Partnering for Occupational Therapy Telehealth Services: Collaboratively developing telehealth and hybrid occupational therapy student placements

In 2020, in Ireland, challenges associated with the COVID-19 pandemic disrupted occupational therapy student practice education placements availability. New innovative placements were required. A collaboration between University of Limerick (UL), Ireland, and Dyspraxia/DCD Ireland (DDCD Ireland) has to date enabled 30 occupational therapy students to undertake practice education placements via telehealth. Originally, this placement was designed to allow students to meet learning objectives remotely. This case report outlines how an area of innovative practice at an Irish occupational therapy student education programme evolved, during the crisis associated with Covid-19, culminating in the establishment of the Partnering for Occupational Therapy Telehealth Services (POTTS), which is now a hybrid service (telehealth and face-to-face service).

The US Department of Veterans Affairs Science and Health Initiative to Combat Infectious and Emerging Life-Threatening Diseases (VA SHIELD): A Biorepository Addressing National Health Threats.

Background: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has demonstrated the need to share data and biospecimens broadly to optimize clinical outcomes for US military Veterans. Methods: In response, the Veterans Health Administration established VA SHIELD (Science and Health Initiative to Combat Infectious and Emerging Life-threatening Diseases), a comprehensive biorepository of specimens and clinical data from affected Veterans to advance research and public health surveillance and to improve diagnostic and therapeutic capabilities. Results: VA SHIELD now comprises 12 sites collecting de-identified biospecimens from US Veterans affected by SARS-CoV-2. In addition, 2 biorepository sites, a data processing center, and a coordinating center have been established under the direction of the Veterans Affairs Office of Research and Development. Phase 1 of VA SHIELD comprises 34 157 samples. Of these, 83.8% had positive tests for SARS-CoV-2, with the remainder serving as contemporaneous controls. The samples include nasopharyngeal swabs (57.9%), plasma (27.9%), and sera (12.5%). The associated clinical and demographic information available permits the evaluation of biological data in the context of patient demographics, clinical experience and management, vaccinations, and comorbidities. Conclusions: VA SHIELD is representative of US national diversity with a significant potential to impact national healthcare. VA SHIELD will support future projects designed to better understand SARS-CoV-2 and other emergent healthcare crises. To the extent possible, VA SHIELD will facilitate the discovery of diagnostics and therapeutics intended to diminish COVID-19 morbidity and mortality and to reduce the impact of new emerging threats to the health of US Veterans and populations worldwide.

LuNER: Multiplexed SARS-CoV-2 detection in clinical swab and wastewater samples.

Clinical and surveillance testing for the SARS-CoV-2 virus relies overwhelmingly on RT-qPCR-based diagnostics, yet several popular assays require 2-3 separate reactions or rely on detection of a single viral target, which adds significant time, cost, and risk of false-negative results. Furthermore, multiplexed RT-qPCR tests that detect at least two SARS-CoV-2 genes in a single reaction are typically not affordable for large scale clinical surveillance or adaptable to multiple PCR machines and plate layouts. We developed a RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (LuNER) to address these shortcomings and meet the testing demands of a university campus and the local community. This cost-effective test is compatible with BioRad or Applied Biosystems qPCR machines, in 96 and 384-well formats, with or without sample pooling, and has a detection sensitivity suitable for both clinical reporting and wastewater surveillance efforts.

Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples.

Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against nasopharyngeal swab specimens and found saliva methods require further optimization to match this gold standard. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.

Resilient structure of nature-based extension programs facilitates transition to online delivery and maintains participant satisfaction.

Restrictions on public gatherings in early 2020 due to the COVID-19 pandemic resulted in cancelation of in-person outreach programs offered by the Florida Master Naturalist Program and Natural Areas Training Academy, two successful University of Florida extension programs that provide natural history and resource management training to lay and professional audiences. In response, both programs rapidly transitioned to blended or 100% online educational methods to continue offering courses and maintain program operations. To assess participant responses to these changes, we used surveys and course registry data to evaluate and compare course enrollment, satisfaction, and outcomes among courses with new online formats to courses offered prior to the COVID-19 pandemic. We also examined logistical challenges and key programmatic elements that facilitated the transition of both programs to increased reliance on online education. Course participants responded favorably to classes offered online. Our results revealed an audience exists for online programming, that satisfaction with online courses was high and comparable to that measured for in-person courses, and that online approaches effectively transferred knowledge and promoted behavior change in participants. The transition to online programming required investments of time, energy, and in some cases, direct costs. However, this transition was greatly facilitated by the existence of well-defined program protocols, educational curricula, strong partnerships, and feedback mechanisms for both programs. Long-term investments in program structure, partnerships, and support systems enabled both programs to be resilient and adaptable and successfully implement online programming in response to the COVID-19 pandemic.

Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus.

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has been center to SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants' experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection.

Cardiac injury and dysfunction occur in COVID-19 patients and increase the risk of mortality. Causes are ill defined but could be through direct cardiac infection and/or inflammation-induced dysfunction. To identify mechanisms and cardio-protective drugs, we use a state-of-the-art pipeline combining human cardiac organoids with phosphoproteomics and single nuclei RNA sequencing. We identify an inflammatory "cytokine-storm", a cocktail of interferon gamma, interleukin 1ß, and poly(I:C), induced diastolic dysfunction. Bromodomain-containing protein 4 is activated along with a viral response that is consistent in both human cardiac organoids (hCOs) and hearts of SARS-CoV-2-infected K18-hACE2 mice. Bromodomain and extraterminal family inhibitors (BETi) recover dysfunction in hCOs and completely prevent cardiac dysfunction and death in a mouse cytokine-storm model. Additionally, BETi decreases transcription of genes in the viral response, decreases ACE2 expression, and reduces SARS-CoV-2 infection of cardiomyocytes. Together, BETi, including the Food and Drug Administration (FDA) breakthrough designated drug, apabetalone, are promising candidates to prevent COVID-19 mediated cardiac damage.

Launching a saliva-based SARS-CoV-2 surveillance testing program on a university campus (preprint)

Regular surveillance testing of asymptomatic individuals for SARS-CoV-2 has played a vital role in SARS-CoV-2 outbreak prevention on college and university campuses. Here we describe the voluntary saliva testing program instituted at the University of California, Berkeley during an early period of the SARS-CoV-2 pandemic in 2020. The program was administered as a research study ahead of clinical implementation, enabling us to launch surveillance testing while continuing to optimize the assay. Results of both the testing protocol itself and the study participants experience show how the program succeeded in providing routine, robust testing capable of contributing to outbreak prevention within a campus community and offer strategies for encouraging participation and a sense of civic responsibility.

"It seems like COVID-19 now is the only disease present on Earth": living with a rare or undiagnosed disease during the COVID-19 pandemic.

PURPOSE: Patients with rare and undiagnosed diseases (RUDs) face significant health challenges, which may be exacerbated during the COVID-19 pandemic. The goal of this study was to identify specific impacts of the pandemic on RUD patients, and targets for improving support and health-care access. METHODS: We conducted an online survey of RUD patients and their family members from 21 April to 8 June 2020, recruited from 76 Facebook groups for RUDs. Questions assessed patient characteristics and impacts of the pandemic on RUD diagnosis and management. RESULTS: Respondents (n = 413), including 274 RUD patients and 139 family members, were predominantly female and white, though income varied. Impacts of the pandemic included (1) barriers to accessing essential health care, (2) specific impacts of restrictive COVID-19 visitation policies on ability to advocate in health-care settings, (3) uncertainty and fear regarding COVID-19 risk, (4) exacerbated physical and mental health challenges, (5) magnified impacts of reduced educational and therapeutic services, and (6) unexpected positive changes due to the pandemic. CONCLUSION: There are specific, serious challenges affecting RUD patients and families during the COVID-19 pandemic. There is an urgent need to develop approaches to mitigate these challenges both during and beyond the pandemic.

Robotic RNA extraction for SARS-CoV-2 surveillance using saliva samples (preprint)

Saliva is an attractive specimen type for asymptomatic surveillance of COVID-19 in large populations due to its ease of collection and its demonstrated utility for detecting RNA from SARS-CoV-2. Multiple saliva-based viral detection protocols use a direct-to-RT-qPCR approach that eliminates nucleic acid extraction but can reduce viral RNA detection sensitivity. To improve test sensitivity while maintaining speed, we developed a robotic nucleic acid extraction method for detecting SARS-CoV-2 RNA in saliva samples with high throughput. Using this assay, the Free Asymptomatic Saliva Testing (IGI-FAST) research study on the UC Berkeley campus conducted 11,971 tests on supervised self-collected saliva samples and identified rare positive specimens containing SARS-CoV-2 RNA during a time of low infection prevalence. In an attempt to increase testing capacity, we further adapted our robotic extraction assay to process pooled saliva samples. We also benchmarked our assay against the gold standard, nasopharyngeal swab specimens. Finally, we designed and validated a RT-qPCR test suitable for saliva self-collection. These results establish a robotic extraction-based procedure for rapid PCR-based saliva testing that is suitable for samples from both symptomatic and asymptomatic individuals.

IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2 (preprint)

Commonly used RT-qPCR-based SARS-CoV-2 diagnostics require 2-3 separate reactions or rely on detection of a single viral target, adding time and cost or risk of false-negative results. Currently, no test combines detection of widely used SARS-CoV-2 E- and N-gene targets and a sample control in a single, multiplexed reaction. We developed the IGI-LuNER RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (NER). This combined, cost-effective test can be performed in 384-well plates with detection sensitivity suitable for clinical reporting, and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=79 SRC="FIGDIR/small/20247338v2_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@74929corg.highwire.dtl.DTLVardef@1457971org.highwire.dtl.DTLVardef@2825ddorg.highwire.dtl.DTLVardef@1cde2b6_HPS_FORMAT_FIGEXP M_FIG C_FIG

Discovery of drugs to treat cytokine storm-induced cardiac dysfunction using human cardiac organoids (preprint)

SARS-CoV2 infection leads to cardiac injury and dysfunction in 20-30% of hospitalized patients1 and higher rates of mortality in patients with pre-existing cardiovascular disease2,3. Inflammatory factors released as part of the cytokine storm are thought to play a critical role in cardiac dysfunction in severe COVID-19 patients4. Here we use human cardiac organoids combined with high sensitivity phosphoproteomics and single nuclei RNA sequencing to identify inflammatory targets inducing cardiac dysfunction. This state-of-the-art pipeline allowed rapid deconvolution of mechanisms and identification of putative therapeutics. We identify a novel interferon-{gamma} driven BRD4 (bromodomain protein 4)-fibrosis/iNOS axis as a key intracellular mediator of inflammation-induced cardiac dysfunction. This axis is therapeutically targetable using BRD4 inhibitors, which promoted full recovery of function in human cardiac organoids and prevented severe inflammation and death in a cytokine-storm mouse model. The BRD inhibitor INCB054329 was the most efficacious, and is a prime candidate for drug repurposing to attenuate cardiac dysfunction and improve COVID-19 mortality in humans.

Ventilator Triage Policies During the COVID-19 Pandemic at U.S. Hospitals Associated With Members of the Association of Bioethics Program Directors.

BACKGROUND: The coronavirus disease 2019 pandemic has or threatens to overwhelm health care systems. Many institutions are developing ventilator triage policies. OBJECTIVE: To characterize the development of ventilator triage policies and compare policy content. DESIGN: Survey and mixed-methods content analysis. SETTING: North American hospitals associated with members of the Association of Bioethics Program Directors. PARTICIPANTS: Program directors. MEASUREMENTS: Characteristics of institutions and policies, including triage criteria and triage committee membership. RESULTS: Sixty-seven program directors responded (response rate, 91.8%); 36 (53.7%) hospitals did not yet have a policy, and 7 (10.4%) hospitals' policies could not be shared. The 29 institutions providing policies were relatively evenly distributed among the 4 U.S. geographic regions (range, 5 to 9 policies per region). Among the 26 unique policies analyzed, 3 (11.3%) were produced by state health departments. The most frequently cited triage criteria were benefit (25 policies [96.2%]), need (14 [53.8%]), age (13 [50.0%]), conservation of resources (10 [38.5%]), and lottery (9 [34.6%]). Twenty-one (80.8%) policies use scoring systems, and 20 of these (95.2%) use a version of the Sequential Organ Failure Assessment score. Among the policies that specify the triage team's composition (23 [88.5%]), all require or recommend a physician member, 20 (87.0%) a nurse, 16 (69.6%) an ethicist, 8 (34.8%) a chaplain, and 8 (34.8%) a respiratory therapist. Thirteen (50.0% of all policies) require or recommend that those making triage decisions not be involved in direct patient care, but only 2 (7.7%) require that their decisions be blinded to ethically irrelevant considerations. LIMITATION: The results may not be generalizable to institutions without academic bioethics programs. CONCLUSION: Over one half of respondents did not have ventilator triage policies. Policies have substantial heterogeneity, and many omit guidance on fair implementation. PRIMARY FUNDING SOURCE: None.