Exploratory Practice as a Professional Development Strategy for English-Language Teachers in Indonesia

The COVID-19 pandemic forced university-based language teachers to rely on technology for teaching. While the challenges of the rushed move to online teaching have been well documented, less is known about how teachers adapted to online teaching through professional development. This article focuses on the experiences of four English-language teachers in Indonesian higher education, who took part in an exploratory practice study for the integration of technology-enhanced pedagogical practices in teaching. In this article, we explore the pedagogical puzzles they explored with their students, the challenges faced by the teachers and the gains achieved by undertaking exploratory practice for integrating technology into language teaching in 2021. Drawing on data gathered through semi-structured interviews and focus group discussions, we identified that the application of exploratory practice principles enabled the participant teachers to tackle a variety of pedagogical puzzles related to online teaching and professional development. We also found that they overcame a variety of challenges and used potentially exploitable pedagogic activities to better understand students and their learning needs, which encouraged them to recognize students as partners in teaching. Further investments of resources and support are necessary to ensure that language teachers fully benefit from exploratory practice in terms of professional development during and beyond the pandemic. © The Author(s) 2023.

A constructive crisis: complex system adaptability during the COVID-19 pandemic

PurposeThis study aims to investigate the response by a multi-campus private higher education provider to a major crisis. This study examined what elements of complex adaptive systems (CAS) were activated and/or developed within the organization during the onset of the COVID-19 global pandemic, through a retrospective analysis of organizational responses. Design/methodology/approachA retrospective qualitative approach has been used. The theory of CAS has been used as the theoretical lens to explore the organizational context, responses and behaviours during the first year of the COVID-19 crisis. A series of semi-structured interviews were conducted with 12 senior leaders across the major functions of the organization spread over multiple campuses. FindingsFindings point to coverage of the main CAS characteristics in the organizational responses to the pandemic, however, in varying degrees. There was strong evidence for the application of guiding principles, for self-organizing, for micro-diversity coupled with independent actors and new generative relationships, all brought about by the chaos the pandemic generated. This study concludes that the global pandemic presented this organization with the impetus for rapid and agile responses to what ultimately has become a constructive crisis, paving the way for key elements of CAS theory to be enacted. This study recommend embedding the conscious creation of an adaptive space within ongoing strategic organizational transformation initiatives. Originality/valueThere is scant literature on CAS as applied to crises from organizations in the higher education sector and notably from outside of the health/medical fields. As a result, this study offers a novel and original approach to applying CAS theory during a major crisis. In addition to the findings above, this study also found an emergent characteristic, that of agility, which could be further tested as a potential theoretical addition to CAS theory.

FXR INHIBITION AS A NEW STRATEGY AGAINST COVID19 T Brevini1, M Maes2, GJ Webb3, CD Fuchs4, G Buescher5

