Category Archives: Clinical Research

A coronavirus vaccine: Where does it stand?

Posted on by • Posted in 2020 Election Issues, Clinical Research, Clinical Research Funding, Clinical Testing, Clinical Trials, Coronavirus, Crisis, Crisis Management, Scientists, Vaccine, Vaccine RNA, World Health Organization (WHO) • Leave a comment

https://www.politifact.com/article/2020/jul/13/coronavirus-vaccine-where-does-it-stand/?fbclid=IwAR3hk04P0N3AuJXsKCr_JqV8vu0qZ6njsHE3if6xX6E2AxsllV1m81LjtX4

Coronavirus vaccines get a biotech boost

IF YOUR TIME IS SHORT

• Scientists are expressing cautious optimism that a vaccine can be ready to go by the late spring of 2021, although it’s unclear how much longer it would take to distribute the vaccine widely.

• Two possible vaccines are in phase 3 clinical trials; once those trials are completed, they would be candidates for approval. Another eight vaccines have begun phase 2 trials. And more than 100 other vaccines that haven’t begun clinical trials are in the pipeline.

• The Food and Drug Administration recently produced guidelines for the minimum effectiveness of vaccines seeking the agency’s approval. Vaccine officials say these guidelines are important to ensure public confidence in vaccines.

 

More than four months into the coronavirus pandemic, how close is the U.S. and the world to a safe and effective vaccine? Scientists say they see steady progress and are expressing cautious optimism that a vaccine could be ready by spring of 2021.

As of early July, there were roughly 160 vaccine projects under way worldwide, according to the World Health Organization. 

Generally, a vaccine trial has several phases. In an initial phase, the vaccine is given to 20 to 100 healthy volunteers. The focus in this phase is to make sure the vaccine is safe, and to note any side effects.

In the second phase, there are hundreds of volunteers. In addition to monitoring safety, researchers try to determine whether shots produce an immune-system response.

The third phase involves thousands of patients. This phase continues the goals of the first two, but adds a focus on how effective the vaccine is. This phase also collects data on more unusual negative side effects.

In ordinary circumstances, these phases take years to complete. But for coronavirus, the timeline is being shortened. This has spurred more public-private partnerships and significantly increased funding.

Here’s a rundown of the 13 vaccine candidates that are furthest along in the clinical phases:

Coronavirus vaccines that are the furthest along:

A Coronavirus Vaccine: Where Does It Stand? – Corridor News

The three vaccine candidates that are furthest along are both in phase 3. 

One is being developed by researchers at Oxford University in the U.K. It uses a weakened version of a virus that causes common colds in chimpanzees. Researchers then added proteins, known as antigens, from the novel coronavirus, in the hope that these could prime the human immune system to fight the virus once it encounters it.

Another candidate in a phase 3 trial is being developed in China. It uses a killed, and thus safe, version of the novel coronavirus to spur an immune reaction.

And on July 15, the biotech company Moderna, which is partnering with the National Institutes of Health, announced that it would be moving to phase 3 within two weeks.

Two others have made it as far as phase 2, while eight others are finishing their phase 1 trials while also beginning phase 2 trials.

These candidates are being developed by a mix of corporations and institutions in several countries. These efforts seek to leverage a range of different technologies.

One uses RNA material that provides the instructions for a body to produce the needed antigens itself. This is a relatively untested approach to vaccination, but if it works, it has aspects that could make it easier to manufacture. Another approach is similar, but uses DNA instead of RNA.

One U.S. biotech firm, Novavax, is receiving federal funding to produce a vaccine that uses a lab-made protein to inspire an immune response.

Beyond these, another 10 vaccine candidates are in phase 1 clinical trials, while another 140 haven’t reached the clinical phase yet.

Having so many potential vaccines this far along is impressive, experts say, given the short time scientists have known about the novel coronavirus. 

“Overall, the pace of development and advancement to Phase 3 trials is impressive,” said Matthew B. Laurens, associate professor at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health. “The public-private partnerships have been highly successful and are achieving goals for rapid vaccine development.”

In addition, the fact that several types of vaccine approaches are being tested means we aren’t putting all of our eggs in one basket.

“We will need several candidates should any one of these experience difficulties in manufacturing or show a safety signal when implemented in larger numbers of people,” Laurens said.

Meanwhile, at a time of rising public skepticism of government and vaccines, the Food and Drug Administration recently released additional guidelines on vaccine effectiveness. The new guidance requires vaccines to prevent or decrease the severity of the disease at least 50% of the time if they are to win the agency’s approval.

