mRNA Technology Gave Us the First COVID-19 Vaccines. It Could Also Upend the Drug Industry

https://time.com/5927342/mrna-covid-vaccine/?fbclid=IwAR1wC2ZhNbrGepu9WiPIsYMFWwA_VNgwppCQQCwzb_wQYt4EXBNF3wd2s40

How mRNA Technology Gave Us the First COVID-19 Vaccines | Time

“No!” The doctor snapped. “Look at me!”

I had been staring her in the eyes, as she had ordered, but when a doctor on my other side began jabbing me with a needle, I started to turn my head. “Don’t look at it,” the first doctor said. I obeyed.

This was in early August in New Orleans, where I had signed up to be a participant in the clinical trial for the Pfizer-BioNTech COVID-19 vaccine. It was a blind study, which meant I was not supposed to know whether I had gotten the placebo or the real vaccine. I asked the doctor if I would really been able to tell by looking at the syringe. “Probably not,” she answered, “but we want to be careful. This is very important to get right.”

I became a vaccine guinea pig because, in addition to wanting to be useful, I had a deep interest in the wondrous new roles now being played by RNA, the genetic material that is at the heart of new types of vaccines, cancer treatments and gene-editing tools. I was writing a book on the Berkeley biochemist Jennifer Doudna. She was a pioneer in determining the structure of RNA, which helped her and her doctoral adviser figure out how it could be the origin of all life on this planet. Then she and a colleague invented an RNA-guided gene-editing tool, which won them the 2020 Nobel Prize in Chemistry.

The tool is based on a system that bacteria use to fight viruses. Bacteria develop clustered repeated sequences in their DNA, known as CRISPRs, that can remember dangerous viruses and then deploy RNA-guided scissors to destroy them. In other words, it’s an immune system that can adapt itself to fight each new wave of viruses—just what we humans need. Now, with the recently approved Pfizer-BioNTech vaccine and a similar one from Moderna being slowly rolled out across the U.S. and Europe, RNA has been deployed to make a whole new type of vaccine that will, when it reaches enough people, change the course of the pandemic.

Drs. Ugur Sahin and Ozlem Tureci, Co-founders, BioNTech. In January 2020, before many in the Western world were paying attention to a new virus spreading in China, Dr. Ugur Sahin was convinced it would spur a pandemic. Sahin, who in 2008 co-founded the German biotech company BioNTech with his wife Dr. Ozlem Tureci, went to work on a vaccine and by March called his contact at Pfizer, a much larger pharmaceutical company with which BioNTech had previously worked on an influenza vaccine using mRNA. Less than a year later, the Pfizer-BioNTech COVID-19 vaccine became the first ever mRNA vaccine available for widespread use. Even so, Sahin, BioNTech’s CEO, and Tureci, its chief medical officer, maintain that BioNTech is not an mRNA company but rather an immunotherapy company. Much of the couple’s work—both at BioNTech and at their previous venture, Ganymed—has focused on treating cancer. But it is mRNA, and the COVID-19 vaccine made possible by the technology, that has pushed the famously hardworking couple into the ­limelight—and helped them become one of the richest pairs in Germany, though they reportedly still bicycle to work and live in a modest apartment near their office.

Up until last year, vaccines had not changed very much, at least in concept, for more than two centuries. Most have been modeled on the discovery made in 1796 by the English doctor Edward Jenner, who noticed that many milkmaids were immune to smallpox. They had all been infected by a form of pox that afflicts cows but is relatively harmless to humans, and Jenner surmised that the cowpox had given them immunity to smallpox. So he took some pus from a cowpox blister, rubbed it into scratches he made in the arm of his gardener’s 8-year-old son and then (this was in the days before bioethics panels) exposed the kid to smallpox. He didn’t become ill.

Before then, inoculations were done by giving patients a small dose of the actual smallpox virus, hoping that they would get a mild case and then be immune. Jenner’s great advance was to use a related but relatively harmless virus. Ever since, vaccinations have been based on the idea of exposing a patient to a safe facsimile of a dangerous virus or other germ. This is intended to kick the person’s adaptive immune system into gear. When it works, the body produces antibodies that will, sometimes for many years, fend off any infection if the real germ attacks.

One approach is to inject a safely weakened version of the virus. These can be good teachers, because they look very much like the real thing. The body responds by making antibodies for fighting them, and the immunity can last a lifetime. Albert Sabin used this approach for the oral polio vaccine in the 1950s, and that’s the way we now fend off measles, mumps, rubella and chicken pox.

At the same time Sabin was trying to develop a vaccine based on a weakened polio virus, Jonas Salk succeeded with a safer approach: using a killed or inactivated virus. This type of vaccine can still teach a person’s immune system how to fight off the live virus but is less likely to cause serious side effects. Two Chinese companies, Sinopharm and Sinovac, have used this approach to develop vaccines for COVID-19 that are now in limited use in China, the UAE and Indonesia.

Another traditional approach is to inject a subunit of the virus, such as one of the proteins that are on the virus’s coat. The immune system will then remember these, allowing the body to mount a quick and robust response when it encounters the actual virus. The vaccine against the hepatitis B virus, for example, works this way. Using only a fragment of the virus means that they are safer to inject into a patient and easier to produce, but they are often not as good at producing long-term immunity. The Maryland-based biotech Novavax is in late-stage clinical trials for a COVID-19 vaccine using this approach, and it is the basis for one of the two vaccines already being rolled out in Russia.

