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UC San Diego Health Sciences

Author: leo

— Research

Necessity is Another Invention

Urgent needs galvanized collaboration between doctors and engineers

— By Ioana Patringenaru

The first months of the COVID-19 pandemic were marked, contrarily, by both scarcity and abundance. Personal protective equipment, such as masks and face shields, were in short supply. Access to ventilators, critical to keeping patients breathing, was limited. That scarcity evoked an abundance of anxiety and concern. 

While UC San Diego Health supply chain administrators scoured sources, known or new, for more of just about everything (often with remarkable success), students and faculty across campus stepped up to fill in the gaps with imagination and invention. 

In particular, UC San Diego Health physicians and engineers at the Jacobs School of Engineering worked hand in hand to build emergency ventilators and tools to help protect clinicians and patients alike. Many labs with laser cutters and 3D-printers began making face shields. Some of these efforts were suspended once regular supply chains were re-established, but others continue.

For example, James Friend, PhD, a professor in the Department of Mechanical and Aerospace Engineering; Lonnie Petersen, MD, PhD, also in the department and an adjunct professor in radiology at UC San Diego Health; and assistant project scientist Casper Petersen, MD, worked with students to design and build an emergency ventilator that converted a manual ventilator (patient face mask and bag that is squeezed by hand to push air into the patient’s lungs) so that it worked mechanically without constant human operation. The team worked closely with anesthesiologists and respiratory therapists to ensure the device met specifications and requirements. 

The resulting ventilator’s blueprints are available under an open source patent. Manufacturing costs are approximately $500, while state-of-the-art mechanical ventilators cost at least $50,000. Components can be rapidly fabricated and assembled in 15 minutes. Researchers are still gathering data about the device.  “Over the next couple of years we will find new applications for this work,” said Petersen. 

“Over the next couple of years we will find new applications for this work”

— Lonnie Petersen, MD, PhD

Friend also collaborated Timothy Morris, MD, a pulmonologist at UC San Diego Health, to develop a vacuum exhausted isolation locker, dubbed VEIL. The device is essentially a large bubble placed over a supine patient’s head and upper body, creating an oxygen-rich environment that also prevents air — and possibly droplets contaminated by the SARS-CoV-2 virus — from leaving the enclosure. The project was supported by the Galvanizing Engineering in Medicine program at UC San Diego, along with seven other projects. The work also received support from the Prototyping Lab at the Qualcomm Institute.

A description of VEIL was published in the Journal Infection Control & Hospital Epidemiology and some of the finished devices were used in clinical practice. A second type of protective box, called Coronavirus Safety during Intubation and Extubation or COSIE, was designed to protect physicians ventilating patients from aerosols and droplets. Field tests for COSIE were published in the Journal of Cardiothoracic and Vascular Anesthesia.

Numerous other projects came to the fore. Among them: Nanoengineers led by Jessie Jokerst, PhD, associate professor, developed a color-changing test strip
that can be applied to face masks to detect SARS-CoV-2 on people’s breath or saliva. The approach is designed for daily COVID-19 surveillance in high-density, indoor settings, such as hospitals, nursing homes, shelters and prisons. 

Ben Smarr, PhD, assistant professor in the Department of Bioengineering, partnered with colleagues at UC San Francisco and Massachusetts Institute of Technology to determine whether data collected by devices worn on the finger can be reliably used to detect the onset of fever, a leading symptom of both COVID-19 and the flu. Early data from a multi-institution research study involving more than 65,000 participants called TemPredict suggests the answer is yes. Research is ongoing. 

Nicole Steinmetz, PhD, professor of nanoengineering; Jon Pokorski, PhD, associate professor of nanoengineering; and colleagues are using plant viruses to develop various technologies related to COVID-19, such as probes for testing and new platforms to create stable vaccines.

UC San Diego scientists, engineers and physicians continue to press ahead on these and other ideas. Some are big and bold, some perhaps less so, like a sensor that can measure temperature and respiration, both key vital signs for monitoring patients with COVID-19 and other conditions. The sensor is tiny, literally as obvious as Lincoln’s nose on a penny.

