The effect of TRV027 on coagulation in COVID 19: A pilot randomized, placebo-controlled controlled trial.

COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear, one hypothesis is that loss of Angiotensin Converting Enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double blind randomised, placebo controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19 (REC ref. 20/HRA/3414), Clinical Trial No. NCT04419610. The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group, however, this did not reach statistical significance (p=0.15). A Bayesian analysis demonstrated there was a 92% probability that this change represented a true drug effect.

Perceived workplace support and mental health, well-being and burnout among health care professionals during the COVID-19 pandemic: a cohort analysis.

BACKGROUND: Little is known about the relationship between workplace support and mental health and burnout among health care professionals (HCPs) during the COVID-19 pandemic. In this cohort study, we sought to evaluate the association between perceived level of (and changes to) workplace support and mental health and burnout among HCPs, and to identify what constitutes perceived effective workplace support. METHODS: Online surveys at baseline (July-September 2020) and follow-up 4 months later assessed the presence of generalized anxiety disorder (using the 7-item Generalized Anxiety Disorder scale [GAD-7]), clinical insomnia, major depressive disorder (using the 9-item Patient Health Questionnaire), burnout (emotional exhaustion and depersonalization) and mental well-being (using the Short Warwick-Edinburgh Mental Wellbeing Score). Both surveys assessed self-reported level of workplace support (single-item Likert scale). For baseline and follow-up, independently, we developed separate logistic regression models to evaluate the association of the level of workplace support (tricohotomized as unsupported, neither supported nor unsupported and supported) with mental health and burnout. We also developed linear regression models to evaluate the association between the change in perceived level of workplace support and the change in mental health scores from baseline and follow-up. We used thematic analyses on free-text entries of the baseline survey to evaluate what constitutes effective support. RESULTS: At baseline (n = 1422) and follow-up (n = 681), HCPs who felt supported had reduced risk of anxiety, depression, clinical insomnia, emotional exhaustion and depersonalization, compared with those who felt unsupported. Among those who responded to both surveys (n = 681), improved perceived level of workplace support over time was associated with significantly improved scores on measures of anxiety (adjusted ß -0.13, 95% confidence interval [CI] -0.25 to -0.01), depression (adjusted ß -0.17, 95% CI -0.29 to -0.04) and mental well-being (adjusted ß 0.19, 95% CI 0.10 to 0.29), independent of baseline level of support. We identified 5 themes constituting effective workplace support, namely concern or understanding for welfare, information, tangible qualities of the workplace, leadership and peer support. INTERPRETATION: We found a significant association between perceived level of (and changes in) workplace support and mental health and burnout of HCPs, and identified potential themes that constitute perceived workplace support. Collectively, these findings can inform changes in guidance and national policies to improve mental health and burnout among HCPs. Trial registration: ClinicalTrials.gov, no. NCT04433260.

Improved lifestyle is associated with improved depression, anxiety and well-being over time in UK healthcare professionals during the COVID-19 pandemic: insights from the CoPE-HCP cohort study.

Background: One potential modifiable factor to improve the mental health of healthcare professionals (HCPs) during the pandemic is lifestyle. Aims: This study aimed to assess whether an improved lifestyle during the pandemic is associated with improved mental health symptoms and mental well-being in HCPs over time. Methods: This was a cohort study involving an online survey distributed at two separate time points during the pandemic (baseline (July-September 2020) and follow-up (December 2020-March 2021)) to HCPs working in primary or secondary care in the UK. Both surveys assessed for major depressive disorder (MDD) (Patient Health Questionnaire-9 (PHQ-9)), generalised anxiety disorder (GAD) (Generalised Anxiety Disorder-7 (GAD-7)), mental well-being (Short Warwick-Edinburgh Mental Well-being Score (SWEMWBS)) and self-reported lifestyle change (compared with the start of the pandemic) on multiple domains. Cumulative scores were calculated to estimate overall lifestyle change compared with that before the pandemic (at both baseline and follow-up). At each time point, separate logistic regression models were constructed to relate the lifestyle change score with the presence of MDD, GAD and low mental well-being. Linear regression models were also developed relating the change in lifestyle scores from baseline to follow-up to changes in PHQ-9, GAD-7 and SWEMWBS scores. Results: 613 HCPs completed both baseline assessment and follow-up assessment. Consistent significant cross-sectional associations between increased lifestyle change scores and a reduced risk of MDD, GAD and low mental well-being were observed at both baseline and follow-up. Over the study period, a whole unit increase in the change in novel scores (ie, improved overall lifestyle) over 4 months was inversely associated with changes in PHQ-9 (adjusted coefficient: -0.51, 95% confidence interval (CI): -0.73 to -0.30, p<0.001) and GAD-7 scores (adjusted coefficient: -0.32, 95% CI: -0.53 to -0.10, p=0.004) and positively associated with the change in SWEMWBS scores (adjusted coefficient: 0.37, 95% CI: 0.18 to 0.55, p<0.001). Conclusions: Improved lifestyle over time is associated with improved mental health and mental well-being in HCPs during the pandemic. Improving lifestyle could be a recommended intervention for HCPs to help mitigate the mental health impact during the current and future pandemics. Trial registration number: NCT04433260.

