COVID-19 Research

Natural history of shedding and household transmission of COVID-19: Constructing patterns of viral spread and evolution
Yvonne Maldonado, MD

Maldonado’s team will combine genomic and epidemiologic data to address questions about the transmission and evolutionary dynamics of COVID-19. Her team plans to use whole-genome sequencing to understand how COVID-19 mutates during the early stages of infection, as well as generate a bio-repository of specimens and associated clinical and epidemiologic data for use in understanding the transmission of COVID-19. 

Repurposing snorkel masks for personal protective equipment
Manu Prakash, PhD, and University of Utah collaborators

Prakash and his lab are repurposing full-face snorkel masks as reusable personal protective equipment for healthcare workers to help combat the shortage of personal protective equipment in hospitals. To ensure protection against airborne pathogens, the group is 3D-printing N95 filter attachments that are fitted to the snorkel masks. The prototypes are currently being tested in the three clinics currently.

Novel aerosol capture tools for understanding COVID-19 infectiousness
Jason Andrews, MD, SM

Andrews’ group is developing and validating tools to capture airborne biological particles and characterize infectiousness, with the goals of understanding predictors and determinants of infectiousness and potentially monitoring environments for presence of SARS-CoV-2.

Clinical trial of remdesivir in hospitalized adults with COVID-19
Neera Ahuja, MD, and Kari Nadeau, MD, PhD

Nadeau and Ahuja are conducting a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the safety and efficacy of the Ebola drug remdesivir in hospitalized adult patients diagnosed with COVID-19. The study is sponsored by the National Institutes of Health and is a multicenter trial that will be conducted at as many as 50 sites globally.

Defining the therapeutic potential of host-targeted approaches for combating COVID-19
Shirit Einav, MD

Einav’s lab is researching repurposed and novel anti-viral approaches targeting two cellular kinases that are an Achilles' heel of multiple unrelated RNA viruses. Their data show that a combination of two already-approved anti-cancer drugs that act against these kinases inhibits replication of multiple viruses in vitro and reduces mortality in mice infected with the dengue or Ebola viruses. The lab has also been developing more selective compounds that target these cellular kinases and have potent activity against multiple RNA viruses, including flaviviruses and coronaviruses, both in vitro and in human primary cells.

Specimen collection during COVID-19 clinical trials and lab biosafety enhancements
Catherine Blish, MD, PhD; with Aruna Subramanian, MD; Philip Grant, MD; Angela Rogers, MD; and other clinical collaborators

Subramanian and Grant are co-principal investigators of a Gilead-sponsored clinical trial that evaluates the safety and efficacy of using the Ebola drug remdesivir to treat patients with COVID-19. In parallel with these trials, Blish wants to collect specimens, such as blood and stool samples, and later expand collection to individuals outside of the trials. These bio-specimens will be crucial in understanding the biological underpinnings of this virus.

Clinical trial of novel therapeutic for mild COVID-19 infection to prevent severe disease and reduce viral shedding
Upinder Singh, MD; Julie Parsonnet, MD; Jason Andrews, MD; Prasanna Jagannathan, MD; and other clinical collaborators

Singh’s team is conducting a trial of a novel therapeutic called Lambda, a broad-spectrum anti-viral compound that’s been given to more than 3,000 patients in clinical trials of hepatitis viruses, for efficacy in outpatients with mild COVID-19. In vitro and animal-model data suggest Lambda may also inhibit replication of respiratory viruses, such as the COVID-19 virus. The team plans to perform a phase 2 randomized controlled trial of Lambda among outpatients with mild COVID-19 to determine whether the drug reduces the duration of symptoms, viral shedding and the risk of hospitalization.

Develop proofs-of-concept for two novel COVID-19 drugs to begin clinical trials
Jeffrey Glenn, MD, PhD, and Rhiju Das, PhD

Glenn is preparing two potential COVID-19 drugs for clinical trials: a lipid kinase inhibitor that could be used to combat COVID-19 and other viruses, and a locked nucleic acid, similar to one that he has successfully developed to target every known strain of the flu and that could potentially be used during any flu pandemic. Both of these drugs could treat multiple viruses and strains, have high barriers to resistance, and, in some cases, could be used in nonviral applications.