The FDA guidelines “reaffirmed the very rigorous FDA process for approving any vaccine. That gives a great deal of reassurance that this was going to be handled by the book,” said William Schaffner, a professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center. “The more we talk about doing things fast, the more the public thinks, ‘They’re probably cutting corners.’”

How fast will we have access to a workable vaccine?

In early April, Kathleen M. Neuzil, director of the University of Maryland’s vaccine center, told PolitiFact that if all went well, there might be five or six vaccines in trials within six months. Now, three and a half months later, there are two to three times that number.

Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, and other officials have remained consistent in their estimation of the timeline: 12 to 18 months from the start of the pandemic, or roughly the late spring of 2021.

Schaffner told PolitiFact that he continues to see the first quarter of 2021 as a reasonable target. “I think that’s where the needle is pointing,” he said.

It remains to be seen how fast vaccines can be manufactured and distributed once approved for general use. Officials are also grappling with which Americans will get access first. So it’s unclear how long a person would have to wait to get vaccinated.

Laurens said he is not overly concerned about the distribution, because that is something that officials have long experience with. “Well-established programs exist for vaccine distribution, including for seasonal vaccination of large numbers of individuals,” he said.

Another hopeful sign, Schaffner said, is that the coronavirus itself seems to be relatively stable. There had been concern that the novel coronavirus, like many other viruses, is mutating over time. If the virus changes enough, that could become a problem that bedevils vaccine researchers.

But so far, that hasn’t happened. Even if evidence emerges that mutations are making the virus more transmissible, or that a new variant is making people sicker, that shouldn’t affect the vaccine process. “The central core of the virus would remain the same,” Schaffner said.

During the past month, there has been relatively little news about how much progress is being made on particular vaccines. Schaffner is not worried by the relative quiet.

“In a vaccine trial, if there’s an adverse safety finding, the guillotine comes down and that trial is stopped,” he said. “So quiet is good, because we’d know if something bad happens.”

 

 

 

Op-Ed: We Still Don’t Know the Risk Posed by COVID-19

Posted on by • Posted in 2020 Election Issues, Clinical Research, Clinical Research Funding, Clinical Testing, Clinical Trials, Coronavirus, Crisis, Crisis Management, Economic Crisis, Economic Recovery, Evidence-based Leadership, Evidence-Based Plan, Evidence-Based Policy, Food and Drug Administration (FDA), Infection Control, Infection Control Plan, Infectious Virus, Leadership Decentralized, Misinformation, Misinterpret, Mislead, Misleading, Mistrust, Mixed Message, Mortality, National Strategy, Pandemic, Public Health, Public Safety, Quarantine, Scientists, Social Distancing, Uncertainty • Leave a comment

https://www.medpagetoday.com/infectiousdisease/covid19/87629?xid=fb_o&trw=no&fbclid=IwAR2V6CbOCIXDf2K9sJCcRb0PhbqM4inXixe_poOFYudOcoUFZCmU2JzyrDg

Op-Ed: We Still Don't Know the Risk Posed by COVID-19 | MedPage Today

The need for a coordinated national research strategy

Confused about the risks of dying from the coronavirus or of catching it from someone who seems healthy? We all are, and the dizzying differences in scientific opinion are now linked to political perspectives. Progressives cite evidence that loosening restrictions would cost lives and offer little benefit to the economy, while conservatives embrace evidence that the risks are low. We offer a guide to help navigate the tangle of numbers and suggest a way forward.

Google and many others display the number of cases and deaths (3.6 million and 138,840, respectively, by July 17). This invites a simple calculation for understanding the risk: divide the number who have died by the number who have been diagnosed. So, the chance of dying if infected is about 3.9%. Right? Well, not so fast. Six months into the pandemic, neither the number of deaths nor the number of people infected is known.

Some argue that deaths have been overemphasized since people who die of COVID are mostly older and sicker. Others suggest deaths have been overcounted since if a patient tests positive for COVID-19, it will likely be listed as the cause of death even if the person succumbs to another illness or, in some jurisdictions, dies due to an accident or suicide. Others argue that deaths have been undercounted.

Missing from the tally on any given day are those who died before testing was available, those who died shortly before or after but whose death has not yet been reported, or who died as an indirect result of the epidemic such as failing to seek medical care for fear of going to the hospital.

One carefully designed recent analysis compared deaths this year to the number of people who die during a “normal” year. The analysis concluded that through May, almost 100,000 people died from COVID-19 in addition to 30,000 who died from other causes related to the pandemic.

In short, uncertainty remains about the number of deaths due to COVID-19, which is supposed to be the easy part.

