Members of the LJI Coronavirus Taskforce are contributing their unique expertise and perspective in the following ways:
Validating a novel, point-of-need diagnostic test
In collaboration with diagnostic company Mologic, Dr. Sujan Shresta is validating a quick diagnostic test that can detect current or past infections with SARS-CoV-2 in the field.
Understanding why and how COVID-19 spreads and kills
Dr. Alessandro Sette, a world leader in analyzing T cells responses, is establishing a global network to comprehensively map the T cell response to SARS-CoV-2. The work will provide an atlas to guide vaccine evaluation, establish the relative value of various viral targets and vaccine designs, and project the impact of viral variants that may be developing throughout the pandemic.
Dr. Pandurangan Vijayanand, a widely recognized expert in analyzing how genes influence immune responses, will carry out genetic analysis of single T cells from groups of patients to quickly reveal what’s wrong with immune cells in blood and lungs of patients with severe disease.
The lab of Dr. Shane Crotty is an acknowledged groundbreaker on devising ways to stimulate protective B cells responses to HIV and other viruses. He will lead the effort to analyze the helper T cells, focused on understanding how they help B cells make antibodies against SARS-CoV-2 in mild and severe disease manifestations, as this is likely important for knowing what will constitute a desirable immune response in the context of a vaccine.
Together with her international network of collaborators, Dr. Sujan Shresta is initiating epidemiological studies in Nepal, Thailand, and Vietnam to create a biorepository of Asian viral isolates and human samples. The samples will be used by several labs at LJI to provide fundamental insights into the virus itself, the role of the host immune system in disease severity as well as the development of long-term immunity to help guide the development of vaccines and antivirals.
The lungs of many COVID-19 patients are filled with hundreds of microclots, while others suffer sudden strokes or heart attacks when errant blood clots break off and block blood vessels in the brain or heart. Dr. Lynn Hedrick’s team studies whether the observed cardiovascular complications of COVID-19 may be influenced by an overactive innate immune system—the body’s first line of defense against pathogens. Dr. Hedrick is using mass cytometry (CyTOF) to analyze innate immune cells known as neutrophils and monocytes from patients with modest and severe manifestations of COVID-19 to determine whether the innate immune system contributes to vascular inflammation and abnormal blood clotting in the lung and other organs.
A mysterious illness, which has been dubbed MIS-C, also called Pediatric Multisystem Inflammatory Syndrome, is afflicting children in areas hit hard by COVID-19. The serious and potentially deadly condition has been linked to coronavirus infections and is similar to Kawasaki disease and another rare pediatric inflammatory condition, DADA2 vasculitis, which lead to massive inflammation of small and medium blood vessels. Dr. Sonia Sharma, who recently uncovered the immune-related metabolic trigger of inflammation in DADA2 vasculitis, has already collected 500 plasma and blood samples from COVID-19 positive and negative individuals (children and adults) in the greater Los Angeles area, with 20,000 more samples on the way, ~4% of which are estimated to be COVID-19 positive. She and her team are using these samples to examine whether the same immune-related metabolic mechanisms underlie multi-organ inflammation and vasculitis in children with PMIS.
Testing therapies and vaccines
Therapeutic antibodies can be launched even before approved vaccines to be administered to protect frontline workers and case contacts from infection. Molecular characterization of potential therapeutic antibodies is essential, and because of her extraordinary talents, Dr. Erica Ollmann Saphire has been funded by Gates foundation to take on a leadership role in this effort. For more information visit covic.lji.org.
Relying on years of experience of modeling viral infections in vitro and in vivo, Dr. Sujan Shresta’s lab is developing experimental systems to assess the efficacy of therapeutic antibodies and vaccines in living cells and animals.