A mouse model of lethal respiratory dysfunction for SARS-CoV-2 infection.

The global spread of SARS-CoV-2 has made millions ill with COVID-19 and even more from the economic fallout of this pandemic. Our quest to test new therapeutics and vaccines require small animal models that replicate disease phenotypes seen in COVID-19 cases. Rodent models of SARS-CoV-2 infection thus far have shown mild to moderate pulmonary disease; mortality, if any, has been associated with prominent signs of central nervous system (CNS) infection and dysfunction. Here we describe the isolation of SARS-CoV-2 variants with propensity for either pulmonary or CNS infection. Using a wild-type SARS-CoV-2 isolated from a COVID-19 patient, we first found that infection was lethal in transgenic mice expressing the human angiotensin I-converting enzyme 2 (hACE2). Fortuitously, full genome sequencing of SARS-CoV-2 from the brain and lung of these animals showed genetic differences. Likewise, SARS-CoV-2 isolates from brains and lungs of these also showed differences in plaque morphology. Inoculation of these brain and lung SARS-CoV-2 isolates into new batch of hACE2 mice intra-nasally resulted in lethal CNS and pulmonary infection, respectively. Collectively, our study suggests that genetic variants of SARS-CoV-2 could be used to replicate specific features of COVID-19 for the testing of potential vaccines or therapeutics.

COVID-19 and Beyond: Safety and Design Considerations for the Development of a Mobile Biocontainment Laboratory.

Introduction: An infectious disease outbreak like the current COVID-19 pandemic can lead to particularly high infection rates in areas where diagnostic laboratory support is limited. The deployment of mobile laboratories can help to detect pathogens, monitor the presence in a population, and inform public health authorities to take measures aimed at reducing pathogen spread. Materials and Methods: Available layouts and operational descriptions of mobile laboratories were analyzed for their suitability for the envisioned purpose and to assure high standards of biosafety and biosecurity. Recent media coverage on creative solutions for the diagnostics of SARS-CoV-2 (drive-through test centers, self-swab, inverse gloveboxes to protect health care workers) from various countries were considered. Results: A minimalistic and optimized design to construct a multifunctional laboratory on the chassis of a regular-sized box truck is proposed and can serve as a blueprint to rapidly develop additional diagnostic capacities. Discussion: For acute health threats including the current COVID-19 outbreak, rapid diagnosis of infection is key to recommend measures aimed at preventing the spread of the pathogen. Laboratory layouts that are similar to the one proposed here are used in stationary setups, and mobile laboratories have been built on varying platforms (trailers, shipping containers, etc).

Self-Administered Acupressure for Caregivers of Older Family Members: A Randomized Controlled Trial.

OBJECTIVE: To test whether self-administered acupressure reduces stress and stress-related symptoms in caregivers of older family members. DESIGN: In this randomized, assessor-blind, controlled trial, 207 participants were randomized (1:1) to an acupressure intervention or a wait-list control group. SETTING: Community centers in Hong Kong, China. PARTICIPANTS: Primary caregivers of an older family member who screened positive for caregiver stress with symptoms of fatigue, insomnia, or depression. INTERVENTION: The 8-week intervention comprised four training sessions on self-administered acupressure, two follow-up sessions for learning reinforcement, and daily self-practice of self-administered acupressure. MEASUREMENTS: The primary outcome was caregiver stress (Caregiver Burden Inventory). Secondary outcomes included fatigue (Piper Fatigue Scale), insomnia (Pittsburgh Sleep Quality Index), depression (Patient Health Questionnaire), and health-related quality of life (QoL) (12-item Short-Form Health Survey version 2). An intention-to-treat analysis was adopted. RESULTS: Of 207 participants, 201 completed the study. Caregiver stress in the intervention group was significantly lower than that in the control group after 8 weeks (difference = -8.12; 95% confidence interval [CI] = -13.20 to -3.04; P = .002) and at 12-week follow-up (difference = -8.52; 95% CI = -13.91 to -3.12; P = .002). The intervention group, relative to the control group, also had significantly improved secondary outcomes of fatigue (difference = -0.84; 95% CI = -1.59 to -0.08; P = .031), insomnia (difference = -1.34; 95% CI = -2.40 to -0.27; P = .014), depression (difference = -1.76; 95% CI = -3.30 to -0.23; P = .025), and physical health-related QoL (difference = 3.08; 95% CI = 0.28-5.88; P = .032) after 8 weeks. CONCLUSION: Self-administered acupressure intervention significantly relieves self-reported caregiver stress and co-occurring symptoms in those caring for older family members. Further studies are needed to measure the symptoms objectively and to examine the clinical importance of the observed improvement in caregiver stress. J Am Geriatr Soc 68:1193-1201, 2020.