Mobilisation practices during the SARS-CoV-2 pandemic: A retrospective analysis (MobiCOVID).

BACKGROUND: Corona Virus Disease 2019 (COVID-19) patients display risk factors for intensive care unit acquired weakness (ICUAW). The pandemic increased existing barriers to mobilisation. This study aimed to compare mobilisation practices in COVID-19 and non-COVID-19 patients. METHODS: This retrospective cohort study was conducted at Charité-Universitätsmedizin Berlin, Germany, including adult patients admitted to one of 16 ICUs between March 2018, and November 2021. The effect of COVID-19 on mobilisation level and frequency, early mobilisation (EM) and time to active sitting position (ASP) was analysed. Subgroup analysis on COVID-19 patients and the ICU type influencing mobilisation practices was performed. Mobilisation entries were converted into the ICU mobility scale (IMS) using supervised machine learning. The groups were matched using 1:1 propensity score matching. RESULTS: A total of 12,462 patients were included, receiving 59,415 mobilisations. After matching 611 COVID-19 and non-COVID-19 patients were analysed. They displayed no significant difference in mobilisation frequency (0.4 vs. 0.3, p = 0.7), maximum IMS (3 vs. 3; p = 0.17), EM (43.2% vs. 37.8%; p = 0.06) or time to ASP (HR 0.95; 95% CI: 0.82, 1.09; p = 0.44). Subgroup analysis showed that patients in surge ICUs, i.e., temporarily created ICUs for COVID-19 patients during the pandemic, more commonly received EM (53.9% vs. 39.8%; p = 0.03) and reached higher maximum IMS (4 vs. 3; p = 0.03) without difference in mobilisation frequency (0.5 vs. 0.3; p = 0.32) or time to ASP (HR 1.15; 95% CI: 0.85, 1.56; p = 0.36). CONCLUSION: COVID-19 did not hinder mobilisation. Those treated in surge ICUs were more likely to receive EM and reached higher mobilisation levels.

Key characteristics impacting survival of COVID-19 extracorporeal membrane oxygenation.

BACKGROUND: Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients. METHODS: 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival. RESULTS: Most patients were between 50 and 70 years of age. PaO2/FiO2 ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events. CONCLUSIONS: Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival. TRIAL REGISTRATION: Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022964 .

COVID-19 Patients Require Prolonged Extracorporeal Membrane Oxygenation Support for Survival Compared With Non-COVID-19 Patients.

To investigate the ICU survival of venovenous extracorporeal membrane oxygenation (ECMO) patients suffering from COVID-19-related acute respiratory distress syndrome (ARDS) versus ECMO patients without COVID-19 (non-COVID-19)-related ARDS. DESIGN: Preliminary analysis of data from two prospective ECMO trials and retrospective analysis of a cohort of ARDS ECMO patients. SETTING: Single-center ICU. PATIENTS: Adult ARDS ECMO patients, 16 COVID-19 versus 23 non-COVID-19 patients. Analysis of retrospective data from 346 adult ARDS ECMO patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: COVID-19 and non-COVID-19 ARDS patients did not differ with respect to preexisting disease or body mass index. ICU survival rate was 62% for COVID-19 ECMO patients and 70% for non-COVID-19 ECMO patients. COVID-19 ECMO survivors were supported with ECMO for a median of 43 days (interquartile range [IQR], 18-58 d) versus 16 days (IQR, 19-39 d; p = 0.03) for non-COVID-19 patients. The median duration of ECMO therapy for all ARDS patients between 2007 and 2018 was 15 days (IQR, 6-28 d). The subgroup of patients suffering from any viral pneumonia received ECMO support for a median of 16 days (IQR, 9-27 d), survivors of influenza pneumonia received ECMO support for 13 days (IQR, 7-25 d). CONCLUSIONS: COVID-19 patients required significant longer ECMO support compared with patients without COVID-19 to achieve successful ECMO weaning and ICU survival.

Sex-Specific Aspects of Skeletal Muscle Metabolism in the Clinical Context of Intensive Care Unit-Acquired Weakness.