— Research

Zoo Gorillas Test Positive for Coronavirus

UC San Diego Health physicians assist in treatment

— By Scott LaFee

Experts say COVID-19 is a zoonotic disease. The virus that causes it — SARS-CoV-2 — jumped from one species, perhaps a bat, to humans. That assumption continues to be investigated, but one thing is clear: COVID-19 is not strictly a human disease.

Though people are its primary victims, there have been SARS-CoV-2-positive cases reported in domestic cats and dogs, minks, ferrets, cougars, lions, leopards and tigers.

In January 2021, western lowland gorillas at the San Diego Zoo Safari Park were added to the list. It became international news, in part because of what it might portend for all life on Earth.

It’s not known exactly how the gorillas became infected. Best guess: They picked up the virus from an infected, but asymptomatic, wildlife care specialist. Nearly half of the pandemic’s spread can be attributed to asymptomatic infections, says the CDC.

“The closer you are on the evolutionary tree, the more likely you are to be susceptible to the same disease. ”

— Pascal Gagneux, PhD

Transmission is also easier when species are related. Both humans and gorillas are primates, sharing approximately 98 percent of the same DNA. “The closer you are on the evolutionary tree, the more likely you are to be susceptible to the same disease,” Pascal Gagneux, PhD, associate director of the Center of Academic Research and Training in Anthropogeny at UC San Diego, told The San Diego Union-Tribune.

Two diagnosed gorillas subsequently infected others in the eight-ape troop, but most of the apes experienced only minor symptoms — sneezing, coughing, lethargy and fatigue — and all fully recovered. A 49-year-old silverback named Winston suffered heart issues and pneumonia, but recovered after receiving experimental antibody treatment.

“UC San Diego Health was involved in
consultations with the zoo.”

— Jess Mandel, MD

“UC San Diego Health was involved in consultations with the zoo,” said Jess Mandel, MD, chief of the Division of Pulmonary, Critical Care and Sleep Medicine. “We helped review Winston’s chest CT and also advised regarding treating him with monoclonal antibodies and other therapies. It was a unique collaboration that combined UC San Diego Health’s expertise in treating patients with COVID-19 and the zoo’s expertise with nonhuman primates.”

In March, the zoo’s four orangutans and five bonobo chimpanzees were inoculated with an experimental vaccine developed by a veterinary pharmaceutical company.

— Research

Necessity is Another Invention

Urgent needs galvanized collaboration between doctors and engineers

— By Michelle Brubaker

As researchers expanded investigations into how the SARS-CoV-2 virus spreads, infects and who is most vulnerable, scientists at UC San Diego School of Medicine, in part supported by the Family Larsson-Rosenquist Foundation, focused on a particular aspect: breastfeeding women and breast milk.

In particular, they launched studies to determine whether COVID-19 is transmitted via human milk and whether human milk can protect infants from COVID-19.

To the first question, the answer appears to be no. A study published August 19, 2020 in JAMA analyzed 64 samples of breast milk collected by the Mommy’s Milk Human Milk Research Biorepository from 18 women across the United States infected with SARS-CoV-2. Although one sample tested positive for viral RNA, subsequent tests found that the virus was unable to replicate, and thus unable to cause infection in breastfed infants.

“The closer you are on the evolutionary tree, the more likely you are to be susceptible to the same disease. ”

— Pascal Gagneux, PhD

“Detection of viral RNA does not equate to infection. It has to grow and multiply in order to be infectious, and we did not find that in any of our samples,” said Christina Chambers, PhD, MPH, co-principal investigator of the study, professor of pediatrics at UC San Diego School of Medicine, director of Mommy’s Milk Human Milk Research Biorepository and co-director of the UC San Diego Center for Better Beginnings. “Our findings suggest breast milk itself is not likely a source of infection for the infant.”

The answer to the second question will take longer. Research is on-going, with study volunteers in the United States and Canada being monitored while breastfeeding and following infection. Scientists will also track infant growth and development via the child’s pediatrician for at least one year following infection.

“We already know breast milk contains properties that help protect infants from diseases, such as diarrhea and pulmonary infections. We want to know whether breast milk components, with their antiviral properties, might actually protect infants from COVID-19,” said Lars Bode, PhD, director of UC San Diego’s Larsson-Rosenquist Foundation Mother-Milk–Infant Center of Research Excellence (MOMI CORE).

