Long-term Follow up (> 1 year) of Plasma Donors and Patients treated with COVID-19 Convalescent Plasma within the CAPSID trial

Background: COVID-19-Convalescent Plasma (CCP) showed beneficial effects when given early in the treatment course or when it contains high-titre of neutralizing antibodies. Here we present a long-term follow up of patients of the multicentric national randomized CAPSID trial that investigated the effect of CCP in hospitalized COVID-19 patients. CCP donors were also included in the follow up and severed as a control group of patients with mild to moderate disease. Method(s): Patients and donors were invited to participate in the long-term follow up. Data on long-term overall survival (OS) were available for n=52 patients (control group: n=22, high titre CCP: n=16, low-titre CCP: n=14) and n=113 donors. Structured interview and a quality of life (QoL) assessment by questionnaires (FACIT fatigue, FACIT dyspnea and EQ-ED- 5DL) were performed. Visits took place online or on site. Laboratory tests included neutralizing antibody testing by PRNT and inflammation markers. Data are given as median with IQR. Medical events were assessed and graded according to CTCAE. For donors the median follow up time was 517 (483-553) days after the first plasmapheresis and for patients 395 (371-417) days after randomization. Result(s): Medical events during follow up were reported in 27% of donors and 16% of patients (p=0.164) with grade 3 or higher in 9% of donors and 22% of patients. More patients than donors reported a decrease in their socioeconomic status and reported more frequently about GI, pulmonal, pain symptoms or alopecia (p<0.02), but no difference in neurologic symptoms including anosmia was observed. Post COVID-Scale was worse in patients with a trend for better outcome in the CCP group (p=0.089). The trend for better OS in the CCP group became more pronounced during the long-term follow up (p=0.08) and OS remained significantly better in the high dose CCP group (p=0.01). All QoL scores showed a consistent trend towards better outcomes of the CCP group. Conclusion(s): To our knowledge, this is the first long-term follow up from a randomized trial of CCP. CCP-donors with mild to moderate COVID- 19 had a significant smaller long-term disease burden than patients with severe disease. The addition of CCP added to standard treatment in severe COVID-19 showed a trend to better OS and QoL. We had previously reported significant better outcomes in the high-titre CCP subgroup (until day 60). This was even more pronounced during the long-term follow up (> 1 year).

A web-based dashboard to visualise regional allocation and prediction of supply and demand of ECMO treatments in Germany

Background: The importance of sufficient medical resources has become evident in the wake of the COVID-19 pandemic. In particular, specialised technology such as extracorporeal membrane oxygenation (ECMO) is a limited resource in the intensive care unit (ICU). Precise knowledge of the regional supply situation and future demand is highly relevant for public health systems. Method(s): German-wide inpatient data and hospital quality reports were analysed over the period from 2006 - 2019 for ECMO treatments based on hospital cases and patient origin. The data visualisation was realised as a publicly available, cross-platform online dashboard using Python and the open-source Plotly Dash library (www.ecmo-project.de). The Auto-Regressive Integrated Moving Average (ARIMA) model was used for forecasting. Result(s): A total of 52 972 ECMO cases were included. The regional distribution at county level for pediatric and adult venovenous and venoarterial ECMO treatments was graphically processed. Based on the origin of the patients and the hospital treatments, regions with oversupply and undersupply were identified and visualised. Future demand and regional patient distribution can be predicted using time series forecasting. Conclusion(s): For the first time, all ECMO treatments German-wide and regionally are presented at the patient and hospital levels. A transparent, public method was created through the supply-demand maps to show the availability of ECMO therapy in Germany. This information is precious to the public, health care workers, scientists, and decision-makers.

Impact of the Covid-19 pandemic on melanoma and non-melanoma skin cancer inpatient treatment in Germany - a nationwide analysis.