(1) Background: Female sex is considered a risk factor for Intensive Care Unit-Acquired Weakness (ICUAW). The aim is to investigate sex-specific aspects of skeletal muscle metabolism in the context of ICUAW. (2) Methods: This is a sex-specific sub-analysis from two prospectively conducted trials examining skeletal muscle metabolism and advanced muscle activating measures in critical illness. Muscle strength was assessed by Medical Research Council Score. The insulin sensitivity index was analyzed by hyperinsulinemic-euglycemic (HE) clamp. Muscular metabolites were studied by microdialysis. M. vastus lateralis biopsies were taken. The molecular analysis included protein degradation pathways. Morphology was assessed by myocyte cross-sectional area (MCSA). Multivariable linear regression models for the effect of sex on outcome parameters were performed. (3) Results: n = 83 (♂n = 57, 68.7%; ♀n = 26, 31.3%) ICU patients were included. ICUAW was present in 81.1%♂ and in 82.4%♀ at first awakening (p = 0.911) and in 59.5%♂ and in 70.6%♀ at ICU discharge (p = 0.432). Insulin sensitivity index was reduced more in women than in men (p = 0.026). Sex was significantly associated with insulin sensitivity index and MCSA of Type IIa fibers in the adjusted regression models. (4) Conclusion: This hypothesis-generating analysis suggests that more pronounced impairments in insulin sensitivity and lower MCSA of Type IIa fibers in critically ill women may be relevant for sex differences in ICUAW.

Key summary of German national treatment guidance for hospitalized COVID-19 patients : Key pharmacologic recommendations from a national German living guideline using an Evidence to Decision Framework (last updated 17.05.2021).

PURPOSE: This executive summary of a national living guideline aims to provide rapid evidence based recommendations on the role of drug interventions in the treatment of hospitalized patients with COVID-19. METHODS: The guideline makes use of a systematic assessment and decision process using an evidence to decision framework (GRADE) as recommended standard WHO (2021). Recommendations are consented by an interdisciplinary panel. Evidence analysis and interpretation is supported by the CEOsys project providing extensive literature searches and living (meta-) analyses. For this executive summary, selected key recommendations on drug therapy are presented including the quality of the evidence and rationale for the level of recommendation. RESULTS: The guideline contains 11 key recommendations for COVID-19 drug therapy, eight of which are based on systematic review and/or meta-analysis, while three recommendations represent consensus expert opinion. Based on current evidence, the panel makes strong recommendations for corticosteroids (WHO scale 5-9) and prophylactic anticoagulation (all hospitalized patients with COVID-19) as standard of care. Intensified anticoagulation may be considered for patients with additional risk factors for venous thromboembolisms (VTE) and a low bleeding risk. The IL-6 antagonist tocilizumab may be added in case of high supplemental oxygen requirement and progressive disease (WHO scale 5-6). Treatment with nMABs may be considered for selected inpatients with an early SARS-CoV-2 infection that are not hospitalized for COVID-19. Convalescent plasma, azithromycin, ivermectin or vitamin D3 should not be used in COVID-19 routine care. CONCLUSION: For COVID-19 drug therapy, there are several options that are sufficiently supported by evidence. The living guidance will be updated as new evidence emerges.

Observational study of changes in utilization and outcomes in mechanical ventilation in COVID-19.

BACKGROUND: The role of non-invasive ventilation (NIV) in severe COVID-19 remains a matter of debate. Therefore, the utilization and outcome of NIV in COVID-19 in an unbiased cohort was determined. AIM: The aim was to provide a detailed account of hospitalized COVID-19 patients requiring non-invasive ventilation during their hospital stay. Furthermore, differences of patients treated with NIV between the first and second wave are explored. METHODS: Confirmed COVID-19 cases of claims data of the Local Health Care Funds with non-invasive and/or invasive mechanical ventilation (MV) in the spring and autumn pandemic period in 2020 were comparable analysed. RESULTS: Nationwide cohort of 17.023 cases (median/IQR age 71/61-80 years, 64% male) 7235 (42.5%) patients primarily received IMV without NIV, 4469 (26.3%) patients received NIV without subsequent intubation, and 3472 (20.4%) patients had NIV failure (NIV-F), defined by subsequent endotracheal intubation. The proportion of patients who received invasive MV decreased from 75% to 37% during the second period. Accordingly, the proportion of patients with NIV exclusively increased from 9% to 30%, and those failing NIV increased from 9% to 23%. Median length of hospital stay decreased from 26 to 21 days, and duration of MV decreased from 11.9 to 7.3 days. The NIV failure rate decreased from 49% to 43%. Overall mortality increased from 51% versus 54%. Mortality was 44% with NIV-only, 54% with IMV and 66% with NIV-F with mortality rates steadily increasing from 62% in early NIV-F (day 1) to 72% in late NIV-F (>4 days). CONCLUSIONS: Utilization of NIV rapidly increased during the autumn period, which was associated with a reduced duration of MV, but not with overall mortality. High NIV-F rates are associated with increased mortality, particularly in late NIV-F.