Introduction: Vaccines revolutionised the management of COVID19. Nevertheless, they lack efficacy in high-risk or vulnerable groups (e.g., immunosuppressed patients), who may not mount an appropriate immune response. Monoclonal antibodies represent the gold-standard agents for such cases;but they are limited by availability, need for parenteral administration and the risk for viral escape because of spike protein mutations. Therefore, there is a pressing need for new prophylactic agents less prone to resistance.The viral receptor ACE2 represents an ideal target as it is essential for viral entry and transmission and because being a host protein it is not affected by viral mutations. However, the regulation of ACE2 remains elusive, due to the lack of appropriatein vitromodels. Cholangiocytes show one of the highest ACE2 expression levels in the body, representing an ideal platform for these studies. Here, we use cholangiocyte organoids as proof-of-principleto identify that the bile acid receptor FXR regulates ACE2 expression and SARS-CoV-2 infectionin vitro. We validate these findings in lung and gut organoids, animal models, human organs perfusedex situand patient cohorts. Aims & Methods: 1. Identify pathways controlling the transcriptional regulation of ACE2 2. Identify drugs modulating these pathways as novel prophylactic and therapeutic agents for COVID19. Organoids were propagated using established protocols. Marker expression was assessed using single-cell RNA sequencing, QPCR, and immunofluorescence. FXR binding on DNA was assessed with chromatin immunoprecipitation. SARS-CoV-2 was isolated from bronchoalveolar lavage of a COVID19 patient. Syrian golden hamsters were infected via direct inoculation and QPCR on oral swab, nasal turbinate and lung samples was used to measure SARS-CoV-2 infection. Human livers and lungs not used for transplantation were perfusedex-situusing normothermic perfusion. Nasopharyngeal swabs were used to measure ACE2 expression in nasal epithelial cells of healthy individuals taking UDCA at the standard therapeutic dose of 15 mg/kg/day. Patient registry data were compared using propensity score matching for sex, age, diabetes, NAFLD and Child- Turcotte-Pugh score. Result(s): We identified that FXR directly regulates ACE2 transcription in cholangiocyte organoids, while FXR inhibition with the approved drug ursodeoxycholic acid (UDCA), reduced ACE2 expression and SARS-CoV-2 infectionin vitro. We confirmed this mechanism in organoids from other COVID19-affected tissues, including the respiratory and intestinal systems. We validated our findingsin vivoin Syrian golden hamsters, showing that treatment with UDCA downregulates ACE2 and prevents SARS-CoV-2 infection. We confirmed that UDCA reduces ACE2 and SARS-CoV-2 infection in human lungs and livers perfusedex-situ. We performed a clinical study demonstrating that UDCA lowers ACE2 levels in the nasal epithelium of 6 healthy volunteers. Finally, we identified a correlation between UDCA and better clinical outcomes (hospitalisation, ICU admission and death) in COVID19 patients receiving UDCA for cholestatic diseases using the COVID-Hep and SECURELiver registry data. Conclusion(s): We identified FXR as a novel regulator of ACE2 expression. Using a bench-to-bedside approach combining in vitroand in vivomodels, exsituperfused human organs and clinical data we showed that FXR inhibition prevents or reduces SARS-CoV-2 infection and identified UDCA as an approved, cost-effective drug which could be repurposed for COVID19, paving the road for future clinical trials.

COVID-19: Understanding Novel Pathogens in Coupled Social–Ecological Systems

The emergence of SARS-CoV-2 and the spread of COVID-19 is explored using a social-ecological systems (SES) framework. From an SES perspective, the pandemic is the outcome of feedback loops and cascading interactions within an anthropologically disturbed system. However, the SES framework tends to overemphasize human agency as drivers of system disequilibrium. Drawing on posthumanism theory in social science, the agency of the non-human world also plays a critical role in disturbances in SES. Non-human agency is incorporated into the SES framework, applying it to the emergence of SARS-CoV-2 and the spread of COVID-19, and public health responses. The paper is interdisciplinary, and a non-systematic literature review was combined with Socratic dialogue to examine how human-induced changes trigger feedbacks in SES, such as SARS-CoV-2. The non-human world, embedded within a coupled system of material relations;the natural/biological element, that finds expression in the emergence of SARS-CoV-2 and in generating the genome novel recombinant, which aligns with the conceptualization of the non-human as “vibrant”, all play a role in shaping systems dynamics. This calls into question the anthropocentric view that human agency has the capacity to drive ecosystem dynamics. The implications for SES theory are discussed and we conclude with a case for a new ethics of interdependency to better serve SES analysis. The implications for practice, particularly considering projected future novel virus outbreaks, are discussed. © 2022 by the authors.

