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1.
Value in Health ; 26(6 Supplement):S302-S303, 2023.
Article in English | EMBASE | ID: covidwho-20239589

ABSTRACT

Objectives: To provide an overview of trends in the current evidence landscape of products and services in development that support remote patient monitoring (RPM) and remote therapeutic monitoring (RTM), given the release of new billing codes for RPM and RTM by Centers for Medicare and Medicaid Services (CMS) in 2019. Method(s): A focused literature review was conducted in PubMed. Articles published between January 1, 2013 and January 1, 2023 were eligible for inclusion if reported technologies were classified as RPM (defined as the collection and interpretation of physiologic data digitally stored and/or transmitted by patients and/or caregivers to qualified health care professionals) or RTM (defined as the use of medical devices to monitor a patient's health or response to treatment using non-physiological data), following CMS definitions. RPM and RTM technologies included hardware, software, telehealth, and blockchain applications. Articles were then categorized using a semi-automated software platform (AutoLit, Nested Knowledge, St. Paul, MN) based on disease area, study design, intervention, and outcomes studied. Result(s): Of the 673 records screened, 245 articles were included. Observational studies (19.6%) were the most common study design, followed by systematic or focused literature reviews (11.0%) and narrative reviews (10.6%). The most common disease areas included cardiology (25.7%), coronavirus disease of 2019 (COVID-19;13.9%), and diabetes (9.4%). The most frequent clinical, non-clinical, and patient-reported outcomes were symptom monitoring (20.8%), all cause readmission and hospitalization rates (both 7.3%), and patient experience (7.8%), respectively. Conclusion(s): CMS policy and coding practices for RPM and RTM are evolving, and this trend is likely to continue into the future. This review provides details on the current evidence trends associated with RPM/RTM technologies. Evidence development of RPM and RTM should be assessed as evidence needs for coverage and reimbursement may receive increased payer management.Copyright © 2023

2.
medrxiv; 2023.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2023.06.18.23291566

ABSTRACT

Background Surrogates of antiviral efficacy are needed for COVID-19. We investigated the relationship between the virological effect of treatment and clinical efficacy as measured by progression to severe disease in unvaccinated outpatients treated for mild to moderate COVID-19. Methods We searched PubMed, Scopus and medRxiv from inception to 27th September 2022, for randomised controlled trials (RCTs) which tested potential treatments for COVID-19 in non-hospitalized patients. We included studies that reported both clinical and virological outcomes. Clinical outcomes were the rate of disease progression (generally hospitalization or death within 28 days of commencing treatment) and virological outcomes were viral load (viral RNA copies in upper respiratory tract swabs) within the first 7 days of treatment. Studies were excluded if they did not report on the outcome of a primary randomised controlled trial, or if results were reported in a more complete form in another publication. Risk of Bias assessment was performed using the RoB 2.0 tool. We used generalised linear models with random effects to assess the association between outcomes and account for study heterogeneity. Findings We identified 1372 unique studies of which 14 (with a total of 9257 participants) met inclusion criteria. Larger virological treatment effects at both day 3 and day 5 were associated with decreased odds of progression to hospitalisation or death in unvaccinated ambulatory subjects. The odds ratio (OR) for each extra two-fold reduction in viral load in treated compared to control subjects was 0.54 on both days 3 and 5 post treatment (day 3 95% CI 0.38 to 0.74, day 5 95%CI 0.41 to 0.72). There was no relationship between the odds of hospitalisation or death and virological treatment effect at day 7 (OR 0.91, 95%CI 0.74 to 1.13). Interpretation Despite the aggregation of studies with differing designs, and evidence of risk of bias in some virological outcomes, this review provides evidence that treatment-induced acceleration of viral clearance within the first 5 days after treatment is a surrogate of clinical efficacy to prevent hospitalisation with COVID-19. This work supports the use of viral clearance as an early phase clinical trial endpoint of therapeutic efficacy. Funding The authors were supported by the Australian Government Department of Health, Medical Research Future Fund, National Health and Medical Research Council and the University of New South Wales.