Estimating the number of people who have been infected is harder still. Most infected people are never formally diagnosed and never become one of the “cases” in the news. The limitations of the tests and the difficulty of attracting a representative population to be tested make it hard to estimate the true number of infections. The preferred test (reverse transcription polymerase chain reaction-based tests) uses RNA technology to see if the virus is present in nasal or oral swabs. It is a good test, but still may miss infections in up to 30% of cases.

A second type of test uses blood samples to look for an antibody called immunoglobulin (Ig)G that implies the person was previously infected. Based on IgG test results, the CDC assumes that 5% to 8% of the population has been infected. That would mean 24 million Americans have already had COVID-19 or a very similar illness. That is more than 10 times the number of confirmed cases.

The number is consequential: a higher infection rate for the same number of deaths implies that the virus is less deadly. A review by a prominent epidemiologist considered 23 population studies with sample sizes of at least 500 people and found the percentage who have positive antibodies ranged from 0.1% to 48% — a 480-fold difference. Although the study was robustly criticized and at odds with highly cited, peer-reviewed research, it has appeared in over 30 news outlets, and the range of estimates allows people to pick a number that justifies their political position.

Contributing to this uncertainty is the FDA decision to, in a hurry to catch up for lost time, temporarily relax its standards for approving tests. Among over 300 antibody tests currently on the market, data on only a handful are publicly available, and some are being recalled.

The other number we need to know is how many people are spreading the infection without knowing it. Estimates are all over the place. Some major employers, including Stanford Healthcare, have systematically tested all of their employees and found very few infected people who do not have symptoms. In contrast, a CDC study of young, healthy adults working on an aircraft carrier found that 20% of those infected reported no symptoms.

So here we are, months into the epidemic without consensus on the basic information about how many people are infected, the risk of death for those infected, or the risk of asymptomatic transmission. In contrast to official agencies that use transparent methods to report the weather or the unemployment rate, trust in our official health statistics agencies has broken down as reports continue to emerge form myriad sources with conflicting methodologies and motivations.

The time has come to activate impartial groups, like the National Academy of Medicine, to build consensus on how to monitor the epidemic. We know the risks are serious. As cases have started to rise, whether or not the number of U.S. deaths is higher or lower than 130,000, the risk of inaction is too high.

We are staying near home, wearing masks, and treating COVID-19 as a serious threat to public health.

 

 

Public’s disconnect from COVID-19 reality worries experts

Posted on by • Posted in 2020 Election Issues, Accountability, Clinical Research, Clinical Testing, Contact Tracing, Coronavirus, Crisis, Crisis Management, Economic Crisis, Economic Recovery, Economy Reopening, Evidence-based Leadership, Evidence-Based Plan, Evidence-Based Policy, Failed Repeatedly, Failure, False Hope, False Narrative, Front Lines, Healthcare Providers, Infection Control, Infection Control Plan, Infectious Virus, Leadership Decentralized, Leadership Will, Misinformation, Mislead, Misleading, Mixed Message, Mortality, National Strategy, Pandemic, Partisanship, Personal Protective Equipment (PPE), Political Will, Public Health, Public Safety, Quarantine, Scientists, Social Distancing, Supply Chain, Transparency, Vaccination, Vaccine, Worker Protection • Leave a comment

Public’s disconnect from COVID-19 reality worries experts

Public's disconnect from COVID-19 reality worries experts | TheHill

The United States is being ravaged by a deadly pandemic that is growing exponentially, overwhelming health care systems and costing thousands of lives, to say nothing of an economic recession that threatens to plague the nation for years to come.

But the American public seems to be over the pandemic, eager to get kids back in schools, ready to hit the bar scene and hungry for Major League Baseball to play its abbreviated season.

 

The startling divergence between the brutal reality of the SARS-CoV-2 virus and the fantasy land of a forthcoming return to normalcy has public health experts depressed and anxious about what is to come. The worst is not behind us, they say, by any stretch of the imagination.

 

“It’s an absolute disconnect between our perceived reality and our actual reality,” said Craig Spencer, a New York City emergency room doctor who directs global health in emergency medicine at New York Presbyterian/Columbia University Medical Center. “To look at the COVID case count and the surge in cases and to think that we can have these discussions as we have uncontrolled spread, to think we can have some national strategy for reopening schools when we don’t even have one for reopening the country, it’s just crazy.”

The number of dead from the virus in the United States alone, almost 136,000, is roughly equal to the populations of Charleston, S.C., or Gainesville, Fla. If everyone in America who had been infected lived in the same city, that city would be the third-largest in the country, behind only New York and Los Angeles. More people in the United States have tested positive for the coronavirus than live in the state of Utah. By the weekend, there are likely to be more confirmed coronavirus cases than there are residents of Connecticut.

There are signs that the outbreak is getting worse, not better. The 10 days with the highest number of new coronavirus infections in the United States have come in the past 11 days.

