Harbor-UCLA wants to recruit most, if not all, of the trial's 500 participants from among the high-risk patients it already treats.

This article was published on Wednesday, August 26, 2020 in Kaiser Health News.

By Arthur Allen The patients at Dr. Eric Daar's hospital are at high risk for serious illness from COVID-19, and he's determined to make sure they're part of the effort to fight the disease.

He also hopes they can protect themselves in the process.

When Daar and his colleagues at Harbor-UCLA Medical Center on Wednesday announce the start of enrollment for a trial to test a COVID-19 vaccine produced by AstraZeneca, they will also unveil the hospital's community-based recruitment strategy.

Harbor-UCLA wants to recruit most, if not all, of the trial's 500 participants from among the high-risk patients it already treats: people over 65, those with chronic illnesses and members of underserved racial and ethnic groups. Hospital officials also expect that the recruitment task will not be easy.

"It's a priority and obligation to make sure our community is well represented in these trials," said Daar, chief of HIV medicine at Harbor-UCLA and a researcher at the UCLA-affiliated Lundquist Institute, who dropped his other research projects last spring to focus on a COVID-19 vaccine.

The safety-net hospital in Torrance, California, serves patients in the South Bay area of Los Angeles County who are predominantly Black, Latino and Pacific Islander. Many live in crowded homes and do "essential" work that requires them to expose themselves to the virus to make a living: They're orderlies and cooks and house cleaners, day laborers and bus drivers and sanitation workers.

The area has high rates of heart disease and stroke.

"If you don't have a community represented in the trial, it's hard to extrapolate your results to the community," said Dr. Katya Corado, one of Daar's colleagues. "We want to find something to protect our patients and loved ones."

Latinos and Blacks in the United States are nearly three times more likely than non-Hispanic whites to be diagnosed with COVID-19 and nearly five times more likely to be hospitalized with the disease. In Los Angeles County, Latinos in particular have been disproportionately stricken by the virus.

Eight of 10 COVID-19 deaths nationwide occur among people 65 and older, according to the Centers for Disease Control and Prevention.

Historically, Blacks and Latinos have been less likely to be included in clinical trials for disease treatment, despite federal guidelines that urge minority and elder participation.

The National Institutes of Health and the Food and Drug Administration have urged infectious disease researchers to focus on these vulnerable populations in the large phase 3 trials that will test how well vaccines prevent COVID-19.

Harbor-UCLA, a public teaching hospital owned and operated by Los Angeles County, is one of roughly 100 sites nationwide testing the AstraZeneca vaccine candidate, which was developed in collaboration with Oxford University in Britain. Phase 3 trials of about the same size for vaccine candidates produced by Moderna and Pfizer are already underway. Each of the three companies seeks to recruit 30,000 people, 20,000 of whom will get the vaccine and 10,000 a placebo, or harmless saline solution, to test whether the vaccine prevents coronavirus disease.

Recruitment at Harbor-UCLA will include patients with well-controlled chronic diseases such as diabetes and hypertension, and people with HIV who've kept the virus under control with medication, Daar said.

According to the AstraZeneca trial protocol, patients will get up to $100 for each of 15 to 20 visits during the two-year trial. The Harbor-UCLA team will also offer car services to bring people to the hospital through L.A. traffic.

To reach its targeted recruits, the hospital will distribute leaflets to clinics and community organizations and create targeted social media campaigns, in addition to taking any free publicity it can get, Daar said.

Recruitment of high-risk patients in other COVID-19 trials so far has been mixed. Moderna, which began the first phase 3 trial of the experimental vaccines on July 27, announced Friday that 18% of its 13,000-plus enrollees so far were Black, Latino or Native American — a high percentage as clinical trials go, but only about one-third of the goal set by NIH officials.

Other AstraZeneca trial sites have also publicized their efforts to reach those most at risk from the virus. The University of Southern California's Keck School of Medicine placed one of its AstraZeneca recruitment sites in Vernon, south of downtown Los Angeles in an area with many factories and meatpacking plants, which have experienced high COVID-19 infection rates.

Clinicians suspect that the higher rates of disease and hospitalization in minority groups are due both to health conditions — such as undertreated diabetes and heart disease — and to higher exposure to the virus in workplaces and crowded housing. Environmental factors like polluted neighborhoods may also have an impact.