Putting the PASS in Class: Peer Mentors' Identities in Science Workshops on Campus and Online

In this paper, we analyse the introduction of peer mentors into timetabled classes to understand how in-class mentoring supports students- learning. The peer mentors in this study are high-achieving students who previously completed the same course and who were hired and trained to facilitate Peer Assisted Study Sessions (PASS). PASS gives students the opportunity to deepen their understanding through revision and active learning and are typically held outside of class time. In contrast, our trial embedded peer mentors into classes for a large (similar to 250 students) first-year workshop-based course. We employed a participatory action research methodology to facilitate the peer mentors-co-creation of the research process. Data sources include peer mentors' journal entries, student cohort data, and a focus group with teaching staff. We found that during face-to-face workshops, peer mentors role-modelled ideal student behaviour (e.g., asking questions) rather than acting as additional teachers, and this helped students to better understand how to interact effectively in class. The identity of embedded peer mentors is neither that of teachers nor of students, and it instead spans aspects of both as described using a three-part schema comprising (i) identity, (ii) associated roles, and (iii) associated practices. As we moved classes online mid-semester in response to the COVID-19 pandemic, mentors' identities remained stable, but mentors adjusted their associated roles and practices, including through the technical aspects of their engagement with students. This study highlights the benefits of embedding mentors in classrooms on campus and online.

Replacing all but essential face-to-face visits with virtual support for gestational diabetes care during the COVID pandemic maintains outcomes

Background: Gestational diabetes mellitus (GDM) is associated with increased perinatal complications. Our service historically saw patients with GDM monthly. Self-monitoring blood glucose (SMBG) levels were reviewed weekly via email. During COVID lockdown (23 March 2020-14 September 2020) we limited face-to-face contact and started using an App-based communication platform (GDm-HealthTM). Patients recorded SMBG on the App. Face-to-face contact was reduced to monthly scans or if insulin start was needed. Otherwise, contact was made via the app or telephone. We wanted to establish whether reduced face-to-face contact had impacted glucose control or postnatal outcomes. Methods: A retrospective analysis was performed comparing fasting glucose data and postnatal outcomes for women with the App (June 2020-31 December 2020) and standard care ( June 2019-31December 2019). Results: There were 62 women in the before App group (BA) and 61 in the with App group (WA). There was no significant difference in baseline characteristics. Results are shown as mean (SD). Treatment at 36 weeks gestation: diet only BA 22 vs WA 26 (p=0.40);metformin only BA 16 vs WA 22 (p=0.28);insulin (+metformin) 24 vs 13 (p=0.06). Fasting glucose at 36 weeks: BA 5.0 (1.1) vs WA 4.7 (0.3) mmol/L (p=0.12). Birth weight: BA 3.4 (0.6) vs WA 3.3 (0.5) kg (p=0.43) and Z score 0.3 (1.1) vs 0.4 (0.9) (p=0.77). Mode of delivery: vaginal BA 27 vs WA 14;instrumental BA 5 vs WA 7;caesarean section BA 30 vs WA 27 (p=0.78). Gestation at birth: BA 40 vs WA 38 weeks (p=0.16). Conclusion: App-based communication is effective with outcomes matching standard face-to-face GDM care.

Piloting of a Toolkit for Delirium Detection and Management at Four Emergency Departments