The plague year of 2020 will be remembered as the time when these traditional vaccines were supplanted by something fundamentally new: genetic vaccines, which deliver a gene or piece of genetic code into human cells. The genetic instructions then cause the cells to produce, on their own, safe components of the target virus in order to stimulate the patient’s immune system.

For SARS-CoV-2—the virus that causes COVID-19—the target component is its spike protein, which studs the outer envelope of the virus and enables it to infiltrate human cells. One method for doing this is by inserting the desired gene, using a technique known as recombinant DNA, into a harmless virus that can deliver the gene into human cells. To make a COVID vaccine, a gene that contains instructions for building part of a coronavirus spike protein is edited into the DNA of a weakened virus like an adenovirus, which can cause the common cold. The idea is that the re-engineered adenovirus will worm its way into human cells, where the new gene will cause the cells to make lots of these spike proteins. As a result, the person’s immune system will be primed to respond rapidly if the real coronavirus strikes.

This approach led to one of the earliest COVID vaccine candidates, developed at the aptly named Jenner Institute of the University of Oxford. Scientists there engineered the spike-protein gene into an adenovirus that causes the common cold in chimpanzees, but is relatively harmless in humans.

The lead researcher at Oxford is Sarah Gilbert. She worked on developing a vaccine for Middle East respiratory syndrome (MERS) using the same chimp adenovirus. That epidemic waned before her vaccine could be deployed, but it gave her a head start when COVID-19 struck. She already knew that the chimp adenovirus had successfully delivered into humans the gene for the spike protein of MERS. As soon as the Chinese published the genetic sequence of the new coronavirus in January 2020, she began engineering its spike-protein gene into the chimp virus, waking each day at 4 a.m.

Her 21-year-old triplets, all of whom were studying biochemistry, volunteered to be early testers, getting the vaccine and seeing if they developed the desired antibodies. (They did.) Trials in monkeys conducted at a Montana primate center in March also produced promising results.

Bill Gates, whose foundation provided much of the funding, pushed Oxford to team up with a major company that could test, manufacture and distribute the vaccine. So Oxford forged a partnership with AstraZeneca, the British-Swedish pharmaceutical company. Unfortunately, the clinical trials turned out to be sloppy, with the wrong doses given to some participants, which led to delays. Britain authorized it for emergency use at the end of December, and the U.S. is likely to do so in the next two months.

Johnson & Johnson is testing a similar vaccine that uses a human adenovirus, rather than a chimpanzee one, as the delivery mechanism to carry a gene that codes for making part of the spike protein. It’s a method that has shown promise in the past, but it could have the disadvantage that humans who have already been exposed to that adenovirus may have some immunity to it. Results from its clinical trial are expected later this month.

In addition, two other vaccines based on genetically engineered adenoviruses are now in limited distribution: one made by CanSino Biologics and being used on the military in China and another named Sputnik V from the Russian ministry of health.

There is another way to get genetic material into a human cell and cause it to produce the components of a dangerous virus, such as the spike proteins, that can stimulate the immune system. Instead of engineering the gene for the component into an adenovirus, you can simply inject the genetic code for the component into humans as DNA or RNA.

Let’s start with DNA vaccines. Researchers at Inovio Pharmaceuticals and a handful of other companies in 2020 created a little circle of DNA that coded for parts of the coronavirus spike protein. The idea was that if it could get inside the nucleus of a cell, the DNA could very efficiently churn out instructions for the production of the spike-protein parts, which serve to train the immune system to react to the real thing.

The big challenge facing a DNA vaccine is delivery. How can you get the little ring of DNA not only into a human cell but into the nucleus of the cell? Injecting a lot of the DNA vaccine into a patient’s arm will cause some of the DNA to get into cells, but it’s not very efficient.

Some of the developers of DNA vaccines, including Inovio, tried to facilitate the delivery into human cells through a method called electroporation, which delivers electrical shock pulses to the patient at the site of the injection. That opens pores in the cell membranes and allows the DNA to get in. The electric pulse guns have lots of tiny needles and are unnerving to behold. It’s not hard to see why this technique is unpopular, especially with those on the receiving end. So far, no easy and reliable delivery mechanism has been developed for getting DNA vaccines into the nucleus of human cells.

That leads us to the molecule that has proven victorious in the COVID vaccine race and deserves the title of TIME magazine’s Molecule of the Year: RNA. Its sibling DNA is more famous. But like many famous siblings, DNA doesn’t do much work. It mainly stays bunkered down in the nucleus of our cells, protecting the information it encodes. RNA, on the other hand, actually goes out and gets things done. The genes encoded by our DNA are transcribed into snippets of RNA that venture out from the nucleus of our cells into the protein-manufacturing region. There, this messenger RNA (mRNA) oversees the assembly of the specified protein. In other words, instead of just sitting at home curating information, it makes real products.

Scientists including Sydney Brenner at Cambridge and James Watson at Harvard first identified and isolated mRNA molecules in 1961. But it was hard to harness them to do our bidding, because the body’s immune system often destroyed the mRNA that researchers engineered and attempted to introduce into the body. Then in 2005, a pair of researchers at the University of Pennsylvania, Katalin Kariko and Drew Weissman, showed how to tweak a synthetic mRNA molecule so it could get into human cells without being attacked by the body’s immune system.