3.
Am J Respir Crit Care Med ; 206(6): 730-739, 2022 09 15.
Article in English | MEDLINE | ID: covidwho-2257568

ABSTRACT

Rationale: Uncertainty regarding the natural history of coronavirus disease (COVID-19) led to difficulty in efficacy endpoint selection for therapeutic trials. Capturing outcomes that occur after hospital discharge may improve assessment of clinical recovery among hospitalized patients with COVID-19. Objectives: Evaluate 90-day clinical course of patients hospitalized with COVID-19, comparing three distinct definitions of recovery. Methods: We used pooled data from three clinical trials of neutralizing monoclonal antibodies to compare: 1) the hospital discharge approach; 2) the TICO (Therapeutics for Inpatients with COVID-19) trials sustained recovery approach; and 3) a comprehensive approach. At the time of enrollment, all patients were hospitalized in a non-ICU setting without organ failure or major extrapulmonary manifestations of COVID-19. We defined discordance as a difference between time to recovery. Measurements and Main Results: Discordance between the hospital discharge and comprehensive approaches occurred in 170 (20%) of 850 enrolled participants, including 126 hospital readmissions and 24 deaths after initial hospital discharge. Discordant participants were older (median age, 68 vs. 59 years; P < 0.001) and more had a comorbidity (84% vs. 70%; P < 0.001). Of 170 discordant participants, 106 (62%) had postdischarge events captured by the TICO approach. Conclusions: Among patients hospitalized with COVID-19, 20% had clinically significant postdischarge events within 90 days after randomization in patients who would be considered "recovered" using the hospital discharge approach. Using the TICO approach balances length of follow-up with practical limitations. However, clinical trials of COVID-19 therapeutics should use follow-up times up to 90 days to assess clinical recovery more accurately.


Subject(s)
COVID-19 , Aftercare , Aged , Antibodies, Monoclonal , Humans , Patient Discharge , SARS-CoV-2 , Treatment Outcome
4.
J Med Virol ; 95(3): e28686, 2023 03.
Article in English | MEDLINE | ID: covidwho-2252520

ABSTRACT

Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface cultures of primary human bronchial epithelial cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active types I (α/ß) and III (λ) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signaling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knockout prevented it. The JAK/STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/STAT signaling. In conclusion, our study (1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, (2) shows that Omicron infection protects cells from influenza A virus super-infection, and (3) indicates that BA.1 and BA.5 induce comparable antiviral states.


Subject(s)
COVID-19 , Influenza A Virus, H1N1 Subtype , Influenza A Virus, H5N1 Subtype , Influenza A virus , Influenza, Human , Janus Kinase Inhibitors , Humans , SARS-CoV-2 , Interferons , Antiviral Agents
5.
iScience ; 26(2): 105944, 2023 Feb 17.
Article in English | MEDLINE | ID: covidwho-2165435

ABSTRACT

Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a readout for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in numerous cell culture models, independently of cytopathogenic effect formation. Compared to other models, the Caco-2 subline Caco-2-F03 displayed superior performance. It possesses a stable SARS-CoV-2 susceptibility phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1,796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of phosphoglycerate dehydrogenase (PHGDH), CDC like kinase 1 (CLK-1), and colony stimulating factor 1 receptor (CSF1R). The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the hexokinase II (HK2) inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2-F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false-positive hits.

7.
Epidemiology ; 34(1): 131-139, 2023 01 01.
Article in English | MEDLINE | ID: covidwho-2152202

ABSTRACT

BACKGROUND: Summarizing the impact of community-based mitigation strategies and mobility on COVID-19 infections throughout the pandemic is critical for informing responses and future infectious disease outbreaks. Here, we employed time-series analyses to empirically investigate the relationships between mitigation strategies and mobility on COVID-19 incident cases across US states during the first three waves of infections. METHODS: We linked data on daily COVID-19 incidence by US state from March to December 2020 with the stringency index, a well-known index capturing the strictness of mitigation strategies, and the trip ratio, which measures the ratio of the number of trips taken per day compared with the same day in 2019. We utilized multilevel models to determine the relative impacts of policy stringency and the trip ratio on COVID-19 cumulative incidence and the effective reproduction number. We stratified analyses by three waves of infections. RESULTS: Every five-point increase in the stringency index was associated with 2.89% (95% confidence interval = 1.52, 4.26%) and 5.01% (3.02, 6.95%) reductions in COVID-19 incidence for the first and third waves, respectively. Reducing the number of trips taken by 50% compared with the same time in 2019 was associated with a 16.2% (-0.07, 35.2%) decline in COVID-19 incidence at the state level during the second wave and 19.3% (2.30, 39.0%) during the third wave. CONCLUSIONS: Mitigation strategies and reductions in mobility are associated with marked health gains through the reduction of COVID-19 infections, but we estimate variable impacts depending on policy stringency and levels of adherence.