Study Objectives: Approximately 10-30% of older patients in the emergency department (ED) exhibit delirium, which goes unrecognized by up to 75% of providers. Delirium is linked to increased lengths of stay, in-hospital falls, cognitive decline, and mortality, yet in a recent national survey of ACEP members, only 14% reported having a protocol addressing delirium in the ED. We conducted a feasibility pilot of a delirium toolkit developed to improve screening and management of delirium in the ED. Methods: Supported by a monthly workgroup, four EDs used the toolkit to develop and implement distinct quality improvement (QI) initiatives contextually appropriate to their ED (sites represented a range of ED environments). QI initiatives included delirium screening (using the CAM, bCAM, and/or DTS instruments) as well as delirium management strategies. Toolkit feasibility testing included assessment of implementation speed, protocol adherence, and qualitative feedback. Sites implemented and reported on process metrics for their QI initiatives from July – November 2020. Results: Findings reflect data from three sites (the fourth site did not contribute quantitative data). Over 73% of ED staff received delirium protocol training across sites in the first month of implementation, and staff participation in additional monthly trainings continued at a lower intensity over time. A total of 7,107 delirium screenings were conducted (representing 43% of older adults visiting the three EDs during the study period) and 4.5% of delirium screenings were positive. Over time, the monthly number and proportion of older adults screened for delirium trended slightly downwards, while the proportion of positive delirium screenings trended upwards. The sites provided 1,460 instances of delirium management activities (some patients received more than one). These activities were grouped into over a dozen different categories, with documenting an updated diagnosis or disposition being most common (300 instances), followed by orientation (239 instances) and hydration/nutrition interventions (196 instances). Conclusion: All pilot sites leveraged the ED-Delirium Toolkit to develop QI initiatives, with three of the four sites contributing data demonstrating successful implementation. These delirium QI initiatives were seen as complementary activities to the concurrent pandemic priorities given the recognition of delirium as both a presenting symptom as well as a common complication of COVID-19. ED nurses may have been able to improve targeted screening of patients over time based on the increasing positivity rate and declining proportion and number of screenings conducted. Given the number of staff trained and scale of delirium management activities, use of the toolkit increased awareness of and interventions for addressing delirium in the ED.

A highly sensitive cell-based luciferase assay for high-throughput automated screening of SARS-CoV-2 nsp5/3CLpro inhibitors.

Effective drugs against SARS-CoV-2 are urgently needed to treat severe cases of infection and for prophylactic use. The main viral protease (nsp5 or 3CLpro) represents an attractive and possibly broad-spectrum target for drug development as it is essential to the virus life cycle and highly conserved among betacoronaviruses. Sensitive and efficient high-throughput screening methods are key for drug discovery. Here we report the development of a gain-of-signal, highly sensitive cell-based luciferase assay to monitor SARS-CoV-2 nsp5 activity and show that it is suitable for the screening of compounds in a 384-well format. A benefit of miniaturisation and automation is that screening can be performed in parallel on a wild-type and a catalytically inactive nsp5, which improves the selectivity of the assay. We performed molecular docking-based screening on a set of 14,468 compounds from an in-house chemical database, selected 359 candidate nsp5 inhibitors and tested them experimentally. We identified two molecules which show anti-nsp5 activity, both in our cell-based assay and in vitro on purified nsp5 protein, and inhibit SARS-CoV-2 replication in A549-ACE2 cells with EC50 values in the 4-8 µM range. The here described high-throughput-compatible assay will allow the screening of large-scale compound libraries for SARS-CoV-2 nsp5 inhibitors. Moreover, we provide evidence that this assay can be adapted to other coronaviruses and viruses which rely on a viral protease.

Introducing Strategic Design in Education (SDxE): an approach to navigating complexity and ambiguity at the micro, meso and macro layers of Higher Education Institutions

Members of the Higher Education (HE) community have embodied the spirit of designers by identifying needs and creatively responding with speed, agility and ingenuity as a direct response to the COVID-19 pandemic. While these rapid changes were required at the time of the pandemic, the lack of an innovation structure in HEIs (Higher Education Institutions) has become evident. We argue it is necessary to implement an innovation structure in a HEI which can be used to guide all types of innovation, to ensure they are desirable, viable, feasible and suitable from the perspective of all stakeholders. This article builds on the ARRIVE innovation process and uses Vaugh et al.’s Principles for Designing Progress to develop the concept of Strategic Design in Education (SDxE). Through embracing the SDxE approach, the HE community has the potential to not only get comfortable in the complexity and ambiguity which will inevitably result in the HEI sector for decades to come, but have an opportunity to shape it into something more desirable. We propose that SDxE offers an actionable scaffold for Human-Centered innovation, one that holds the potential to affect change, improve collaboration and produce more successful outcomes across the micro, meso and macro layers of HEIs. © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Heroin and fentanyl overdose deaths among cases age 50+ in the National Poison Data System, 2015-2020.

