A time-resolved proteomic and prognostic map of COVID-19

COVID-19 is highly variable in its clinical presentation, ranging from asymptomatic infection to severe organ damage and death. We characterized the time-dependent progression of the disease in 139 COVID-19 inpatients by measuring 86 accredited diagnostic parameters, such as blood cell counts and enzyme activities, as well as untargeted plasma proteomes at 687 sampling points. We report an initial spike in a systemic inflammatory response, which is gradually alleviated and followed by a protein signature indicative of tissue repair, metabolic reconstitution, and immunomodulation. We identify prognostic marker signatures for devising risk-adapted treatment strategies and use machine learning to classify therapeutic needs. We show that the machine learning models based on the proteome are transferable to an independent cohort. Our study presents a map linking routinely used clinical diagnostic parameters to plasma proteomes and their dynamics in an infectious disease

A randomised controlled feasibility trial of family and social network intervention for young people who misuse alcohol and drugs : study protocol (Y-SBNT)

Background: A growing body of research has identified family interventions to be effective in treating young people’s substance use problems. However, despite this evidence, take-up of family-based approaches in the UK has been low. Key factors for this appear to include the resource-intensive nature of most family interventions which challenges implementation and delivery in many service settings and the cultural adaptation of approaches developed in the USA to a UK setting. This study aims to demonstrate the feasibility of recruiting young people to a specifically developed family- and wider social network-based intervention by testing an adapted version of adult social behaviour and network therapy (SBNT). Methods: A pragmatic, randomised controlled, open feasibility trial delivered in two services for young people in the UK. Potential participants are aged 12–18 years referred for drug or alcohol problems to either service. The main purpose of this study is to demonstrate the feasibility of recruiting young people to a specifically developed family and social network-based intervention. The feasibility and acceptability of this intervention will be measured by recruitment rates, treatment retention, follow-up rates and qualitative interviews. The feasibility of training staff from existing services to deliver this intervention will be explored. Using this opportunity to compare the effectiveness of the intervention against treatment as usual, Timeline Follow-Back interviews will document the proportion of days on which the main problem substance was used in the preceding 90-day period at each assessment point. The economic component will examine the feasibility of conducting a full incremental cost-effectiveness analysis of the two treatments. The study will also explore and develop models of patient and public involvement which support the involvement of young people in a study of this nature. Discussion: An earlier phase of work adapted social behaviour and network therapy (adult approach) to produce a purpose-designed youth version supported by a therapy manual and associated resources. This was achieved by consultation with young people with experience of services and professionals working in services for young people. This feasibility trial alongside ongoing consultations with young people will offer a meaningful understanding of processes of delivery and implementation. Trial registration: ISRCTN93446265; Date ISRCTN assigned 31/05/2013

A proteomic survival predictor for COVID-19 patients in intensive care

Global healthcare systems are challenged by the COVID-19 pandemic. There is a need to optimize allocation of treatment and resources in intensive care, as clinically established risk assessments such as SOFA and APACHE II scores show only limited performance for predicting the survival of severely ill COVID-19 patients. Additional tools are also needed to monitor treatment, including experimental therapies in clinical trials. Comprehensively capturing human physiology, we speculated that proteomics in combination with new data-driven analysis strategies could produce a new generation of prognostic discriminators. We studied two independent cohorts of patients with severe COVID-19 who required intensive care and invasive mechanical ventilation. SOFA score, Charlson comorbidity index, and APACHE II score showed limited performance in predicting the COVID-19 outcome. Instead, the quantification of 321 plasma protein groups at 349 timepoints in 50 critically ill patients receiving invasive mechanical ventilation revealed 14 proteins that showed trajectories different between survivors and non-survivors. A predictor trained on proteomic measurements obtained at the first time point at maximum treatment level (i.e. WHO grade 7), which was weeks before the outcome, achieved accurate classification of survivors (AUROC 0.81). We tested the established predictor on an independent validation cohort (AUROC 1.0). The majority of proteins with high relevance in the prediction model belong to the coagulation system and complement cascade. Our study demonstrates that plasma proteomics can give rise to prognostic predictors substantially outperforming current prognostic markers in intensive care

A survey among physicians in surgery and anesthesiology departments after the first surge of SARS-CoV-2 infections in Germany : Preparing for further challenges ahead

BACKGROUND: The SARS-CoV‑2 pandemic has extensively challenged healthcare systems all over the world. Many elective operations were postponed or cancelled, changing priorities and workflows in surgery departments. AIMS: The primary aim of this cross-sectional study was to assess the workload and psychosocial burden of surgeons and anesthesiologists, working in German hospitals during the first wave of SARS-CoV‑2 infections in 2020. METHODS: Quantitative online survey on the workplace situation including psychosocial and work-related stress factors among resident and board-certified surgeons and anesthesiologists. Physicians in German hospitals across all levels of healthcare were contacted via departments, professional associations and social media posts. RESULTS: Among 154 total study participants, 54% of respondents stated a lack of personal protective equipment in their own wards and 56% reported increased staff shortages since the onset of the pandemic. While routine practice was reported as fully resumed in 71% of surgery departments at the time of the survey, work-related dissatisfaction among responding surgeons and anesthesiologists increased from 24% before the pandemic to 36% after the first wave of infections. As a countermeasure, 94% of participants deemed the establishment of action plans to increase pandemic preparedness and strengthening German public health systems a useful measure to respond to current challenges. CONCLUSION: The aftermath of the first wave of SARS-CoV‑2 infections in Germany has left the surgical staff strained, despite temporarily decreased workloads. Overall, a critical review of the altered conditions is indispensable to identify and promote effective solutions and prudent action plans required to address imminent challenges.Not heldaccepted version (12 month embargo

Functional limitations 12 months after SARS-CoV-2 infection correlate with initial disease severity: an observational study of cardiopulmonary exercise capacity testing in COVID-19 convalescents

BACKGROUND: Cardiopulmonary Exercise Testing (CPET) provides a comprehensive assessment of pulmonary, cardiovascular and musculosceletal function. Reduced CPET performance could be an indicator for chronic morbidity after COVID-19. METHODS: Patients >/=18 years with confirmed PCR positive SARS-CoV-2 infection were offered to participate in a prospective observational study of clinical course and outcomes of COVID-19. 54 patients completed CPET, questionnaires on respiratory quality of life and performed pulmonary function tests 12 months after SARS-CoV-2 infection. RESULTS: At 12 months after SARS-CoV-2 infection, 46.3% of participants had a peak performance and 33.3% a peak oxygen uptake of <80% of the predicted values, respectively. Further impairments were observed in diffusion capacity and ventilatory efficiency. Functional limitations were particularly pronounced in patients after invasive mechanical ventilation and extracorporeal membrane oxygenation treatment. Ventilatory capacity was reduced 25 points (OR 3.48, p = 0.03) and reduced DLCO (OR 3.01, p = 0.054). CONCLUSIONS: Functional limitations causing chronic morbidity in COVID-19 survivors persist over 12 months after SARS-CoV-2 infection. These limitations were particularly seen in parameters of overall performance and gas exchange resulting from muscular deconditioning and lung parenchymal changes. Patient reported reduced respiratory quality of life was a risk factor for adverse CPET performance

Soluble urokinase receptor (SuPAR) in COVID-19-Related AKI

Background AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. Methods In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. Results Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR,4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels.6.86 ng/ml (third tertile). None of the patients with suPAR,4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. Conclusions Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19. Copyright © 2020 by the American Society of Nephrolog