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2.
Anaesthesist ; 71(4): 281-290, 2022 Apr.
Article in German | MEDLINE | ID: covidwho-1777695

ABSTRACT

BACKGROUND: In the context of COVID-19, the German CEOsys project (COVID-19 Evidenz Ökosystem, www.covid-evidenz.de ) identifies, evaluates and summarizes the results of scientific studies to obtain evidence on this disease. The evidence syntheses are used to derive specific recommendations for clinical practice and to contribute to national guidelines. Besides the necessity of conducting good quality evidence syntheses during a pandemic, just as important is that the dissemination of evidence needs to be quick and efficient, especially in a health crisis. The CEOsys project has set itself this challenge. OBJECTIVE: Preparing the most suitable distribution of evidence syntheses as part of the CEOsys project tasks. METHODS: Intensive care unit (ICU) personnel in Germany were surveyed via categorical and free text questions. The survey focused on the following topics: evidence syntheses, channels and strategies of distribution, possibility of feedback, structure and barriers of dissemination and trustworthiness of various organizations. Profession, qualification, setting and size of the facility were recorded. Questionnaires were pretested throughout the queried professions (physician, nurse, others). The survey was anonymously carried out online through SosciSurvey® and an e­mail was sent directly to 940 addresses. The survey was launched on 3 December, a reminder was sent after 14 days and it ended on 31 December. The survey was also announced via e­mail through DIVI. RESULTS: Of 317 respondents 200 completed the questionnaire. All information was analyzed including the responses from incomplete questionnaires. The most stated barriers were lack of time and access. Especially residents and nurses without specialization in intensive care mentioned uncertainty or insufficient experience in dealing with evidence syntheses as a barrier. Active distribution of evidence syntheses was clearly preferred. More than half of the participants chose websites of public institutions, medical journals, professional societies and e­mail newsletters for drawing attention to new evidence syntheses. Short versions, algorithms and webinars were the most preferred strategies for dissemination. Trust in organizations supplying information on the COVID-19 pandemic was given to professional societies and the Robert Koch Institute (RKI) as the German governmental institute for infections and public health. The respondents' prioritized topics are long-term consequences of the disease, protection of medical personnel against infection and possibilities of ventilation treatment. CONCLUSION: Even though universally valid, evidence syntheses should be actively brought to the target audience, especially during a health crisis such as the COVID-19 pandemic with its exceptional challenges including lack of time and uncertainties in patient care. The contents should be clear, short (short versions, algorithms) and with free access. E­mail newsletters, websites or medical journals should continuously report on new evidence syntheses. Professional societies and the governmental institute for infections and public health should be involved in dissemination due to their obvious trustworthiness.


Subject(s)
COVID-19 , Pandemics , Critical Care , Germany/epidemiology , Humans , Pandemics/prevention & control , Surveys and Questionnaires
3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316350

ABSTRACT

Extracorporeal membrane oxygenation (ECMO) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic Coronavirus Disease 2019 (COVID-19) with ECMO have been restrained. In the meantime, ECMO has been shown to produce similar outcomes in patients with severe COVID-19 compared to existing data on ARDS mortality.Objective: We performed an international email survey to assess how ECMO providers worldwide have previously used ECMO during the treatment of critically ill patients with COVID-19.MethodsA questionnaire with 45 questions (covering e.g. indication, technical aspects, benefit and reasons for treatment discontinuation), mostly multiple-choice, was distributed by email to ECMO centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO).Results: 276 centers worldwide responded that they employed ECMO for very severe COVID-19 cases, mostly in veno-venous configuration (87%). The most common reason to establish ECMO was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno-arterial cannulation due to heart failure (3%). Time on ECMO varied between less than two and more than four weeks. The main reason to discontinue ECMO treatment prior to patient’s recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators were responsible for discontinuation of ECMO support. Most ECMO physicians (66% ± 26%) agreed that patients with COVID-19 induced ARDS (CARDS) benefitted from ECMO. Overall mortality of COVID-19 patients on ECMO was estimated to be about 55%, scoring higher than what has previously been reported for Influenza patients on ECMO (29 – 36%).Conclusion: ECMO has been utilized successfully during the COVID-19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECMO. Triage situations were rarely a concern. ECMO providers stated that patients with severe COVID-19 benefitted from ECMO. An increasing use in patients with respiratory failure in a future stage of the pandemic may be expected.Funding Statement: COVID-19 research was funded by the Federal state of Saarland, Saarland University and Dr. Rolf M. Schwiete Foundation.Declaration of Interests: Robert Bals declares funding from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis, CLS Behring, the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), Sander-Stiftung, Schwiete-Stiftung, Krebshilfe and Mukoviszidose eV. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. All other authors: No potential conflicts of interest.Ethics Approval Statement: The ethical committee (Ärztekammer des Saarlandes) waived the need for a formal approval since the questionnaire did not retrieve actual patient data.

