidence so far has not been conclusive about whether it works, when to administer it and what dose is needed.

The FDA emergency authorization is expected to increase its availability to additional hospitals. But more than 70,000 Americans have already received the therapy under FDA’s “expanded access” program. That program tracks patients’ response, but cannot prove whether the plasma played a role in their recovery.

Some scientists worry the broadened FDA access to the treatment will make it harder to complete studies of whether the treatment actually works. Those studies require randomizing patients to either receive plasma or a dummy infusion.

 

 

 

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.