[Intensive care bed requirements for COVID-19 in the fall/winter of 2021 : Simulation of different scenarios under consideration of incidences and vaccination rates]. / Intensivbettenbedarf für COVID­19 im Herbst/Winter 2021 : Simulation unterschiedlicher Szenarien unter Berücksichtigung von Inzidenzen und Impfquoten.

BACKGROUND: Despite the increasing vaccination rates against SARS-CoV­2, there is a risk of a renewed wave of infections in autumn 2021 due to the high seasonality of the pathogen, with the associated renewed possible heavy burden on intensive care. In the following manuscript we simulated different scenarios using defined mathematical models to estimate the burden of intensive care treatment by COVID-19 patients within certain limits during the coming autumn. METHODS: The simulation of the scenarios uses a stationary model supplemented by the effect of vaccinations. The age group-specific risk profile for intensive care unit (ICU)-associated disease progression is calculated using third wave ICU admission data from sentinel hospitals, local DIVI registry occupancy data and the corresponding local incidence rates by linear regression with time lag. We simulated vaccination rates of 15% for the over 18-year-old cohort, 70% for the 15-34 year cohort, 75%/80%/85% for the 35-59 year cohort and 85%/90%/95% for the over 60-year-old cohort. The simulations take into account that vaccination provides 100% protection against disease progression requiring intensive care. Regarding protection against infection in vaccinated persons the simulations are depicted for the scenario of 70% protection against infection in vaccinated persons and for the scenario of 85% protection against infection in vaccinated persons. RESULTS: The incidence is proportional to ICU bed occupancy. The proportionality factor is higher than in the second and third waves, so that comparable ICU bed occupancy is only achieved at a higher incidence. A 10% increase in vaccination rates of the over 35-year-olds to 85% and of the over 60-year-olds to 95% leads to a significant reduction in ICU bed occupancy. DISCUSSION: There will continue to be a close and linear relationship between SARS-CoV­2 incidence and ICU bed occupancy in the coming months. Even above incidences of 200/100,000 a considerable burden of ICUs with more than 3000 COVID-19 patients can be expected again, unless the vaccination rate is significantly increased. A few percentage points in the vaccination rate have a significant impact on potential ICU occupancy in the autumn, so efforts to increase vaccination acceptance should be a priority in the coming weeks. For intensive care medicine, the vaccination rate of those over 35 years of age is crucial.

6-month mortality and readmissions of hospitalized COVID-19 patients: A nationwide cohort study of 8,679 patients in Germany.

BACKGROUND: COVID-19 frequently necessitates in-patient treatment and in-patient mortality is high. Less is known about the long-term outcomes in terms of mortality and readmissions following in-patient treatment. AIM: The aim of this paper is to provide a detailed account of hospitalized COVID-19 patients up to 180 days after their initial hospital admission. METHODS: An observational study with claims data from the German Local Health Care Funds of adult patients hospitalized in Germany between February 1 and April 30, 2020, with PCR-confirmed COVID-19 and a related principal diagnosis, for whom 6-month all-cause mortality and readmission rates for 180 days after admission or until death were available. A multivariable logistic regression model identified independent risk factors for 180-day all-cause mortality in this cohort. RESULTS: Of the 8,679 patients with a median age of 72 years, 2,161 (24.9%) died during the index hospitalization. The 30-day all-cause mortality rate was 23.9% (2,073/8,679), the 90-day rate was 27.9% (2,425/8,679), and the 180-day rate, 29.6% (2,566/8,679). The latter was 52.3% (1,472/2,817) for patients aged ≥80 years 23.6% (1,621/6,865) if not ventilated during index hospitalization, but 53.0% in case of those ventilated invasively (853/1,608). Risk factors for the 180-day all-cause mortality included coagulopathy, BMI ≥ 40, and age, while the female sex was a protective factor beyond a fewer prevalence of comorbidities. Of the 6,235 patients discharged alive, 1,668 were readmitted a total of 2,551 times within 180 days, resulting in an overall readmission rate of 26.8%. CONCLUSIONS: The 180-day follow-up data of hospitalized COVID-19 patients in a nationwide cohort representing almost one-third of the German population show significant long-term, all-cause mortality and readmission rates, especially among patients with coagulopathy, whereas women have a profoundly better and long-lasting clinical outcome compared to men.