Stéphane Bancel, CEO, Moderna. Moderna’s COVID-19 vaccine was first tested in humans less than three months after news of the novel virus broke. But that lightning-fast development process belies the years of work that got Moderna to where it is today. The startup was founded in 2010 with the belief that mRNA technology, then still fairly new, could help treat any number of ailments. CEO Stéphane Bancel, pictured above, joined a year later. Moderna wasn’t originally focused on vaccines, but over time, its scientists began working toward vaccines against several infectious diseases as well as some forms of cancer. That experience came in handy when the COVID-19 pandemic arrived, leaving the world clamoring for a vaccine that could fight the deadly virus—and fast. Bancel’s company took the challenge in stride, using its mRNA platform to develop a vaccine around 95% effective at protecting against COVID-19 disease in less than a year.

When the COVID-19 pandemic hit a year ago, two innovative young pharmaceutical companies decided to try to harness this role played by messenger RNA: the German company BioNTech, which formed a partnership with the U.S. company Pfizer; and Moderna, based in Cambridge, Mass. Their mission was to engineer messenger RNA carrying the code letters to make part of the coronavirus spike protein—a string that begins CCUCGGCGGGCA … —and to deploy it in human cells.

BioNTech was founded in 2008 by the husband-and-wife team of Ugur Sahin and Ozlem Tureci, who met when they were training to be doctors in Germany in the early 1990s. Both were from Turkish immigrant families, and they shared a passion for medical research, so much so that they spent part of their wedding day working in the lab. They founded BioNTech with the goal of creating therapies that stimulate the immune system to fight cancerous cells. It also soon became a leader in devising medicines that use mRNA in vaccines against viruses.

In January 2020, Sahin read an article in the medical journal Lancet about a new coronavirus in China. After discussing it with his wife over breakfast, he sent an email to the other members of the BioNTech board saying that it was wrong to believe that this virus would come and go as easily as MERS and SARS. “This time it is different,” he told them.

BioNTech launched a crash project to devise a vaccine based on RNA sequences, which Sahin was able to write within days, that would cause human cells to make versions of the coronavirus’s spike protein. Once it looked promising, Sahin called Kathrin Jansen, the head of vaccine research and development at Pfizer. The two companies had been working together since 2018 to develop flu vaccines using mRNA technology, and he asked her whether Pfizer would want to enter a similar partnership for a COVID vaccine. “I was just about to call you and propose the same thing,” Jansen replied. The deal was signed in March.

By then, a similar mRNA vaccine was being developed by Moderna, a much smaller company with only 800 employees. Its chair and co-founder, Noubar Afeyan, a Beirut-born Armenian who immigrated to the U.S., had become fascinated by mRNA in 2010, when he heard a pitch from a group of Harvard and MIT researchers. Together they formed Moderna, which initially focused on using mRNA to try to develop personalized cancer treatments, but soon began experimenting with using the technique to make vaccines against viruses.

In January 2020, Afeyan took one of his daughters to a restaurant near his office in Cambridge to celebrate her birthday. In the middle of the meal, he got an urgent text message from the CEO of his company, Stéphane Bancel, in Switzerland. So he rushed outside in the freezing temperature, forgetting to grab his coat, to call him back.

Bancel said that he wanted to launch a project to use mRNA to attempt a vaccine against the new coronavirus. At that point, Moderna had more than 20 drugs in development but none had even reached the final stage of clinical trials. Nevertheless, Afeyan instantly authorized him to start work. “Don’t worry about the board,” he said. “Just get moving.” Lacking Pfizer’s resources, Moderna had to depend on funding from the U.S. government. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, was supportive. “Go for it,” he declared. “Whatever it costs, don’t worry about it.”

It took Bancel and his Moderna team only two days to create the RNA sequences that would produce the spike protein, and 41 days later, it shipped the first box of vials to the National Institutes of Health to begin early trials. Afeyan keeps a picture of that box on his cell phone.

An mRNA vaccine has certain advantages over a DNA vaccine, which has to use a re-engineered virus or other delivery mechanism to make it through the membrane that protects the nucleus of a cell. The RNA does not need to get into the nucleus. It simply needs to be delivered into the more-accessible outer region of cells, the cytoplasm, which is where proteins are constructed.

The Pfizer-BioNTech and Moderna vaccines do so by encapsulating the mRNA in tiny oily capsules, known as lipid nanoparticles. Moderna had been working for 10 years to improve its nanoparticles. This gave it one advantage over Pfizer-BioNTech: its particles were more stable and did not have to be stored at extremely low temperatures.

Katalin Kariko, Senior vice president, BioNTech. In 1995, after years of struggle, Hungarian-born Katalin Kariko was pushed off the path to full professorship at the University of Pennsylvania. Her work on mRNA, molecules she believed could fundamentally change the way humans treat disease, had stalled. Then, in 1997, she met and began working with immunologist Drew Weissman. In 2005, they published a study describing a modified form of artificial ­mRNA—a discovery, they argued, that opened the door to mRNA’s use in vaccines and other therapies. Eventually, Kariko and Weissman licensed their technology to the German company BioNTech, where Kariko, shown here in a portrait shot by a photographer working remotely, is now a senior vice president. Her patience paid off this year. The mRNA-based Pfizer-­BioNTech corona­virus vaccine, which Kariko helped develop, has been shown to be 95% effective at preventing COVID-19.
Katalin Kariko, Senior vice president, BioNTech. In 1995, after years of struggle, Hungarian-born Katalin Kariko was pushed off the path to full professorship at the University of Pennsylvania. Her work on mRNA, molecules she believed could fundamentally change the way humans treat disease, had stalled. Then, in 1997, she met and began working with immunologist Drew Weissman. In 2005, they published a study describing a modified form of artificial ­mRNA—a discovery, they argued, that opened the door to mRNA’s use in vaccines and other therapies. Eventually, Kariko and Weissman licensed their technology to the German company BioNTech, where Kariko, shown here in a portrait shot by a photographer working remotely, is now a senior vice president. Her patience paid off this year. The mRNA-based Pfizer-­BioNTech corona­virus vaccine, which Kariko helped develop, has been shown to be 95% effective at preventing COVID-19.

