Emergence and spread of SARS-CoV-2 variants from farmed mink to humans and back during the epidemic in Denmark, June-November 2020. (preprint)

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has not only caused the COVID-19 pandemic but also had a major impact on farmed mink production in several European countries. In Denmark, the entire population of farmed mink (over 15 million animals) was culled in late 2020. During the period of June to November 2020, mink on 290 farms (out of about 1100 in the country) were shown to be infected with SARS-CoV-2. Genome sequencing identified changes in the virus within the mink and it is estimated that about 4000 people in Denmark became infected with these mink virus variants. Phylogenetic analysis revealed the generation of multiple clusters of the virus within the mink. A detailed analysis of the changes in the virus during replication in mink and, in parallel, in the human population in Denmark, during the same time period, has been performed here. The majority of cases in mink involved variants that had the Y435F substitution and the H69/V70 deletion within the Spike (S) protein; these changes emerged early on during the outbreak. However, further introductions of the virus, with variants lacking these changes, from the human population into mink also occurred. Based on phylogenetic analysis of the available viral genome data, we estimate that there were a minimum of about 17 separate examples of mink to human transmission of the virus in Denmark, using a conservative approach, but up to 60 such events (95% credible interval: (35-77)) were identified using parsimony to count cross-species jumps on transmission trees inferred using a Bayesian method. Using the latter approach, it was estimated that there were 136 jumps (95% credible interval: (112-164)) from humans to mink. Thus, transmission of these viruses from humans to mink, mink to mink, from mink to humans and between humans were all observed.

Role of Angiotensin II in Cardiovascular Diseases: Introducing Bisartans as a Novel Therapy for Coronavirus 2019.

Cardiovascular diseases (CVDs) are the main contributors to global morbidity and mortality. Major pathogenic phenotypes of CVDs include the development of endothelial dysfunction, oxidative stress, and hyper-inflammatory responses. These phenotypes have been found to overlap with the pathophysiological complications of coronavirus disease 2019 (COVID-19). CVDs have been identified as major risk factors for severe and fatal COVID-19 states. The renin-angiotensin system (RAS) is an important regulatory system in cardiovascular homeostasis. However, its dysregulation is observed in CVDs, where upregulation of angiotensin type 1 receptor (AT1R) signaling via angiotensin II (AngII) leads to the AngII-dependent pathogenic development of CVDs. Additionally, the interaction between the spike protein of severe acute respiratory syndrome coronavirus 2 with angiotensin-converting enzyme 2 leads to the downregulation of the latter, resulting in the dysregulation of the RAS. This dysregulation favors AngII/AT1R toxic signaling pathways, providing a mechanical link between cardiovascular pathology and COVID-19. Therefore, inhibiting AngII/AT1R signaling through angiotensin receptor blockers (ARBs) has been indicated as a promising therapeutic approach to the treatment of COVID-19. Herein, we review the role of AngII in CVDs and its upregulation in COVID-19. We also provide a future direction for the potential implication of a novel class of ARBs called bisartans, which are speculated to contain multifunctional targeting towards COVID-19.

Computational and Enzymatic Studies of Sartans in SARS-CoV-2 Spike RBD-ACE2 Binding: The Role of Tetrazole and Perspectives as Antihypertensive and COVID-19 Therapeutics.

This study is an extension of current research into a novel class of synthetic antihypertensive drugs referred to as "bisartans", which are bis-alkylated imidazole derivatives bearing two symmetric anionic biphenyltetrazoles. Research to date indicates that bisartans are superior to commercially available hypertension drugs, since the former undergo stronger docking to angiotensin-converting enzyme 2 (ACE2). ACE2 is the key receptor involved in SARS-CoV-2 entry, thus initiating COVID-19 infection and in regulating levels of vasoactive peptides such as angiotensin II and beneficial heptapeptides A(1-7) and Alamandine in the renin-angiotensin system (RAS). In previous studies using in vivo rabbit-iliac arterial models, we showed that Na+ or K+ salts of selected Bisartans initiate a potent dose-response inhibition of vasoconstriction. Furthermore, computational studies revealed that bisartans undergo stable binding to the vital interfacial region between ACE2 and the SARS-CoV-2 "receptor binding domain" (i.e., the viral RBD). Thus, bisartan homologs are expected to interfere with SARS-CoV-2 infection and/or suppress disease expression in humans. The primary goal of this study was to investigate the role of tetrazole in binding and the network of amino acids of SARS-CoV-2 Spike RBD-ACE2 complex involved in interactions with sartans. This study would, furthermore, allow the expansion of the synthetic space to create a diverse suite of new bisartans in conjunction with detailed computational and in vitro antiviral studies. A critical role for tetrazole was uncovered in this study, shedding light on the vital importance of this group in the binding of sartans and bisartans to the ACE2/Spike complex. The in silico data predicting an interaction of tetrazole-containing sartans with ACE2 were experimentally validated by the results of surface plasmon resonance (SPR) analyses performed with a recombinant human ACE2 protein.