Case counts, hospitalizations and even deaths are on the rise across the nation, not only in Southern states that were slow to embrace lockdowns in March and April.

California, the first state to completely lock down, has reported more than 54,000 new cases over both of the last two weeks. Nevada, about one-thirteenth the size of California, reported 5,200 new cases last week. States where early lockdowns helped limit the initial peak like Pennsylvania, Illinois and Ohio are all seeing case counts grow and hospital beds fill up.

Only two states — Maine and New Jersey — have seen their case counts decline for two consecutive weeks.

 

“We are nearing the point where pretty much most of the gains we had achieved have been lost,” said Christine Petersen, an epidemiologist at the University of Iowa. “All of us are hoping we magically get our acts together and we can look like Europe in two months. But all the data shows we are not doing that right now.”

It is in that dismal context that schools are preparing some sort of return to learning, whether in person or remote. President Trump and Education Secretary Betsy DeVos have threatened schools that do not fully reopen.

But even though the coronavirus appears to have less severe consequences among children, sending them back to schools en masse does not carry zero risk. Children have died from the virus, and the more who are exposed mean more opportunities for the virus to kill again, even before considering the millions of teachers who may be vulnerable or the parents and grandparents asymptomatic children might be exposed to.

Already, school districts in Los Angeles and San Diego have delayed reopening plans as case counts rise.

“We do know that kids can get sick and they can even die. It’s definitely a much lower number,” Petersen said. “Even if they aren’t as infectious, if there are millions of them gathering in schools not having great hygiene, it’s a multiplier effect.”

 

The painful lockdowns that were supposed to reduce viral transmissions bought time to bolster testing and hospital capacity, to speed production of the equipment needed to test patients and protect front-line health care workers.

But that hasn’t happened; laboratories in the United States have tested as many as 823,000 people in a day, a record number but far shy of the millions a day necessary to wrestle the virus under control. Arizona and Los Angeles have canceled testing appointments for lack of supplies. Hospitals are reporting new shortages of protective gear and N95 masks.

The Trump administration used the Defense Production Act to order meat processing plants to stay open; it has only awarded contracts sufficient to produce 300 million N95 masks by the end of the year, far short of what health experts believe will be necessary to protect health care workers.

 

“A failure of national leadership has led us to a place where we are back where we were before, no national testing strategy, no national strategy for supply,” said Kelli Drenner, who teaches public health at the University of Houston. “States are still on their own to scramble for reagents and swabs and PPE and all of that, still competing against each other and against nations for those resources.”

There are troubling signs that the promise of a vaccine may not be the cure-all for which many had hoped. Early studies suggest that the immune system only retains coronavirus antibodies for a few months, or perhaps a year, raising the prospect that people could become reinfected even after they recover. A growing, if still fringe, movement of anti-vaccination activists may refuse a vaccine altogether, putting others at risk.

“A vaccine is not going to solve this. People die of vaccine-preventable diseases every day. All the failures with testing and diagnostics and all the inequities and access to care with those are going to be the same things that are going to be magnified with a vaccine,” said Nita Bharti, a biologist at Penn State’s Center for Infectious Disease Dynamics.

 

More than a dozen states hit hardest by the latest wave of disease have paused or reversed their reopening processes. But only 24 states and the District of Columbia have ordered residents to wear masks in public, and compliance varies widely by both geography and political affiliation.

“This is the critical time. If we are going to try to reverse this, we have to get back to the mental space and the resolute action we had in March. I’m not sure we have the energy and the wherewithal to do it,” Petersen said.

 

Without a dramatic recommitment to conquering the virus, health officials warn, the new normal in which the country exists will be one of serious and widespread illness, and a steady drumbeat of death.

“None of this was inevitable. None of this should be acceptable. There are ways we can do better,” Spencer said. “This will continue to be our reality for as long as we don’t take it seriously.”

But after months of repeating the same warnings — wear a mask, stay socially distant, stay home if possible, avoid places where people congregate in tight quarters — some health experts worry their message has been lost amid a sea of doubt, skepticism and mixed signals.

“It’s like a learned helplessness when we’re not helpless,” Drenner said. “There are some pretty effective strategies, but we don’t seem to have the political will to do it.”

 

 

 

 

Fauci warns U.S. is “knee-deep” in coronavirus first wave

Posted on by • Posted in 2020 Election Issues, Centers for Disease Control & Prevention (CDC), Clinical Research, Clinical Testing, Coronavirus, Crisis, Crisis Management, Economic Crisis, Economy Reopening, Epidemic, Infection Control, Infection Control Plan, Infectious Virus, Mortality, Pandemic, Public Health, Public Safety, Quarantine, Social Distancing, Vaccine • Leave a comment

https://www.cbsnews.com/news/fauci-warns-us-knee-deep-coronavirus-first-wave/

 

The United States is still “knee-deep” in its first wave of coronavirus infections and must act immediately to tackle the recent surge, the country’s top infectious diseases expert said Monday.