By November, the results of the Pfizer-BioNTech and Moderna late-stage trials came back with resounding findings: both vaccines were more than 90% effective. A few weeks later, with COVID-19 once again surging throughout much of the world, they received emergency authorization from the U.S. Food and Drug Administration and became the vanguard of the biotech effort to beat back the pandemic.

The ability to code messenger RNA to do our bidding will transform medicine. As with the COVID vaccines, we can instruct mRNA to cause our cells to make antigens—molecules that stimulate our immune system—that could protect us against many viruses, bacteria, or other pathogens that cause infectious disease. In addition, mRNA could in the future be used, as BioNTech and Moderna are pioneering, to fight cancer. Harnessing a process called immunotherapy, the mRNA can be coded to produce molecules that will cause the body’s immune system to identify and kill cancer cells.

RNA can also be engineered, as Jennifer Doudna and others discovered, to target genes for editing. Using the CRISPR system adapted from bacteria, RNA can guide scissors-like enzymes to specific sequences of DNA in order to eliminate or edit a gene. This technique has already been used in trials to cure sickle cell anemia. Now it is also being used in the war against COVID. Doudna and others have created RNA-guided enzymes that can directly detect SARS-CoV-2 and eventually could be used to destroy it.

More controversially, CRISPR could be used to create “designer babies” with inheritable genetic changes. In 2018, a young Chinese doctor used CRISPR to engineer twin girls so they did not have the receptor for the virus that causes AIDS. There was an immediate outburst of awe and then shock. The doctor was denounced, and there were calls for an international moratorium on inheritable gene edits. But in the wake of the pandemic, RNA-guided genetic editing to make our species less receptive to viruses may someday begin to seem more acceptable.

Throughout human history, we have been subjected to wave after wave of viral and bacterial plagues. One of the earliest known was the Babylon flu epidemic around 1200 B.C. The plague of Athens in 429 B.C. killed close to 100,000 people, the Antonine plague in the 2nd century killed 5 million, the plague of Justinian in the 6th century killed 50 million, and the Black Death of the 14th century took almost 200 million lives, close to half of Europe’s population.

The COVID-19 pandemic that killed more than 1.8 million people in 2020 will not be the final plague. However, thanks to the new RNA technology, our defenses against most future plagues are likely to be immensely faster and more effective. As new viruses come along, or as the current coronavirus mutates, researchers can quickly recode a vaccine’s mRNA to target the new threats. “It was a bad day for viruses,” Moderna’s chair Afeyan says about the Sunday when he got the first word of his company’s clinical trial results. “There was a sudden shift in the evolutionary balance between what human technology can do and what viruses can do. We may never have a pandemic again.”

The invention of easily reprogrammable RNA vaccines was a lightning-fast triumph of human ingenuity, but it was based on decades of curiosity-driven research into one of the most fundamental aspects of life on planet earth: how genes are transcribed into RNA that tell cells what proteins to assemble. Likewise, CRISPR gene-editing technology came from understanding the way that bacteria use snippets of RNA to guide enzymes to destroy viruses. Great inventions come from understanding basic science. Nature is beautiful that way.

The kids are not all right

https://mailchi.mp/0e13b5a09ec5/the-weekly-gist-august-21-2020?e=d1e747d2d8

Many children heading back to school—in whichever form that that may take this fall—have skipped their annual visit to the pediatrician. The graphic above highlights the sluggish rebound in pediatric ambulatory volume. While adult primary care visits have mostly bounced back, pediatric visits are still 26 percent below pre-COVID levels.

The drop in visits early in the pandemic also impacted immunizations, with 2.5M regular childhood vaccinations missed in the US during the first quarter of 2020—and early data suggests those seem to be rebounding at a similarly anemic rate.

This lack of pediatric routine care is particularly worrisome as COVID-19 cases in children are climbing, with a 90 percent increase from July to August. Though most of the nation’s largest public school districts have opted to begin the school year with online learning, some districts have already returned to in-person classes, and, unsurprisingly, new cases are already being reported.

While COVID-19 is normally neither severe nor fatal in children, infections among school-age kids put others at risk. According to the Kaiser Family Foundation, nearly a quarter of teachers (1.5M) are considered high-risk and almost six percent of seniors (3.3M) live with school-aged children.

Without the traditional back-to-school push for well-child visits, sports physicals, and immunization updates, healthcare providers must think creatively about how to give children with the care they need, whether through personalized communication from pediatricians that assuages parental concerns about office safety, or through more innovative means such as drive-thru vaccination services.

 

 

 

‘I’m fighting a war against COVID-19 and a war against stupidity,’ says CMO of Houston hospital

https://www.beckershospitalreview.com/hospital-physician-relationships/i-m-fighting-a-war-against-covid-19-and-a-war-against-stupidity-says-cmo-of-houston-hospital.html?utm_medium=email

 

After two hours of sleep a night for four months and seeing a member of his team contract the virus, Joseph Varon, MD, is growing exasperated.