Subject(s)
COVID-19 , United States/epidemiology , Humans , COVID-19/epidemiology , Incidence , Pandemics , Basic Reproduction Number
8.
PLoS One ; 17(11): e0277570, 2022.
Article in English | MEDLINE | ID: covidwho-2116520

ABSTRACT

N95/FFP3 respirators have been critical to protect healthcare workers and their patients from the transmission of COVID-19. However, these respirators are characterised by a limited range of size and geometry, which are often associated with fitting issues in particular sub-groups of gender and ethnicities. This study describes a novel methodology which combines magnetic resonance imaging (MRI) of a cohort of individuals (n = 8), with and without a respirator in-situ, and 3D registration algorithm which predicted the goodness of fit of the respirator. Sensitivity analysis was used to optimise a deformation value for the respirator-face interactions and corroborate with the soft tissue displacements estimated from the MRI images. An association between predicted respirator fitting and facial anthropometrics was then assessed for the cohort.


Subject(s)
COVID-19 , Respiratory Protective Devices , Humans , COVID-19/prevention & control , N95 Respirators , Ventilators, Mechanical , Health Personnel
10.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.11.22.22282199

ABSTRACT

Multiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies in preventing symptomatic SARS-CoV-2 infection. We use data on changes in the in vivo concentration of monoclonal antibodies, and the associated protection from COVID-19, over time to model the dose-response relationship of monoclonal antibodies for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a monoclonal antibody concentration of 939-fold of the in vitro IC50 (95% CI: 135 - 2073). This relationship provides a quantitative tool allowing prediction of the prophylactic efficacy and duration of protection for new monoclonal antibodies administered at different doses and against different SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either monoclonal antibody treatment or vaccination. We find no evidence for a difference between the 50% protective titer for monoclonal antibodies and vaccination, although vaccination is predicted to be capable of achieving a higher maximum level of protection.

11.
medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.10.21.22281366

ABSTRACT

The COVID-19 pandemic and the associated prevention measures did not only impact on the transmission of COVID-19 but also on the spread of other infectious diseases in an unprecedented natural experiment. Here, we analysed the transmission patterns of 22 different infectious diseases during the COVID-19 pandemic in England. Our results show that the COVID-19 prevention measures generally reduced the spread of pathogens that are transmitted via the air and the faecal-oral route. Moreover, the COVID-19 prevention measures resulted in the sustained suppression of vaccine-preventable infectious diseases also after the removal of restrictions, while non-vaccine preventable diseases displayed a rapid rebound. Despite concerns that a lack of exposure to common pathogens may affect population immunity and result in large outbreaks by various pathogens post-COVID-19, only four of the 22 investigated diseases and disease groups displayed higher post- than pre-pandemic levels without an obvious causative relationship. Notably, this included chickenpox for which an effective vaccine is available but not used in the UK, which provides strong evidence supporting the inclusion of the chickenpox vaccination into the routine vaccination schedule in the UK. In conclusion, our findings provide unique, novel insights into the impact of non-pharmaceutical interventions on the spread of a broad range of infectious diseases.

12.
PLoS One ; 17(9): e0274900, 2022.
Article in English | MEDLINE | ID: covidwho-2039432

ABSTRACT

BACKGROUND: Several ecologic studies have suggested that the bacillus Calmette-Guérin (BCG) vaccine may be protective against SARS-CoV-2 infection including a highly-cited published pre-print by Miller et al., finding that middle/high- and high-income countries that never had a universal BCG policy experienced higher COVID-19 burden compared to countries that currently have universal BCG vaccination policies. We provide a case study of the limitations of ecologic analyses by evaluating whether these early ecologic findings persisted as the pandemic progressed. METHODS: Similar to Miller et al., we employed Wilcoxon Rank Sum Tests to compare population medians in COVID-19 mortality, incidence, and mortality-to-incidence ratio between countries with universal BCG policies compared to those that never had such policies. We then computed Pearson's r correlations to evaluate the association between year of BCG vaccination policy implementation and COVID-19 outcomes. We repeated these analyses for every month in 2020 subsequent to Miller et al.'s March 2020 analysis. RESULTS: We found that the differences in COVID-19 burden associated with BCG vaccination policies in March 2020 generally diminished in magnitude and usually lost statistical significance as the pandemic progressed. While six of nine analyses were statistically significant in March, only two were significant by the end of 2020. DISCUSSION: These results underscore the need for caution in interpreting ecologic studies, given their inherent methodological limitations, which can be magnified in the context of a rapidly evolving pandemic in which there is measurement error of both exposure and outcome status.


