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A Research Community Comes Together to Fight COVID-19
Researchers at CHOP moved quickly to develop methods of tracking SARS CoV-2, the virus that causes COVID-19, as it spread across the nation, through our local community, and within the human body itself. David Rubin, MD, MSCE, director of PolicyLab, and an interdisciplinary team at CHOP created a modeling tool using data from 819 U.S. counties to help state and local officials determine appropriate social distancing measures. The team shared their insights across local and national media, from guidance for in-person learning to predicting transmission waves in areas across the country.
Much to Learn
Closer to home, Brian Fisher, DO, MPH, MSCE, physician in the Division of Infectious Diseases, and co-investigator Jeffrey Gerber, MD, PhD, associate chief clinical research officer, assessed immune responses to SARS CoV-2 among CHOP employees to inform the best strategies for protecting our community. Through serology tests, they aimed to detect the number of people with symptomatic or asymptomatic infections and antibodies.
Meanwhile, Audrey Odom-John, MD, PhD, chief of the Division of Infectious Diseases, enlisted the help of working dogs to develop a novel way for detecting COVID-19 by tracking olfactory traces it may leave in the breath. Working with the Penn Vet Working Dog Center, Dr. John, who conducts similar research in malaria, aimed to identify the biomarkers needed to develop a “breathalyzer” test for COVID-19. Dr. John is also tracing the concordance of SARS CoV-2 in the upper and lower respiratory tracts to determine whether a patient might receive a negative result in current standard COVID tests but still have the virus present in their lungs or lower tract — insights that could help healthcare providers protect themselves and others.
As some CHOP researchers trace COVID-19’s reach, other scientists are working toward treatments using a variety of approaches. In the lab of John Maris, MD, physician in the Division of Oncology, researchers adapted computational tools to identify the regions, or epitopes, of SARS CoV-2 to focus on when developing a safe, effective vaccine. The team identified 65 peptide sequences to prioritize for vaccine development, publishing their work in Cell Reports Medicine.
Meanwhile, David Teachey, MD, co-leader of the Immune Dysregulation Frontier Program, and colleagues explored the use of convalescent plasma, taken from recovered patients, to treat critically ill COVID-19 patients. Alongside a host of other departments at CHOP and the University of Pennsylvania, Dr. Teachey also began studying why, with some exceptions, pediatric patients seem to fare better in recovery than adults. The team opened a protocol to collect blood from consenting patients with COVID-19 for comparison with adult patients.
Working in the lab of Ophir Shalem, PhD, trainee Stephanie Sansbury began to adapt the CRISPR-based genetic screens typically used to study neurodegenerative diseases to learn more about COVID-19’s pathology. Sansbury aims to identify a list of genes necessary to produce two proteins that SARS CoV-2 grasps onto to enter a cell. Her goals are to produce recommendations for which genes to target with drugs and to better understanding how the proteins are regulated.
Harnessing their expertise in children’s health, researchers at CHOP sought to explore how the virus specifically affects pediatric patients. Susan Coffin, MD, MPH, associate chief of Infectious Diseases, began a natural history study that aims to understand the course of COVID-19 in children and why they seem to be largely spared from severe illness. Using information collected within CHOP’s pediatric care network and with plans to partner with other U.S. children’s hospitals, Dr. Coffin’s team will analyze the data on a rolling basis and study how many diagnoses are being made, how frequently diagnoses are being made, and how children are presenting with the disease.
Meanwhile, a multidisciplinary team of researchers are unraveling the mysteries of multisystem inflammatory disease (MIS-C) that affects some children after coronavirus infection. Katie Chiotos, MD, a physician in Critical Care Medicine, published a study of six children with MIS-C at CHOP, describing the cases as “a type of immune-mediated phenomenon” and COVID-19 that did not appear in a way they recognized. Building on Dr. Chiotos’ data, research led by Ed Behrens, MD, chief of the Division of Rheumatology, reported that children with MIS-C harbored high levels of two particular cytokines, TNF-alpha and IL-10, compared to children with a severe SARS CoV-2 infection.
Pathways of Discovery
Dr. Behrens also is studying what role cytokine storms, an overzealous immune reaction, may play in some severe cases of COVID-19. By completely characterizing the immune landscape of children infected with COVID-19 — from looking at the kind of antibody response children make to the cytokines they produce — Dr. Behrens hopes to learn something new about what makes people sick that might lead to better therapies or earlier diagnoses.
Alongside the clinical impact of COVID-19, CHOP researchers also addressed the mental effects of the pandemic and the virus. A team at the Lifespan Brain Institute (LiBI) including psychiatrist Ran Barzilay, MD, PhD, sought to study how to help individuals exercise resilience in challenging times. The researchers developed a 10-minute online survey to be used as a research tool that investigates the moderating effect of risk factors (such as negative relationships) and resilience factors (such as self-reliance) on mental health and sleep during the pandemic. “We expect the results to shed light on how and why some people manage to overcome adversity, while others struggle and develop stress-related disorders,” Dr. Barzilay said.
Alongside Penn colleagues within LiBI, Wanjiku Njoroge, MD, psychiatrist at CHOP, is studying the challenges faced by Black women living in Philadelphia amidst two pandemics (COVID-19 and structural racism), and the ways in which interventions could be helpful. Dr. Njoroge’s study surveys postpartum mental health, physician trust, perceived discrimination, and other factors in peripartum women during the pandemic, aiming to create nuanced, supportive, and culturally appropriate care models.
Christopher Forrest, MD, PhD, director of the Center for Applied Clinical Research, is also leading an effort to help the wider community adapt to the “new normal” brought on by the COVID-19 pandemic. As part of a wider network of institutions, Dr. Forrest is CHOP’s leader in the Healthcare Worker Exposure Response and Outcomes (HERO) Registry, which seeks to understand the needs and concerns of healthcare workers during the pandemic.
“This is a community that stands ready and willing to be involved in studies that can help address their needs during this pandemic,” said Dr. Forrest of the HERO Registry. “We’re in COVID time now, and we need to be ready. I want tools to help healthcare workers available in weeks not years.”