“I’m pretty much fighting two wars: A war against COVID and a war against stupidity,” Dr. Varon, MD, CMO and chief of critical care at United Memorial Medical Center in Houston, told NBC News. “And the problem is the first one, I have some hope about winning. But the second one is becoming more and more difficult.”

Dr. Varon noted that whether it’s information backed by science or common sense, people throughout the U.S. are not listening. “The thing that annoys me the most is that we keep on doing our best to save all these people, and then you get another batch of people that are doing exactly the opposite of what you’re telling them to do.”

In an interview with NPR, Dr. Varon said he has woken up at dawn every day for the past four months and has headed to the hospital. There, he spends six to 12 hours on rounds before seeing new admissions. He then returns home to sleep two hours, at most.

He said his staff is physically and emotionally drained. 

UMMC nurse Christina Mathers spoke with NBC News from a hospital bed in the segment, noting that she had recently tested positive for COVID-19 after not feeling well during one of her shifts. “All the fighting, all the screaming, all the finger pointing — enough is enough,” Ms. Mathers told NBC. “People just need to listen to us. We’re not going to lie. Why would we lie?” 

Ms. Mathers has worked every other day since April 29, according to The Atlantic, which created a photo essay of Dr. Varon and the UMMC team at work.

 

 

The Constitution doesn’t have a problem with mask mandates

https://theconversation.com/the-constitution-doesnt-have-a-problem-with-mask-mandates-142335?utm_medium=email&utm_campaign=Latest%20from%20The%20Conversation%20for%20July%2022%202020%20-%201684316250&utm_content=Latest%20from%20The%20Conversation%20for%20July%2022%202020%20-%201684316250+Version+A+CID_3a4842bdc1542ab5ad1725fad090f099&utm_source=campaign_monitor_us&utm_term=The%20Constitution%20doesnt%20have%20a%20problem%20with%20mask%20mandates

The Constitution doesn't have a problem with mask mandates

Many public health professionals and politicians are urging or requiring citizens to wear face masks to help slow the spread of the COVID-19 virus.

Some Americans have refused, wrongly claiming mask decrees violate the Constitution. An internet search turns up dozens of examples.

“Costco Karen,” for instance, staged a sit-in in a Costco entrance in Hillsboro, Oregon after she refused to wear a mask, yelling “I am an American … I have rights.”

A group called Health Freedom Idaho organized a protest against a Boise, Idaho, mask mandate. One protester said, “I’m afraid where this country is headed if we just all roll over and abide by control that goes against our constitutional rights.”

As one protester said, “The coronavirus doesn’t override the Constitution.”

Speaking as a constitutional law scholar, these objections are nonsense.

The objections

It is not always clear why anti-maskers think government orders requiring face coverings in public spaces or those put in place by private businesses violate their constitutional rights, much less what they think those rights are. But most of the mistaken objections fall into two categories:

Mandatory masks violate the First Amendment right to speech, assembly, and especially association and mandatory masks violate a person’s constitutional right to liberty and to make decisions about how to their own health and bodily integrity.

They’re not mutually exclusive claims:lawsuit filed by four Florida residents against Palm Beach County, for example, argues that mask mandates “interfere with … personal liberty and constitutional rights,” such as freedom of speech, right to privacy, due process, and the “constitutionally protected right to enjoy and defend life and liberty.” The lawsuit asks the court to issue a permanent injunction against the county’s mask mandate.

Responding to a reporter who asked why President Donald Trump appeared unconcerned about the absence of masks and social distancing at a campaign rally in Tulsa, Vice President Mike Pence said: “I want to remind you again freedom of speech and the right to peaceably assemble is in the Constitution of the U.S. Even in a health crisis, the American people don’t forfeit our constitutional rights.”

What the First Amendment does – and doesn’t – do

The First Amendment protects freedom of speech, press, petition, assembly and religion.

There are two reasons why mask mandates don’t violate the First Amendment.

First, a mask doesn’t keep you from expressing yourself. At most, it limits where and how you can speak. Constitutional law scholars and judges call these “time, place, and manner” restrictions. If they do not discriminate on the basis of the content of the speech, such restrictions do not violate the First Amendment. An example of a valid time, place and manner restriction would be a law that limits political campaigning within a certain distance of a voting booth.

Additionally, the First Amendment, like all liberties ensured by the Constitution, is not absolute.

All constitutional rights are subject to the goverment’s authority to protect the health, safety and welfare of the community. This authority is called the “police power.” The Supreme Court has long held that protecting public health is sufficient reason to institute measures that might otherwise violate the First Amendment or other provisions in the Bill of Rights. In 1944, in the case of Prince v. Massachusetts, for example, the Supreme Court upheld a law that prohibited parents from using their children to distribute religious pamphlets on public streets.

The right to liberty

Some anti-maskers object that masks violate the right to liberty.

The right to liberty, including the right to make choices about one’s health and body, is essentially a constitutional principle of individual autonomy, neatly summarized as “My body, my choice.”

The 1905 case of Jacobsen v. Massachusetts shows why mask mandates don’t violate any constitutional right to privacy or health or bodily integrity. In that case, the Supreme Court upheld a smallpox vaccination requirement in Cambridge, Massachusetts.

The court said that the vaccination requirement did not violate Jacobsen’s right to liberty or “the inherent right of every freeman to care for his own body and health in such way as to him seems best.”

As the court wrote, “There are manifold restraints to which every person is necessarily subject for the common good. On any other basis, organized society could not exist with safety to its members.” In a 1995 New York case, a state court held that an individual with active tuberculosis could be forcibly detained in a hospital for appropriate medical treatment.