4.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316141

ABSTRACT

Background: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods: . A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results: . 1,039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions: . Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration. “ClinicalTrials” (clinicaltrials.gov) under NCT04455451

5.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311563

ABSTRACT

Background: Identifying preventive strategies in Covid-19 patients will help to improve resource-allocation and reduce mortality. In this Journal, we recently demonstrated in a post-mortem cohort that SARS-CoV-2 renal tropism was associated with kidney injury, disease severity and mortality. We also proposed an algorithm to predict the risk of adverse outcomes in Covid-19 patients harnessing urinalysis and protein/coagulation parameters on admission for signs of kidney injury. Here, we aimed to validate this hypothesis in a multicenter cohort.Methods: Patients hospitalized for Covid-19 at four tertiary centers were screened for an available urinalysis, serum albumin (SA) and antithrombin-III activity (AT-III) obtained prospectively within 48h upon admission. The respective presumed risk for an unfavorable course was categorized as “low”, “intermediate” or “high”, depending on a normal urinalysis, an abnormal urinalysis with SA ≥2 g/dl and AT-III ≥70%, or an abnormal urinalysis with at least one SA or AT-III abnormality. Time to ICU or death within ten days served as primary, in-hospital mortality and required organ support served as secondary endpoints.Findings: Among a total of N=223 screened patients, N=145 were eligible for enrollment, falling into the low (N=43), intermediate (N=84), and high risk (N=18) categories. The risk for ICU transfer or death was 100% in the high risk group and significantly elevated in the composite of high and intermediate risk as compared to the low risk group (63·7% vs. 27·9%;HR 2·6;95%-CI 1·4 to 4·9;P=0·0020). Having an abnormal urinalysis was associated with mortality, need for mechanical ventilation, extra-corporeal membrane oxygenation (ECMO) or renal replacement therapy (RRT).Interpretation: Our data confirm that Covid-19-associated urine abnormalities on admission predict disease aggravation. This supports the conceptual relevance of Covid-19-associated kidney injury. By engaging a simple urine dipstick our algorithm allows for early preventive measures and appropriate patient stratification. Trial Registration: (ClinicalTrials.gov number NCT04347824)Funding Statement: This work was supported by the DFG (GR 1852/6-1 to OG;CRC1192 to JET, EH and TBH), (HU 1016/8-2, HU 1016/11-1, HU 1016/ 12-1 to TBH) and (GR 1852/6-1 to OG);by the BMBF (STOP-FSGS-01GM1518C and NephrESA-031L0191E to TBH), by the Else-Kröner Fresenius Foundation (Else Kröner-Promotionskolleg –iPRIME to TBH), and by the H2020-IMI2 consortium BEAt-DKD (115974 to TBH). In addition, the UMG Göttingen applied for Government funding (Covid-19 program) by The German Federal Ministry of Education and Research and the application currently is under consideration.Declaration of Interests: All authors report no conflict of interest in relation to this observational cohort-study. Ethics Approval Statement: According to the German Medicines Act, the study was approved by the leading institutional review board (IRB) of the UMG Göttingen (41/4/20), and all others.

