Human cells and networks of pain: Transforming pain target identification and therapeutic development.

Chronic pain is a disabling disease with limited treatment options. While animal models have revealed important aspects of pain neurobiology, therapeutic translation of this knowledge requires our understanding of these cells and networks of pain in humans. We propose a multi-institutional collaboration to rigorously and ethically address this challenge.

Hospital Collaboration in Response to the COVID-19 Pandemic in Kansas City Metropolitan Region.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, aka COVID-19) virus has evolved into a World Health Organization-declared pandemic which has strained our regional critical care and hospital resources. METHODS: A Critical Care Task Force was established between Kansas City area intensive care units to allow for preparedness for potential surges by sharing of bed capacity both in the ICU and hospital, and ventilator capacity as well as weekly web-based meetings to share resource concerns and best practice. This Task Force also collected patient information to understand the dynamics of community impact and resource needs better. This effort allowed for compilation and dissemination of information regarding data that describe characteristics of patients with COVID-19 compared to a random sample of medical ICU patients with conditions other than COVID-19.Demographic and therapeutic factors affecting patients admitted to medical intensive care units in the Kansas City metro area are reported from May 5, 2020 until June 2, 2020 using a retrospective case-control study examining gender, race, and therapeutic options including modes of ventilation, vasopressor requirements, renal-replacement therapy, and disposition. RESULTS: During data collection, patients being treated for COVID-19 in intensive care units in the Kansas City metropolitan area were more likely to be older, less likely to be white, and less likely to be immunosuppressed as compared to those being treated for non-COVID illnesses. They were more likely to require non-invasive ventilation and undergo prone positioning but were equally likely to require invasive ventilation and other organ supportive therapy. CONCLUSIONS: Hospitalized patients being treated for COVID-19 in the Kansas City metropolitan area have similar demographics to those being reported in the U.S. including age and race. Additionally, establishing a Critical Care Task Force in response to the pandemic allowed for preparation for a potential surge, establishing capacity, and disseminating timely information to policy makers and critical care workers on the front line.

A pharmacological interactome between COVID-19 patient samples and human sensory neurons reveals potential drivers of neurogenic pulmonary dysfunction.

The SARS-CoV-2 virus infects cells of the airway and lungs in humans causing the disease COVID-19. This disease is characterized by cough, shortness of breath, and in severe cases causes pneumonia and acute respiratory distress syndrome (ARDS) which can be fatal. Bronchial alveolar lavage fluid (BALF) and plasma from mild and severe cases of COVID-19 have been profiled using protein measurements and bulk and single cell RNA sequencing. Onset of pneumonia and ARDS can be rapid in COVID-19, suggesting a potential neuronal involvement in pathology and mortality. We hypothesized that SARS-CoV-2 infection drives changes in immune cell-derived factors that then interact with receptors expressed by the sensory neuronal innervation of the lung to further promote important aspects of disease severity, including ARDS. We sought to quantify how immune cells might interact with sensory innervation of the lung in COVID-19 using published data from patients, existing RNA sequencing datasets from human dorsal root ganglion neurons and other sources, and a genome-wide ligand-receptor pair database curated for pharmacological interactions relevant for neuro-immune interactions. Our findings reveal a landscape of ligand-receptor interactions in the lung caused by SARS-CoV-2 viral infection and point to potential interventions to reduce the burden of neurogenic inflammation in COVID-19 pulmonary disease. In particular, our work highlights opportunities for clinical trials with existing or under development rheumatoid arthritis and other (e.g. CCL2, CCR5 or EGFR inhibitors) drugs to treat high risk or severe COVID-19 cases.