CONTEXT: Illicit opioid use and heroin treatment admissions among individuals age 50+ have increased. Little research has, however, examined correlates of illicit opioid overdose deaths in this age group before or during the COVID-19 pandemic or the healthcare services used in these cases. METHODS: The sample included illicit opioid (heroin, fentanyl, or other synthetic, nonpharmaceutical opioids) poisoning cases age 50+ (N = 5576) in the National Poison Data System (NPDS), 2015-2020. Using descriptive statistics and logistic regression models, we report changes in overdose death rates during the study period and associations of death with healthcare service use, naloxone administration, and clinical and demographic characteristics. RESULTS: The 6-year average overdose death rate from illicit opioids among those age 50+ was 2.9%, increasing from 1.4% in 2015 to 4.0% in 2019 and 3.6% in 2020. Logistic regression results showed that exposure year was not a significant factor in the odds of overdose death; however, odds were significantly higher among cases that were not managed at any healthcare facility (HCF) (adjusted odds ratio [AOR] = 4.60, 95% confidence interval [CI] = 3.19-6.63) and lower among those who received naloxone therapy (AOR = 0.64, 95% CI = 0.45-0.92). The odds of death were also higher among cases involving exposure at own or another's home and co-use of prescription opioids, alcohol, and other illicit drugs. CONCLUSIONS: Although the NPDS did not show increases in illicit opioid overdose death rates among cases age 50+ in 2020 compared to 2019, overdose deaths were greater among cases that were not managed at HCF and did not receive naloxone therapy. Many appear to have died before they received any intervention to prevent death. Improved access to healthcare services and social support and access to naloxone therapy for older adults with opioid use problems are needed.

Fxr as a new therapeutic target for COVID-19

Background: Despite recent advances, the management of COVID19 is complicated by vaccine availability, the modest efficacy of existing treatments, and the potential for viral resistance. Therefore, there is a pressing need for new prophylactic and therapeutic agents. Modifying the expression of the SARS-CoV-2 entry receptor ACE2 could prevent viral infection and limit disease progression. Here, we identify that ACE2 expression is controlled by the transcription factor farnesoid X receptor (FXR) and demonstrate that ACE2 downregulation through FXR antagonism, using approved drugs, such as ursodeoxycholic acid (UDCA), could represent a novel therapeutic strategy to complement current approaches. Methods: Primary cholangiocyte, pulmonary and intestinal organoids were propagated using established protocols. Marker expression was assessed using singlecell RNA sequencing, QPCR, immunofluorescence and flow cytometry. FXR binding on DNA was assessed with chromatin immunoprecipitation. SARS-CoV-2 was isolated from bronchoalveolar lavage of a COVID19 patient. Viral load was measured via QPCR. Human livers not used for transplantation were perfused ex-situ using the metra (OrganOx) normothermic perfusion device. Serum ACE2 activity was measured with commercial kits. Patient data from the COVID-Hep and SECURE-Liver registries were compared using propensity score matching. Results: FXR activation directly upregulated ACE2 transcription in organoids from COVID19 affected tissues, including the biliary, gastrointestinal and respiratory systems. Conversely, FXR antagonism with z-guggulsterone or UDCA, had the opposite effect. Importantly, both drugs reduced susceptibility to SARS-CoV-2 infection in lung, cholangiocyte and gut organoids. Furthermore, systemic administration of UDCA in human organs perfused ex-situ downregulated ACE2 and reduced SARS-CoV-2 infection ex-vivo. Oral UDCA rapidly reduced serum ACE2 in vivo. Registry data showed a correlation between UDCA administration and better clinical outcomes in COVID19 patients, including hospitalisation, ICU admission, mechanical ventilation and death. Conclusion: We discovered FXR as a novel therapeutic target against SARS-CoV-2 and we identified approved FXR inhibitors which could be repurposed to potentially treat COVID19, paving the road for future clinical trials to validate these results.