Even if you assume that mask mandates infringe upon what the Supreme Court calls “fundamental rights,” or rights that the court has called the “very essence of a scheme of ordered liberty,” it has consistently ruled states can act if the restrictions advance a compelling state interest and do so in the least restrictive manner.

Rights are conditional

As the Jacobsen ruling and the doctrine of time, place and manner make clear, the protection of all constitutional liberties rides upon certain necessary – but rarely examined – assumptions about communal and public life.

One is that is constitutional rights – whether to liberty, speech, assembly, freedom of movement or autonomy – are held on several conditions. The most basic and important of these conditions is that our exercise of rights must not endanger others (and in so doing violate their rights) or the public welfare. This is simply another version of the police power doctrine.

Unfortunately, a global pandemic in which a serious and deadly communicable disease can be transmitted by asymptomatic carriers upsets that background and justifies a wide range of reasonable restrictions on our liberties. Believing otherwise makes the Constitution a suicide pact – and not just metaphorically.

 

 

 

 

Fitch: Nonprofit hospital margins unlikely to recover until COVID-19 vaccine

https://www.beckershospitalreview.com/finance/fitch-nonprofit-hospital-margins-unlikely-to-recover-until-covid-19-vaccine.html?utm_medium=email

What Happens When A Nonprofit Hospital Goes 'For-Profit' : Shots ...

Median financial ratios for nonprofit hospitals and health systems improved before the COVID-19 pandemic, which will provide some financial cushion to withstand financial pressures, according to a report from Fitch Ratings. 

The medians for 2019, based on 2018 data, showed the nonprofit hospital and health system sector stabilized after a period of operational softness. The medians for 2020, based on 2019 audited data, are expected to show improvement in operating margins driven by higher revenues, cost reductions and increased cash flow, Fitch said.

“We expect the 2020 medians will represent peak performance levels until the sector is able to recover from the effects of the pandemic on operations,” Fitch said. 

The credit rating agency said the nonprofit healthcare sector is unlikely to stabilize until a COVID-19 vaccine is widely available.

“The sector has shown considerable resiliency over the years, weathering significant events such as the Great Recession and legislative changes to funding,” Fitch said. “However, the coronavirus presents entirely new and fundamental challenges for the sector in the short term in the form of volume and revenue disruption, and over the medium to longer term with expected deterioration of individual provider payor mixes and possible changes in the behavior of healthcare consumers.”

 

 

 

 

Public’s disconnect from COVID-19 reality worries experts

https://thehill.com/policy/healthcare/507334-publics-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: Surge States Must Pause Reopening

https://www.medpagetoday.com/infectiousdisease/covid19/87527?utm_source=Sailthru&utm_medium=email&utm_campaign=Weekly%20Review%202020-07-12&utm_term=NL_DHE_Weekly_Active

Fauci: Surge States Must Pause Reopening | MedPage Today

NIAID chief pins hopes for long-term containment on vaccine.

States facing COVID-19 surges must hit “pause” on their reopenings and begin to truly follow the CDC guidelines for mitigating its spread, NIAID Director Anthony Fauci, MD, told The Hill during an online webinar hosted by the website on Thursday.

Cases in the U.S. peaked in April but instead of falling to near zero, as happened in many European countries, new daily diagnoses plateaued at about 20,000 per day.

That ended in late May, when new cases began rising again, driven by big increases in California, Texas, Florida, and Arizona. The national rate has been topping 50,000 per day; the widely cited Johns Hopkins University tracker’s count spiked by 113,000 in the 24 hours ending at 8:00 a.m. ET Friday.

“We need to get our arms around that … and we need to do something about it quickly,” Fauci said.

One major challenge is the nature of the virus itself, which is “spectacularly transmissible,” he noted.

But the other problem is that some states ignored public health experts’ advice.

“We went from shutting down to opening up in a way that essentially skipped over all the guideposts,” he said, referring to the benchmarks for each phase of the reopening process. “That’s not the way to go.”

Fauci said he hopes it won’t be necessary for sunbelt states to return to a total shutdown.

“We’ve got to get them to do very fundamental things: closing bars, avoiding congregations of large numbers of people, getting the citizenry in those states to wear masks, maintain six-foot distance, washing hands,” he said. “If we can do that consistently, I will tell you almost certainly you’re going to see a down curve of those infections.”

Fauci also offered his projections for vaccine development.

“We’re really cautiously optimistic that things are moving along quite well with more than one candidate.”

He said the Moderna vaccine, which the NIH helped to develop, “will very likely be going into advanced phase III clinical trials, by the end of this month, July.”

Other “equally promising” vaccine candidates will begin these trials “a little bit later.”

“[W]ith any vaccine development program you never can guarantee success … but the early signs are proving favorable,” he said.

Fauci said he hopes “by the end of this calendar year and the beginning of 2021, that we will have a vaccine that we will be able to begin to deploy to people who need it.”

 

 

 

 

Providence, Humana back ad campaign urging patients to stop ‘medical distancing’

https://www.healthcaredive.com/news/providence-humana-back-ad-campaign-urging-patients-to-stop-medical-distan/581172/

Dive Brief:

  • A coalition of providers, payers and other healthcare organizations on Tuesday launched an ad campaign to encourage patients not to put off important care during the COVID-19 pandemic.
  • The announcement encourages people to continue social distancing but not “medical distancing” by putting off routine care or avoiding checking on concerning symptoms. That could be either through telemedicine or an in-person visit.
  • The campaign will be on TV, in print and across social media. The 11 organizations behind it include Providence, Humana, Baylor Scott & White, LabCorp and Walgreens.