Post-Secondary Student Belonging in a Virtual Learning Environment during Covid-19

Psychological and social adjustment and academic success in post-secondary institutions are supported by a sense of belonging to a social group and having meaningful relationships with other students, staff, and faculty members. This exploratory study used a qualitative approach to investigate post-secondary students' sense of belonging in the virtual learning environment during the COVID-19 pandemic. The study was conducted at a small Western Canadian university. Semi-structured interviews were conducted with 20 participants who were undergraduate students, from various faculties, and in different years in their programs. Findings were clustered into three themes: (1) student expectations of university, (2) impact of virtual learning environments on students, and (3) the role of educators. Recommendations are included to enhance support and belonging for post-secondary students in virtual learning environments.

COVID-19 vaccination in pregnancy: How discrepant public health discourses shape responsibility for fetal health.

Early in COVID-19 vaccine rollout, expert recommendations about vaccination while pregnant and breastfeeding changed rapidly. This paper addresses the (re)production of gendered power relations in these expert discourses and recommendations in Canada. We collected texts about COVID-19 vaccine use in pregnancy (N â€‹= â€‹52) that Canadian health organizations (e.g., professional societies, advisory groups, health authorities) and vaccine manufacturers made publicly available online. A discourse analysis was undertaken to investigate intertextuality (relations between texts), social construction (incorporation of assumptions about gender), and contradictions between and within texts. National expert recommendations varied in stating COVID-19 vaccines are recommended, should be offered, or may be offered, while manufacturer texts consistently stated there was no evidence. Provincial and territorial texts reproduced discrepancies between the Society of Obstetricians and Gynaecologists of Canada and National Advisory Committee on Immunization recommendations, including that COVID-19 vaccines should be versus may be offered in pregnancy. Our findings suggest gaps in data and discrepant COVID-19 vaccine recommendations, eligibility, and messaging limit guidance regarding vaccination in pregnancy. We argue that these discrepancies magnified the already common practice of deferring responsibility for the uncertainties of vaccination in pregnancy onto parents and healthcare providers. The deferral of responsibility could be reduced by harmonizing recommendations, regularly updating texts that describe evidence and recommendations, and prioritizing research into disease burden, vaccine safety, and efficacy before vaccine rollout.

Improvements in metagenomic virus detection by simple pretreatment methods

Highlights • Methods assessed for non-viral nucleic acid depletion from clinical samples.• SARS-CoV-2, human papillomavirus (HPV) and molluscum contagiosum virus (MCV) detection used as test of concept.• DNase I treatment followed by filtration dramatically improved virus detection efficiency.• Presenting a metagenomic workflow with Nanopore sequencing for prompt RNA and DNA virus detection.• The Delta variant of SARS-CoV-2, HPV-genotype and a co-infection of HPV and MCV-1 were correctly identified with this workflow. Early detection of pathogens at the point of care helps reduce the threats to human and animal health from emerging pathogens. Initially, the disease-causing agent will be unknown and needs to be identified;this often requires specific laboratory facilities. Here we describe the development of an unbiased detection assay for RNA and DNA viruses using metagenomic Nanopore sequencing and simple methods that can be transferred into a field setting. Human clinical samples containing the RNA virus SARS-CoV-2 or the DNA viruses human papillomavirus (HPV) and molluscum contagiosum virus (MCV) were used as a test of concept. Firstly, the virus detection potential was optimized by investigating different pretreatments for reducing non-viral nucleic acid components. DNase I pretreatment followed by filtration increased the proportion of SARS-CoV-2 sequenced reads > 500-fold compared with no pretreatments. This was sufficient to achieve virus detection with high confidence and allowed variant identification. Next, we tested individual SARS-CoV-2 samples with various viral loads (measured as CT-values determined by RT-qPCR). Lastly, we tested the assay on clinical samples containing the DNA virus HPV and co-infection with MCV to show the assay's detection potential for DNA viruses. This protocol is fast (same day results). We hope to apply this method in other settings for point of care detection of virus pathogens, thus eliminating the need for transport of infectious samples, cold storage and a specialized laboratory.