Energy insecurity and the urgent need for utility disconnection protections

Millions of Americans are unable to pay their energy bills and face the risk of being disconnected from their energy providers. This problem has grown significantly worse during the COVID-19 pandemic, with low-income households, households of color, and households with vulnerable populations particularly hard-hit by these conditions. In the early months of the pandemic, many states imposed temporary protections on utility disconnection but, as time has evolved, nearly all of these protections have lapsed. An increasing lack of protection has serious implications for vulnerable populations. Here, we present the extent of the energy insecurity problem in the United States, discuss the design and evolution of state disconnection protections, and offer policy recommendations for addressing this imminent challenge. © 2021 Elsevier Ltd

Fxr antagonists as new agents for COVID19

Introduction The management of COVID19 is complicated by vaccine availability, the modest efficacy of existing treatments, and the potential for viral resistance. Therefore, there is a pressing need for new prophylactic and therapeutic agents. The viral receptor ACE2 is an ideal target as it is required for SARS-CoV-2 entry in host cells. Modifying ACE2 expression could prevent infection and/or limit disease progression. Nevertheless, the mechanisms controlling ACE2 expression remain elusive. Aims To identify pathways controlling the transcriptional regulation of ACE2, and exploit them to reduce SARS-CoV-2 infection. Methods Organoids from primary biliary, intestinal and pulmonary epithelia were derived and cultured as previously described. Single-cell RNA sequencing, QPCR, immunofluorescence and flow cytometry were used to assess marker expression. Chromatin immunoprecipitation was used to assess FXR binding on DNA. Bronchoalveolar lavage SARS-CoV-2 patient isolates were used for infection experiments. Human livers not used for transplantation were connected to the metra (OrganOx) normothermic perfusion device and perfused ex-situ using therapeutic doses of UDCA for 12 hours. ACE2 activity was measured following manufacturer's instructions. Patient data from the COVID-Hep and SECURE-Liver registries were compared using propensity score matching for sex, age and Child-Turcotte-Pugh score. Results We first demonstrated that cholangiocytes are susceptible to SARS-CoV-2 infection in vivo and in organoid culture. We then used cholangiocyte organoids to identify FXR as a transcriptional regulator of ACE2. We validated our results in pulmonary and intestinal organoids, showing that ACE2 regulation by FXR represents a broad mechanism present in multiple COVID19-affected tissues. We then demonstrated that approved FXR inhibitors, such as ursodeoxycholic acid (UDCA) and z-guggulsterone (ZGG), decrease ACE2 levels and reduce viral infection in vitro in primary biliary, intestinal and pulmonary organoids. We interrogated the impact of systemic UDCA administration in human livers perfused ex-situ, demonstrating reduced ACE2 levels and SARS-CoV-2 infection. Furthermore, we showed that commencing UDCA treatment lowers ACE2 levels in primary biliary cholangitis (PBC) patients. Finally, we identified a correlation between UDCA treatment and better clinical outcome in COVID-19 patients, including hospitalisation, ICU admission, mechanical ventilation and death, using registry data. Conclusion We identified FXR as a novel master regulator of ACE2 expression. Using a bench-to-bedside approach we combined in vitro, ex-vivo and patient data to demonstrate the efficacy of ACE2 downregulation against SARS-CoV-2 infection and identified approved and inexpensive drugs (UDCA, ZGG) which could be repurposed as prophylactic and therapeutic agents against SARS-CoV-2 infection, paving the road for future clinical trials.

Using disasters to estimate the impact of uncertainty

Uncertainty rises in recessions and falls in booms. But what is the causal relationship? We construct cross-country panel data on stock market levels and volatility and use natural disasters, terrorist attacks, and political shocks as instruments in regressions and VAR estimations. We find that increased volatility robustly lowers growth. We also structurally estimate a heterogeneous firms business cycle model with uncertainty and disasters and use this to analyze our empirical results. Finally, using our VAR results we estimate COVID-19 will reduce US GDP by 9% in 2020 based on the initial stock market returns and volatility response.