While there's little evidence that vaccines affect Blacks or Latinos differently than white people, the subject hasn't really been studied, said Dr. Akilah Jefferson Shah, an allergist/immunologist and bioethicist at the University of Arkansas for Medical Sciences. That's another reason for making sure these groups are well represented in trials, she said.

"We know now there are subgroup responses to drugs by sex, but no one figured it out until they started including women in these studies," Jefferson Shah said. "Race is not genetic. It's a social construct. But there are genetic variants more prevalent in certain populations. We won't know until we look."

Perhaps most important, diversity in the research will be needed to build trust and uptake of the vaccine, Corado said. In a May poll from the Associated Press-NORC Center for Public Affairs Research, just 25% of Blacks and 37% of Hispanics said they would definitely seek vaccination against the coronavirus, compared with 56% of whites.

In July, the Harbor-UCLA vaccine team began holding weekly Zoom meetings with about 25 activists and clergy members to learn what their communities were saying about the vaccine and get tips on how to design educational materials for the trial.

What they've heard suggests they'll have an uphill recruitment battle.

One member of the community council, HIV activist Dontá Morrison, noted that people frequently say on social media that the vaccine is designed to give them COVID-19 as part of a plot to get rid of Black voters. (None of the vaccines contains infectious COVID virus.)

"It may seem far-fetched, but those are the conversations because we have an administration that has not shown itself to be trustworthy," Morrison said.

He noted that the first challenge UCLA researchers face is to convince community leaders, particularly clergy members, of the vaccine's safety. Church leaders worry they'll be blamed for supporting the trial if the vaccine ends up making their congregants sick, he said.

If done right, the trial could build trust in medical science while helping minorities help themselves — and the rest of us — find a way out of the current mess, Morrison said.

Dr. Raphael Landovitz, another UCLA scientist working on the trial, agreed.

"We're hoping that people understand this is a chance — if we succeed — to take back some power and control in this situation that has made so many of us feel so powerless," he said.

This KHN story first published on California Healthline, a service of the California Healthcare Foundation.

Arthur Allen: ArthurA@kff.org

Most Americans alive today have never before had to make that self-assessment.

This article was published on Tuesday, August 25, 2020 in Kaiser Health News.

By Elisabeth Rosenthal, MD.

As some parts of America gingerly begin to open up after months of near-total lockdown, people have questions. Will it be safe to take a train? A plane? Visit the hair salon? An indoor restaurant?

There are many knowable parameters in the equation: your health; the prevalence of cases where you live; the safety precautions being taken anyplace you want to visit. But the final answer may depend on your individual risk tolerance for exposure to infectious disease.

Most Americans alive today have never before had to make that self-assessment.

In the past, deadly outbreaks of plague, flu and polio were regular occurrences. Up until the mid- to late 20th century there were mumps, measles and chickenpox to contend with.

In a world of effective antibiotics and antivirals and other treatments, deaths or even serious illnesses from infectious disease seem nearly incomprehensible. So our fear is enormous, and our risk tolerance for exposure is just about zero.

I hear too many people saying "I'm not going back to life until there's a vaccine" — as if that will immediately eliminate the risk. It won't. Even if one of the current vaccine candidates works, it could be quite a while before it's widely distributed. And to be approved by the Food and Drug Administration, it must protect only half of the people taking it from infection.

For the foreseeable future, we will be living in a world with some level of the coronavirus out there. So if we want to get out of our bunkers, we all need to take stock of our risk tolerance.

As a doctor, I worked in a New York City emergency room and in a remote coastal clinic in Kenya, and then I became a journalist covering disease. I've had to measure my risk tolerance for infection in different situations.

Once, collecting blood from an AIDs patient, I couldn't feel the artery through my glove. The glove came off.

Treating a patient with multi-drug-resistant tuberculosis, I pulled my surgical mask a little tighter, made sure the windows were open and — irrationally — tried to breathe in less.

Reporting from the animal market where the SARS outbreak is thought to have started, I told myself that I should be OK, since it was outdoors. But I stayed away from animals being slaughtered, didn't touch any surfaces and took off my shoes before entering my hotel room.

Note that these decisions do not mean ignoring the data and infectious disease specialists' recommendations, as some conservatives are doing as they push ahead to reopen schools, businesses, restaurants and sports events.