BACKGROUND: SARS-CoV-2 has massively changed the care situation in hospitals worldwide. Although tumour care should not be affected, initial reports from European countries were suggestive for a decrease in skin cancer during the first pandemic wave and only limited data are available thereafter. OBJECTIVES: The aim of this study was to investigate skin cancer cases and surgeries in a nationwide inpatient dataset in Germany. METHODS: Comparative analyses were performed in a prepandemic (18 March 2019 until 17 March 2020) and a pandemic cohort (18 March 2020 until 17 March 2021). Cases were identified and analysed using the WHO international classification of diseases codes (ICDs) and process key codes (OPSs). RESULTS: Comparing the first year of the pandemic with the same period 1 year before, a persistent decrease of 14% in skin cancer cases (n = 19 063) was observed. The largest decrease of 24% was seen in non-invasive in situ tumours (n = 1665), followed by non-melanoma skin cancer (NMSC) with a decrease of 16% (n = 15 310) and malignant melanoma (MM) with a reduction of 7% (n = 2088). Subgroup analysis showed significant differences in the distribution of sex, age, hospital carrier type and hospital volume. There was a decrease of 17% in surgical procedures (n = 22 548), which was more pronounced in minor surgical procedures with a decrease of 24.6% compared to extended skin surgery including micrographic surgery with a decrease of 15.9%. CONCLUSIONS: Hospital admissions and surgical procedures decreased persistently since the beginning of the pandemic in Germany for skin cancer patients. The higher decrease in NMSC cases compared to MM might reflect a prioritization effect. Further evidence from tumour registries is needed to investigate the consequences of the therapy delay and identify the upcoming challenges in skin cancer care.

Late versus early administration of convalescent plasma in hospitalized patients with covid-19: Results from the randomized open label clinical trial capsid

Background: Several observational studies suggested efficacy of COVID-19 convalescent plasma (CCP) but the results of several randomized clinical trials of CCP are not consistent. The trials differ in treatment schedules in terms of timing, volume and antibody content of CCP as well as enrolled patient populations and endpoints. The CAPSID was designed at the beginning of the pandemic and assessed the efficacy of neutralizing antibody containing high-dose COVID-19 convalescent plasma (CCP) in hospitalized patients with severe COVID-19. Methods: Patients (n=105) in 13 hospitals in Germany were randomized to either receive standard treatment and three units of CCP on days 1, 3 and 5 (total dose 846 ml) (n=53) or standard treatment alone (n=52). Patients in the control group with progress on day 14 could receive CCP (crossover group;n=7) on days 15, 17 and 19. The primary outcome was a dichotomous composite outcome of survival and no longer fulfilling criteria of severe COVID-19 on day 21. For Cross over patients a propensity matching with patients of the plasma group was performed. Results: Neutralizing antibodies were present at baseline in 18.2% of CCP and 19.2% of control group patients. In the ITT analysis the primary outcome occurred in 43.4% of patients in the CCP and 32.7% in the control group (p=0.32). The CCP group showed a trend for shorter times to clinical improvement (40 days, p=0.27) and discharge from hospital (20 days, p=0.24). Among those in the CCP group who received a higher or lower cumulative amount of neutralizing antibodies the primary outcome occurred in 56.0% and 32.1% of patients The high titer group showed significantly shorter intervals to clinical improvement or hospital discharge and a better overall survival (p=0.02). None of the patients in the crossover group (CG) achieved clinical improvement and survived. Comparing the CG to 14 CCP patients matched by baseline characteristics resulted in worse OS in the CG group (p=0.02) while comparison with 6 day 14 matched patients showed equal OS. Interpretation: CCP added to standard treatment did not result in a significant difference in the primary and secondary outcomes. A pre-defined subgroup analysis showed a signal of benefit for CCP among those who received a larger amount of neutralizing antibodies. A progress on day 14 is an indicator for poor outcome in COVID-19. Late administration of CCP is not supported by our results.

Intensive care medicine: A multidisciplinary competence-based approach

During the Covid-19 pandemic general interest in intensive care medicine emerged as besides a majority of other diseases and conditions also patients with Covid-19 pneumonia were treated by intensivists. This acute demand was taken as the rationale by the European Society of Intensive Care Medicine (ESICM), which represents only a small portion of all intensivists throughout Europe, to launch an initiative to recognize Intensive Care Medicine in Europe as a medical specialty according to Annexe V of the European Directive on the recognition of professional qualifications. The discussion having intensive care medicine as a primary discipline is old and the disadvantages have been clearly stated long ago. Intensive care medicine according to the Multidisciplinary Joint Committee of Intensive Care Medicine (MJCICM) of the European Union of Medical Specialists (UEMS) should be multidisciplinary as this serves our patients best. During the pandemic, we learned that all specialties that cover Intensive Care Medicine in their training were able to treat affected patients and to provide intensivists to additionally built ICUs. Most of them were anaesthesiologists who were set free from the operating theatres because of the cancellation of many elective operations. However, other disciplines that provide high-level ICU care, such as internal medicine, surgery, neurosurgery and cardiac surgery were also recruited to face the pandemic. With a single, primary specialty, this would have not been possible on that scale. Certainly, for all highly trained specialists, free movement throughout Europe is an important goal. Therefore, training in Intensive Care Medicine throughout Europe should be according to a common competence-based curriculum and this training and examination on top of a mother discipline should be recognized as a ‘particular qualifications’ throughout Europe. From our point of view, regarding Intensive Care Medicine, this approach in combination with competence-based training and examination in tandem with a primary discipline allows free movement of our doctors and also serves our patients best, for the future and also for the current and future pandemics. © Anästh Intensivmed 2021;62:513–516 Aktiv Druck & Verlag GmbH.