“We want to know whether breast milk components, with their antiviral properties, might actually protect infants from COVID-19.”
Lars Bode, PhD

— Research

Necessity is Another Invention

Urgent needs galvanized collaboration between doctors and engineers

For the first few months of the pandemic, SARS-CoV-2 was called simply “the novel coronavirus,” “novel,” meaning scientists hadn’t seen it before. And yet the ability to see — really see, at the atomic level — what a microbe looks like and how it interacts with human cells is crucial in helping researchers design better methods to prevent or disrupt those interactions.

Rommie E. Amaro, PhD, professor in the UC San Diego Department of Chemistry & Biochemistry, and collaborators, were among the first to get a close look. They created models of the virus and its interactions with human cells, based on structural data generated from cryo-electron tomography and cryo-electron microscopy — leading-edge techniques that allow researchers to glimpse molecular structures at unprecedented resolution — and a combination of computer modeling and molecular dynamics simulations.

The models revealed a trove of information. For example, SARS-CoV-2’s infamous spike protein, protrusions that help it grab hold of human cells, is coated in sugar molecules known as glycans. These glycans change the spike protein’s shape — important information for researchers trying to target it with new drugs, or drum up antibodies against it with vaccines.

A

THE VIRUS. The spike proteins protruding from the virus’ spherical lipid bilayer are shown in gray, with glycans highlighted in dark blue.

B

The spike protein. This is the SARS-CoV-2’s spike protein in its open state. The spike protein is shown in cyan and the sugars forming a so-called “glycan shield” are depicted in dark blue. The spike is embedded in the viral membrane, shown at the bottom as multicolored carpeting.

C

The infection. SARS-CoV-2 (top) latches onto the ACE-2 receptor (yellow), a molecule on the surface of human cells that the virus uses like a doorknob to gain entry and establish infection.

A. THE VIRUS
Image credit: Lorenzo Casalino
Modeling credit: Abigail C. Dommer, Lorenzo Casalino
Zied Gaieb, Rommie E. Amaro

B. THE SPIKE PROTEIN
Image credit: Lorenzo Casalino
Modeling credit: Lorenzo Casalino, Zied Gaieb, Rommie E. Amaro

C. THE INFECTION
Image credit: Lorenzo Casalino
Modeling credit: Lorenzo Casalino, Abigail C. Dommer Zied Gaieb, Emilia P. Barros, Rommie E. Amaro

— Research

Necessity is Another Invention

Urgent needs galvanized collaboration between doctors and engineers

— By Scott LaFee with David Pride, MD

Q&A

  • Question

    In the beginning of the pandemic, there was much concern and angst regarding COVID-19 testing in terms of accuracy of results, capacity and timing. You were deeply involved in developing and advancing testing throughout the pandemic. How would you describe that experience, the highs and lows?

    Answer:It was very difficult for clinical laboratories like ours early in the pandemic. We are accustomed to evaluating tests much more deeply than we were able to do before we started offering some of the tests we did earlier in the pandemic. It was also very problematic not to be able to give physicians definitive answers when they asked about the sensitivity and specificity of our tests. They simply hadn’t been studied well enough for us to have those answers. It was also quite problematic for laboratories like ours to have so many different tests simultaneously that all checked for the same virus. In general, we evaluate all the available tests and choose the one that works best or that best suits our institutional needs. Because there was such a limited supply of testing available, we often had to choose tests, even before we were able to evaluate how well they worked. This was, in essence, a lab director’s worst nightmare. In retrospect, we are relieved that most of the tests we chose work really well, and most importantly, are still available on the market because of their superior performances.

  • Question

    There is talk of an almost instantaneous breath test for COVID-19. Do you think that might happen, maybe before the next pandemic?

    Answer:It will be difficult for a COVID-19 breath test to rival the sensitivity/specificity that we have with our assays based on quantitative PCR. We find for many of the more rapid antigen assays the sensitivity would likely be too low to have a performance that would give us confidence in telling people they are not infected.