Subject(s)
COVID-19 , Tuberculosis , BCG Vaccine , COVID-19/epidemiology , COVID-19/prevention & control , Humans , SARS-CoV-2 , Tuberculosis/epidemiology , Vaccination
13.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.09.06.506799

ABSTRACT

Recent findings in permanent cell lines suggested that SARS-CoV-2 Omicron BA.1 induces a stronger interferon response than Delta. Here, we show that BA.1 and BA.5 but not Delta induce an antiviral state in air-liquid interface (ALI) cultures of primary human bronchial epithelial (HBE) cells and primary human monocytes. Both Omicron subvariants caused the production of biologically active type I (alpha/beta) and III (lambda) interferons and protected cells from super-infection with influenza A viruses. Notably, abortive Omicron infection of monocytes was sufficient to protect monocytes from influenza A virus infection. Interestingly, while influenza-like illnesses surged during the Delta wave in England, their spread rapidly declined upon the emergence of Omicron. Mechanistically, Omicron-induced interferon signalling was mediated via double-stranded RNA recognition by MDA5, as MDA5 knock-out prevented it. The JAK/ STAT inhibitor baricitinib inhibited the Omicron-mediated antiviral response, suggesting it is caused by MDA5-mediated interferon production, which activates interferon receptors that then trigger JAK/ STAT signalling. In conclusion, our study 1) demonstrates that only Omicron but not Delta induces a substantial interferon response in physiologically relevant models, 2) shows that Omicron infection protects cells from influenza A virus super-infection, and 3) indicates that BA.1 and BA.5 induce comparable antiviral states.

14.
iScience ; 25(9): 104925, 2022 Sep 16.
Article in English | MEDLINE | ID: covidwho-1983262

ABSTRACT

Pharmacologically active compounds with known biological targets were evaluated for inhibition of SARS-CoV-2 infection in cell and tissue models to help identify potent classes of active small molecules and to better understand host-virus interactions. We evaluated 6,710 clinical and preclinical compounds targeting 2,183 host proteins by immunocytofluorescence-based screening to identify SARS-CoV-2 infection inhibitors. Computationally integrating relationships between small molecule structure, dose-response antiviral activity, host target, and cell interactome produced cellular networks important for infection. This analysis revealed 389 small molecules with micromolar to low nanomolar activities, representing >12 scaffold classes and 813 host targets. Representatives were evaluated for mechanism of action in stable and primary human cell models with SARS-CoV-2 variants and MERS-CoV. One promising candidate, obatoclax, significantly reduced SARS-CoV-2 viral lung load in mice. Ultimately, this work establishes a rigorous approach for future pharmacological and computational identification of host factor dependencies and treatments for viral diseases.

15.
Clin Transl Sci ; 15(10): 2279-2292, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1978434

ABSTRACT

Emergency Use Authorization (EUA) allows the US Food and Drug Administration (FDA) to expedite the availability of therapeutics in the context of a public health emergency. To date, an evidentiary standard for clinical efficacy to support an EUA has not yet been established. This review examines the clinical data submitted in support of EUA for antiviral and anti-inflammatory therapeutics for coronavirus disease 2019 (COVID-19) through December of 2021 and the resilience of the authorization as new clinical data arose subsequent to the authorization. In the vast majority of cases, EUA was supported by at least one well-powered randomized controlled trial (RCT) where statistically significant efficacy was demonstrated. This included branded medications already approved for use outside of the context of COVID-19. When used, the standard of a single RCT seemed to provide adequate evidence of clinical efficacy, such that subsequent clinical studies generally supported or expanded the EUA of the therapeutic in question. The lone generic agent that was granted EUA (chloroquine/hydroxychloroquine) was not supported by a well-controlled RCT, and the EUA was withdrawn within 3 months time. This highlighted not only the ambiguity of the EUA standard, but also the need to provide avenues through which high quality clinical evidence for the efficacy of a generic medication could be obtained. Therefore, maintaining the clinical trial networks assembled during the COVID-19 pandemic could be a critical component of our preparation for future pandemics. Consideration could also be given to establishing a single successful RCT as regulatory guidance for obtaining an EUA.


Subject(s)
COVID-19 Drug Treatment , Pandemics , Humans , Antiviral Agents/therapeutic use , Chloroquine/therapeutic use , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , Treatment Outcome , Randomized Controlled Trials as Topic
17.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.07.22.501169