Anthony Fauci said the number of cases had never reached a satisfactory baseline before the current resurgence, which officials have warned risks overwhelming hospitals in the South and West.

“It’s a serious situation that we have to address immediately,” Fauci said in a web interview with National Institutes of Health director Francis Collins.

But Fauci added he didn’t strictly consider the ongoing rise in cases a “wave.”

“It was a surge or a resurgence of infections superimposed upon a baseline,” he said.

“If you look at the graphs from Europe, the European Union as an entity, it went up and then came down to the baseline. Now they’re having little blips, as you might expect, as they try to reopen. We went up, never came down to baseline, and now we’re surging back up.”

The death toll from the virus in the U.S. hit 130,000 Monday, according to a tally by Johns Hopkins University, and the number of infections is nearing three million.

A worrisome number of new cases are being reported amid a resurgence that’s forced several states to suspend phased economic reopenings.

Fauci, who heads the National Institute of Allergy and Infectious Diseases, is a leading member of President Trump’s Coronavirus Task Force and has become a trusted face in the administration’s battle against the epidemic.

The U.S. is the world’s hardest-hit nation from the virus and has been struggling to come to grips with a new normal of social distancing and mask-wearing.

Officials have warned that some of the country’s hospitals are in danger of being overwhelmed by the influx of COVID-19 patients.

Hospital beds are full in parts of Texas, while calls for fresh stay-at-home orders are growing.

Some mayors have said their cities reopened too early as Mr. Trump tries to downplay the severity of the crisis, prioritizing economic reopening instead.

 

 

Coronavirus autopsies: A story of 38 brains, 87 lungs and 42 hearts

Posted on by • Posted in Autopsy, Blood Clots, Clinical Research, Coronavirus, Coronavirus Treatment, Oxygen Deprivation, Stroke • Leave a comment

https://www.washingtonpost.com/health/2020/07/01/coronavirus-autopsies-findings/?fbclid=IwAR2UIzjRRkEDq-1e-NEe9pC2Mf7AIVKc5mPwwOLc8hlymiFKFe7QKM0bLVg

Coronavirus autopsies: A story of 38 brains, 87 lungs and 42 ...

What we’ve learned from the dead that could help the living.

When pathologist Amy Rapkiewicz began the grim process of opening up the coronavirus dead to learn how their bodies went awry, she found damage to the lungs, kidneys and liver consistent with what doctors had reported for months.

But something was off.

Rapkiewicz, who directs autopsies at NYU Langone Health, noticed that some organs had far too many of a special cell rarely found in those places. She had never seen that before, yet it seemed vaguely familiar. She raced to her history books and — in a eureka moment — found a reference to 1960′s report on a patient with dengue fever.

In dengue, a mosquito-borne tropical disease, she learned, the virus appeared to destroy these cells, which produce platelets, leading to uncontrolled bleeding. The novel coronavirus seemed to amplify their effect, causing dangerous clotting.

She was struck by the parallels: “Covid-19 and dengue sound really different, but the cells that are involved are similar.”

Autopsies have long been a source of breakthroughs in understanding new diseases, from HIV/AIDS and Ebola to Lassa fever — and the medical community is counting on them to do the same for covid-19, the disease caused by the coronavirus. With a vaccine probably many months away in even the most optimistic scenarios, autopsies are becoming a critical source of information for research into possible treatments.

When the pandemic hit the United States in late March, many hospital systems were too overwhelmed trying to save lives to spend too much time delving into the secrets of the dead. But by late May and June, the first large batch of reports — from patients who died at a half-dozen institutions — were published in quick succession. The investigations have confirmed some of our early hunches of the disease, refuted others — and opened up new mysteries about the pathogen that has killed more than 500,000 people worldwide.

Among the most important findings, consistent across several studies, is confirmation the virus appears to attack the lungs the most ferociously. They also found the pathogen in parts of the brain, kidneys, liver, gastrointestinal tract and spleen and in the endothelial cells that line blood vessels, as some had previously suspected. Researchers also found widespread clotting in many organs.

But the brain and heart yielded surprises.

“It’s about what we are not seeing,” said Mary Fowkes, an associate professor of pathology who is part of a team at Mount Sinai Health that has performed autopsies on 67 covid-19 patients.