Post-Secondary Student Belonging in a Virtual Learning Environment During COVID-19

Psychological and social adjustment and academic success in post-secondary institutions are supported by a sense of belonging to a social group and having meaningful relationships with other students, staff, and faculty members. This exploratory study used a qualitative approach to investigate post-secondary students' sense of belonging in the virtual learning environment during the COVID-19 pandemic. The study was conducted at a small Western Canadian university. Semi-structured interviews were conducted with 20 participants who were undergraduate students, from various faculties, and in different years in their programs. Findings were clustered into three themes: (1) student expectations of university, (2) impact of virtual learning environments on students, and (3) the role of educators. Recommendations are included to enhance support and belonging for post-secondary students in virtual learning environments. © 2022, Canadian Society for Studies in Higher Education. All rights reserved.

Mental health walk-in clinics for children and families: a provincial survey

Mental health walk-in clinics (MHWCs) provide unscheduled and immediate support to children and families and remove common administrative barriers. This study explored the implementation of MHWCs across Ontario, CA. A brief provincial survey was conducted to identify agencies that provided MHWCs, which were then invited to complete an in-depth survey. The in-depth survey questions were formatted as multiple choice, yes/no, Likert scale, and open-ended questions, taking 20–25 min with the option of online or phone-based completion. A total of 18 (86%) agencies participated in the in-depth survey between September 2020 and April 2021. MHWCs are being used to provide timely and accessible services, as well as to serve as a point of intake. MHWCs are provided in different locations (e.g. agencies, schools) using different modalities (e.g. consulting break) and approaches (e.g. cognitive behavioural therapy, narrative therapy, solution focused therapy). Most agencies quickly adapted to COVID-19 restrictions by providing virtual MHWCs. The most common reasons for implementing MHWCs were to reduce waitlists, the strong evidence base, and an effort to meet families' needs. Different benefits and challenges associated with the implementation of MHWCs were reported. The results of this provincial study help better understand the implementation of MHWCs and how agencies adapted to COVID-19 and associated restrictions. [ABSTRACT FROM AUTHOR] Copyright of Advances in Mental Health is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Cell death and barrier disruption by clinically used iodine concentrations.

Povidone-iodine (PVP-I) inactivates a broad range of pathogens. Despite its widespread use over decades, the safety of PVP-I remains controversial. Its extended use in the current SARS-CoV-2 virus pandemic urges the need to clarify safety features of PVP-I on a cellular level. Our investigation in epithelial, mesothelial, endothelial, and innate immune cells revealed that the toxicity of PVP-I is caused by diatomic iodine (I2), which is rapidly released from PVP-I to fuel organic halogenation with fast first-order kinetics. Eukaryotic toxicity manifests at below clinically used concentrations with a threshold of 0.1% PVP-I (wt/vol), equalling 1 mM of total available I2 Above this threshold, membrane disruption, loss of mitochondrial membrane potential, and abolition of oxidative phosphorylation induce a rapid form of cell death we propose to term iodoptosis. Furthermore, PVP-I attacks lipid rafts, leading to the failure of tight junctions and thereby compromising the barrier functions of surface-lining cells. Thus, the therapeutic window of PVP-I is considerably narrower than commonly believed. Our findings urge the reappraisal of PVP-I in clinical practice to avert unwarranted toxicity whilst safeguarding its benefits.

Regular, intermittent, and spontaneous: Patterns of preschool Children's nap behavior and their correlates.