Actually it's kind of the opposite: Accepting risk doesn't mean throwing caution to the wind. It means taking all precautions and deciding you can live with the very reduced risk that remains.

With the coronavirus, the only way to possibly eliminate risk is essentially to move to a house in the countryside and live in your family bubble. And many Americans, particularly wealthy ones, have done just that. This personal response was extreme, but it felt rational to many people because our national response to the coronavirus was so scattershot, flat-footed and incompetent.

But isolation is wearing thin.

So as states and cities engineer sensible reopening policies, everyone is going to have to assess their risk tolerance and cautiously push their personal boundaries bit by bit.

Some, of course, never got to make this decision. Risk tolerance is about duty and conscience but very often it's also about how much you need a paycheck.

Doctors, nurses and others who work in healthcare had no choice but to dive in. These folks did not, as so many have claimed, go into the profession "knowing the risks." They came to work knowing that the risk of infectious diseases could be controlled with careful precautions. That's why they felt angry and betrayed when they were asked to fight the novel coronavirus without an adequate supply of protective gear or (in some places) training about the new pathogen. And, tragically, some died as a result.

Now many physicians I know in COVID-19 hot spots say they actually feel safest in the hospital, where procedures like masking and sanitizing are assiduously followed. (Hell hath no fury like a surgeon who witnesses a medical student touch a sterile surface with an unsterile hand.) In contrast, on the sidewalk, the coronavirus could be roaming free if people aren't wearing masks.

Which is why masking should be mandated and enforced. It's not just about your individual risk tolerance but about keeping everyone safe.

In addition to wearing masks and social distancing when not at home, we should avoid prolonged periods in indoor spaces with crowds or strangers; wash or sanitize our hands — a lot — and try not to touch "high-touch" surfaces that hundreds of people have grabbed before. (Note to my local post office: You should have some kind of automatic door rather than require everyone to pull the handle!)

And we have to demand that anywhere we go — bookstores, medical offices, trains or hair salons — requires that patrons follow these guidelines. I, for one, won't enter if they don't.

I do not blame teachers for being unwilling to return to school in places where administrators and officials have been in denial about COVID-19 or have been unwilling or unable to do this preparatory work. But once schools have put in place appropriate science-based steps, most teachers (those not in high-risk groups) should return to their jobs.

COVID-19 is a very serious disease. But it is not the Black Death, which killed up to half of Europe in the 14th century. A vaccine, when and if it arrives, will be a big help. But in the meantime, we have science. We know what causes COVID-19. We are learning more about how to detect, prevent and treat it every day.

So instead of taking your temperature and checking your pulse oximeter reading twice a day, it may be time to take stock of your risk tolerance. In those places where governments, businesses and administrators have set the stage properly, we can — with sensible precautions — begin to live again.

Elisabeth Rosenthal: erosenthal@kff.org, @rosenthalhealth

Two manufacturers that have received FDA authorization say their antigen tests are intended for patients with symptoms, calling into question how valuable the tests would be for broad screenings.

This article was published on Monday, August 24, 2020 in Kaiser Health News.

By Rachana Pradhan

The Trump administration's latest effort to use COVID-19 rapid tests — touted by one senior official as a "turning point" in arresting the coronavirus's spread within nursing homes — is running into roadblocks likely to limit how widely they'll be used.

Federal officials are distributing point-of-care antigen tests — which are cheaper and faster than tests that must be run by a lab — to 14,000 nursing homes to increase routine screening of residents and staff. The initial distribution targets nursing homes in hot spots and those with at least three COVID-19 cases, senior Trump administration officials said in July, hailing it as a tool that could root out asymptomatic carriers who might still infect others.

But there's a hitch: Two manufacturers that have received Food and Drug Administration authorization and whose instruments are being delivered — Becton, Dickinson and Co., known as BD, and Quidel — say their antigen tests are intended for patients with symptoms, calling into question how valuable the tests would be for broad screening purposes. The Centers for Disease Control and Prevention estimates 40% of infected people may be asymptomatic.

"It's important always to use a diagnostic in the way that it has been designed to be used," said Elizabeth Talbot, New Hampshire's deputy state epidemiologist. "We simply don't know how [the tests] will perform in persons who are asymptomatic."

Perhaps the highest-profile example of the problem occurred in Ohio this month, when Gov. Mike DeWine had no symptoms and tested positive for COVID-19 with Quidel's antigen test. Within hours, the Republican governor's diagnosis was reversed after he got a PCR test.

