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UC San Diego Health Sciences

Category: Research

— Research

Building Trust with Communities of Color: Lessons from the COVID-19 Pandemic

— By Edward “Lalo” Cachay, MD

People of color have died disproportionally due to COVID-19, highlighting the deep socioeconomic and health disparities that persist in our country.

The pandemic produced scientific innovation, from treatments to vaccines, at an unprecedented pace. Yet, only a small proportion of people who participated in COVID-19 clinical trials and vaccine development were people of color. To overcome this pandemic, we need broad acceptance and use of COVID-19 vaccines, especially among those most affected.

Unfortunately, vaccine hesitancy historically runs high among communities of color. At the core of this lack of participation in research by communities of color and vaccine hesitancy is enduring mistrust in the systems of medical research and care.

Medical mistrust results from an evolutionary form of resilience and a survival mechanism in response to chronic oppression. It provides a sense of control for people who feel powerless in the face of discrimination or who expect to be victims of future mistreatment. Medical mistrust becomes problematic when it prevents people from engaging in healthy behaviors or accessing appropriate health care.

The COVID-19 pandemic provided painful lessons on how we can reduce mistrust in the communities we are supposed to serve.

First, we must acknowledge our mistakes from the past. We must speak frankly and honestly about the legacy of exploiting minorities through research. The notorious U.S. Public Health Service study at Tuskegee followed black Americans infected with syphilis from 1932 to 1972, never treating them despite the availability of penicillin. In a less well-known incident, researchers misused blood samples from the Havasupai tribe for purposes not authorized by participants. American researchers in Guatemala infected vulnerable people with sexually transmitted diseases to explore treatments.

These studies underscore the need to protect our vulnerable and minority communities through the establishment of robust and representative human subjects’ protection programs.

But we cannot pretend that abuses of the past are entirely in the past.

Structural racism and inequities in health care persist, as COVID-19 tragically reminded us. We must take this moment to champion UC San Diego Health as a leading center of excellence for diversity, equity and inclusion for underserved, vulnerable and historically marginalized communities.

Second, COVID-19 reminded us that treating communities of color as “research subjects” is not an adequate approach for regaining trust and engagement in research. When they are involved in framing the questions that affect them, when there is a community-based approach, we have observed that these communities are more likely to be involved and engaged.

Indeed, when people of color were involved as full partners, they helped establish testing sites in churches and vaccination sites in local auditoriums. They encouraged their community members to participate. Without their critical involvement and support, our mobile clinics in underserved communities would have remained without visitors.

We need to empower our communities of color. They need to know that they can be involved at many levels. They can participate as community members of an institutional review board, which helps ensure the rights and welfare of human research subjects. They can work with scientists in community advisory boards or with university groups for community-based research efforts that address particular concerns in their own neighborhoods.

This cannot be a neo-colonialist, paternalistic process. It must involve full partnerships that enhance the dignity and self-efficacy of the community and concomitantly reduce health disparities.

Third, COVID-19 helped facilitate the broader implementation of electronic consent documents. But this innovation became problematic for communities of color with limited computer access, challenges in health literacy and chronic suspicion of unknown processes promoted by unfamiliar entities.

Our informed consent process must strive to become more transparent and to assure full understanding of every participant. We need to make it simpler, more direct and more relevant to participants’ lives.
Finally, our academic systems encourage young investigators to prove themselves by publishing, securing extramural funding and achieving promotion and tenure through this path. We must aggressively support them in these efforts. As essential as it is to grapple with research methods and applications, it is equally important to teach awareness of cultural differences, perspectives and conflicts of interest.

One can see how real-world crises can focus and elevate speed and efficiency. Building relationships with our communities of color takes time. It requires conversation, most especially listening and commitment. We need to enhance the training of our younger investigators to minimize implicit bias and promote empathic engagement.

We must be worthy of trust in order to gain it.

Edward “Lalo” Cachay, MD, is an infectious disease specialist and professor of medicine at UC San Diego School of Medicine. Cachay specializes in caring for people with HIV, but during the pandemic, his role expanded to the oversight of clinical trials investigating new treatments for COVID-19.

— Research

Fomentando la confianza en las comunidades de color

Lecciones que nos deja la pandemia de COVID-19

— Escrito por Edward “Lalo” Cachay, MD

Las personas de color han muerto desproporcionadamente a causa del COVID-19, lo que resalta las profundas desigualdades socioeconómicas y de salud que persisten en nuestro país.

