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Upon hearing that a surge of COVID-19 cases could consume all hospital ventilators, Dr. Stephen Richardson rummaged for parts in the medical device lab at the University of Minnesota and built a homemade version.

In a first test last week, the prototype kept a pig breathing for an hour and raised the prospect that low-budget ventilators could be built to solve a shortage. The makeshift ventilator was made from $150 in parts, with a motor ripped from another device and a red metal toolbox tray as its base.

"We just went full-on MacGyver," said Richardson, a cardiac anesthesiologist at the U. "This device is designed to give people a chance."

The attempt is one of several launched in one week at the U, which has refocused its know-how in translational research on how to prevent, treat and manage the global COVID-19 pandemic, which is caused by a new strain of coronavirus. The U has issued rapid response grants to researchers such as Richardson who are eager to test solutions, and has its institutional review board on standby to quickly consider the ethics of any human trials.

"We're going to learn an enormous amount about the virus and where the targets are" to attack it, said Dr. Timothy Schacker, the U medical school's vice dean of research.

The U already has two clinical drug studies underway and a third awaiting approval by the U.S. Food and Drug Administration. A cell therapy trial could come next.

One trial involves a 65-year-old drug for malaria that is already being used off-label by some doctors and has shown potential in a handful of studies worldwide. Chloroquine and its cousin, hydroxychloroquine, drew immediate interest from researchers because prior studies unexpectedly found that they have an impact on the ACE-2 receptor in cells — the same receptor that the coronavirus uses to infiltrate cells and multiply.

While other studies are exploring its ability to treat COVID-19, the U's Dr. David Boulware decided to recruit 1,500 people at high risk of COVID-19 infection to see if the malaria drug could stave off symptoms.

"There's a little bit of a window there to intervene and prevent infection," he said.

If successful, the drug would be a powerful tool in the back pockets of doctors and nurses working with infected patients. People living with infected patients also could take it to reduce their risks, rather than simply waiting in quarantine themselves to see if they also get sick.

"Instead of just using 14th-century quarantine technology, can we do something better than that?" Boulware asked. "We're using 1955 technology instead, so we've advanced a couple centuries at least."

Flurry of activity

The number of Minnesotans under self-quarantine is far beyond the household contacts of the more than 115 confirmed COVID-19 cases. The current state recommendations don't even require a COVID-19 diagnosis. Anyone living with someone who has fever or respiratory illness should remain in quarantine for 14 days to see if they get sick themselves.

The university also is one arm of a multisite national trial of remdesivir, an experimental drug that failed in prior studies to treat infections from the Ebola and Marburg viruses. Animal studies found it had potential against coronaviruses, such as the one responsible for the 2002 SARS epidemic, so the U and others will test it on hospitalized patients with severe COVID-19 disease.

A third U-generated trial, awaiting FDA approval, would test whether a blood pressure-lowering medication, losartan, minimizes the damage of COVID-19. When infection stops ACE-2 receptors from working, there is a buildup of a hormone called angiotensin II that causes lungs to constrict and fluid to build up, explained Dr. Michael Puskarich, who will be leading an arm of this trial at Hennepin Healthcare in downtown Minneapolis.

"Our main goal is to essentially stop that process," he said.

The trial would consist of 700 patients treated for COVID-19 in a group of local hospitals or clinics.

The flurry of activity on campus started March 13, when the university agreed to review and fund rapid response grants from its scientists. Eleven of 20 have been funded, and others are being reviewed.

Richardson said he awoke two days later with the gut feeling that he could quickly create a ventilator using common "ambu" bags that paramedics and emergency medicine specialists use to manually resuscitate patients. All that was needed was an automated mechanism that could press the bag, and a way to adjust it to control the volume and limit the pressure of air being pushed into patients.

"This is not a device that anyone would choose to use if they had a ... super high-end alternative," he said. But it could be sold as a cheap backup, or its plans could be distributed online so hospitals could build their own.

Richardson called friends from MGC Diagnostics in Vadnais Heights, and soon they were scavenging parts from devices and soldering them together for the prototype. After success in maintaining lung function in a pig, Richardson sought a more sophisticated prototype and gained custom parts from Protolabs in Maple Plain, and motors and electrical equipment from Digi-Key of Thief River Falls and other companies.

FDA approval could be a hurdle, because the federal agency is deliberate in reviewing the safety and efficacy of devices before allowing them to be used clinically. However, Richardson said the agency has already issued emergency declarations for rapid production of new diagnostic and personal protective equipment amid this pandemic, and could issue a similar declaration for ventilator equipment.

Other startup efforts at the U include research by virologist Ryan Langlois to use methods he developed for studying influenza on the novel coronavirus and potential drug therapies instead.

The U also has been a leader in the study of NK (natural killer) cells, and researchers are eyeing ways to coax these human immune system cells into fighting COVID-19 as well.

Cautious optimism

U researchers are tempering optimism, though. Promising global studies haven't panned out yet. Use of an antiviral HIV treatment in China failed to produce a benefit for COVID-19 patients, according to a study last week in the New England Journal of Medicine.

The malaria drug trial to prevent COVID-19 in high-risk patients could be among the quickest to produce results. Recruiting started last week for 1,500 people at high risk for COVID-19 exposure who are living with infected patients.

Volunteers will either have the medication or non-medicating placebo pills delivered to them and will then submit updates about whether they develop symptoms or need to be hospitalized.

The U's IRB wrestled with the question of giving placebo pills to a control group amid a pandemic, especially given that some doctors are already prescribing the real drug off-label. Researchers also had to figure out a way to make sure that they were mailing study drugs to patients with truly high risks of exposure, and not just hoarders in search of COVID-19 drugs.

Boulware said the trial was deemed ethically appropriate because the drug has promise, but also potential risks that can only be assessed through research. Some researchers have theorized that drugs targeting ACE-2 receptors could actually accelerate the replication of the novel coronavirus.

"Some people are ... just giving the drug to people, and fair enough," Schacker said. "But we are trying to see: Is this the safe thing to do and does it help people?"