Coronavirus antiviral research database
Robert Shafer, MD

Shafer’s team has created an online database of compounds with proven or potential anti-COVID-19 activity. The compounds include targeted anti-virals, repurposed drugs, investigational agents and other compounds that inhibit virus replication. The data come from published biochemical, cellular, small animal, nonhuman primate and human clinical studies. The goal of the database is to provide a uniform way to report experimental results, enabling comparisons between different compounds and allowing prioritization for further development.

Using artificial intelligence to predict drugs that may inhibit COVID-19
Russ Altman, MD, PhD, and other collaborators

Altman and his group have used artificial intelligence to computationally predict six drugs that could inhibit TMPRSS2, a protein that plays a key role in SARS-CoV-2 infections. Altman and his collaborators outside of Stanford Medicine plan to conduct experimental follow-up studies to explore the efficacy of two of the drugs in blocking SARS-CoV-2 from causing infection. While promising, the potential drugs are still part of a preliminary computational analysis and would be dangerous to use clinically at this time.

Crowdsourcing solutions to better understand molecular structures of COVID-19
Howard Chang, MD, PhD, and Rhiju Das, PhD

The Chang and Das labs are engaging participants of the online-gaming platform Eterna to understand how the RNA genome of SARS-CoV-2 virus might change during the pandemic. Eterna educates and enables its players to “be the virus,” simulating how it shifts its sequence over time to evade diagnostics, therapeutics and vaccines being developed to fight COVID-19. The project seeks to provide RNA-structure-informed predictions and analyses that are not available through other computational efforts, while engaging and educating millions of citizens worldwide through compelling puzzles.

Stanford Medicine National Daily Health Survey for Coronavirus 
Lawrence “Rusty” Hofmann, MD

Hofmann is leading an effort to track COVID-19 symptoms nationally using self-reported data from a daily, digital survey. The goal is to create a novel coronavirus heat map that can be used to target and inform national efforts and public health interventions. The creation of this data set is dependent on participation across Stanford Medicine and our broader communities.

Genomic surveillance to identify silent transmission clusters of COVID-19
Jason Andrews, MD, MS

Andrews’ team is developing and testing novel tools that utilize microbial whole-genome sequences to identify chains of transmission between individuals. Andrews proposes to work with local hospitals and the state and county health departments to perform whole-genome sequencing on all COVID-19-positive samples and apply these methods in real-time to characterize transmission chains and help guide public health investigations.

Stanford Coronavirus Study to understand behavioral and societal impacts
Eleni Linos, MD, DrPH with Melissa Bondy, PhD 

Linos and her team are developing a website with reliable public health information about COVID-19 and surveys about the social and behavioral impact of the evolving pandemic. They also plan to share survey results to directly inform public health practitioners, health care systems, clinicians and policymakers about the informational, social and health needs of community members in their regions.

Determining pathogenicity of various variants and strains of COVID-19
Michael Snyder, PhD and Ben Pinsky, MD, PhD

Snyder and his group plan to track different variants and strains of COVID-19 and quantitatively determine which ones correlate with different phenotypes, such as levels of pathogenicity. His team also plans to study the false negative rate of COVID-19, seeking to better understand how many people receive a false negative test result during early stages of the disease.

COVID-19 and Stanford WELL for Life study to understand the effects of shelter-in-place on well-being
Ann Hsing, PhD

Hsing and the Stanford WELL for Life team are investigating the effect of COVID-19 and the shelter-in-place order on well-being. They are surveying existing Stanford WELL for Life participants (about 5,000) with the WELL questionnaire, which measures distress and multiple dimensions of well-being longitudinally at six time points over the next 12 months. This approach will enable the evaluation of the short- and long-term effects of COVID-19 quarantine and social distancing on emotions, social connectedness and physical health.