BACKGROUND: Daytime sleep during the preschool years (i.e., 1-5-years-old) is characterized by high inter-child variability in several components of nap behavior, including nap duration, nap timing, and the proportion of sleep during daytime. We used an empirical approach to examine variations amongst children in these aspects of napping and investigated correlates of these components of nap behavior. METHODS: A large, nationally representative sample (N = 702) of Canadian parents completed an online survey, including a one-month retrospective report of their 1.5-5 year old's daytime and nighttime sleep behavior and other questionnaires. To understand patterns of children's nap behaviors we applied Latent Profile Analysis (LPA) to typical nap duration, typical timing of naps, frequency of naps, proportion of sleep during the daytime, and the proportion of naps which were spontaneous (i.e., child just fell asleep). Then, multinominal logistic regression was used to examine correlates of profile membership. RESULTS: Four profiles of children emerged: (1) regular nappers; (2) intermittent nappers; (3) spontaneous nappers; and (4) non-nappers. After controlling for demographic variables (e.g., child age, sex, ethnicity) and known correlates of napping behaviors (e.g., birthweight, nighttime sleep duration), profile membership was related to parents' beliefs about napping, parents' own nap behaviors, family functioning, and child nighttime sleep problems in a multinominal logistic regression. CONCLUSIONS: An empirical approach aided in understanding the inter-child variability in napping amongst preschool-age children. Parental beliefs about napping and the home environment were shown to be critical factors influencing this variability.

Virtual Peer-to-Peer Mentoring for Adolescents with Congenital Heart Disease: An Implementation Study

Background/Purpose: Congenital heart disease (CHD) is the most common birth defect in Canada, affecting approximately 1 in every 100 children. Adolescents with CHD (AWCHD) must learn to independently manage their disease and transition to adult care, yet many young Canadians fail to attend an adult CHD clinic. Patients who do not receive follow-up care have increased risks of requiring urgent interventions and hospital admission. Interventions designed to support coping and self-management are key strategies to improve the ability of AWCHD to manage their health and successfully transition to adult care. Peer support is one intervention that has been shown to improve health outcomes and symptoms in people with chronic disease, however no study to date has examined the role of peer mentorship in supporting AWCHD. This project tailored an existing virtual peer-to-peer mentorship program (iPeer2Peer© (iP2P) program) to meet the needs of AWCHD. The study aims were twofold: (1) To determine whether the iP2P program can be sustainably integrated into clinical practice within the CHD Transition Program at The Hospital for Sick Children, and (2) To examine the impact of the iP2P program on self-management and quality of life. Methods/Results: A prospective feasibility study of the iP2P CHD program was conducted to determine whether the program could be integrated and sustained in practice (primary outcome) and to examine program effectiveness (secondary outcome). A mixed methods design was used to measure feasibility of implementation (i.e. acceptability, adoption, appropriateness, etc.) and effectiveness of the iP2P CHD program (i.e. self-management and transition readiness, quality of life, perceived social support, etc.). Semi-structured interviews were conducted to determine program satisfaction and engagement. At the time of submission, 8 peer mentors had been successfully recruited and completed the 3-day training program. Early analysis of implementation outcomes demonstrated that identification and recruitment of suitable mentors may be more challenging in this population than previous groups. This may be related to factors such as range of disease severity and the nature of co-occurring developmental, social and mental health challenges in this population. Conclusion/Implications for Practice: There is an urgent need to implement virtual support interventions as the COVID-19 pandemic has limited opportunities for AWCHD to receive social support. Preliminary results suggest that the iP2P CHD virtual peer support program can be feasibly implemented within the CHD Transition Program. Peer mentor recruitment and training is feasible, and participation in the peer mentorship program is of interest to both mentors and mentees. Copyright © 2022

Experimental Infection of Pigs with Recent European Porcine Epidemic Diarrhea Viruses.

Porcine epidemic diarrhea virus (PEDV), belonging to the genus Alphacoronavirus, can cause serious disease in pigs of all ages, especially in suckling pigs. Differences in virulence have been observed between various strains of this virus. In this study, four pigs were inoculated with PEDV from Germany (intestine/intestinal content collected from pigs in 2016) and four pigs with PEDV from Italy (intestine/intestinal material collected from pigs in 2016). The pigs were re-inoculated with the same virus on multiple occasions to create a more robust infection and enhance the antibody responses. The clinical signs and pathological changes observed were generally mild. Two distinct peaks of virus excretion were seen in the group of pigs inoculated with the PEDV from Germany, while only one strong peak was seen for the group of pigs that received the virus from Italy. Seroconversion was seen by days 18 and 10 post-inoculation with PEDV in all surviving pigs from the groups that received the inoculums from Germany and Italy, respectively. Attempts to infect pigs with a swine enteric coronavirus (SeCoV) from Slovakia were unsuccessful, and no signs of infection were observed in the inoculated animals.

Improvements in metagenomic virus detection by simple pretreatment methods.