Dive Insight:

While some hospitals in hotspots in Texas, Florida, California and Arizona have had to once again put off non-emergency procedures, providers in other areas of the country are trying to ramp up regular patient volumes as the number of positive cases eases.

Surveys show, however, that people are wary of returning to the doctor’s office, either because they worry about exposure to the novel coronavirus or have lost coverage to help pay for care.

The new ad campaign seeks to ease these concerns. No dollar figure was attached to the plan, which advertising agency MullenLowe U.S. took on pro bono. It follows an ad the American Hospital Association launched in May to ensure the public facilities are still available for non-COVID-19 care.

Since the pandemic’s onset in the United States, health officials have been concerned about the short- and long-term consequences of routine and preventive care being delayed or put off entirely. Chronic diseases that are caught early can be managed more easily and less expensively.

Also, research shows even some crucial services aren’t being sought even for issues such as strokes and heart attacks. In April, emergency room visits nationwide dropped more than 40%, according to the Centers for Disease Control and Prevention.

Public health experts are also beginning to fear vaccinations may be avoided, which could cause trouble with the upcoming flu season.

For providers the reduction in patient volumes has meant a major revenue loss. Some patient volume has been recaptured, but that rolled back again in recent weeks with hospitals in large states like Texas and Florida again reaching capacity with a COVID-19 surge.

At the end of June, hospital traffic in Arizona, New York and Texas was down week over week, according to an analysis from Jefferies.

Primary care has particularly suffered. Visits to medical offices were down nearly 60% in March and April, meaning losses to those practices could top $15 billion this year, according to a recent Health Affairs study.

The ad campaign stresses that providers have guidelines in place to keep patients safe, such as isolation of those suspected of having COVID-19 and increased virtual options.

“While we understand the fears that many people have around contracting the virus, our country’s medical facilities have adopted CDC guidelines and best practices and even telemedicine options to make your visit as safe as possible to prevent the spread of the virus,” Humana CMO William Shrank said in a statement. “The intent of the campaign is to let people know that protecting yourself against getting this virus does not need to come at the expense of your overall health.”

 

 

 

 

Re-examining the delivery of high-value care through COVID-19

https://thehill.com/opinion/healthcare/502851-examining-the-delivery-of-high-value-care-through-covid-19#bottom-story-socials

Re-examining the delivery of high-value care through COVID-19 ...

Over the past months, the country and the economy have radically shifted to unchartered territory. Now more than ever, we must reexamine how we spend health care dollars. 

While the COVID-19 pandemic has exposed challenges with health care in America, we see two overarching opportunities for change:

1) the under-delivery of evidence-based care that materially improves the lives and well-being of Americans and

2) the over-delivery of unnecessary and, sometimes, harmful care.

The implications of reallocating our health care spending to high-value services are far-ranging, from improving health to economic recovery. 

To prepare for coronavirus patients and preserve protective equipment, clinicians and hospitals across the country halted non-urgent visits and procedures. This has led to a substantial reduction in high-value care: emergency care for strokes or heart attacks, childhood vaccinations, and routine chronic disease management. However, one silver lining to this near shutdown is that a similarly dramatic reduction in the use of low-value services has also ensued.

As offices and hospitals re-open, we have a once in a century opportunity to align incentives for providers and consumers, so patients get more high-value services in high-value settings, while minimizing the resurgence of low-value care. For example, the use of pre-operative testing in low-risk patients should not accompany the return of elective procedures such as cataract removal. Conversely, benefit designs should permanently remove barriers to high-value settings and services, like patients receiving dialysis at home or phone calls with mental health providers.   

People with low incomes and multiple chronic conditions are of particular concern as unemployment rises and more Americans lose their health care coverage. Suboptimal access and affordability to high-value chronic disease care prior to the COVID-19 pandemic was well documented  As financially distressed providers re-open to a new normal, hopeful to regain their financial footing, highly profitable services are likely to be prioritized.

Unfortunately, clinical impact and profitability are frequently not linked. The post-COVID reopening should build on existing quality-driven payment models and increase reimbursement for high-value care to ensure that compensation better aligns with patient-centered outcomes.

At the same time, the dramatic fall in “non-essential care” included a significant reduction in services that we know to be harmful or useless. Billions are spent annually in the US on routinely delivered care that does not improve health; a recent study from 4 states reports that patients pay a substantial proportion (>10 percent) of this tab out-of-pocket. This type of low-value care can lead to direct harm to patients — physically or financially or both — as well as cascading iatrogenic harm, which can amplify the total cost of just one low-value service by up to 10 fold. Health care leaders, through the Smarter Health Care Coalition, have hence called on the Department of Health and Human Services Secretary Azar to halt Medicare payments for services deemed low-value or harmful by the USPSTF. 

As offices and hospitals reopen with unprecedented clinical unmet needs, we have a unique opportunity to rebuild a flawed system. Payment policies should drive incentives to improve individual and population health, not the volume of services delivered. We emphasize that no given service is inherently high- or low-value, but that it depends heavily on the individual context. Thus, the implementation of new financial incentives for providers and patients needs to be nuanced and flexible to allow for patient-level variability. The added expenditures required for higher reimbursement rates for highly valuable services can be fully paid for by reducing the use of and reimbursement for low-value services.  