Longitudinal comparisons of mental health, burnout and well-being in patient-facing, non-patient-facing healthcare professionals and non-healthcare professionals during the COVID-19 pandemic: findings from the CoPE-HCP study.

BACKGROUND: The COVID-19 pandemic may disproportionately affect the mental health of healthcare professionals (HCPs), especially patient-facing HCPs. AIMS: To longitudinally examine mental health in HCPs versus non-HCPs, and patient-facing HCPs versus non-patient-facing HCPs. METHOD: Online surveys were distributed to a cohort at three phases (baseline, July to September 2020; phase 2, 6 weeks post-baseline; phase 3, 4 months post-baseline). Each survey contained validated assessments for depression, anxiety, insomnia, burnout and well-being. For each outcome, we conducted mixed-effects logistic regression models (adjusted for a priori confounders) comparing the risk in different groups at each phase. RESULTS: A total of 1574 HCPs and 147 non-HCPs completed the baseline survey. Although there were generally higher rates of various probable mental health issues among HCPs versus non-HCPs at each phase, there was no significant difference, except that HCPs had 2.5-fold increased risk of burnout at phase 2 (emotional exhaustion: odds ratio 2.50, 95% CI 1.15-5.46, P = 0.021), which increased at phase 3 (emotional exhaustion: odds ratio 3.32, 95% CI 1.40-7.87, P = 0.006; depersonalisation: odds ratio 3.29, 95% CI 1.12-9.71, P = 0.031). At baseline, patient-facing HCPs (versus non-patient-facing HCPs) had a five-fold increased risk of depersonalisation (odds ratio 5.02, 95% CI 1.65-15.26, P = 0.004), with no significant difference in the risk for other outcomes. The difference in depersonalisation reduced over time, but patient-facing HCPs still had a 2.7-fold increased risk of emotional exhaustion (odds ratio 2.74, 95% CI 1.28-5.85, P = 0.009) by phase 3. CONCLUSIONS: The COVID-19 pandemic had a huge impact on the mental health and well-being of both HCPs and non-HCPs, but there is disproportionately higher burnout among HCPs, particularly patient-facing HCPs.

The Relationship Between Availability and Changes to Perceived Workplace Support and Their Impact on the Mental Health, Well-being and Burn-Out of Healthcare Professionals (HCP): Insight and Mitigating Strategies From the CoPE-HCP Cohort Study

Aims To examine the relationship between self-reported level of workplace support (WS) and various mental health outcomes in HCPs and non-HCPs at different time-points during the COVID-19 pandemic, and to examine whether improved WS is associated with improved mental health outcomes over time. Lastly, to identify what support healthcare professionals (HCPs) perceive to be most helpful. Methods Cohort survey study at baseline (July-September 2020) and follow-up (approximately four months later). Setting HCPs working in primary or secondary care, from UK and other countries, and non-HCP controls from primarily London-based universities. Participants 1574 HCPs and 147 non-HCPs (academic and research staff at London-based universities). The inclusion criteria for the study were: 1) aged 18 or older, 2) electronic consent given, and 3) identified as HCP or non-healthcare academic staff or self-declared non-HCPs. Main outcome measures Presence of generalized anxiety disorder (assessed using the GAD-7), clinical insomnia (ISI), major depressive disorder (PHQ-9), well-being (SWEMWBS), and burnout (emotional exhaustion and depersonalization;EEDP2Q). Qualitative data exploring what support HCPs perceive as most useful was gathered using free-text inputs. Results At baseline and follow-up, consistently, compared to those who felt unsupported, those who felt supported had significantly reduced risk (odds) of generalized anxiety disorder (baseline: 59% [95% CI of OR, 0.29 to 0.57], follow-up: 41% [0.38 to 0.92]), clinical insomnia (51% [0.34 to 0.69], 66% [0.20 to 0.55]), major depressive disorder (58% [0.31 to 0.58], 54% [0.31 to 0.74]), emotional exhaustion (65% [0.26 to 0.46], 61% [0.27 to 0.56]) and depersonalization (58% [0.28 to 0.61], 68% [0.21 to 0.50]). At follow-up, self-reported improved WS (vs. baseline) was associated with significantly improved GAD-7 (adjusted difference. −1.73 [-2.54 to −0.91]), ISI (-0.96 [-1.88 to −0.04]), PHQ−9 (-1.32 [-2.16 to −0.49]), SWEMWBS (0.97 [0.37 to 1.57]) and EEDP2Q (burnout) (-1.30 [-1.82 to −0.79]) scores, independent of baseline level of support. Five themes were identified constituting WS: ‘managerial support’ was the largest sub-theme. Conclusion A consistent association was observed between level of WS and the mental health of HCPs and non-HCPs. Improved WS was associated with improved mental health scores over a four-month period during the pandemic.