Investigation of possible oral-fecal transmission of SARS-CoV-2 in the Bay Area
Ami Bhatt, MD, PhD; Angela Rogers, MD, Andrew Rezvani, MD; Niaz Banaei, MD; and Ben Pinsky, MD, PhD

The Bhatt group and collaborators are investigating whether SARS-CoV-2 was circulating through oral-fecal cycles in the Bay Area community. The lab plans to screen stool samples collected through a biobank at Stanford for signs of SARS-CoV-2 from December 2019 through December 2020. Depending on sample availability, the team also plans to research whether a patient’s gut microbiome composition affects gastrointestinal symptoms of COVID-19, as well as other details about how the virus sheds.

Using human organoids to understand COVID-19 infection 
Calvin Kuo, MD, PhD; Manuel Amieva, MD, PhD; and Catherine Blish, MD, PhD

Kuo, Amieva and Blish are recreating the SARS-CoV-2 infection in three-dimensional human mini-organs, or “organoids.” SARS-CoV-2 is the virus that causes COVID-19. Kuo and Amieva are investigating details behind how the virus infects human lung and intestinal tissues through organoid models, and Blish is studying the response of individual cells infected with SARS-CoV-2.

Systems biological “multi-omics” analysis of immunity to COVID-19 infection
Bali Pulendran, PhD

Pulendran is investigating the interaction between the human immune system and the SARS-CoV-2 virus through systems-biological methods. His group will use a “multi-omics” approach to probe the host immune system response to SARS-CoV-2 during asymptomatic and symptomatic phases of infection. Their goal is to determine why some people get more severe symptoms than others and to identify biomarkers that predict disease severity in vulnerable populations. His group will also study the immune mechanisms by which vaccines confer protection against SARS-CoV-2.

Multi-omics assessment of individuals infected with COVID-19
Michael Snyder, PhD; Sam Yang, MD, FACEP; and Maya Kasowski, PhD

The Snyder group will collect biological samples from individuals ill with COVID-19 and those most at risk for the disease, observing and assessing levels of certain molecules involved in several biological pathways, including metabolism and immune function. The team will use this information to create “omics” profiles to look for potential molecular signatures of COVID-19 infection, as well as signs that an individual might have a strong adverse reaction to the virus.

Comparative pathology and pathogenesis of COVID-19 infections in humans and animal models
Garry Nolan, PhD; David McIlwain, PhD; Sizun Jiang, PhD; Brice Gaudilliere, MD, PhD; and other collaborators

Nolan and his team are applying multiplexed technologies to achieve in-depth profiling of immune responses to SARS-CoV-2 in nonclinical and clinical studies. Their goal is to identify immune markers associated with outcomes for COVID-19 and understand the arrangement of immune cells relative to lung tissue cells during infection.

Inflammatory bowel disease treatment in the time of COVID: Patient perceptions and decision-making 
Cindy Kin, MD; Elizabeth Shelton; Kreeti Shankar; and Sarah Streett, MD

Kin and Streett are exploring how people with inflammatory bowel diseases, including people with Crohn's disease and ulcerative colitis whose treatment frequently involves chronic immunosuppressive therapies, are affected by the COVID-19 outbreak. The study aims to understand the primary concerns that patients with inflammatory bowel diseases have about their illnesses and treatments as they relate to the COVID-19 epidemic so that physicians and the health care team can effectively engage them in shared decision-making.

SARS-CoV-2 infection and cardiovascular complications
Sean Wu, MD;  Patricia Nguyen, MD;  Catherine Blish, MD, PhD, and Jan Carette, PhD

Wu and Nguyen are researching cardiovascular complications of COVID-19. The scientists are addressing the relationship between SARS-CoV-2 infection in heart muscle and vascular cells and the consequences of taking common drugs for high blood pressure. Their research employs muscle and vascular cells derived from human induced pluripotent stem cells to determine how these blood pressure drugs affect the virus’ ability to enter cells. 

Optimized remote work during the COVID-19 pandemic
Pablo Paredes, PhD

Paredes and collaborators are creating digital tools to support and maintain productivity levels while managing stress associated with the COVID-19 pandemic, social distancing and long-term telecommuting. The researchers propose a collection of tools, dubbed “Home Sweet Office,” that can support personal productivity by managing procrastination caused by online behaviors, such as overuse of social media, and provide stress-management tactics and emotion-regulation interventions.