ABSTRACT

Omicron BA.1 variant isolates were previously shown to replicate less effectively in interferon-competent cells and to be more sensitive to interferon treatment than a Delta isolate. Here, an Omicron BA.2 isolate displayed intermediate replication patterns in interferon-competent Caco-2-F03 cells when compared to BA.1 and Delta isolates. Moreover, BA.2 was less sensitive than BA.1 and similarly sensitive as Delta to betaferon treatment. Delta and BA.1 displayed similar sensitivity to the approved anti-SARS-CoV-2 drugs remdesivir, nirmatrelvir, EIDD-1931 (the active metabolite of molnupiravir) and the protease inhibitor aprotinin, whereas BA.2 was less sensitive than Delta and BA.1 to EIDD-1931, nirmatrelvir and aprotinin. Nirmatrelvir, EIDD-1931, and aprotinin (but not remdesivir) exerted synergistic antiviral activity in combination with betaferon, with some differences in the extent of synergism detected between the different SARS-CoV-2 variants. In conclusion, even closely related SARS-CoV-2 (sub)variants can differ in their biology and in their response to antiviral treatments. Betaferon combinations with nirmatrelvir and, in particular, with EIDD-1931 and aprotinin displayed high levels of synergism, which makes them strong candidates for clinical testing. Notably, effective antiviral combination therapies are desirable, as a higher efficacy is expected to reduce resistance formation.

18.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.07.17.500346

ABSTRACT

Reliable, easy-to-handle phenotypic screening platforms are needed for the identification of anti-SARS-CoV-2 compounds. Here, we present caspase 3/7 activity as a read-out for monitoring the replication of SARS-CoV-2 isolates from different variants, including a remdesivir-resistant strain, and of other coronaviruses in a broad range of cell culture models, independently of cytopathogenic effect formation. Compared to other cell culture models, the Caco-2 subline Caco-2-F03 displayed superior performance, as it possesses a stable SARS-CoV-2 susceptible phenotype and does not produce false-positive hits due to drug-induced phospholipidosis. A proof-of-concept screen of 1796 kinase inhibitors identified known and novel antiviral drug candidates including inhibitors of PHGDH, CLK-1, and CSF1R. The activity of the PHGDH inhibitor NCT-503 was further increased in combination with the HK2 inhibitor 2-deoxy-D-glucose, which is in clinical development for COVID-19. In conclusion, caspase 3/7 activity detection in SARS-CoV-2-infected Caco-2F03 cells provides a simple phenotypic high-throughput screening platform for SARS-CoV-2 drug candidates that reduces false positive hits.

19.
Am J Physiol Lung Cell Mol Physiol ; 323(1): L84-L92, 2022 07 01.
Article in English | MEDLINE | ID: covidwho-1891936

ABSTRACT

Increased plasma mitochondrial DNA concentrations are associated with poor outcomes in multiple critical illnesses, including COVID-19. However, current methods of cell-free mitochondrial DNA quantification in plasma are time-consuming and lack reproducibility. Here, we used next-generation sequencing to characterize the size and genome location of circulating mitochondrial DNA in critically ill subjects with COVID-19 to develop a facile and optimal method of quantification by droplet digital PCR. Sequencing revealed a large percentage of small mitochondrial DNA fragments in plasma with wide variability in coverage by genome location. We identified probes for the mitochondrial DNA genes, cytochrome B and NADH dehydrogenase 1, in regions of relatively high coverage that target small sequences potentially missed by other methods. Serial assessments of absolute mitochondrial DNA concentrations were then determined in plasma from 20 critically ill subjects with COVID-19 without a DNA isolation step. Mitochondrial DNA concentrations on the day of enrollment were increased significantly in patients with moderate or severe acute respiratory distress syndrome (ARDS) compared with those with no or mild ARDS. Comparisons of mitochondrial DNA concentrations over time between patients with no/mild ARDS who survived, patients with moderate/severe ARDS who survived, and nonsurvivors showed the highest concentrations in patients with more severe disease. Absolute mitochondrial DNA quantification by droplet digital PCR is time-efficient and reproducible; thus, we provide a valuable tool and rationale for future studies evaluating mitochondrial DNA as a real-time biomarker to guide clinical decision-making in critically ill subjects with COVID-19.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/diagnosis , COVID-19/genetics , Critical Illness , DNA, Mitochondrial/genetics , Humans , Intensive Care Units , Polymerase Chain Reaction , Reproducibility of Results , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/genetics
20.
Handbook of research on remote work and worker well-being in the post-COVID-19 era ; : 264-285, 2021.
Article in English | APA PsycInfo | ID: covidwho-1887856

ABSTRACT

The COVID-19 pandemic has led to widespread adoption of virtual teams (VTs), the prevalence of which had already been increasing steadily. However, studies show that VTs often fail to meet their potential, highlighting the centrality of trust to their success. While trust is important at the team member level and the focus of much of the extant research, it also underpins effective virtual leadership. Following a review of VT and trust literatures, research conducted within three global technology companies across Europe, Middle East, and Africa is used to provide insights into trust development in virtual leader- member dyads. These highlight leaders' behaviours that can both demonstrate their own trustworthiness to VT members and their trust of VT members. These behaviours are integrated into a framework for enabling high trust VT leadership which emphasises member-centricity. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

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