Predicting lethal courses in critically ill COVID-19 patients using a machine learning model trained on patients with non-COVID-19 viral pneumonia.

In a pandemic with a novel disease, disease-specific prognosis models are available only with a delay. To bridge the critical early phase, models built for similar diseases might be applied. To test the accuracy of such a knowledge transfer, we investigated how precise lethal courses in critically ill COVID-19 patients can be predicted by a model trained on critically ill non-COVID-19 viral pneumonia patients. We trained gradient boosted decision tree models on 718 (245 deceased) non-COVID-19 viral pneumonia patients to predict individual ICU mortality and applied it to 1054 (369 deceased) COVID-19 patients. Our model showed a significantly better predictive performance (AUROC 0.86 [95% CI 0.86-0.87]) than the clinical scores APACHE2 (0.63 [95% CI 0.61-0.65]), SAPS2 (0.72 [95% CI 0.71-0.74]) and SOFA (0.76 [95% CI 0.75-0.77]), the COVID-19-specific mortality prediction models of Zhou (0.76 [95% CI 0.73-0.78]) and Wang (laboratory: 0.62 [95% CI 0.59-0.65]; clinical: 0.56 [95% CI 0.55-0.58]) and the 4C COVID-19 Mortality score (0.71 [95% CI 0.70-0.72]). We conclude that lethal courses in critically ill COVID-19 patients can be predicted by a machine learning model trained on non-COVID-19 patients. Our results suggest that in a pandemic with a novel disease, prognosis models built for similar diseases can be applied, even when the diseases differ in time courses and in rates of critical and lethal courses.

Conservative management of COVID-19 associated hypoxaemia.

This correspondence argues that the conclusion given in the article "Conservative management of COVID-19-associated hypoxaemia" is not supported by the data https://bit.ly/3qAn7la.

Critical Illness and Systemic Inflammation Are Key Risk Factors of Severe Acute Kidney Injury in Patients With COVID-19.

INTRODUCTION: Acute kidney injury (AKI) is an important complication in COVID-19, but its precise etiology has not fully been elucidated. Insights into AKI mechanisms may be provided by analyzing the temporal associations of clinical parameters reflecting disease processes and AKI development. METHODS: We performed an observational cohort study of 223 consecutive COVID-19 patients treated at 3 sites of a tertiary care referral center to describe the evolvement of severe AKI (Kidney Disease: Improving Global Outcomes stage 3) and identify conditions promoting its development. Descriptive statistics and explanatory multivariable Cox regression modeling with clinical parameters as time-varying covariates were used to identify risk factors of severe AKI. RESULTS: Severe AKI developed in 70 of 223 patients (31%) with COVID-19, of which 95.7% required kidney replacement therapy. Patients with severe AKI were older, predominantly male, had more comorbidities, and displayed excess mortality. Severe AKI occurred exclusively in intensive care unit patients, and 97.3% of the patients developing severe AKI had respiratory failure. Mechanical ventilation, vasopressor therapy, and inflammatory markers (serum procalcitonin levels and leucocyte count) were independent time-varying risk factors of severe AKI. Increasing inflammatory markers displayed a close temporal association with the development of severe AKI. Sensitivity analysis on risk factors of AKI stage 2 and 3 combined confirmed these findings. CONCLUSION: Severe AKI in COVID-19 was tightly coupled with critical illness and systemic inflammation and was not observed in milder disease courses. These findings suggest that traditional systemic AKI mechanisms rather than kidney-specific processes contribute to severe AKI in COVID-19.

Evaluation of PEEP and prone positioning in early COVID-19 ARDS.

