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Transcription factor programs mediating the immune response to coronavirus disease 2019 (COVID-19) are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped small RNA sequencing (csRNA-seq), in contrast to capturing steady-state transcripts by conventional RNA-seq, allows unbiased identification of the underlying transcription factor activity and regulatory pathways. Here, we profile transcription initiation in critically ill COVID-19 patients, identifying transcription factor motifs that correlate with clinical lung injury and disease severity. Unbiased clustering reveals distinct subsets of cis-regulatory elements that delineate the cell type, pathway-specific, and combinatorial transcription factor activity. We find evidence of critical roles of regulatory networks, showing that STAT/BCL6 and E2F/MYB regulatory programs from myeloid cell populations are activated in patients with poor disease outcomes and associated with COVID-19 susceptibility genetic variants. More broadly, we demonstrate how capturing acute, disease-mediated changes in transcription initiation can provide insight into the underlying molecular mechanisms and stratify patient disease severity.

The coronavirus disease 2019 (COVID-19) pandemic began in the United States around March 2020. Because of limited access to extracorporeal membrane oxygenation (ECMO) in the authors' region, a mobile ECMO team was implemented by April 2020 to serve patients with COVID-19. Several logistical and operational needs were assessed and addressed to ensure a successful program, including credentialing, equipment management, and transportation. A multidisciplinary team was included in the planning, decision-making, and implementation of the mobile ECMO. From April 2020 to January 2021, mobile ECMO was provided to 22 patients in 13 facilities across four southern California counties. The survival to hospital discharge of patients with COVID-19 who received mobile ECMO was 52.4% (11 of 21) compared with 45.2% (14 of 31) for similar patients cannulated in-house. No significant patient or transportation complications occurred during mobile ECMO. Neither the ECMO nor transport teams experianced unprotected exposures to or infections with severe acute respiratory syndrome coronavirus 2. Herein, the implementation of the mobile ECMO team is reviewed, and patient characteristics and outcomes are described.

ObjectivesTo describe a ventilator and extracorporeal membrane oxygenation management strategy for patients with acute respiratory distress syndrome complicated by bronchopleural and alveolopleural fistula with air leaks.Design setting and participantsCase series from 2019 to 2020. Single tertiary referral center-University of California, San Diego. Four patients with various etiologies of acute respiratory distress syndrome, including influenza, methicillin-resistant Staphylococcus aureus pneumonia, e-cigarette or vaping product use-associated lung injury, and coronavirus disease 2019, complicated by bronchopleural and alveolopleural fistula and chest tubes with air leaks.Measurements and main resultsBronchopleural and alveolopleural fistula closure and survival to discharge. All four patients were placed on extracorporeal membrane oxygenation with ventilator settings even lower than Extracorporeal Life Support Organization guideline recommended ultraprotective lung ventilation. The patients bronchopleural and alveolopleural fistulas closed during extracorporeal membrane oxygenation and minimal ventilatory support. All four patients survived to discharge.ConclusionsIn patients with acute respiratory distress syndrome and bronchopleural and alveolopleural fistula with persistent air leaks, the use of extracorporeal membrane oxygenation to allow for even lower ventilator settings than ultraprotective lung ventilation is safe and feasible to mediate bronchopleural and alveolopleural fistula healing.

Pneumomediastinum is a rare complication of substance use, likely due to a Valsalva maneuver after drug inhalation. There are no previously documented associations between pneumomediastinum and opioid use. A 30-year-old man with a history of recent heroin and fentanyl inhalation presented to the emergency department in respiratory distress requiring intubation. His course was complicated by pneumomediastinum which subsequently developed tension physiology. He required emergent surgical decompression with a "blowhole incision" to his anterior chest. Although a rare complication of polysubstance use, pneumomediastinum can progress to tension physiology, requiring prompt diagnosis and management.