6.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-311562

ABSTRACT

Purpose: Identifying preventive strategies in Covid-19 patients helps to improve ICU-resource-allocation and reduce mortality. We recently demonstrated in a post-mortem cohort that SARS-CoV-2 renal tropism was associated with kidney injury, disease severity and mortality. We also proposed an algorithm to predict the need for ICU-resources and the risk of adverse outcomes in Covid-19 patients harnessing urinalysis and protein/coagulation parameters on admission for signs of kidney injury. Here, we aimed to validate this hypothesis in a multicenter cohort. Methods: : Patients hospitalized for Covid-19 at four tertiary centers were screened for an available urinalysis, serum albumin (SA) and antithrombin-III activity (AT-III) obtained prospectively within 48h upon admission. The respective presumed risk for an unfavorable course was categorized as “low”, “intermediate” or “high”, depending on a normal urinalysis, an abnormal urinalysis with SA ≥2 g/dl and AT-III ≥70%, or an abnormal urinalysis with at least one SA or AT-III abnormality. Time to ICU or death within ten days served as primary, in-hospital mortality and required organ support served as secondary endpoints. Results: : Among a total of N=223 screened patients, N=145 were eligible for enrollment, falling into the low (N=43), intermediate (N=84), and high risk (N=18) categories. The risk for ICU transfer or death was 100% in the high risk group and significantly elevated in the composite of high and intermediate risk as compared to the low risk group (63.7% vs. 27.9%;HR 2.6;95%-CI 1.4 to 4.9;P=0.0020). Having an abnormal urinalysis was associated with mortality, need for mechanical ventilation, extra-corporeal membrane oxygenation (ECMO) or renal replacement therapy (RRT). Conclusion: Our data confirm that Covid-19-associated urine abnormalities on admission predict disease aggravation and need for ICU. By engaging a simple urine dipstick on hospital admission our algorithm allows for early preventive measures and appropriate patient stratification. (ClinicalTrials.gov number NCT04347824)

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311539

ABSTRACT

Background: The surge in patients during the COVID-19 pandemic has exacerbated the looming problem of staff shortage in German ICUs possibly leading to worse outcomes for patients. Methods: Within the German Evidence Ecosystem CEOsys network, we conducted an online national mixed-methods survey assessing the standard of care in German ICUs treating patients with COVID-19. Results: A total of 171 German ICUs reported a median ideal number of patients per intensivist of 8 (interquartile range, IQR = 3rd quartile - 1st quartile = 4.0) and per nurse of 2.0 (IQR = 1.0). For COVID-19 patients, the median target was a maximum of 6.0 (IQR = 2.0) patients per intensivist or 2.0 (IQR = 0.0) patients per nurse. Targets for intensivists were rarely met by 15.2% and never met by 3.5% of responding institutions. Targets for nursing staffing could rarely be met in 32.2% and never in 5.3% of responding institutions. Conclusions: Shortages of staffing in the critical care setting are eminent during the COVID-19 pandemic and might not only negatively affect patient outcomes, but also staff wellbeing and healthcare costs. A joint effort that scrutinizes the demands and structures of our health care system seems fundamental to be prepared for the future.

8.
Front Immunol ; 12: 784989, 2021.
Article in English | MEDLINE | ID: covidwho-1603282

ABSTRACT

Effective treatment strategies for severe coronavirus disease (COVID-19) remain scarce. Hydrolysis of membrane-embedded, inert sphingomyelin by stress responsive sphingomyelinases is a hallmark of adaptive responses and cellular repair. As demonstrated in experimental and observational clinical studies, the transient and stress-triggered release of a sphingomyelinase, SMPD1, into circulation and subsequent ceramide generation provides a promising target for FDA-approved drugs. Here, we report the activation of sphingomyelinase-ceramide pathway in 23 intensive care patients with severe COVID-19. We observed an increase of circulating activity of sphingomyelinase with subsequent derangement of sphingolipids in serum lipoproteins and from red blood cells (RBC). Consistent with increased ceramide levels derived from the inert membrane constituent sphingomyelin, increased activity of acid sphingomyelinase (ASM) accurately distinguished the patient cohort undergoing intensive care from healthy controls. Positive correlational analyses with biomarkers of severe clinical phenotype support the concept of an essential pathophysiological role of ASM in the course of SARS-CoV-2 infection as well as of a promising role for functional inhibition with anti-inflammatory agents in SARS-CoV-2 infection as also proposed in independent observational studies. We conclude that large-sized multicenter, interventional trials are now needed to evaluate the potential benefit of functional inhibition of this sphingomyelinase in critically ill patients with COVID-19.


