RESUMO
Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.
Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , Modelos Animais de Doenças , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/virologia , COVID-19/imunologia , COVID-19/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Suscetibilidade a Doenças , Predisposição Genética para Doença , Queratina-18/genética , Pulmão/imunologia , Pulmão/patologia , Pulmão/virologia , Camundongos , Camundongos Transgênicos , Mortalidade , Regiões Promotoras Genéticas/genética , Mucosa Respiratória/imunologia , Mucosa Respiratória/patologia , Mucosa Respiratória/virologia , Viroses/imunologia , Viroses/patologiaRESUMO
PURPOSE: Lean healthcare is highlighted in the literature as an approach to quality improvement and operational efficiency. The purpose of this paper is to study how Lean healthcare has been implemented by analyzing empirical outcomes. DESIGN/METHODOLOGY/APPROACH: The authors used a literature review as the primary research method, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Peer-reviewed journals were analyzed - searching for Lean healthcare implementation, tools used, wastes addressed, outcomes and sustainability. FINDINGS: Evidence suggests that Lean can improve healthcare operational effectiveness. However, empirical studies show implementation is still highly localized with small successes. Most transformations are focused on implementing one or two Lean tools that primarily target patient waiting times and there is minimal evidence about sustainability. Establishing clear definitions for healthcare-related Lean terminology may improve practice, especially episodic care and service quality. ORIGINALITY/VALUE: This work provides a Lean healthcare case review. The research makes a significant contribution to Lean healthcare by increasing understanding (scale, scope and sustainability). From a theory building perspective, the authors suggest that barriers to adoption include a common healthcare-specific Lean terminology, and a need to expand implementation beyond small successes. This understanding will help identify key areas for further research in Lean healthcare management.