Given widespread reports about neurological symptoms related to the coronavirus, Fowkes said, she expected to find virus or inflammation — or both — in the brain. But there was very little. When it comes to the heart, many physicians warned for months about a cardiac complication they suspected was myocarditis, an inflammation or hardening of the heart muscle walls — but autopsy investigators were stunned that they could find no evidence of the condition.

Another unexpected finding, pathologists said, is that oxygen deprivation of the brain and the formation of blood clots may start early in the disease process. That could have major implications for how people with covid-19 are treated at home, even if they never need to be hospitalized.

The early findings come as new U.S. infections have overtaken even the catastrophic days of April, amid what some critics say is a premature easing of social distancing restrictions in some states, mainly in the South and West. A new modeling study has estimated that about 22 percent of the population — or 1.7 billion people worldwide, including 72 million in the United States — may be vulnerable to severe illness if infected with the virus. According to the analysis published this month in Lancet Global Health, about 4 percent of those people would require hospitalization — underscoring the stakes as autopsy investigators continue their hunt for clues.

Microclots in lungs

At their best, autopsies can reconstruct the natural course of the disease, but the process for a new and highly infectious disease is tedious and requires meticulous work. To protect pathologists and avoid sending virus into the air, they must use special tools to harvest organs and then dunk them in a disinfecting solution for several weeks before they are studied. They must then section each organ and collect small bits of tissue for study under different types of microscopes.

One of the first American investigations to be made public, on April 10, was out of New Orleans. The patient was a 44-year-old man who had been treated at LSU Health. Richard Vander Heide remembers cutting the lung and discovering what was probably hundreds or thousands of microclots.

“I will never forget the day,” recalled Vander Heide, who has been performing autopsies since 1994. “I said to the resident, ‘This is very unusual.’ I had never seen something like this.”

But as he moved onto the next patient and the next, Vander Heide saw the same pattern. He was so alarmed, he said, that he shared the paper online before submitting it to a journal so the information could be used immediately by doctors. The findings caused a stir at many hospitals and influenced some doctors to start giving blood thinners to all covid-19 patients. It is now common practice. The final, peer-reviewed version involving 10 patients was subsequently published in the Lancet in May.

Other lung autopsies — including those described in papers from Italy of 38 patients, a Mount Sinai Health study on 25 patients, a collaboration between Harvard Medical School and German researchers on seven and an NYU Langone Health study on seven — have reported similar findings of clotting.

Most recently, a study out this month in the Lancet’s eClinicalMedicine, found abnormal clotting in the heart, kidney and liver, as well as the lungs of seven patients, leading the authors to suggest this may be a major cause of the multiple-organ failure in covid-19 patients.

Heart cells

The next organ studied up close was the heart. One of the most frightening early reports about the coronavirus from China was that a significant percentage of hospitalized patients — up to 20 to 30 percent — appeared to have a heart problem known as myocarditis that could lead to sudden death. It involves the thickening of the muscle of the heart so that it can no longer pump efficiently.

Classic myocarditis is typically easy to identify in autopsies, pathologists say. The condition occurs when the body perceives the tissue to be foreign and attacks it. In that situation, there would be large dead zones in the heart, and the muscle cells known as myocytes would be surrounded by infection-fighting cells known as lymphocytes. But in the autopsy samples taken so far, the dead myocytes were not surrounded by lymphocytes — leaving researchers scratching their heads.

Fowkes, from Mount Sinai, and her colleague, Clare Bryce, whose work on 25 hearts has been published online but not yet peer reviewed, said they saw some “very mild” inflammation of the surface of the heart but nothing that looked like myocarditis.

NYU Langone’s Rapkiewicz, who studied seven hearts, was struck by the abundance of a rare cell called megakaryocytes in the heart. Megakaryocytes, which produce platelets that control clotting, typically exist only in the bone marrow and lungs. When she went back to the lung samples from the coronavirus patients, she discovered those cells were too plentiful there, too.

“I could not remember a case before where we saw that,” she said. “It was remarkable they were in the heart.”

Vander Heide, from LSU, who reported preliminary findings on 10 patients in April and has a more in-depth paper with more case studies under review at a journal, explained that “when you look at a covid heart, you don’t see what you’d expect.”

He said a couple of patients he performed autopsies on had gone into cardiac arrest in the hospital, but when he examined them, the primary damage was in the lungs — not the heart.

Brain grid

Of all the coronavirus’s manifestations, its impact on the brain has been among the most vexing. Patients have reported a host of neurological impairments, including reduced ability to smell or taste, altered mental status, stroke, seizures — even delirium.