  • Question

    One observation you’ve made is that, even if a person isn’t infected by SARS-CoV-2, they are not virus-free. Quite the contrary: Bacteria residing in and on each of us outnumber human cells, and viruses outnumber bacteria — we each carry an estimated 380 trillion viruses. Your point is that most of these viruses are not dangerous, but simply part of the human virome. What is a virome and what’s currently known about it?

    Answer:Regardless of whether we are healthy or sick, we’ve all got viromes, which essentially are just collections of viruses that inhabit the human body. Many of these viruses infect the many bacteria that also live in the human body, and thus, we probably need to think about ourselves slightly differently than we probably do. That is, that we are collections of microbes that vastly outnumber our own cells, and that our bodies are fertile hunting grounds for viruses to attack their bacterial hosts. All of this goes on pretty much every second of every day, and we have very little insight into the fact that this is happening. We know that most, if not all human body surfaces, are inhabited by viruses. This competition for space and resources in the human body probably plays a role in our homeostasis, but this hasn’t been borne out so well by studies yet. We know that these viruses can change the bacterial communities and that these viruses can be readily shared with our close contacts. We believe that, because our bacterial microbiomes can be involved in helping determine healthy and disease phenotypes among us, the fact that viruses can attack these bacteria suggests that they may be involved in this process as well.

  • Question

    You’ve said the development of COVID-19 vaccines, and the underlying research, was the top scientific breakthrough of 2020. Why?

    Answer:Simply put, science doesn’t typically move at the speed that was observed earlier in the COVID-19 pandemic. Not only were vaccines developed in record time using existing technologies, but they were also tested in thousands of people to ensure they were safe and effective prior to being rolled out to millions across the world. This will go down as one of the top scientific breakthroughs, perhaps of all time, and we have to thank the scientists who developed the vaccines, the people who were willing to participate in these clinical trials without having foreknowledge of the potential beneficial or deleterious outcomes, and the regulatory agencies that worked closely with scientists to make all this happen. I don’t think the average person realizes how much everyone involved had to set aside their own personal biases, difficult working relationships, and even political disagreements to work together to do the most beneficial thing that they could to benefit the health of everyone.

  • Question

    Like many of your colleagues, you have cautioned about the dangers of antibiotic resistance, which you say is here to stay. But you also argue that there is much that can be done to mitigate antibiotic resistant bacteria, a public health challenge that the World Health Organization predicts might kill 10 million people annually by 2050. Antibiotics don’t work against viruses, which have different structures and methods of replication compared to bacteria. Apart from developing vaccines to prevent viral infections or reduce transmission, what is the remedy?

    Answer:Unfortunately, bacteria respond to what we do to them by developing resistance to antibiotics. It’s remarkable how bacteria will develop resistance specifically to antibiotics that are used in a particular hospital, but not some of those antibiotics that are used in other hospital systems. This reveals a key feature of bacteria: that they continually evolve to solve the problems that they are faced with, such as antibiotics. It is interesting to see that this is exactly what we are observing in the current virus pandemic. We responded by rapidly developing vaccines that had the potential to significantly reduce, if not eradicate, SARS-CoV-2. Instead of simply going away, the virus has evolved specific means to respond to what we have done. The virus has chosen to infect largely those who are unvaccinated and has even mutated to become clever enough to infect some who are vaccinated. This persistence despite our best efforts is real-time proof that this virus will continue to try to respond to what we do to eliminate it. It also strongly suggests that we must all get on the same page and have a coordinated response if we expect to eliminate it. If we do anything less, SARS-CoV-2 has proven that it will seek out refuge, mutate, and then potentially come roaring back

— Research

Necessity is Another Invention

Urgent needs galvanized collaboration between doctors and engineers

— By Heather Buschman, PhD

A molecule known as ACE2 sits like a doorknob on the outer surfaces of cells that line the lungs’ passageways. Since early 2020, researchers have known that SARS-CoV-2 primarily uses the ACE2 doorknob to enter these cells and establish a COVID-19 respiratory infection. Finding a way to lock out that interaction as a means to treat infection has become the goal of many research studies.

To speed up the search, many researchers have turned to testing repurposed drugs — medicines already known to be safe for human use because they are FDA-approved for other conditions.