"People should not take away from my experience that testing is not reliable or doesn't work," DeWine said on CNN after his false-positive diagnosis. "The antigen tests are fairly new," he said. "We're going to be very careful in how we use it."

The bigger problem is false-negative results, which show someone isn't infected when they actually are. BD's false-negative rate — how often a test incorrectly says someone isn't infected — is about 15%; Quidel's is 3%.

Quidel and BD say their tests are intended to be used for people within the first five days of showing symptoms. A spokesperson for BD said its test should not be used on asymptomatic individuals. Quidel through a spokesperson deferred to FDA guidelines, which allow asymptomatic testing in certain scenarios.

"For routine surveillance, this is a great tool and these are our best tools that we have available," said Adm. Brett Giroir, assistant secretary for health at the Department of Health and Human Services, on a July call with nursing home officials, according to a recording obtained by KHN. Seema Verma, the administrator of the federal Centers for Medicare & Medicaid Services, on the call referred to the effort as a "turning point" in the fight against the virus.

A month after the initial announcement, the Trump administration invoked the Defense Production Act to bump its contracts with the two companies to the front of the line and expedite shipments. BD will send roughly 11,000 devices and 3.75 million tests to nursing homes; Quidel and HHS declined to answer questions about its volume.

As states and the federal government move to mandate COVID testing inside nursing homes, whose patients are deemed highly vulnerable to infection and severe complications, several industry officials have said they hoped to use the tests on asymptomatic people. But many states restrict the use of antigen tests or still require lab-based testing because of accuracy concerns.

If a person with a negative test result has to default to getting a more accurate PCR test, "then we simply have just added time and cost," Talbot said. "That's a problem."

Officials said the antigen test announcement caught them by surprise, underscoring the administration's chaotic testing strategy. Separate from the federal effort, 10 states have banded together through the Rockefeller Foundation to secure 5 million tests from the two companies in hopes of curbing the virus's spread this fall.

After nursing homes receive an initial batch of tests — each facility gets between 150 and 900 — they would have to buy future supplies. Medicare will cover the costs of diagnostic tests but not expenses for routine surveillance.

"I just have a lot of skepticism," said Brendan Williams, president of the New Hampshire Healthcare Association, which represents nursing homes and assisted living facilities in the state. "Basically you're giving some lousy tests for nursing homes and you're making them pay for them. I don't see that as a win; I see that as a risk."

Public health experts have become increasingly vocal that frequent rapid testing is the best tool for stopping the virus — which has killed more than 174,000 Americans including tens of thousands in nursing care — rather than relying on more accurate lab-based tests that have been plagued by delays and shortages. In a call this month with the industry, Verma estimated that half of the country's nursing homes have experienced cases.

"I don't see an avenue where these will not help to stop transmission chains, and I don't see another option on the table for us," said Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health and a proponent of rapid tests. "It is what we need to be doing right now."

"This is better for the folks in our buildings, without a doubt," added Jason Belden, director of emergency preparedness and physical plant services for the California Association of Health Facilities.

In theory, antigen tests can serve dual purposes — diagnosing a person with a suspected infection or screening a group of people to more quickly identify sick individuals. The tests by Quidel and BD, under their FDA authorizations, can be used on certain asymptomatic individuals, including those suspected of having COVID-19 after exposure to an infected person. The companies would need additional FDA authorization to screen any asymptomatic person regardless of whether they're suspected of being sick, according to agency guidelines.

The CDC has suggested antigen tests could be useful in high-risk settings if performed repeatedly. It said there was limited data to guide using them to screen asymptomatic people.

Nonetheless, HHS recommends universal screening of nursing home residents at least once and regular screening of staff regardless of symptoms, said agency spokesperson Mia Heck, citing the fact that COVID-19 viral loads are similar between patients with and without symptoms. "Only one test in the U.S. is authorized for asymptomatic individuals," she said, referring to a PCR test from LabCorp, "yet the overwhelming majority of testing is being done on asymptomatic individuals."

"If the world were ideal we'd say, 'Oh, we want the more accurate test.' But the more accurate test takes forever to get the results back," said Peter Van Runkle, executive director of the Ohio Healthcare Association, which represents the state's nursing homes.

