Modeling Diagnostic Testing Strategies for SARS-CoV-2 to Minimize Societal Costs and Return People to Work

Background. The shift to more transmissible but less virulent strains of SARS-CoV-2 has altered the risk calculation for infection. Particularly among young adults, the economic burden of lost work due to isolation exceeds the economic burden of morbidity due to infection. Testing strategies must adapt to these changing circumstances. Methods. We modeled six testing strategies to estimate total societal costs for symptomatic people 18-49 years old: isolation of all individuals with no testing, rapid antigen test (RAg), RAg followed by a second RAg 48h later if first negative, RAg followed by a polymerase chain reaction (PCR) if negative, RAg followed by a PCR if positive, and PCR alone. We calculated costs for hypothetical cohorts of 100 symptomatic healthcare workers tested with each strategy;we included testing costs, lost wages, and hospitalization costs for the index, secondary, and tertiary cases. Key assumptions were 5% prevalence of infection, sensitivity of first/second RAg 40/80% with 97% specificity, PCR sensitivity/specificity 95/99%, all individuals isolate at symptom onset, are tested the same day, and isolate for 5 days if positive. RAg results were available the same day, PCR results were available the next day (Figure 1). One-way sensitivity analyses were performed for RAg sensitivity (20-80%) and positivity rate (1-80%). Results. The least expensive strategy was RAg alone (Figure 2). This was primarily driven by its low sensitivity, which reduced lost wages at the expense of missing cases. At a threshold for RAg sensitivity lower than 29%, PCR testing alone became the cheapest strategy. When the positivity rate was > 6% confirming a negative RAg with a PCR became the cheapest strategy, closely followed by PCR alone. At a positivity rate of > 29%, isolation without testing was cheapest followed by confirming a negative RAg with a PCR and by the serial RAg test strategies (Figure 3). Conclusion. In relatively young, healthy populations, a single rapid test was the least expensive strategy when the positivity rate was < 6%, testing that included PCR became cheapest at intermediate positivity, and empiric isolation was cheapest at positivity > 29%. Calibrating SARS-CoV-2 test strategies based on epidemiology may save societal costs.

Impact of COVID-19 on helpline calls for activities related to technology overuse in Ontario, Canada

Background: Video gaming revenues have increased dramatically during the COVID-19 pandemic. Trending social games and hyper-casual games are attracting new audiences that require further study. While engaging in video games and Internet-related behaviors inherently may help promote social connection and alleviate stress during the pandemic, a small proportion of individuals develop problematic habits that interfere with daily functioning. Therefore, the aim of this study is to examine the impact of COVID-19 lockdowns on the number of helpline calls for gaming disorder and problematic Internet use in the province of Ontario, Canada. Methods: Helpline calls were collected from a provincial mental health & addiction treatment service hotline from January 2019 to December 2021. This free and confidential service is for people who experience problems with alcohol, drugs, mental illness, and behavioral disorders. Growth modeling will be employed to examine the links between the number of calls received, the number of COVID-19 cases reported province-wide and the accumulated lockdown days across the different months. Results: The associations between the linear, quadratic and cubic growth/change curve factors of the number of calls received in relation to the progress of the pandemic will be reported for time variant, time-invariant and parallel growth moderators. Conclusions: Helpline calls are expected to increase during lockdowns and decrease when restrictions are lifted. This study serves to inform preventive measures that should be considered with the implementation of lockdown during a pandemic to prevent problematic forms of gaming or Internet use.