Before it became infamous for its role in COVID-19 infections, ACE2 was known to regulate blood pressure. And since prescription statins — widely used cholesterol-lowering drugs — can affect ACE2, UC San Diego Health researchers analyzed the electronic medical records of 170 statin-taking patients with COVID-19 to see what effect the medications had on virus vulnerability.

They found that statin use prior to hospital admission for COVID-19 was associated with a more than 50 percent reduction in risk of developing severe COVID-19, compared to those with COVID-19 but who were not taking statins. Patients with COVID-19 who were taking statins prior to hospitalization also recovered faster. The study, led by Lori Daniels, MD, professor and director of the Cardiovascular Intensive Care Unit at UC San Diego Health, and Karen Messer, PhD, professor and chief of the Division of Biostatics and Bioinformatics, was published in the American Journal of Cardiology.

Another UC San Diego School of Medicine team discovered that SARS-CoV-2 can’t grab onto ACE2 without a carbohydrate called heparan sulfate, also found on lung cell surfaces, where it acts as a co-receptor for viral entry. “ACE2 is only part of the story,” said Jeffrey Esko, PhD, Distinguished Professor of Cellular and Molecular Medicine at UC San Diego School of Medicine and co-director of the Glycobiology Research and Training Center. “It isn’t the whole picture.”

“The closer you are on the evolutionary tree, the more likely you are to be susceptible to the same disease. ”

— Pascal Gagneux, PhD

Esko’s team discovered that heparin — an FDA-approved form of heparan sulfate widely used to prevent and treat blood clots — reduces the ability of SARS-CoV-2 to infect human cells cultured in the lab by up to 90 percent. Essentially, the heparin acts as bait to lure and bind the coronavirus, keeping it away from human cells. The study was published in Cell.

Elsewhere, UC San Diego physician-scientists like Constance Benson, MD, professor of medicine, and Dan Sweeney, MD, helped conduct clinical trials of remdesivir, an antiviral originally designed to treat Ebola and Marburg infections, and the first repurposed drug approved by the FDA for treating COVID-19. It was found to shorten hospital stays and recovery time.

Not every repurposed drug is a success story. Atul Malhotra, MD, research chief of pulmonary, critical care and sleep medicine at UC San Diego Health, led a Phase III clinical trial investigating whether tocilizumab, a monoclonal antibody treatment for arthritis and other inflammatory diseases, might significantly improve the outcomes of patients with severe COVID-19 pneumonia.

It did not, Malhotra and colleagues reported in The New England Journal of Medicine, though they did observe a modest decrease in length of hospital stays and days on mechanical ventilators. Even when repurposed drugs do not achieve hoped-for results, Malhotra said, lessons are learned, which can guide new studies and help focus attention where it is most effective.

— Research

Necessity is Another Invention

Urgent needs galvanized collaboration between doctors and engineers

— By Scott LaFee

Some of the resistance to wearing masks during the pandemic was fueled by the notion that the nose-and-mouth coverings impaired breathing, and thus cardiopulmonary function, especially during physical activity.

But a November 16, 2020 study published in the Annals of the American Thoracic Society by UC San Diego School of Medicine researchers, with colleagues in Canada and Washington state, found that while masks might feel uncomfortable, perhaps making one’s face hot and sweaty, there was virtually no empirical evidence that they significantly impaired lung function, even during heavy exercise.

“The closer you are on the evolutionary tree, the more likely you are to be susceptible to the same disease. ”

— Pascal Gagneux, PhD

“There might be a perceived greater effort with activity, but the effects of wearing a mask on the work of breathing, on gases like oxygen and CO2 in blood or other physiological parameters are small, often too small to be detected,” said first author Susan Hopkins, MD, PhD, professor of medicine and radiology.

Hopkins and co-authors reviewed all known scientific literature on the topic, including analyses of inhaled and exhaled gases, blood oxygen levels, effects on muscle blood flow, cardiac function and blood flow to the brain. There were no detectable physiological differences based on gender or age. The only exception were persons with severe cardiopulmonary disease in which even the smallest resistance to breathing might prompt dyspnea, the medical term for shortness of breath.

70% Reduced risk of SARS-CoV-2 infection when wearing a mask during high-risk exposures compared to not wearing a mask.