La pandemia produjo innovación científica, desde tratamientos hasta vacunas, a un ritmo sin predecentes. Sin embargo, solo una pequeña fracción de personas que participaron en los estudios clínicos de COVID-19 y en el desarrollo de vacunas fueron personas de color. Para superar esta pandemia, necesitamos una amplia aceptación y uso de las vacunas contra el COVID-19, especialmente entre aquellos más afectados.

Desafortunadamente, se conoce que la vacilación en vacunarse es alta entre las comunidades de color. En el centro de esta falta de participación en la investigación por parte de las comunidades de color y sus titubeos para recibir las vacunas está la desconfianza permanente en los sistemas de investigación y atención médica.

La desconfianza médica es el resultado de una forma evolutiva de resistencia que se convirtió en un mecanismo de supervivencia en respuesta a la opresión crónica. Esto da una sensación de control a las personas que se sienten impotentes frente a la discriminación o que esperan ser víctimas de malos tratos en el futuro. Sin embargo, la desconfianza médica se vuelve problemática cuando impide que las personas adopten comportamientos saludables o accedan a una atención médica adecuada.

“La pandemia de COVID-19 nos dejó lecciones muy dolorosas sobre cómo podemos reducir la desconfianza en las comunidades que más deberíamos servir.”

Primero, debemos reconocer nuestros errores del pasado. Es fundamental hablar con franqueza y honestidad sobre el legado de la explotación de las minorías por medio de la investigación. El notorio estudio del Servicio de Salud Pública de EE. UU. en Tuskegee siguió a personas afroamericanas infectadas con sífilis desde 1932 hasta 1972, y nunca se les administró tratamiento a pesar de la disponibilidad de penicilina. Otros ejemplos infames menos conocidos incluyen el estudio en La tribu Havasupai que había almacenado muestras de sangre que se utilizaron indebidamente para fines no autorizados por los participantes. Asi como cuando, investigadores estadounidenses en Guatemala infectaron a personas vulnerables con enfermedades de transmisión sexual para explorar tratamientos.

Estos estudios denotan la necesidad de proteger a nuestras comunidades minoritarias y vulnerables mediante el establecimiento de programas de protección de sujetos humanos sólidos y representativos.

Pero no podemos pretender que los abusos del pasado hayan desaparecido por completo.

El racismo estructural y las inigualdades en la atención médica persisten, como nos recordó trágicamente el COVID-19. Debemos aprovechar este momento para convertir a UC San Diego Health en un centro líder de excelencia para la diversidad, la equidad y la inclusión para las comunidades minoritarias, desatendidas y vulnerables.

En segundo lugar, el COVID-19 nos recordó que tratar a las comunidades de color como “sujetos de investigación” no es del todo adecuado para romper la desconfianza y la falta de compromiso con la investigación. Cuando están involucrados en diseñar las preguntas que los afectan, cuando hay un enfoque basado en la comunidad, hemos observado que estas comunidades tienen más probabilidades de involucrarse y comprometerse.

De hecho, cuando las personas de color participaron como socios de pleno derecho, ayudaron a establecer sitios de prueba en iglesias, sitios de vacunación en auditorios locales y alentaron a los miembros de su comunidad a que participen. Sin su colaboración y apoyo críticos, nuestras clínicas móviles en comunidades necesitadas se habrían quedado sin visitantes.

Necesitamos empoderar a nuestras comunidades de color. Ellos necesitan saber que pueden participar en muchos niveles. Por ejemplo, pueden participar como miembros representates de la comunidad de un Comité Ético de Investgiación Institucional, que tiene como objetivo ayudar a garantizar los derechos y el bienestar de las personas que participan en diversos estudios de investigación. También, podrían trabajar con investigadores en juntas asesoras comunitarias o con grupos universitarios para unir esfuerzos de investigación basado en beneficios para la comunidad que aborden preocupaciones álgidas en sus propios vecindarios.

Este no puede ser un proceso neocolonialista ni tampoco paternalista. Deben ser alianzas plenas que mejoren la dignidad y la autoeficacia de la comunidad y, simultáneamente, reduzcan las desigualdades en la salud.

En tercer lugar, el COVID-19 ayudó a facilitar la implementación a gran escala de documentos de consentimiento electrónicos. Pero esta innovación se volvió problemática para las comunidades de color que tienen acceso limitado a computadoras, menor alfabetización en salud y desconfianza histórica en los procesos nuevos promovidos por entidades desconocidas.