Early detection of pathogens at the point of care helps reduce the threats to human and animal health from emerging pathogens. Initially, the disease-causing agent will be unknown and needs to be identified; this often requires specific laboratory facilities. Here we describe the development of an unbiased detection assay for RNA and DNA viruses using metagenomic Nanopore sequencing and simple methods that can be transferred into a field setting. Human clinical samples containing the RNA virus SARS-CoV-2 or the DNA viruses human papillomavirus (HPV) and molluscum contagiosum virus (MCV) were used as a test of concept. Firstly, the virus detection potential was optimized by investigating different pretreatments for reducing non-viral nucleic acid components. DNase I pretreatment followed by filtration increased the proportion of SARS-CoV-2 sequenced reads > 500-fold compared with no pretreatments. This was sufficient to achieve virus detection with high confidence and allowed variant identification. Next, we tested individual SARS-CoV-2 samples with various viral loads (measured as CT-values determined by RT-qPCR). Lastly, we tested the assay on clinical samples containing the DNA virus HPV and co-infection with MCV to show the assay's detection potential for DNA viruses. This protocol is fast (same day results). We hope to apply this method in other settings for point of care detection of virus pathogens, thus eliminating the need for transport of infectious samples, cold storage and a specialized laboratory.

Decreased Mortality from Sars-CoV-2 Infection in Kidney Transplant Recipients Over the Course of the Pandemic

Purpose: We aimed to investigate the mortality from SARS-CoV-2 in kidney transplant recipients in the Bronx, New York since the beginning of the pandemic Methods: Between March 16, 2020 and November 5, 2021, 453 patients were diagnosed with SARS-CoV-2 infection. 316 were diagnosed by RT-PCR while the remaining 137 tested positive for anti-SARS-CoV-2 nucleocapsid IgG and did not have significant symptoms and had not been previously tested by RT-PCR Results: Of the 316 patients diagnosed by RT-PCR, 214 patients were hospitalized while 102 patients were managed at home as outpatient. 194 (61.3%) were male, median age 61 years old (IQR: 48-69), predominantly Hispanic (56.2%) and African American (29.5%). 75% received a deceased-donor renal transplant, 58% received anti-thymocyte induction. Most patients were on triple immunosuppression (95% on calcineurin inhibitors, 87% on anti-metabolite, and 97% on prednisone). Hypertension was the most common comorbidity followed by diabetes mellitus, heart disease and lung disease. A total of 65 patients (20.5%) died. The mortality rate was 37 % (47/128) in patients diagnosed between March 16 and April 30, 2020. From May 1, 2020 to end of December 2020 mortality rate has significantly decreased to 11% (7/61). Since the beginning of 2021 till November 5, 2021 the mortality rate is 7.7% (10/129). Twenty-seven patients were diagnosed with COVID-19 despite being partially of fully vaccinated (25 fully vaccinated, 2 after one dose of vaccine). 13/27 (48%) were managed at home while 14/27 (52%) were hospitalized and 2 (7%) of them died. Twenty-eight patients received treatment with casirivimab and imdevimab post diagnosis of SARS-CoV-2 starting 2021 and none of those patients have died. Conclusion(s): In summary, mortality from SARS-CoV-2 infection in kidney transplant recipients was higher earlier at the pandemic and has significantly decreased over time. This could be explained by initial exposure of the patients with higher viral load due to lack of personal protection and social distancing. However, since the judicious use of monoclonal antibodies and vaccination, in addition to social distancing protocols and use of facemask, the mortality in kidney transplant recipients has decreased over time.

Actions of Novel Angiotensin Receptor Blocking Drugs, Bisartans, Relevant for COVID-19 Therapy: Biased Agonism at Angiotensin Receptors and the Beneficial Effects of Neprilysin in the Renin Angiotensin System.

