Biorisk Management Features of a Temporary COVID-19 Hospital.

Introduction: Yale University designed and constructed a temporary field hospital for 100 COVID-19 symptomatic patients. Conservative biocontainment decisions were made in design and operational practices. Objectives of the field hospital included the safe flow of patients, staff, equipment and supplies, and obtaining approval by the Connecticut Department of Public Health (CT DPH) for opening as a field hospital. Methods: The CT DPH regulations for mobile hospitals were used as primary guidance for the design, equipment, and protocols. References for BSL-3 and ABSL-3 design from the National Institutes of Health (NIH) and Tuberculosis isolation rooms from the United States Centers for Disease Control and Prevention (CDC) were also utilized. The final design involved an array of experts throughout the university. Results and Conclusion: Vendors tested and certified all High Efficiency Particulate Air (HEPA) filters and balanced the airflows inside the field hospital. Yale Facilities designed and constructed positive pressure access and exit tents within the field hospital, established appropriate pressure relationships between zones, and added Minimum Efficiency Reporting Value 16 exhaust filters. The BioQuell ProteQ Hydrogen Peroxide decontamination unit was validated with biological spores in the rear sealed section of the biowaste tent. A ClorDiSys Flashbox UV-C Disinfection Chamber was also validated. Visual indicators were placed the doors of the pressurized tents and spaced throughout the facility to verify airflows. The plans created to design, construct and operate the field hospital provide a blueprint for recreating and reopening a field hospital in the future if ever needed at Yale University.

Short-Term Use Biocontainment Bubbles: Innovative Source Containment of Potentially Infectious SARS-CoV-2 Aerosols.

Introduction: This article will review the processes utilized to develop simple effective containment engineering controls. Short-Term Use Biocontainment Bubbles-Yale (STUBB-Ys), as Yale refers to them, were designed, built, tested, and implemented to protect members of the Yale University community from exposure to SARS-CoV-2 aerosols. STUBB-Ys were designed and created in conjunction with end users, constructed by Environmental Health and Safety (EHS) or partner groups, and tested onsite after installation to verify effective operation and containment. Methods: A wide variety of devices in different settings were developed and installed. STUBB-Ys were used at COVID-19 indoor test centers, laboratories, and clinics. The devices were pursued to create infection prevention measures where existing processes could not be utilized or were inadequate. Each STUBB-Y was tested with a C-Breeze Condensed Moisture Airflow Visualizer to generate smoke and a Fluke 985 Particle Counter, which gives the particle counts from 0.3 to 10 µm to measure particle escape visually and quantitatively. Airflow rates were also tested where applicable with a TSI VelociCalc 9525 Air Velocity Meter. Results: Students and faculty were able to safely continue vital research or clinical study in the targeted areas with the addition of these simple containment devices to confine aerosols. Conclusion: From a biorisk management point of view, EHS was able to confine aerosols at their potential source using simple designs and equipment and adhering to the hierarchy of controls. This article demonstrates how a straightforward design process can be used to enhance worker protection during a pandemic.

Neuroinvasion of SARS-CoV-2 in human and mouse brain.

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.

Procedures for Flow Cytometry-Based Sorting of Unfixed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infected Cells and Other Infectious Agents.

In response to the recent COVID-19 pandemic, many laboratories are involved in research supporting SARS-CoV-2 vaccine development and clinical trials. Flow cytometry laboratories will be responsible for a large part of this effort by sorting unfixed antigen-specific lymphocytes. Therefore, it is critical and timely that we have an understanding of risk assessment and established procedures of infectious cell sorting. Here we present procedures covering the biosafety aspects of sorting unfixed SARS-CoV-2-infected cells and other infectious agents of similar risk level. These procedures follow the ISAC Biosafety Committee guidelines and were recently approved by the National Institutes of Health Institutional Biosafety Committee for sorting SARS-CoV-2-infected cells. © 2020 International Society for Advancement of Cytometry.