COVID-induced economic uncertainty

Assessing the economic impact of the COVID-19 pandemic is essential for policymakers, but challenging because the crisis has unfolded with extreme speed. We identify three indicators - stock market volatility, newspaper-based economic uncertainty, and subjective uncertainty in business expectation surveys - that provide real-time forward-looking uncertainty measures. We use these indicators to document and quantify the enormous increase in economic uncertainty in the past several weeks. We also illustrate how these forward-looking measures can be used to assess the macroeconomic impact of the COVID-19 crisis. Specifically, we feed COVID-induced first-moment and uncertainty shocks into an estimated model of disaster effects developed by Baker, Bloom and Terry (2020). Our illustrative exercise implies a year-on-year contraction in U.S. real GDP of nearly 11 percent as of 2020 Q4, with a 90 percent confidence interval extending to a nearly 20 percent contraction. The exercise says that about half of the forecasted output contraction reflects a negative effect of COVID-induced uncertainty.

Development of a Mouse Model of Human Coronavirus NL63 (HCoV-NL63) Infection

Introduction: The SARS CoV2 pandemic has produced morbidity and mortality worldwide which depends on age, body mass index, cardiovascular disease and other factors. Of the human coronaviruses, only SARS-CoV2 and HCoV-NL63 bind the ACE2 protein. HCoV-NL63 causes upper respiratory tract infections in children but has also been reported to cause pneumonia and even Kawasaki disease. Hypothesis: HCoV-NL63 produces lung inflammation in mice expressing the human ACE2 protein. Methods: HCoV-NL63 (BEI Resources) was propagated in Caco-2 cells. Cells were harvested and concentrated to produce a working virus stock. Virus cytopathic effect in Vero cells at 48 h infection was determined by TCID50. B6.Cg-Tg(K18-ACE2)2Prlmn mice (Jackson Laboratories) express the human ACE2 protein in epithelial cells under the direction of the keratin 18 promoter. Eight-10 week-old K18-hACE2 or C57BL6/J mice were infected with 50 μ L (100,000 TCID50 units) HCoV-NL63 or sham Caco-2 extract intranasally and euthanized at 2, 4, and 7 days post-treatment. Mouse lungs were assessed for histology, IFN and cytokine mRNAs, ACE2, viral RNA and HCoV-NL63 proteins (nucleoprotein, Nsp3 and Nsp4). Primers designed from HCoV-NL63 sequence (NC-005831.2) were used to measure vRNA by qPCR. Polyclonal antibodies to Nsp3 and Nsp4 were generated (Chen et al, J Virol 2007). Antibodies to human ACE2 (InVitrogen), HCoV-NL63 nucleoprotein (clone 2D5, Eurofins), Nsp3 and Nsp4 were conjugated with AlexaFluor dyes. Results: HCoV-NL63 produced cytopathic effects in Vero cells colocalized with viral nucleoprotein. Virus propagated in K18-hACE2 but not C57BL6/J mice. vRNA levels plateaued 4 days after infection and were detectable 7 days after infection. Lung mRNA expression of IFN-α, IFN-β, IFN-λ, CXCL1 and IL-6 were significantly increased 48 h after infection in HCoV-NL63-treated K18-hACE2 but not C57BL6/J mice (N=3, p<0.05, Kruskal-Wallis test). Sections of mouse lung demonstrated bronchovascular and peribronchial inflammation that were most evident 7 days after infection. Nucleoprotein was found on the apical surface of airway epithelial cells of HCoV-NL63- but not sham-infected K18-hACE2 mice, and Nsp3 and Nsp4 were found in the basal and perinuclear cytoplasm of airway epithelial cells. Conclusion: Human coronavirus NL63 infects K18-ACE2 mice inducing an airway inflammatory response. Viral replication is evidenced by vRNA levels, interferon mRNA expression and production non-structural viral proteins. This model may be used to study HCoV-NL63-induced exacerbation of allergic airways disease;the effect of allergy, obesity and aging on human coronavirus infection, and possible cross-immunity between HCoV-NL63 and other respiratory viruses.