Pneumomediastinum is a rare complication of substance use, likely due to a Valsalva maneuver after drug inhalation. There are no previously documented associations between pneumomediastinum and opioid use. A 30-year-old man with a history of recent heroin and fentanyl inhalation presented to the emergency department in respiratory distress requiring intubation. His course was complicated by pneumomediastinum which subsequently developed tension physiology. He required emergent surgical decompression with a "blowhole incision" to his anterior chest. Although a rare complication of polysubstance use, pneumomediastinum can progress to tension physiology, requiring prompt diagnosis and management.

Over the past 20 years, despite significant advancements in pulmonary arterial hypertension (PAH) medical therapy, many patients require admission to the hospital and are at risk for in-hospital cardiac arrest (IHCA). Prior data found poor survival in PAH patients after cardiac arrest. The purpose of this study was to explore post-IHCA outcomes in PAH patients receiving advanced medical therapies. This is a single-center retrospective study of PAH patients who underwent cardiopulmonary resuscitation for IHCA between July 2005 and May 2021. Patients were identified through an internal cardiac arrest database. Twenty six patients were included. Half of the cohort had idiopathic PAH, with 54% of patients on combination therapy, 27% on monotherapy, and 19% of patients on no therapy. Mean right atrial pressure, mean pulmonary artery pressure, cardiac index, and pulmonary vascular resistance were 13 ± 6 mmHg, 57 ± 13 mmHg, 2.0 ± 0.7 L/min/m2, and 14.5 ± 7.6 Wood units, respectively. Most common etiology of cardiac arrest was circulatory collapse. Initial arrest rhythm in all but one patient was pulseless electrical activity. Six patients (23%) achieved return of spontaneous circulation (ROSC) and one patient (4%) survived to hospital discharge. Rates of ROSC and survival to discharge after IHCA are poor in patients with PAH. Even patients with mild hemodynamics had low likelihood of survival. In patients who are lung transplant candidates, there should be early consideration of extracorporeal support before cardiac arrest.

Introduction: Infection by SARS-CoV-2 and subsequent COVID-19 can cause viral sepsis. We investigated plasma protease activity patterns in COVID-19-induced sepsis with bacterial superinfection, as well as plasma proteomics and peptidomics in order to assess the possible implications of enhanced proteolysis on major protein systems (e.g., coagulation). Methods: Patients (=4) admitted to the intensive care units (ICUs) at the University of California, San Diego (UCSD) Medical Center with confirmed positive test for COVID-19 by real-time reverse transcription polymerase chain reaction (RT-PCR) were enrolled in a study approved by the UCSD Institutional Review Board (IRB# 190699, Protocol #20-0006). Informed consent was obtained for the collection of blood samples and de-identified use of the data. Blood samples were collected at multiple time points and analyzed to quantify a) the circulating proteome and peptidome by mass spectrometry; b) the aminopeptidase activity in plasma; and c) the endopeptidase activity in plasma using fluorogenic substrates that are cleaved by trypsin-like endopeptidases, specific clotting factors and plasmin. The one patient who died was diagnosed with bacterial superinfection on day 7 after beginning of the study. Results: Spikes in protease activity (factor VII, trypsin-like activity), and corresponding increases in the intensity of peptides derived by hydrolysis of plasma proteins, especially of fibrinogen degradation products and downregulation of endogenous protease inhibitors were detected on day 7 for the patient who died. The activity of the analyzed proteases was stable in survivors. Discussion: The combination of multiomics and enzymatic activity quantification enabled to i) hypothesize that elevated proteolysis occurs in COVID-19-induced septic shock with bacterial superinfection, and ii) provide additional insight into malfunctioning protease-mediated systems, such as hemostasis.

0, info:eu-repo/semantics/published, From Conference Volume 5925Nanophotonic Materials and Systems IISan Diego, California, USA

0, info:eu-repo/semantics/published, From Conference Volume 5925Nanophotonic Materials and Systems IISan Diego, California, USA