Project description:Our work illustrates how high-resolution molecular and spatial profiling of COVID-19 patient tissues collected during rapid autopsies can serve as a hypothesisgenerating tool to identify key mediators driving the pathophysiology of COVID-19 for diagnostic and therapeutic target testing. Here we employ bulk RNA sequencing to identify key regulators of COVID-19 and list specific mediators for further study as potential diagnostic and therapeutic targets. We use single-nuclei RNA sequencing to highlight the diversity and heterogeneity of coronavirus receptors within the brain, suggesting that it will be critical to expand the focus from ACE2 to include other receptors, such as BSG and ANPEP, and we perform digital spatial profiling of lung and lymph node tissue to compare two patients with different clinical courses and symptomatology.
Project description:Our work illustrates how high-resolution molecular and spatial profiling of COVID-19 patient tissues collected during rapid autopsies can serve as a hypothesisgenerating tool to identify key mediators driving the pathophysiology of COVID-19 for diagnostic and therapeutic target testing. Here we employ bulk RNA sequencing to identify key regulators of COVID-19 and list specific mediators for further study as potential diagnostic and therapeutic targets. We use single-nuclei RNA sequencing to highlight the diversity and heterogeneity of coronavirus receptors within the brain, suggesting that it will be critical to expand the focus from ACE2 to include other receptors, such as BSG and ANPEP, and we perform digital spatial profiling of lung and lymph node tissue to compare two patients with different clinical courses and symptomatology.
Project description:Our work illustrates how high-resolution molecular and spatial profiling of COVID-19 patient tissues collected during rapid autopsies can serve as a hypothesisgenerating tool to identify key mediators driving the pathophysiology of COVID-19 for diagnostic and therapeutic target testing. Here we employ bulk RNA sequencing to identify key regulators of COVID-19 and list specific mediators for further study as potential diagnostic and therapeutic targets. We use single-nuclei RNA sequencing to highlight the diversity and heterogeneity of coronavirus receptors within the brain, suggesting that it will be critical to expand the focus from ACE2 to include other receptors, such as BSG and ANPEP, and we perform digital spatial profiling of lung and lymph node tissue to compare two patients with different clinical courses and symptomatology.
Project description:Interrogation of the DNA methylome from lung autopsies of 36 patients who died of SARS-CoV-2 vs 18 control non-COVID-19 individuals.
Project description:We profiled 116,314 cells using snRNA-seq of 20 frozen lungs obtained from 19 COVID-19 decedents and seven control patients with short postmortem interval (PMI) autopsies. The COVID-19 cohort comprises seven female and 12 male decedents, including 13 patients of Hispanic ethnicity, with an age range from 58 to >89 years who had acquired SARS-CoV-2 infection and succumbed to the disease. The average time from symptom onset to death was 27.5 days (range, 4–63 days). After rapid autopsy with a median PMI of 4 hours (range 2–9 hours) collected tissues were either flash-frozen or frozen following OCT (optimal cutting temperature) embedment and subjected to snRNA-seq using a droplet-based platform (10x Genomics). All included patients had underlying hypertensive disorder and frequently one or more additional co-morbidities associated with increased risk for severe COVID-19.