BACKGROUND: In face of the Coronavirus Disease (COVID)-19 pandemic, best practice for mechanical ventilation in COVID-19 associated Acute Respiratory Distress Syndrome (ARDS) is intensely debated. Specifically, the rationale for high positive end-expiratory pressure (PEEP) and prone positioning in early COVID-19 ARDS has been questioned. METHODS: The first 23 consecutive patients with COVID-19 associated respiratory failure transferred to a single ICU were assessed. Eight were excluded: five were not invasively ventilated and three received veno-venous ECMO support. The remaining 15 were assessed over the first 15 days of mechanical ventilation. Best PEEP was defined by maximal oxygenation and was determined by structured decremental PEEP trials comprising the monitoring of oxygenation, airway pressures and trans-pulmonary pressures. In nine patients the impact of prone positioning on oxygenation was investigated. Additionally, the effects of high PEEP and prone positioning on pulmonary opacities in serial chest x-rays were determined by applying a semiquantitative scoring-system. This investigation is part of the prospective observational PA-COVID-19 study. FINDINGS: Patients responded to initiation of invasive high PEEP ventilation with markedly improved oxygenation, which was accompanied by reduced pulmonary opacities within 6 h of mechanical ventilation. Decremental PEEP trials confirmed the need for high PEEP (17.9 (SD ± 3.9) mbar) for optimal oxygenation, while driving pressures remained low. Prone positioning substantially increased oxygenation (p<0.01). INTERPRETATION: In early COVID-19 ARDS, substantial PEEP values were required for optimizing oxygenation. Pulmonary opacities resolved during mechanical ventilation with high PEEP suggesting recruitment of lung volume. FUNDING: German Research Foundation, German Federal Ministry of Education and Research.

Invasive and Non-Invasive Ventilation in Patients With COVID-19.

BACKGROUND: The reported high mortality of COVID-19 patients in intensive care has given rise to a debate over whether patients with this disease are being intubated too soon and might instead benefit from more non-invasive ventilation. METHODS: This review is based on articles published up to 12 June 2020 that were retrieved by a selective literature search on the topic of invasive and non-invasive ventilation for respiratory failure in COVID-19. Guideline recommendations and study data on patients with respiratory failure in settings other than COVID-19 are also considered, as are the current figures of the intensive care registry of the German Interdisciplinary Association for Intensive Care and Emergency Medicine (Deutsche Interdisziplinäre Vereinigung für Intensiv- und Notfallmedizin). RESULTS: The high mortality figures among patients receiving invasive ventilation that have been reported in studies from abroad cannot be uncritically applied to the current situation in Germany. Study data on ventilation specifically in COVID-19 patients would be needed to do justice to the special pathophysiology of this disease, but such data are lacking. Being intubated too early is evidently associated with risks for the patient, but being intubated too late is as well. A particularly im - portant consideration is the potential harm associated with prolonged spontaneous breathing, with or without non-invasive assistance, as any increase in respiratory work can seriously worsen respiratory failure. On the other hand, it is clearly unacceptable to intubate patients too early merely out of concern that the medical staff might become infected with COVID-19 if they were ventilated non-invasively. CONCLUSION: Nasal high flow, non-invasive ventilation, and invasive ventilation with intubation should be carried out in a stepwise treatment strategy, under appropriate intensive-care monitoring and with the observance of all relevant anti-infectious precautions. Germany is better prepared that other countries to provide COVID-19 patients with appropriate respiratory care, in view of the high per capita density of intensive-care beds and the availability of a nationwide, interdisciplinary intensive care registry for the guidance and coordination of intensive care in patients who need it.

Case characteristics, resource use, and outcomes of 10 021 patients with COVID-19 admitted to 920 German hospitals: an observational study.