EVALUATING HEALTH ADVISER ACTIVITY AND MODEL OF PREP DELIVERY IN A POST COVID-19 AND NHS PREP LANDSCAPE

Introduction In April 2020 a London sexual health clinic temporarily closed due to the Covid-19 pandemic. Full reopening of the service coincided with HIV PrEP becoming available on the NHS and the clinic continued using the Health Adviser (HA) model of PrEP delivery adopted during the IMPACT trial. We aimed to review how these events impacted HA activity. Method A retrospective review of patients booked into the HA clinic and those with an HA diagnosis code was undertaken. Information on number of attendances, diagnosis codes and income was compared for 2019, 2020 and 2021. Results There was a drop in attendances prior to the clinic closing in April 2020. After re-opening, activity levels in 2020 and early 2021 did not reach those of 2019. However, the average monthly activity increased by approximately 17% in the latter half of 2021. Average per patient income was 61% higher in December 2020 (£161.48) than December 2019 (£100.33). This increased further in 2021 to £171.57 per patient (74% increase on 2019). Discussion Although it took a year after the initial pandemic for attendances to reach pre Covid-19 levels, the income generated from the HA appointments increased before this, due to the model of PrEP delivery implemented. However this has had an impact on other aspects of Health Advising such as risk reduction and safeguarding, with fewer patients recorded as having specialist HA input in these areas. Further work is needed to determine the true impact of this change of focus and to ensure patients still receive optimal care. (Figure Presented).

Good Grief Festival: Evaluation of a UK Public Engagement Initiative on Grief and Bereavement

Background/aims: Good Grief Festival was initially planned as an inclusive face-to-face festival on the topic of grief. Due to COVID-19, the festival was held online over 3 days in October 2020. We aimed to evaluate the festival's reach and impact. Methods: A pre/post evaluation was conducted via online surveys. Prefestival surveys assessed reasons for attending and attitudes to bereavement across 4 items (being scared of saying the wrong thing, avoiding talking to someone bereaved, knowing what to do if someone bereaved was having trouble, knowing what kind of help/support to offer). Postfestival surveys evaluated audience experiences and the 4 attitude items. Results: 8500+ people attended, with most attending 2-5 events. Prefestival survey participants (n=3785) were mostly women (91%) and White (91%). 9% were from Black or minority ethnic communities. 14% were age ≥65 years, 16% age ≤34 years. 44% were members of the public. A third had been bereaved in the last year;6% had never been bereaved. People attended to learn about grief/bereavement (77%), be inspired (52%) and feel part of a community (49%). Post-festival participants (n=685) reported feeling part of a community (68%), learning about grief/bereavement (68%) and being inspired (66%). 89% rated the festival as excellent/very good. 75% agreed that through attending they felt more confident talking about grief. Higher ratings and confidence were associated with attending a greater number of events. Post-festival attitudes were significantly higher across all 4 items (P<0.001). Free-text data showed appreciation e.g., for the online format, connection in the context of lockdown and speakers' ethnic diversity. Suggestions included improving registration, more interactive/arts-based events and reducing the volume of content. Conclusions: Good Grief Festival was successful at reaching a large public audience, with data indicating benefit in terms of engagement, confidence and community-building. The evaluation was critical in shaping future events.

Primary results of the cTRAK TN trial: A clinical trial utilising ctDNA mutation tracking to detect minimal residual disease and trigger intervention in patients with moderate and high risk early stage triple negative breast cancer