An early study from China, published in the BMJ, formerly the British Medical Journal, in March, found 22 percent of the 113 patients had experienced neurological issues ranging from excessive sleepiness to coma — conditions typically grouped together as disorders of consciousness. In June, researchers in France reported that 84 percent of patients in intensive care had neurological problems, and a third were confused or disoriented at discharge. Also this month, those in the United Kingdom found that 57 of 125 coronavirus patients with a new neurological or psychiatric diagnosis had had a stroke due to a blood clot in the brain, and 39 had an altered mental state.

Based on such data and anecdotal reports, Isaac Solomon, a neuropathologist at Brigham and Women’s Hospital in Boston, set out to systematically investigate where the virus might be embedding itself in the brain. He conducted autopsies of 18 consecutive deaths, taking slices of key areas: the cerebral cortex (the gray matter responsible for information processing), thalamus (modulates sensory inputs), basal ganglia (responsible for motor control) and others. Each was divided into a three-dimensional grid. Ten sections were taken from each and studied.

He found snippets of virus in only some areas, and it was unclear whether they were dead remnants or active virus when the patient died. There were only small pockets of inflammation. But there were large swaths of damage due to oxygen deprivation. Whether the deceased were longtime intensive care patients or people who died suddenly, Solomon said, the pattern was eerily similar.

“We were very surprised,” he said.

When the brain does not get enough oxygen, individual neurons die, and that death is permanent. To a certain extent, people’s brains can compensate, but at some point, the damage is so extensive that different functions start to degrade.

On a practical level, Solomon said, if the virus is not getting into the brain in large amounts, that helps with drug development because treatment becomes trickier when it is pervasive, for instance, in some patients with West Nile or HIV. Another takeaway is that the findings underscore the importance of getting people on supplementary oxygen quickly to prevent irreversible damage.

Solomon, whose work was published as a June 12 letter in the New England Journal of Medicine, said the findings suggest the damage had been happening over a longer period of time, which makes him wonder about the virus’s effect on people who are less ill. “The big lingering question is what happens to people who survive covid,” he said. “Is there a lingering effect on the brain?”

The team from Mount Sinai Health, which took tissue findings from 20 brains, was also perplexed not to find a lot of virus or inflammation. However, the group noted in a paper that the widespread presence of tiny clots was “striking.”

“If you have one blood clot in the brain, we see that all the time. But what we’re seeing is, some patients are having multiple strokes in blood vessels that are in two or even three different territories,” Fowkes said.

Rapkiewicz said it is too early to know whether the newest batch of autopsy findings can be translated into treatment changes, but the information has opened new avenues to explore. One of her first calls after noticing the unusual platelet-producing cells was to Jeffrey Berger, a cardiac specialist at NYU who runs a National Institutes of Health-funded lab that focuses on platelets.

Berger said the autopsies suggest anti-platelet medications, in addition to blood thinners, may be helpful to stem the effects of covid-19. He has pivoted a major clinical trial looking at optimal doses of 38 to examine that question as well.

“It’s only one piece of a very big puzzle, and we have a lot more to learn,” he said. “But if we can prevent significant complications and if more patients can survive the infection, that changes everything.”

 

 

 

 

Comparing COVID-19 to past pandemics

Posted on by • Posted in Clinical Research, Clinical Testing, Coronavirus, Infection Control, Infection Control Plan, Infectious Virus, Mortality, Pandemic, Public Health, Public Safety, Quarantine, Social Distancing • Leave a comment

https://mailchi.mp/d594e7a0c816/the-weekly-gist-june-19-2020?e=d1e747d2d8

 

Although the coronavirus is easily the most disruptive disease event of our lifetimes, pandemics have ravaged humanity over history, leaving devastating death tolls in their tracks. This graphic compares lives lost in some of the worst worldwide pandemics on record. While a staggering 450,000 people have died from COVID-19 worldwide, the current pandemic represents a mere 0.2 percent of the deadliest plague in recorded human history, the Black Death.

Caused by the bubonic plague, the Black Death took an estimated 200 million lives over just a five-year span during the Middle Ages, killing an estimated 30 to 50 percent of Europe’s population. Arguably, the entire course of history was altered by the Black Death—will the same be true for COVID-19?

The 1918 Spanish Flu, the deadliest pandemic in modern history, claimed 40-50 million lives worldwide across 15 months. Unlike COVID-19, the Spanish Flu—caused by the H1N1 virus—was notable for being atypically fatal in otherwise healthy people, including in children younger than five and especially in adults between the ages of 20 and 40.

The Spanish Flu ebbed and flowed over three very distinct waves across two years, killing 675,000 Americans in total. That’s more than five-and-a-half times the current US COVID-19 death toll, but today we’re less than six months into the coronavirus pandemic.

The vast majority of Spanish Flu deaths occurred in the illness’s second wave, beginning in the fall of 1918—if history repeats itself, the worst of our current pandemic could still be in front of us. 