Quantifying the Excess Risk of Adverse COVID-19 Outcomes in Unvaccinated Individuals With Diabetes Mellitus, Hypertension, Ischaemic Heart Disease or Myocardial Injury: A Meta-Analysis.

Background: More than 80% of individuals in low and middle-income countries (LMICs) are unvaccinated against coronavirus disease 2019 (COVID-19). In contrast, the greatest burden of cardiovascular disease is seen in LMIC populations. Hypertension (HTN), diabetes mellitus (DM), ischaemic heart disease (IHD) and myocardial injury have been variably associated with adverse COVID-19 outcomes. A systematic comparison of their impact on specific COVID-19 outcomes is lacking. We quantified the impact of DM, HTN, IHD and myocardial injury on six adverse COVID-19 outcomes: death, acute respiratory distress syndrome (ARDS), invasive mechanical ventilation (IMV), admission to intensive care (ITUadm), acute kidney injury (AKI) and severe COVID-19 disease (SCov), in an unvaccinated population. Methodology: We included studies published between 1st December 2019 and 16th July 2020 with extractable data on patients ≥18 years of age with suspected or confirmed SARS-CoV-2 infection. Odds ratios (OR) for the association between DM, HTN, IHD and myocardial injury with each of six COVID-19 outcomes were measured. Results: We included 110 studies comprising 48,809 COVID-19 patients. Myocardial injury had the strongest association for all six adverse COVID-19 outcomes [death: OR 8.85 95% CI (8.08-9.68), ARDS: 5.70 (4.48-7.24), IMV: 3.42 (2.92-4.01), ITUadm: 4.85 (3.94-6.05), AKI: 10.49 (6.55-16.78), SCov: 5.10 (4.26-6.05)]. HTN and DM were also significantly associated with death, ARDS, ITUadm, AKI and SCov. There was substantial heterogeneity in the results, partly explained by differences in age, gender, geographical region and recruitment period. Conclusion: COVID-19 patients with myocardial injury are at substantially greater risk of death, severe disease and other adverse outcomes. Weaker, yet significant associations are present in patients with HTN, DM and IHD. Quantifying these associations is important for risk stratification, resource allocation and urgency in vaccinating these populations. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, registration no: CRD42020201435 and CRD42020201443.

Post-COVID symptoms reported at asynchronous virtual review and stratified follow-up after COVID-19 pneumonia.

BACKGROUND: The COVID-19 pandemic has strained healthcare systems and how best to address post-COVID health needs is uncertain. Here we describe the post-COVID symptoms of 675 patients followed up using a virtual review pathway, stratified by severity of acute COVID infection. METHODS: COVID-19 survivors completed an online/telephone questionnaire of symptoms after 12+ weeks and a chest X-ray. Dependent on findings at virtual review, patients were provided information leaflets, attended for investigations and/or were reviewed face-to-face. Outcomes were compared between patients following high-risk and low-risk admissions for COVID pneumonia, and community referrals. RESULTS: Patients reviewed after hospitalisation for COVID pneumonia had a median of two ongoing physical health symptoms post-COVID. The most common was fatigue (50.3% of high-risk patients). Symptom burden did not vary significantly by severity of hospitalised COVID pneumonia but was highest in community referrals. Symptoms suggestive of depression, anxiety and post-traumatic stress disorder were common (depression occurred in 24.9% of high-risk patients). Asynchronous virtual review facilitated triage of patients at highest need of face-to-face review. CONCLUSION: Many patients continue to have a significant burden of post-COVID symptoms irrespective of severity of initial pneumonia. How best to assess and manage long COVID will be of major importance over the next few years.

Current Perspectives on Coronavirus Disease 2019 and Cardiovascular Disease: A White Paper by the JAHA Editors.