Aerosol exposure during surgical tracheotomy with and without laminar air flow

Introduction In the context of the current SARS-CoV-2 pandemic, aerosol generating activities have moved into focus. In the field of ENT surgery, one such activity is tracheotomy. The aim of this study was to clarify the aerosol exposure during tracheotomy. Material and method To simulate the air flow during a tracheotomy an airway model filled with artificial fog was developed. With the help of a projector the dispersion of the fog was visualized and video documented for further evaluation. The evaluation was performed with and without a laminar airflow system. Results Without LAF the aerosol was only slowed down by gravity. Approximately 50% of the aerosol volume reached the face of the surgeon. With LAF the aerosol rose about 40 cm upwards for about 1.6 seconds. During this ascent was noticeably slowed down. Afterwards, the flow was reversed to a large extent and began sinking. Nevertheless, approx. 4.8 ± 3.4% of the aerosol volume reached the surgeon's face. Discussion Although the LAF systems mandatory in German operating theatres considerably reduce the amount of aerosol that reaches the surgeon's face, a relevant measurable proportion still was detected in front of the surgeon's face mask. Wherever possible the protective measures in the context of a surgical tracheotomy should include performing the tracheotomy under a laminar air flow.

Studies on COVID-19 lethality: Causes and dynamics at German University Hospitals

Background: In the initial phase of the COVID-19 pandemic, a lower incidence and death rate was observed in Germany compared to its neighbouring countries, but some studies showed comparatively high death rates in ventilated COVID-19 patients. Methods: In this retrospective analysis, hospital stays of COVID-19 patients at 14 German university hospitals were analysed. For this purpose, local data integration centres of the German Medical Informatics Initiative (MII) combined their data to present death rates in different subgroups depending on gender, age, length of stay in the intensive care unit, ventilation and in combination with different comorbidities. Results: The total lethality rate in 1,318 COVID-19 patients was 18.8 %. In ventilated cases, the lethality rate was 38.8%. Common comorbidities were renal insufficiency (35.2 %), aplastic and other anaemia (26.0 %) diabetes mellitus (21.1 %). The average length of stay was 18 days, or 28 days in case of ventilated patients. Lethality decreased from 20.7 % to 12.7 % over the observation period. Conclusion: The observed decline in lethality rates may be explained with the continuous optimisation of COVID-19 treatment, increasing experience and improved therapy recommendations. The progress made so far by the MII allows cross-consortium analyses to be carried out just in time to better address the challenges of the COVID-19 pandemic.

COVID-19: Intensive care patients – current pharmacological strategies

A causal pharmacotherapeutic approach for COVID-19 is still lacking. Numerous repurposing approaches have so far failed to provide satisfactory results in larger prospective randomized trials. At its core, symptom control is the only pharmacological option, in addition to numerous nonpharmacological interventions ranging from abdominal positioning to extracorporeal membrane oxygenation. The main pharmacological pillars here are anticoagulation and anti-(hyper)inflammatory therapy with dexamethasone. What becomes clear in this situation is how much clinical therapy benefits from current, qualitative scientific basis, but also how much scientific answers to open questions depend on the experience of clinicians. Many findings for treatment optimization will only be established over time. All the more impressive is the rapid progress in some areas, but also the need to regularly question treatment concepts and answer open questions through high-quality clinical studies. © 2021 Wissenschaftliche Verlagsgesellschaft mbH. All rights reserved.