Background Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage triple negative breast cancer (TNBC) is associated with a very high risk of future relapse. Identifiying those at high risk of subsequent relapse may allow tailoring of further therapy to delay or prevent recurrence. The c-TRAK TN trial assessed the utility of prospective ctDNA surveillance in pts treated for TNBC and the activity of pembrolizumab (P) in pts with ctDNA detected. Methods c-TRAK TN, a multi-centre phase II trial with integrated prospective screening component, enrolled pts with early-stage TNBC and either residual disease following neoadjuvant chemotherapy, or tumour size >20mm and/or axillary lymph node involvement if adjuvant chemotherapy was given. Tumour tissue was sequenced to identify somatic mutations suitable for tracking using personalised digital PCR ctDNA assays (BioRad QX200). Pts had "active" ctDNA surveillance via blood sample testing every 3 months to 12 months (potential up to 18 months if S samples missed due to COVID) during which time if ctDNA was detected (ctDNA+) pts could be randomised 2:1 to P (200mg i.v. q 3 weeks for 1 year) or observation (Obs). Pts and clinicians were blinded to ctDNA+ results unless they were allocated P, when staging scans were done and those free of clinical recurrence started treatment. Following advice from the Independent Data Monitoring Committee, the Obs arm closed on 16/06/2020 with all subsequent ctDNA+ pts allocated P. Following the completion of active ctDNA surveillance, 3-monthly visits continued to 24 months to be analysed retrospectively. The aim was to recruit 150 pts to ctDNA surveillance, assuming 30% would be ctDNA+ within 12 months, allowing ctDNA+ rate to be estimated with a 2-sided 95%CI of +/-7.3%. Co-primary endpoints are i) rates of ctDNA detection by 12 and 24 months from start of ctDNA surveillance;ii) rates of sustained ctDNA clearance on P defined as absence of detectable ctDNA, or disease recurrence 6 months after starting P. Results 208 pts were registered between 30/01/18 and 06/12/19, 185 had tumour sequenced, 171 (92.4%) had trackable mutations, and 161 entered ctDNA surveillance. The rate of ctDNA detection by 12 months after start of surveillance was 27.3% (44/161, 95% CI 20.6-34.9). ctDNA+ rates from baseline, 3, 6, 9 and 12 month ctDNA samples were 23/161 (14.3%), 6/115 (5.2%), 6/99 (5.1%), 7/84 (8.3%), and 2/84 (2.4%) respectively. An additional 2 pts were ctDNA+ on COVID extended active surveillance at 15 (1/51, 2%) or 18 months (1/11, 9%). 7 pts relapsed without prior ctDNA detection. 45 pts entered the therapeutic component of the trial (initially 31 to P and 14 to Obs). 1 Obs pt was re-allocated to P. Of pts allocated to P, 72% (23/32) had metastatic disease at time of ctDNA detection on staging scans (75% (12/16) who were ctDNA+ at baseline and 69% (11/16) at other timepoints). 4 pts declined to start P, largely due to COVID concerns. Of the 5 pts who commenced P, at the time of analysis none achieved sustained ctDNA clearance and 4 had recurred. In pts allocated to Obs, median time to recurrence was 4.1 months (95% CI: 3.2-not-defined). Conclusion The c-TRAK TN trial is to our knowledge the first study to assess the proof-of-principle of whether ctDNA assays have clinical utility in guiding further therapy in TNBC. Relatively few pts commenced P treatment precluding assessment of potential activity. At enrollment, patients had a relatively high of rate of undiagnosed metastatic disease when imaged. Our findings have implications for future trial design, emphasizing the importance of early start of ctDNA testing, and more sensitive and/or more frequent ctDNA testing regimes.

How COVID-19 Impacted The Tacit Knowledge and Social Interaction of Global NPD Project Teams: The complexity framework offers managers an effective way to analyze problems and to generate solutions to manage tacit knowledge and social interaction in dispersed global NPD project teams

: Overview: Multinational, technology-intensive companies routinely use globally distributed R&D teams, but COVID-19 represented an additional challenge. Lockdowns and home-office working severely limit human interaction and can impact the communication, social interaction, and knowledge sharing critical to successful R&D. Our study investigated how COVID-19 affected R&D processes at three global companies, using a project complexity perspective. Although R&D managers responsible for global projects are accustomed to the challenges of managing communications, the fact that teams were forced into home-office working made new product development more difficult in several ways. Ensuring that technical details are understood by all members of dispersed teams is crucial. Of particular note, and central to our findings, is the emphasis that R&D managers placed on maintaining a high level of social interaction in their teams, and special efforts were needed to keep interactions at a sufficient level to foster the generation and transfer of tacit knowledge. The findings have strong implications for the way that R&D project management is likely to be conducted in a post-COVID-19 world, and we demonstrate how the complexity framework we used can benefit managers in navigating this and other challenges. © Copyright © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Early childhood education staff are falling through a vaccination policy gap in New Zealand

The recent COVID-19 vaccine mandate among early childhood education (ECE) staff highlights the important role ECE staff have in the transmission of infectious diseases. However, there are no data on general vaccine uptake for this group in New Zealand. Additionally, the importance of ECE staff vaccination as a strategy to prevent illness has been rarely promoted in the past, and recommendations for other vaccinations in this group are lacking. Here we present a section of data accessed from an ECE-sector employment survey of more than 4,000 teaching staff, which inquired into the immunisation status of respondents. The data indicated that self-reported immunisation coverage for whooping cough, hepatitis A, and hepatitis B among ECE staff was approximately 50%. Self-reported immunisation status was higher for measles, mumps, rubella, and chickenpox in this group. The findings highlight the need for more comprehensive vaccination policy and research in ECE settings. © NZMA.