The delivery of evidence-based care should be the foundation of the new normal. We all agree that there is more than enough money in U.S. health care; it’s time that we start spending it on services that will make us a healthier nation.

 

 

 

A few superspreaders transmit the majority of coronavirus cases

https://theconversation.com/a-few-superspreaders-transmit-the-majority-of-coronavirus-cases-139950?utm_medium=email&utm_campaign=Latest%20from%20The%20Conversation%20for%20June%2012%202020%20-%201650015873&utm_content=Latest%20from%20The%20Conversation%20for%20June%2012%202020%20-%201650015873+Version+A+CID_db6d6c973ccfe2fa9f80ca414a282efe&utm_source=campaign_monitor_us&utm_term=A%20few%20superspreaders%20transmit%20the%20majority%20of%20coronavirus%20cases

Corona A few superspreaders transmit the majority of coronavirus ...

The coronavirus has traveled the globe, infecting one person at a time. Some sick people might not spread the virus much further, but some people infected with the SARS-CoV-2 are what epidemiologists call “superspreaders.”

Elizabeth McGraw, the director of the Center for Infectious Disease Dynamics at Pennsylvania State University, explains the evidence and why superspreaders can be crucial to a disease’s transmission.

What is a superspreader?

Early in the outbreak, researchers estimated that a person carrying SARS-CoV-2 would, on average, infect another two to three people. More recent studies have argued, however, that this number may actually be higher.

As early as January, though, there were reports out of Wuhan, China, of a single patient who infected 14 health care workers. That qualifies him as a super spreader: someone who is responsible for infecting an especially large number of other people.

Since then, epidemiologists have tracked a number of other instances of SARS-CoV-2 superspreading. In South Korea, around 40 people who attended a single church service were infected at the same time. At a choir practice of 61 people in Washington state, 32 attendees contracted confirmed COVID-19 and 20 more came down with probable cases. In Chicago, before social distancing was in place, one person that attended a dinner, a funeral and then a birthday party was responsible for 15 new infections.

During any disease outbreak, epidemiologists want to quickly figure out whether superspreaders are part of the picture. Their existence can accelerate the rate of new infections or substantially expand the geographic distribution of the disease.

 

What are the characteristics of a superspreader?

Whether someone is a superspreader or not will depend on some combination of the pathogen, the patient’s biology and their environment or behavior.

Some infected individuals might shed more virus into the environment than others if their immune system has trouble subduing the invader. Additionally, asymptomatic individuals – up to 50% of all those who get COVID-19 – will continue their normal activities, inadvertently infecting more people. Even people who ultimately do show symptoms are capable of transmitting the virus during a pre-symptomatic phase.

A person’s behaviors, travel patterns and degree of contact with others can also contribute to superspreading. An infected shopkeeper might come in contact with a large number of people and goods each day. An international business traveler may crisscross the globe in a short period of time. A sick health care worker might come in contact with large numbers of people who are especially susceptible, given the presence of other underlying illnesses.

Public protests – where it’s challenging to keep social distance and people might be raising their voices or coughing from tear gas – are conducive to superspreading.

 

How big a part of COVID-19 are superspreaders?

Several recent preprint studies, which haven’t yet been peer-reviewed, have shed light on the role of superspreading in COVID-19’s dispersion around the globe.

Researchers in Hong Kong examined a number of disease clusters by using contact tracing to track down everyone with whom individual COVID-19 patients had interacted. In the process, they identified multiple situations where a single person was responsible for as many as six or eight new infections.

The researchers estimated that only 20% of all those infected with SARS-CoV-2 were responsible for 80% of all local transmission. Importantly, they also showed that these transmission events were associated with people who had more social contacts – beyond just family members – highlighting the need to rapidly isolate people as soon as they test positive or show symptoms.

Another study by researchers in Israel took a different approach. They compared the genetic sequences of coronavirus samples from patients inside the country to those from other places. Based on how different the genomes were, they could identify each time SARS-CoV-2 entered Israel and then follow how it spread domestically.

These scientists estimated that 80% of community transmission events – one person spreading the coronavirus to another – could be tracked back to just 1-10% of sick individuals.

And when another research group modeled the variation in how many other SARS-CoV-2 infections a single infected person tends to cause, they also found there were occasionally individuals who were very infectious. These people accounted for over 80% of transmissions in a population.

 

When have superspreaders played a key role in an outbreak?

There are a number of historical examples of superspreaders. The most famous is Typhoid Mary, who in the early 20th century purportedly infected 51 people with typhoid through the food she prepared as a cook.

During the last two decades, superspreaders have started a number of measles outbreaks in the United States. Sick, unvaccinated individuals visited densely crowded places like schools, hospitals, airplanes and theme parks where they infected many others.

Superspreaders have also played a key role in the outbreaks of other coronaviruses, including SARS in 2003 and MERS in 2015. For both SARS and MERS, superspreading mainly occurred in hospitals, with scores of people being infected at a time.

 

Can superspreading occur in all infectious diseases?

Yes. Researchers have identified superspreaders in outbreaks of diseases caused by bacteria, such as tuberculosis, as well as those caused by viruses, including measles and Ebola. Just as appears to be the case with the coronavirus, some scientists estimate that in an outbreak of any given pathogen, 20% of the population is usually responsible for causing over 80% of all cases of the disease.

The good news is that the right control practices specific to how pathogens are transmitted – hand-washing, masks, quarantine, vaccination, reducing social contacts and so on – can slow the transmission rate and halt a pandemic.