A comprehensive presentation of SARS-CoV-2 infection - A systematic review and meta-analysis

Objective: In December 2019, the first case of pneumonia caused by SARSCoV-2 was reported in the Chinese province Wuhan, China. Due to a rapid spread of the infection, more than 17 million cases worldwide have been registered so far. Methods: A systematic literature survey was performed using PubMed, Google Scholar and Web of Science until 19 March 2020. Infections had to be confirmed by polymerase chain reaction. Eligible studies had to report data pertaining to comorbidities, clinical symptoms, laboratory alterations or treatment options. Studies with missing data, opinion articles and letters were excluded. For the meta-analysis, a binary random effect model was used to calculate prevalences and the 95% confidence intervals (95% CI). Results: In total, 958 articles were identified, 80 studies involving 5,053 patients were included. Cardiovascular (20.5%, 95% CI 16.5% to 24.5%) and endocrine diseases (9.6%, 95% CI 7.7% to 11.6%) were the most prevalent comorbidities. Patients presented with fever (77.0%, 95% CI 73.3% to 80.7%) and malaise (31.1%, 95% CI 25.0 to 37.3). Lymphocytes were decreased in 42.2% (95% CI 35.2% to 49.3%). Radiological lung changes were predominantly bilateral (74.0%, 95% CI 66.3% to 81.6%). Conclusions: This meta-analysis provides a comprehensive presentation of all aspects of infection. Early detection of symptoms and patients at risk is crucial for beneficial treatment. © Anästh Intensivmed 2020

Health and personal safety at work during the SARS-CoV-2 pandemic. A Germany-wide survey of the emergency medical and rescue services

Background: The SARS-CoV-2 pandemic has significantly changed the daily work of emergency medical services. Occupational health and safety concepts should take the individual risk profile of the employees into account. This is necessary to maintain the operational capability of the emergency medical services and ensure personal health protection. Objectives: How do emergency physicians and rescue personnel perceive their personal security during the SARSCoV-2 pandemic? How high is the percentage of rescue staff at particular risk for serious COVID-19 cases and what personal protection measures are being provided to the staff? Materials and methods: An online-based survey with 20 questions on demography, risk profile and occupational health and safety was sent to all medical directors of emergency medical services. In addition, the survey was shared via Facebook® and Twitter Inc. and included emergency medical keywords. Single and multiple-choice questions, evaluations using school grades from 1-6 (very good - unsatisfactory) and free text comments were used for the survey. Results: A total of 1055 employees from the rescue and emergency medical services participated in the survey (21.0% emergency medical personnel and 79.0% rescue service personnel). The personal perception of security was rated 1-2 in 60.3% of cases. There was no significant difference between the occupational groups (emergency doctors MRang=449.98;paramedics MRang=491.87), U=68125.0;Z=1.93;p=0.054;r=-0.06). Potential predisposing factors for a severe COVID-19 course were reported by 53.5% of the participants. Personal protective equipment was provided daily to most workers, but there was a lack of face shields (48.0%) and FFP3 masks (51.5%). Contact with SARS-CoV-2 was suspected to have occurred in 41.3% of respondents not guarded by adequate protective devices. Conclusion: In the context of the SARSCoV-2 pandemic, the quantity and quality of protective material available to emergency personnel is not always sufficient. Overall, the personnel feels well protected. Multiple unprotected contacts with COVID-19 patients underline the need for basic personal protection during every rescue service mission.

Patient blood management during the COVID-19 pandemic: a narrative review.

As COVID-19 disease escalates globally, optimising patient outcome during this catastrophic healthcare crisis is the number one priority. The principles of patient blood management are fundamental strategies to improve patient outcomes and should be given high priority in this crisis situation. The aim of this expert review is to provide clinicians and healthcare authorities with information regarding how to apply established principles of patient blood management during the COVID-19 pandemic. In particular, this review considers the impact of the COVID-19 pandemic on blood supply and specifies important aspects of donor management. We discuss how preventative and control measures implemented during the COVID-19 crisis could affect the prevalence of anaemia, and highlight issues regarding the diagnosis and treatment of anaemia in patients requiring elective or emergency surgery. In addition, we review aspects related to patient blood management of critically ill patients with known or suspected COVID-19, and discuss important alterations of the coagulation system in patients hospitalised due to COVID-19. Finally, we address special considerations pertaining to supply-demand and cost-benefit issues of patient blood management during the COVID-19 pandemic.