One stark difference between 1918 and today: the advancement of medical science in the last century has allowed a swift, global effort to create a COVID-19 vaccine—over 125 vaccines are currently in development and 18 have progressed to human trials.

 

 

Coronavirus drugmakers’ latest tactics: Science by press release

Posted on by • Posted in Clinical Research, Clinical Trials, Coronavirus, Coronavirus Treatment, False Hope, False Narrative, Food and Drug Administration (FDA), Hydroxychloroquine, Marketing, Mislead, Misleading, National Institute of Health (NIH), Partisanship, Pharmaceutical Industry, Political Pressure, Press Release, Remdesivir, Stock Manipulation, Vaccine, Whistleblower, Wishful Thinking • Leave a comment

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

Posted on by • Posted in Clinical Research, Coronavirus, Coronavirus Treatment, Dexamethasone, Hope, Hydroxychloroquine, National Institute of Health (NIH), Remdesivir • Leave a comment

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.

 

 

 

Masks Help Stop The Spread Of Coronavirus, Studies Say—But Wearing Them Still A Political Issue

Posted on by • Posted in 2020 Election Issues, Centers for Disease Control & Prevention (CDC), Clinical Research, Clinical Testing, Contact Tracing, Coronavirus, Crisis, Crisis Management, Economic Crisis, Economy Reopening, Evidence, Health Policy, Infection Control, Infection Control Plan, Infectious Virus, Leadership Decentralized, Mortality, Pandemic, Partisanship, Personal Protective Equipment (PPE), Public Health, Public Safety, Quarantine, Social Distancing • Leave a comment

https://www.forbes.com/sites/sarahhansen/2020/06/13/masks-help-stop-the-spread-of-coronavirus-studies-say-but-wearing-them-still-a-political-issue/#1d0be5a0604e

Trump administration and Cuomo finally agree on one thing ...

TOPLINE

Despite a raft of data suggesting that wearing face masks (in conjunction with hand washing and social distancing) is effective in preventing person-to-person transmission of the coronavirus, the practice is still a partisan political issue in some places even as new cases continue to rise. 

 

KEY FACTS

A new review published in The Lancet looked at 172 observational studies and found that masks are effective in many settings in preventing the spread of the coronavirus (though the results cannot be treated with absolute certainty since they were not obtained through randomized trials, the Washington Post notes).

Another recent study found that wearing a mask was the most effective way to reduce the transmission of the virus.

90% of Americans now say they’re wearing a mask in compliance with the CDC’s recommendations, up from 78% in April, according to a new poll conducted by NORC at the University of Chicago for the Data Foundation.

But despite the conclusive research and what seems to be a public consensus, masks remain a divisive subject. 

As new coronavirus cases surge in Arizona, where cases have jumped 300% since the beginning of May, for instance, Governor Doug Ducey has not made it mandatory to wear masks in public, and in Orange County, California, officials on Friday rescinded a mask mandate after public backlash, even as cases rise; when cases peaked in April, on the other hand, New York made wearing a mask mandatory when people could not socially distance from others, and other states passed similar restrictions.

Part of the politicization of masks may have to do with resistance to heavy-handed government mandates, which in this case could cause people who are already skeptical of wearing face coverings to dig in their heels.

 

CRUCIAL QUOTE

Lindsay Wiley, an American University Washington College of Law professor specializing in public health law and ethics, told NPR last month that stringent mask requirements “can actually cause people who are skeptical of wearing masks to double down.” And in turn, that “reinforce[s] what they perceive to be a positive association with refusing to wear a mask … that they love freedom, that they’re smart and skeptical of public health recommendations.” 

 

KEY BACKGROUND

Masks have also become a heavily politicized issue in recent weeks: Senate Majority Leader Mitch McConnell (R-Ky.) last month voiced his support of mask wearing in public, for instance, in contrast to President Trump and other GOP leaders who have portrayed masks as a sign of weakness. Trump infamously refused to wear a face mask as he toured a Ford facility in Michigan last month. When asked about the mask, he said that he wore one in private but “didn’t want to give the press the pleasure of seeing it.” House Speaker Nancy Pelosi has  voiced her support for the practice: “real men wear masks,” she said earlier this month.

 

TANGENT

A video posted to Twitter on Friday showed a street in New York City’s East Village that was packed with people ignoring social distancing guidelines, most of whom were not wearing masks, drew widespread criticism. “When there’s a new spike people will blame the (masked) protests, but it’s really gonna be maskless crap like this,” one Twitter user wrote. 

New York Governor Andrew Cuomo even weighed in on the scene. “Don’t make me come down there,” he tweeted.