All targeted nursing homes will receive tests by the end of September, according to federal officials, who recently announced that facilities in states with a positivity rate of at least 5% must test staff each week.

"I don't see this as a federal strategy so much as a stopgap method to bring a little relief to nursing homes," said Katie Smith Sloan, president of LeadingAge, which represents nonprofit nursing homes. "It's really tragic that we are where we are right now."

Boosted by $71 million in federal funds for Quidel and $24.3 million for BD, Quidel plans to produce 1.8 million tests weekly by September; BD will produce similar volumes by October.

"The situation is much too urgent to wait a few months so we can put bows and lipstick on the program. So we're going to build this plane a little bit while we're flying it," Giroir told nursing homes in July. "Just work with us. We want to get you what you need. And then in September, October you can get what you want."

States take different approaches in deploying antigen tests in nursing homes; in at least seven — including California, Illinois and Maryland — officials say PCR tests should still be used to confirm results or to screen patients without symptoms. In Massachusetts, nursing homes must use PCR tests to meet surveillance requirements.

In Maryland, "our goal is to screen out staff who are positive as quickly as possible, particularly asymptomatic folks," said Dennis Schrader, chief operating officer of the health department.

Maryland nursing homes can use antigen tests for weekly staff testing if there isn't an outbreak. But if at least one person tests positive for the coronavirus, all staff and residents must be tested with PCR tests.

Rachana Pradhan: rpradhan@kff.org, @rachanadixit

Inspired to help during the COVID pandemic, a volunteer SWAT team of engineering and medical talent combines old-fashioned problem-solving and advanced 3D printing — but will it actually help?

This article was first published on Monday, August 24, 2020 in Kaiser Health News.

By Erin Schulte

As the coronavirus crisis lit up this spring, headlines about how the U.S. could innovate its way out of a pending ventilator shortage landed almost as hard and fast as the pandemic itself.

The New Yorker featured "The MacGyvers Taking on the Ventilator Shortage," an effort initiated not by a doctor or engineer but a blockchain activist. The University of Minnesota created a cheap ventilator called the Coventor; MIT had the MIT Emergency Ventilator; Rice University, the ApolloBVM. NASA created the VITAL, and a fitness monitor company got in the game with Fitbit Flow. The price tags varied from $150 for the Coventor to $10,000 for the Fitbit Flow — all significantly less than premium commercially available hospital ventilators, which can run $50,000 apiece.

Around the same time, C. Nataraj, a Villanova College of Engineering professor, was hearing from front-line doctors at Philadelphia hospitals fearful of running out of ventilators for COVID-19 patients. Compelled to help, Nataraj put together a volunteer SWAT team of engineering and medical talent to invent the ideal emergency ventilator. The goal: build something that could operate with at least 80% of the function of a typical hospital ventilator, but at 20% or less of the cost.

For decades, Nataraj has worked on medical projects — like finding a better way to diagnose a potentially deadly brain injury in premature infants — primarily with doctors at Children's Hospital of Philadelphia and the Geisinger Health system in rural Pennsylvania, so key clinical players came together swiftly. By March 23, he had approached engineering faculty about collaborating on a monthslong effort to build the NovaVent, a basic, low-cost ventilator with parts that cost about $500. The schematics would be open-sourced, so others could use them free of charge to mass-manufacture the device.

The New Yorker wasn't alone in referencing the '80s TV series "MacGyver," whose protagonist was a Swiss Army knife-carrying secret agent who got the job done with wits and whatever was at hand. The suggestion was that these ventilators were simple enough to throw together with parts from a medical supply closet or your neighborhood hardware store. "Everybody can make it," one headline read, enticingly. These miracle machines, the thinking went, could be helpful in U.S. hospitals facing critical shortages, perhaps in cities surging with sick patients.

To understand the potential utility and true costs of these emergency ventilators, KHN followed Villanova's team for three months as it developed, tested and prepared to submit the NovaVent for Food and Drug Administration approval.

The team tapped a maker of car parts, along with roboticists. It gathered input from anesthesiologists as well as electrical, mechanical, fluid systems and computer engineers. It tapped nurses to help ensure that users would immediately know how to operate the ventilator. Local manufacturers 3D-printed pieces of the machine.

Nataraj and his team realized that some of the other ultra-bare-bones machines wouldn't meet the standards of the modern U.S. healthcare system. But they also believed there was a lot of room for Villanova's team to innovate between those and the high-end, expensive devices from corporations like Philips or Medtronic.