Coronavirus Disease 2019 (COVID-19) has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020. In this White Paper, we address the cardiovascular co-morbidities of COVID-19 infection; the diagnosis and treatment of standard cardiovascular conditions during the pandemic; and the diagnosis and treatment of the cardiovascular consequences of COVID-19 infection. In addition, we will also address various issues related to the safety of healthcare workers and the ethical issues related to patient care in this pandemic.

Early and Mid-Term Implications of the COVID-19 Pandemic on the Physical, Behavioral and Mental Health of Healthcare Professionals: The CoPE-HCP Study Protocol.

INTRODUCTION: The COVID-19 pandemic has led to unprecedented strain to healthcare systems worldwide and posed unique challenges to the healthcare professionals (HCPs) and the general public. OBJECTIVES: The aim of this study is to evaluate the impact of COVID-19 on the mental health, behavioral, and physical wellbeing of HCPs in the early and mid-term periods of the pandemic in comparison to non-HCPs. Thus, facilitating and guiding optimum planning and delivery of support to HCPs. METHODS AND ANALYSIS: An observational cross-sectional survey and cohort study aiming to enroll over 1050 participants (minimum, 800 HCPs and 250 controls). Study questionnaires will be completed at baseline and after 6-weeks and 4-months. Recruitment initiated July 2020. The study was designed in London, United Kingdom, but open to participants worldwide. Baseline: Questionnaires comprising of validated self-administered screening tools for depression, anxiety, sleep-related issues, wellbeing, and burnout. The questionnaires also explore changes in behavior and physical wellbeing of the participants. In addition, associations of these mental health and behavioral factors with work-related factors and support will be explored. Six-weeks and 4-months follow-up: Follow-up questionnaires will assess change in symptoms of anxiety and depression, sleep disorders, use of alcohol and other substances, behavioral or interpersonal relationship changes. Physical wellbeing will be assessed through the presence of suspected or confirmed COVID-19 infection and absence from work. We will also evaluate the impact of variable provision of personal protection equipment (supply and training), extended working hours, and concern for the wellbeing of family members, anxiety levels, and evidence of burnout. STATISTICAL CONSIDERATIONS: The study has 80% power to detect a 10% difference of combined depression and/or anxiety symptoms between the groups using two-sided type 1 error at 0.05 at baseline. Assuming that only 50% of these HCPs agree to be a part of a cohort survey, we will have 80% power to detect around 12% difference in the two groups in reported physical symptoms (20% vs. 32.3%), or prevalence of depression and/or anxiety at the end of the study. ETHICS: The study was approved by the Cambridge East, Research Ethics Committee (20/EE/0166). TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04433260.

Healthcare Workers Bioresource: Study outline and baseline characteristics of a prospective healthcare worker cohort to study immune protection and pathogenesis in COVID-19.

Background: Most biomedical research has focused on sampling COVID-19 patients presenting to hospital with advanced disease, with less focus on the asymptomatic or paucisymptomatic. We established a bioresource with serial sampling of health care workers (HCWs) designed to obtain samples before and during mainly mild disease, with follow-up sampling to evaluate the quality and duration of immune memory. Methods: We conducted a prospective study on HCWs from three hospital sites in London, initially at a single centre (recruited just prior to first peak community transmission in London), but then extended to multiple sites 3 weeks later (recruitment still ongoing, target n=1,000). Asymptomatic participants attending work complete a health questionnaire, and provide a nasal swab (for SARS-CoV-2 RNA by RT-PCR tests) and blood samples (mononuclear cells, serum, plasma, RNA and DNA are biobanked) at 16 weekly study visits, and at 6 and 12 months. Results: Preliminary baseline results for the first 731 HCWs (400 single-centre, 331 multicentre extension) are presented. Mean age was 38±11 years; 67% are female, 31% nurses, 20% doctors, and 19% work in intensive care units. COVID-19-associated risk factors were: 37% black, Asian or minority ethnicities; 18% smokers; 13% obesity; 11% asthma; 7% hypertension and 2% diabetes mellitus. At baseline, 41% reported symptoms in the preceding 2 weeks. Preliminary test results from the initial cohort (n=400) are available: PCR at baseline for SARS-CoV-2 was positive in 28 of 396 (7.1%, 95% CI 4.9-10.0%) and 15 of 385 (3.9%, 2.4-6.3%) had circulating IgG antibodies. Conclusions: This COVID-19 bioresource established just before the peak of infections in the UK will provide longitudinal assessments of incident infection and immune responses in HCWs through the natural time course of disease and convalescence. The samples and data from this bioresource are available to academic collaborators by application  https://covid-consortium.com/application-for-samples/.