Background Nationwide, unbiased, and unselected data of hospitalised patients with COVID-19 are scarce. Our aim was to provide a detailed account of case characteristics, resource use, and outcomes of hospitalised patients with COVID-19 in Germany, where the health-care system has not been overwhelmed by the pandemic. METHODS: In this observational study, adult patients with a confirmed COVID-19 diagnosis, who were admitted to hospital in Germany between Feb 26 and April 19, 2020, and for whom a complete hospital course was available (ie, the patient was discharged or died in hospital) were included in the study cohort. Claims data from the German Local Health Care Funds were analysed. The data set included detailed information on patient characteristics, duration of hospital stay, type and duration of ventilation, and survival status. Patients with adjacent completed hospital stays were grouped into one case. Patients were grouped according to whether or not they had received any form of mechanical ventilation. To account for comorbidities, we used the Charlson comorbidity index. FINDINGS: Of 10 021 hospitalised patients being treated in 920 different hospitals, 1727 (17%) received mechanical ventilation (of whom 422 [24%] were aged 18-59 years, 382 [22%] were aged 60-69 years, 535 [31%] were aged 70-79 years, and 388 [23%] were aged ≥80 years). The median age was 72 years (IQR 57-82). Men and women were equally represented in the non-ventilated group, whereas twice as many men than women were in the ventilated group. The likelihood of being ventilated was 12% for women (580 of 4822) and 22% for men (1147 of 5199). The most common comorbidities were hypertension (5575 [56%] of 10 021), diabetes (2791 [28%]), cardiac arrhythmia (2699 [27%]), renal failure (2287 [23%]), heart failure (1963 [20%]), and chronic pulmonary disease (1358 [14%]). Dialysis was required in 599 (6%) of all patients and in 469 (27%) of 1727 ventilated patients. The Charlson comorbidity index was 0 for 3237 (39%) of 8294 patients without ventilation, but only 374 (22%) of 1727 ventilated patients. The mean duration of ventilation was 13·5 days (SD 12·1). In-hospital mortality was 22% overall (2229 of 10 021), with wide variation between patients without ventilation (1323 [16%] of 8294) and with ventilation (906 [53%] of 1727; 65 [45%] of 145 for non-invasive ventilation only, 70 [50%] of 141 for non-invasive ventilation failure, and 696 [53%] of 1318 for invasive mechanical ventilation). In-hospital mortality in ventilated patients requiring dialysis was 73% (342 of 469). In-hospital mortality for patients with ventilation by age ranged from 28% (117 of 422) in patients aged 18-59 years to 72% (280 of 388) in patients aged 80 years or older. INTERPRETATION: In the German health-care system, in which hospital capacities have not been overwhelmed by the COVID-19 pandemic, mortality has been high for patients receiving mechanical ventilation, particularly for patients aged 80 years or older and those requiring dialysis, and has been considerably lower for patients younger than 60 years. FUNDING: None.

Studying the pathophysiology of coronavirus disease 2019: a protocol for the Berlin prospective COVID-19 patient cohort (Pa-COVID-19).

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing a global health emergency. Pa-COVID-19 aims to provide comprehensive data on clinical course, pathophysiology, immunology and outcome of COVID-19, to identify prognostic biomarkers, clinical scores, and therapeutic targets for improved clinical management and preventive interventions. METHODS: Pa-COVID-19 is a prospective observational cohort study of patients with confirmed SARS-CoV-2 infection treated at Charité - Universitätsmedizin Berlin. We collect data on epidemiology, demography, medical history, symptoms, clinical course, and pathogen testing and treatment. Systematic, serial blood sampling will allow deep molecular and immunological phenotyping, transcriptomic profiling, and comprehensive biobanking. Longitudinal data and sample collection during hospitalization will be supplemented by long-term follow-up. RESULTS: Outcome measures include the WHO clinical ordinal scale on day 15 and clinical, functional, and health-related quality-of-life assessments at discharge and during follow-up. We developed a scalable dataset to (i) suit national standards of care, (ii) facilitate comprehensive data collection in medical care facilities with varying resources, and (iii) allow for rapid implementation of interventional trials based on the standardized study design and data collection. We propose this scalable protocol as blueprint for harmonized data collection and deep phenotyping in COVID-19 in Germany. CONCLUSION: We established a basic platform for harmonized, scalable data collection, pathophysiological analysis, and deep phenotyping of COVID-19, which enables rapid generation of evidence for improved medical care and identification of candidate therapeutic and preventive strategies. The electronic database accredited for interventional trials allows fast trial implementation for candidate therapeutic agents. TRIAL REGISTRATION: Registered at the German registry for clinical studies (DRKS00021688).

German recommendations for critically ill patients with COVID­19.

Since December 2019, a novel coronavirus (severe acute respiratory syndrome-coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The majority of patients presents with mild symptoms of coronavirus disease 2019 (COVID-19). However, about 5% become critically ill and require intensive care treatment. Acute hypoxemic failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to ICU admission. At that point, bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS). To date there is no specific treatment available-the main goal of supportive therapy is to ascertain adequate oxygenation. Early intubation and repeated prone positioning are key elements in treating hypoxemic COVID-19 patients. Strict adherence to basic infection control measures (including hand hygiene) and use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be avoided where possible and carried out with utmost precaution.