Nuestro proceso de consentimiento informado debe esforzarse por ser más transparente y asegurar la comprensión plena de cada participante. Necesitamos hacerlo más simple, más directo y más relevante para la vida de los participantes.

Finalmente, nuestras universidades alientan a los investigadores jóvenes a demostrar su valía publicando y asegurando fondos externos que les permite lograr promoción y asegurar su posición académica. Debemos apoyarlos enfática e incondicionalmente en estos esfuerzos. Sin embargo, tan esencial como lidiar con los métodos de investigación a aplicar, es igualmente importante enseñarles a tomar conciencia de las diferencias culturales, las perspectivas y los propios conflictos de intereses.

Uno puede ver cómo las crisis vividas pueden enfocarse y aumentar la velocidad y la eficiencia. Empero, establecer relaciones con nuestras comunidades de color lleva tiempo. Requiere comunicación, especialmente capacidad de escucha y compromiso. Necesitamos mejorar la formación de nuestros investigadores más jóvenes para minimizar sesgo implícitos y promover relaciones con autenticidad y empatía.

“Debemos ser dignos de confianza para poder obtenerla.”

Edward “Lalo” Cachay — MD, especialista en enfermedades infecciosas y profesor de medicina en UC San Diego. Cachay se especializa en el cuidado de personas que viven con VIH, pero durante la pandemia, amplió su función para supervisar los ensayos clínicos que investigan nuevos tratamientos para el COVID-19.

— 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.

— Research

Pooling Patient Data to Answer Big Questions

Health system consortium enabled clinicians, researchers, patients and the general public to submit questions to be answered by COVID-19 patient medical record data from 200+ hospitals

— Heather Buschman, PhD

Throughout the COVID-19 pandemic, there has been an urgent need to better understand who is at greatest risk for severe disease, how the disease and treatments have evolved, and how to better predict the need for resources. But answers require lots of data, such as what patients have experienced and what factors are associated with different treatment outcomes.

To provide this information, a research consortium quickly formed in the summer of 2020. The team built a system in which clinicians, researchers, patients — anyone, really — could submit questions that could be answered by COVID-19 patient record data from more than 200 participating hospitals. Questions are submitted and select answers are provided via a web portal at COVID19questions.org.

The consortium, called Reliable Response Data Discovery (R2D2), was led by Lucila Ohno-Machado, MD, PhD, chair of the Department of Biomedical Informatics at UC San Diego Health, and made possible by seed funding from the Gordon and Betty Moore Foundation. R2D2 comprised 14 health systems.

“No single hospital alone has treated enough patients with COVID-19 to be able to see reliable patterns emerge and use that information to guide the direction of new studies,” Ohno-Machado said. “That’s why we formed the R2D2 Consortium.”

Here’s how the COVID19questions.org site works: Users submit questions about adults hospitalized with COVID-19. Consortium team members evaluate the submissions for clinical utility and the likelihood that available data can provide answers. Questions are then translated into a computer code that queries a variety of electronic medical records. Each health system runs the code on their own patient records and provides the results to the consortium. When sufficient results accrue to be statistically meaningful, the answers are posted back to COVID19questions.org — not as definitive conclusions, but as data in the form of charts or other graphics, which researchers can further pursue.


Among the questions explored:

• What is the mortality rate for hospitalized COVID-19 patients with each blood type?
• What is the mortality rate for COVID-19 patients with a history of hypertension who received anti-hypertensive medications?
• How does the mortality rate compare between hospitalized adult COVID-19 patients who received glucocorticoids and those who didn’t?

Between January 1, 2020 and March 13, 2021, the COVID19questions.org site drew from data on more than 55 million patients, including more than 3.4 million patients who were tested for COVID-19, 320,000 diagnosed with the disease, 80,000 hospitalized and 10,000 who died.

“The scientific community has talked about using electronic medical records for guiding research and for answering relevant questions for a long time,” Ohno-Machado said. “But until this pandemic, we hadn’t been doing it in a way that the public can see — this is much different than when only scientists can ask questions and publish their findings in academic journals.”

While the consortium’s seed funding has come to an end, the site continues to answer questions with the support of several consortium institutions.

Ohno-Machado said she’s looking forward to beginning to characterize “long COVID” — the long-term health effects experienced by many survivors. She’s curious about the types of symptoms people experience the most and whether they differ by gender, race and ethnicity.

Already, the consortium is finding that among COVID-19 survivors, mental health issues are most prevalent. And hair loss is more prevalent in female survivors than male.

“As the nature of the pandemic is changing, so is the nature of the questions,” she said.