One thing is clear: The $500 ventilator is something of a unicorn.

While the parts for the NovaVent cost about that much, the brainpower and people hours added uncounted value. In the early phases, the core group — all volunteers — worked 20 to 25 hours a week, Nataraj said, mainly via Zoom calls from home on top of their day jobs.

Teams of two or three were allowed into the lab to work — virtually the only people on campus. The effort, after all, was in line with the university's Augustinian mission, which values the pursuit of knowledge, stewardship and community over the individual.

By the time they realized what they could achieve with the $500 model, the first wave of crisis had passed. Yet in those weeks, an alarm resounded across the land about the dismal state of America's public health system.

So the NovaVent mission pivoted: build better low-cost vents for hospitals in poor and rural U.S. communities that have few, if any, ventilators.

One immediate legacy of the innovation happening at Villanova and elsewhere is the public-spirited nature of the effort, said Dr. Julian Goldman, an anesthesiologist at Massachusetts General Hospital who helps set standards for medical devices: "People from different walks of life in terms of their skills — engineers, clinicians, pure scientists — all thinking and working to try to figure out how to move very quickly to solve a national emergency with many dimensions: How do we make the patient safer? How do we make the caregiver safer? How do we deal with supply chain limitations?"

From other ventures, new designs have already been used as a jumping-off point to build emergency ventilators overseas. They've also bolstered New York City's stockpile and could add to state and national reserves as well.

The early, urgent concerns about a looming ventilator shortage were well founded: On March 13, the U.S. had about 200,000 ventilators, according to the Society of Critical Care Medicine. But because of the surge of COVID patients, it was predicted the country could soon need as many as 960,000.

In early April, New York Gov. Andrew Cuomo said the state would run out of ventilators in six days, leaving doctors with the sort of grim calculation they'd heard about from hard-hit northern Italy: "If a person comes in and needs a ventilator and you don't have a ventilator, the person dies."

In Philadelphia, 12 miles east of Villanova, hospital administrators braced for shortages and reported short supplies of the drugs required to sedate patients on ventilators.

President Donald Trump invoked the Defense Production Act to get major manufacturers to make ventilators, though GM was already working on it. When GM signed a $500 million contract to deliver 30,000 ventilators to the U.S. government by August, the NovaVent team wondered whether its own efforts would be futile.

"We said, 'Well, GM is making it. Why are we making it?'" Nataraj said. "But there was a lot of uncertainty with the epidemiological models. We didn't know how bad it was going to get. Or [the curve] could completely collapse and there'd be no need at all."

And for a few weeks, it did seem the worst was over. The rate of new cases began to slow in the nation's early epicenters. Hot spots flared in nearly every pocket of the country, but those too were mostly contained.

People spilled back into normal life, gathering in backyards, beaches and bars. In June, news coverage moved on to the calls for racial justice and mass protests after the videotaped killing of George Floyd in the custody of Minneapolis police.

In the background, the highly contagious coronavirus tore across the South, through Florida, Georgia, Texas and Arizona, and surged in California. Some states reported ICU beds were quickly at or above capacity. This mercurial virus had proved uncontrollable, and the prospect of ventilator shortages had bubbled up once again.

Past pandemics have been mothers of innovation. Progress in mechanical ventilation began in earnest after a 1952 polio outbreak in Copenhagen, Denmark. According to the American Journal of Respiratory and Critical Care Medicine, 50 patients a day arrived at the Blegdams Infectious Disease Hospital. Many had paralyzed respiratory muscles; nearly 90% died.

An anesthesiologist at the hospital realized patients were dying from respiratory failure rather than renal failure, as was previously believed, and recommended forcing oxygen into the lungs of patients. This worked — mortality dropped to 40%. But one big problem remained: Patients had to be "hand-bagged," with more than 1,500 medical students squeezing resuscitator bags for 165,000 total hours.

"They'd recruit nurses and medical students to stand there and squeeze a bag," says Dr. S. Mark Poler, a Geisinger Health system anesthesiologist on the NovaVent team. "Sometimes they were just so exhausted that they would fall asleep and stop ventilating. It was obviously a catastrophe, so that was the motivation for creating mechanical ventilators."