Corynebacterium striatum Outbreak among Ventilated COVID-19 Patients in an Acute Care Hospital - California, 2021

Background. Corynebacterium striatum (CS), a common human commensal colonizing the skin and nasopharynx, has been associated with nosocomial infections in immunocompromised and chronically ill patients. During the winter 2020-2021 COVID-19 surge, a 420-bed California hospital reported a marked increase in CS respiratory cultures among ventilated COVID-19 patients. We conducted a public health investigation to assess and mitigate nosocomial transmission and contributing infection prevention and control (IPC) practices. Methods. A case was defined as a patient with CS in respiratory cultures from January 1, 2020 - February 28, 2021. We reviewed clinical characteristics on a subset of cases in 2021 and IPC practices in affected hospital locations. CS respiratory isolates collected on different dates and locations were assessed for relatedness by whole genome sequencing (WGS) on MiSeq. Results. Eighty-three cases were identified, including 75 among COVID-19 patients (Figure 1). Among 62 patients identified in 2021, all were ventilated;58 also had COVID-19, including 4 cases identified on point prevalence survey (PPS). The median time from admission to CS culture was 19 days (range, 0-60). Patients were critically ill;often it was unclear whether CS cultures represented colonization or infection. During the COVID-19 surge, two hospital wings (7W and 7S) were converted to negative-pressure COVID-19 units. Staff donned and doffed personal protective equipment in anterooms outside the units;extended use of gowns was practiced, and lapses in glove changes and hand hygiene (HH) between patients likely occurred. In response to the CS outbreak, patients were placed in Contact precautions and cohorted. Staff were re-educated on IPC for COVID-19 patients. Gowns were changed between CS patients. Subsequent PPS were negative. Two CS clusters were identified by WGS: cluster 1 (5 cases) in unit 7W, and cluster 2 (2 cases) in unit 7S (Figure 2). Conclusion. A surge in patients, extended use of gowns and lapses in core IPC practices including HH and environmental cleaning and disinfection during the winter 2020-2021 COVID-19 surge likely contributed to this CS outbreak. WGS provides supportive evidence for nosocomial CS transmission among critically ill COVID-19 patients.

Covid-19 response of an additive manufacturing cluster in Australia

Purpose The sudden arrival of Covid-19 severely disrupted the supply chain of personal protective equipment (PPE) in Australia. This paper aims to examine the development of a geographical cluster, which, through the application of additive manufacturing (AM), responded to the PPE supply crisis. Design/methodology/approach This longitudinal case study focuses on an AM cluster, which was developed to supply PPE in a responsive and flexible manner from 2019/2020. The study gathered data over three stages of cluster evolution: pre, during and post-peak Covid-19. Findings The type and nature of exchanges between organizations involved in the cluster established important insights into success factors for cluster creation and development. Using an established complexity framework, this study identifies the characteristics of establishing a cluster. The importance of cluster alignment created initially by a common PPE supply goal led to an emerging commercial and relational imperative to address the longer-term configuration after the disruption. Practical implications Clusters can be a viable option for a technology-driven sector when there is a "buzz" that drives and rapidly diffuses knowledge to support cluster formation. This research identifies the structural, socio-political and emergent dimensions, which need to be considered by stakeholders when aiming at improving competitiveness using clusters. Originality/value Covid-19 has rapidly and unexpectedly disrupted the supply chain for many industries. Responding to challenges, businesses will investigate different pathways to improve the overall resilience including on-/near-shoring. The results provide insights into how clusters are formed, grow and develop and the differentiating factors that result in successful impacts of clusters on local economies.