Angiotensin receptor blockers (ARBs) used in the treatment of hypertension and potentially in SARS-CoV-2 infection exhibit inverse agonist effects at angiotensin AR1 receptors, suggesting the receptor may have evolved to accommodate naturally occurring angiotensin 'antipeptides'. Screening of the human genome has identified a peptide (EGVYVHPV) encoded by mRNA, complementary to that encoding ANG II itself, which is an inverse agonist. Thus, opposite strands of DNA encode peptides with opposite effects at AR1 receptors. Agonism and inverse agonism at AR1 receptors can be explained by a receptor 'switching' between an activated state invoking receptor dimerization/G protein coupling and an inverse agonist state mediated by an alternative/second messenger that is slow to reverse. Both receptor states appear to be driven by the formation of the ANG II charge-relay system involving TyrOH-His/imidazole-Carboxylate (analogous to serine proteases). In this system, tyrosinate species formed are essential for activating AT1 and AT2 receptors. ANGII is also known to bind to the zinc-coordinated metalloprotease angiotensin converting enzyme 2 (ACE2) used by the COVID-19 virus to enter cells. Here we report in silico results demonstrating the binding of a new class of anionic biphenyl-tetrazole sartans ('Bisartans') to the active site zinc atom of the endopeptidase Neprilysin (NEP) involved in regulating hypertension, by modulating humoral levels of beneficial vasoactive peptides in the RAS such as vasodilator angiotensin (1-7). In vivo and modeling evidence further suggest Bisartans can inhibit ANG II-induced pulmonary edema and may be useful in combatting SARS-CoV-2 infection by inhibiting ACE2-mediated viral entry to cells.

Single vs replicate Real-Time PCR SARS-CoV-2 testing: Lessons learned for effective pandemic management.

Coronavirus Disease 19 (COVID-19) caused by the SARS-CoV-2 virus remains a global pandemic having a serious impact on national economies and healthcare infrastructure. Accurate infection detection protocols are key to policy guidance and decision making. In this pilot study, we compared single versus replicate PCR testing for effective and accurate SARS-CoV-2 infection detection. One-Step Real-Time RT-PCR was employed for the detection of SARS-CoV-2 RNA isolated from individual nasopharyngeal swabs. A total of 10,014 swabs, sampled from the general public (hospital admissions, A&E, elective surgeries, cancer patients, care home residents and healthcare staff), were tested using standard replicate testing. Our analysis demonstrates that approximately 19% of SARS-CoV-2 infected individuals would have been reported as false negative if single sample Real-Time PCR testing was used. Therefore, two replicate tests can substantially decrease the risk of false negative reporting and reduce hospital and community infection rates. As the number of variants of concern increases, we believe that replicate testing is an essential consideration for effective SARS-CoV-2 infection detection and prevention of further outbreaks. A strategic approach limiting the number of missed infections is crucial in controlling the rise of new SARS-CoV-2 variants as well as the management of future pandemics.

Limitations of High Flow Nasal Cannula at End of Life

Rationale Many patient with end-stage fibrotic lung disease die in the hospital due to dependence on High Flow Nasal Cannula (HFNC), not available at home. Despite available technical maturity, HFNC is not sufficiently available due to size and portability, energy requirement and oxygen (O2) capacity. This has become particularly problematic during the current Covid-19 pandemic, when many had to die alone in hospital due to these constraints. ObjectiveThe objective of this investigation was to appreciate the number of patients who die in hospital on comfort care, who could benefit from HFNC at home to support person-centered care (self-determination, family involvement, comforts of home) at end of life (EOL). MethodsWe collected data from a convenience sampling of patients who received care at a 449-bed acute-care community hospital in Southern California between June 2020 and June 2021. Data from this retrospective review of the electronic health record included demographics (age, gender, BMI and ethnicity). Other variables collected were length of stay (LOS), Covid status (+/-), comfort care orders, and HFNC requirement. Data were analyzed for frequencies, means and percentages. Chi square (categorical) and t- tests (continuous) were performed to determine statistical significance and Pearson r (categorical) and eta (continuous) were performed to test strength of association.ResultsOf the sample (n = 91), mean age was 78 years (+/- 10.6) and mostly female (38.8%, n = 42). Mean LOS was 13.7 days (+/- 12.1). Most (71.4%) patients in the sample were Hispanic (n = 65). 63 patients had orders for comfort care (69.2%), and 61 patients were Covid positive (67%). There was a statistically significant difference in mean flow rate (p = 0.022, η = 0.564) and fi02 (p < 0.001, η = 0.688) for patients discharged to hospice vs. those who died in hospital. For patients who died in hospital, mean fi02 was 0.94 (12.2) and mean flow rate (in liters) was 48.6 (16.4). ConclusionsThe pandemic has highlighted many healthcare disparities in the United States, and made apparent the needs of persons with fibrotic lung disease at EOL. This investigation revealed that most patients in hospital opting for comfort care died in hospital as their needs for increased flow rates and fi02 far exceeds what is currently available for outpatient use of HFNC. Investments should be made into developing technologies to support these individuals with the benefits of decreased need for hospitalization and promoting self-determination at EOL.