The first ones were simple machines, much like the basic emergency-use ventilators created during the COVID crisis. But those came with hazards such as damaging the lungs by forcing in too much air. More sophisticated machines would deliver better control. These engineering marvels — the monitors, the different modes of ventilation, the slick touch-screen controls designed to minimize the risk of injury or error — improved patient treatment but also drove costs sky-high.

The emergency ventilators of 2020 focused on models that, typically, used an Ambu bag and some sort of mechanical "arm" to squeeze it. Most people are familiar with Ambu bags from scenes in TV programs like "ER" where paramedics compress the manual resuscitator bags to help patients breathe as they're rushed inside from an ambulance. The bags are already widely available in hospitals, cost $30 to $40 and are FDA-approved.

But making machines that are that simple could render them effectively useless (or, worse, dangerous). Medical experts watching university and hospital teams coalesce across the country this spring to develop low-cost emergency ventilators took notice — and worried.

Goldman, the Massachusetts General anesthesiologist, was among the medical experts nervous about all the slapped-together ventilators.

"We had the maker community being stood up very quickly, but they don't know what they don't know," said Goldman, chair of the COVID-19 working group for the Association for the Advancement of Medical Instrumentation, the primary source of standards for the medical device industry. "There were videos of harebrained ideas for building ventilators online by people who don't know any better, and we were very concerned about that."

The general public doesn't really understand the nuances required to build a safe medical device, Goldman said.

"They look at something and think, well, this can't be that hard to build. It just blows air," he said. "'I'll take a vacuum cleaner and turn it on reverse. … It's a ventilator!'"

AAMI wanted to encourage innovation, but also safety. So Goldman assembled a meeting of 38 engineers, regulators and clinicians to quickly write boiled-down guidelines for emergency-use ventilators.

The simplest ventilators were based on the idea of a piston in a car engine, Poler said: Put a piston on a crankshaft, hook it up to a motor and use a paddle or "arm" to compress the Ambu bag.

"It's better than no ventilator at all, but it goes at one speed. It doesn't really have any controls," Poler said — not ideal when patients need to be monitored for changes in how their lungs are responding, or not, to treatment.

Villanova's team of engineers, doctors and nurses realized that the simplest ventilators, the ones that AAMI was concerned about, seemed to ignore some basic, practical considerations: What sort of hospitals would these be used in, and under what conditions? What sorts of patients would be put on these ventilators? For how long? Would they be used as backups for higher-end ventilators? What about error alarms?

All good questions, Poler said, but the answer to all of them essentially is "we hope to never use these."

Their best use? "A surge situation where you simply don't have enough of the sophisticated ventilators."

Rather than go totally bare-bones, the Villanova team designed the devices as though they would one day be deployed in modern healthcare.

Flow sensors, which monitor patient ventilation, cost several hundred dollars, so the team designed its own in the lab and 3D-printed it at a cost of 50 cents, Nataraj said, enabled by strides in 3D-printing technology that have vastly cut the price of so many devices. Southco, a Pennsylvania-based global manufacturer that makes parts like the latch on your car's glove box, was tapped to use its 3D printers to make airflow tubes and couplings for the ventilator.

Garrett Clayton, director of Villanova's Center for Nonlinear Dynamics and Control, was the day-to-day keeper of the prototype. He was particularly excited about the addition of a handle, which made it easier for him, and eventually others, to lug the 20-pound device from the lab to home and back.

Clayton's computerized control system measures the flow rate of air going into the patient and converts it into volume, much as commercial ventilators do. That controls how hard and fast the Ambu bag is squeezed; it's made of a hobby-grade Arduino microcontroller board. A direct-current motor attached to a linear actuator with a fist-shaped piece of PVC on the end pushes the bag in and out. The operator of the ventilator can control the respiratory rate (the number of breaths per minute), as well as the ratio between inspiration and expiration and the volume of air going in.

While traditional ventilators have many control methods, Clayton's team focused on just one: how much volume is forced into the airway. "We have a set point so we don't damage the lung," he said.

Polly Tremoulet, a research psychologist and human factors consultant for ECRI and Children's Hospital of Philadelphia, was pulled in to focus on error messages and make sure the ventilators' buttons and displays "spoke the user's language," whether that user was an anesthesiologist in New Jersey or a nurse in India pulled into an ICU COVID ward.

Graduate student Emily Hylton and other nursing students were brought in to provide feedback about using the NovaVent and ask questions such as: Would all the controls and monitors look familiar to nurses at the bedside?