TMEM41B and VMP1 are scramblases and regulate the distribution of cholesterol and phosphatidylserine

TMEM41B and VMP1 are integral membrane proteins of the endoplasmic reticulum (ER) and regulate the formation of autophagosomes, lipid droplets (LDs), and lipoproteins. Recently, TMEM41B was identified as a crucial host factor for infection by all coronaviruses and flaviviruses. The molecular function of TMEM41B and VMP1, which belong to a large evolutionarily conserved family, remains elusive. Here, we show that TMEM41B and VMP1 are phospholipid scramblases whose deficiency impairs the normal cellular distribution of cholesterol and phosphatidylserine. Their mechanism of action on LD formation is likely to be different from that of seipin. Their role in maintaining cellular phosphatidylserine and cholesterol homeostasis may partially explain their requirement for viral infection. Our results suggest that the proper sorting and distribution of cellular lipids are essential for organelle biogenesis and viral infection.

Delivering a community-based covid-19 Rehabilitation service using existing Pulmonary rehabilitation teams is safe and Feasible

Background University Hospitals of Morecambe Bay NHS Trust, witnessed an early peak of COVID-19 with related hospital admissions in early 2020, this created a need for a coordinated approach to post COVID-19 rehabilitation needs across the area. Objectives A three-armed COVID-19 rehabilitation pathway was devised in March 2020 with Arm 1 aiming to assess and address the immediate rehabilitation needs of those leaving hospital following an admission for respiratory complications of COVID-19. Methods Existing Pulmonary Rehabilitation teams were repurposed by integrated care network (MBRN) to be a new 'Virtual' rehabilitation service. A register of patients discharged from hospital sites was remotely screened for pathway suitability. Then, using a multi-professional template a holistic assessment needs was conducted using telephone and/or home visit consultations. Clinical assessment tools were built into the assessment process. Weekly 'acute-community' virtual in-service training sessions and multi-disciplinary case discussions supported the clinicians. Results To date 207 patients have entered the service for virtual triage, 138 patients were deemed suitable for further assessment and interventions. 427 direct clinician consultations were delivered to these 138 patients [122 initial telephone assessments;53 initial home visit assessments;168 follow-up telephone consultations;84 follow-up home visits]. Two of the 138 patients assessed died, both were expected deaths. No clinical incidents occurred and no staff contracted COVID-19 during this period. Feedback from the services' staff survey was very positive highlighting the supportive value of virtual training and MDT and the enjoyment of being part of creating and delivering this new service to patients recovering from COVID-19. Conclusions Utilising the skills of pulmonary rehabilitation staff to deliver a holistic rehabilitation and treatment service to those discharged from hospital after suffering respiratory complications of COVID-19 was feasible, safe and well tolerated by staff and patients. This service is now being used to address the needs of post-COVID-19 patients presenting with respiratory needs in the community. We aim also to assess clinical outcome.

Managing breast gangrene during the COVID-19 pandemic.

At the onset of the COVID-19 crisis, a 63-year-old woman with multiple life-limiting comorbidities was referred with a necrotic infected left breast mass on a background of breast cancer treated with conservation surgery and radiotherapy 22 years previously. The clinical diagnosis was locally advanced breast cancer, but four separate biopsies were non-diagnostic. Deteriorating renal function and incipient sepsis and endocarditis resulted in urgent salvage mastectomy during the peak of the COVID19 pandemic. The final diagnosis was infected ischaemic/infarcted breast (wet gangrene) secondary to vascular insufficiency related to diabetes, cardiac revascularisation surgery and breast radiotherapy.

P35 Delivering a community-based COVID-19 rehabilitation service using existing pulmonary rehabilitation teams is safe and feasible

P35 Figure 1ConclusionsUtilising the skills of pulmonary rehabilitation staff to deliver a holistic rehabilitation and treatment service to those discharged from hospital after suffering respiratory complications of COVID-19 was feasible, safe and well tolerated by staff and patients. This service is now being used to address the needs of post-COVID-19 patients presenting with respiratory needs in the community. We aim also to assess clinical outcome.