The very prospect of these low-cost devices is relatively new, Nataraj said, because of the price of microcontrollers with any real capacity: "Twenty years ago, they cost, oh gosh, $20,000 — and now they're $20."

By May 30, the first NovaVent prototype was complete. It was successfully tested on an artificial lung at Children's Hospital of Philadelphia on June 12. Villanova has applied for a patent for the NovaVent, to help ensure it won't be commercialized by others.

"If you make it free without having a patent, other people can take it and charge for it," Clayton said. "A patent protects the open-source nature of it."

Once a provisional patent is received, the team will submit the ventilator for Emergency Use Authorization from the FDA — hewing to the guidelines set up by AAMI.

Within weeks of kicking off the NovaVent project, the curve in the East Coast had indeed flattened, and states had enough standard ventilators to treat every patient. The life-threatening ventilator shortage had not materialized. Some of the emergency-use ventilators based on designs by other teams, like the one at MIT, did go into production — but even those didn't end up in hospitals, and instead went into city stockpiles meant to reduce potential future reliance on the federal government. So the Villanova team seized on a new, global mission.

"We thought if it wasn't useful in the U.S. market," Nataraj said, "we know the developing world, especially sub-Saharan Africa, Latin America and Central America, they don't have the same kind of facilities that we do here."

Where the ventilators might end up remains to be seen. Early on, Pennsylvania showed interest in helping Villanova find manufacturing partners. The team has spoken with engineers in India, Cambodia and Sudan (which reportedly has only 80 ventilators in the entire country) who are interested in possibly finding a way to manufacture the NovaVent.

Six thousand emergency ventilators based on the design by the University of Minnesota have been manufactured in the U.S., according to Dr. Stephen Richardson, a cardiac anesthesiologist who worked on that project. Three thousand were made by North Dakota aviation and agricultural manufacturer Appareo for state emergency stockpiles in North Dakota and South Dakota. UnitedHealth Group provided $3 million in funding to manufacture another 3,000 units made by Boston Scientific, which were donated to countries like Peru and Honduras through U.S. organizations; others were sent to the U.S. government.

Like the Villanova team, Richardson said he thinks the most promising potential for these ventilators is in developing countries.

"When we were arranging to get these donated to Honduras, we were speaking with a physician who was telling me that [at] his hospital right now, the med students are just hand-ventilating patients. For everything, and for COVID specifically," Richardson said. "Right now, in Pakistan or in any low-resource country, a family member is hand-ventilating a toddler. Before COVID and after COVID, this is a problem."

For Poler, the project was a reminder that the country needs to tend to its stockpiles. "People were thinking about [ventilator reserves] in the '90s, and then they basically quit thinking about it," he said. "COVID is a shocking reminder that we shouldn't have stopped thinking about it."

Goldman said the national efforts may not result in a flood of cheap ventilators in U.S. hospitals. International use could also be tricky. In countries with few resources, even very low-cost ventilators may not be feasible because of lack of electricity or compressed oxygen, though there is "potentially a sweet spot of need and capability where these things could be deployed."

On the upside, he said, the pandemic kicked off a nearly unprecedented global engineering effort to share information and solve the problem.

"If there's going to be a magic bullet to come out of this, it's going to be the capability of our communities and our infrastructure," he said. "People stood up, put in the appropriate processes and spirit, worked hard, made it happen. We've added resilience to the healthcare sector. That's the outcome here."

As for the NovaVent, team members were relieved they didn't have to rush it into manufacturing as COVID-19 was ripping through the Northeast this spring, thanks to aggressive efforts to flatten the curve. "We ended up without a ventilator shortage, which is excellent," Clayton said. "But with the increase in cases now, it's very possible some of them may get used."

To build on the project, Villanova is raising money for a laboratory for affordable medical technologies called NovaMed. The lab formalizes the process of making inexpensive medical equipment that follows the 80-20 function-to-cost rule. The university says the lab is "motivated by the belief that income should not determine who has access to lifesaving care."

The effort to prevent a ventilator shortage, Nataraj said, made him think more critically about the American healthcare system overall.

"How come we haven't built the technology, the economic and social systems that are able to handle a situation like this — especially when something like this was predicted?" he said. "It's absolute nonsense. Why should a single person die because we weren't prepared?"