Subject(s)
COVID-19/metabolism , Ceramides/metabolism , Signal Transduction , Sphingomyelin Phosphodiesterase/metabolism , Anti-Inflammatory Agents/therapeutic use , COVID-19/drug therapy , COVID-19/virology , Ceramides/blood , Enzyme Activation , Erythrocyte Membrane/metabolism , Erythrocytes/metabolism , Fatty Acids/metabolism , Humans , Intensive Care Units , Patient Acuity , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Sphingomyelin Phosphodiesterase/blood , Sphingomyelins/metabolism
9.
Clin Sci (Lond) ; 135(24): 2781-2791, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1599254

ABSTRACT

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Erythrocytes/metabolism , Lysophospholipids/blood , Sphingosine/analogs & derivatives , Aged , Cells, Cultured , Humans , Lipoproteins, HDL/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , SARS-CoV-2 , Serum Albumin/metabolism , Sphingosine/blood
10.
Dtsch Arztebl Int ; (Forthcoming)2022 01 21.
Article in English | MEDLINE | ID: covidwho-1598405

ABSTRACT

BACKGROUND: When the SARS-CoV-2 pandemic began, no uniform treatment and care strategies for critically ill COVID-19 patients were yet available. National and international treatment recommendations were formulated under time pressure, initially on the basis of indirect evidence from the treatment of similar diseases. In this article, we give an overview of the content, currency, and methodological quality of the existing national and international guidelines, with special attention to the care of critically ill patients. METHODS: Guidelines were identified by a comprehensive search, the included guidelines were assessed in standardized fashion with the AGREE II guideline assessment instrument and according to the AMWF rulebook criteria, and the core recommendations of the included and methodologically high-quality guidelines were compared. RESULTS: Nine of the 97 guidelines that were identified fulfilled the content criteria for inclusion, and 6 of these fulfilled the qualitative criteria; these 6 guidelines still differed, however, in the topics to which they devoted the most attention, as well as in their methodological quality and currency. The treatment strategies for patients with severe respiratory failure (lung-protective ventilation strategies and rescue measures) deviated little from established standards. Uniform recommendations were made, among other things, for the administration of dexamethasone, which was recommended in all of the guidelines for patients requiring oxygen treatment, as well as for antithrombotic drug prophylaxis and for the prone positioning of ventilated patients. Many recommendations were based on insufficient evidence, and some were contradictory, e.g., those regarding antibiotic treatment or the choice between high-flow oxygen administration via nasal canula (HFNC) and noninvasive ventilation (NIV). CONCLUSION: The consultation of multiple high-quality international guidelines and guideline recommendations shared in online portals such as MagicApp are helpful sources of information for clinicians. In view of the continuing lack of strong evidence, further research on intensive care treatments is needed (aspects of ventilation, positioning therapy, and the role of extracorporeal membrane oxygenation [ECMO]).

11.
Clin Sci (Lond) ; 135(24): 2781-2791, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1559238

ABSTRACT

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.


Subject(s)
COVID-19/blood , COVID-19/physiopathology , Erythrocytes/metabolism , Lysophospholipids/blood , Sphingosine/analogs & derivatives , Aged , Cells, Cultured , Humans , Lipoproteins, HDL/metabolism , Phosphotransferases (Alcohol Group Acceptor)/metabolism , SARS-CoV-2 , Serum Albumin/metabolism , Sphingosine/blood
12.
Front Immunol ; 12: 753849, 2021.
Article in English | MEDLINE | ID: covidwho-1523705

ABSTRACT

Background: CD14+ monocytes present antigens to adaptive immune cells via monocytic human leukocyte antigen receptor (mHLA-DR), which is described as an immunological synapse. Reduced levels of mHLA-DR can display an acquired immune defect, which is often found in sepsis and predisposes for secondary infections and fatal outcomes. Monocytic HLA-DR expression is reliably induced by interferon- γ (IFNγ) therapy. Case Report: We report a case of multidrug-resistant superinfected COVID-19 acute respiratory distress syndrome (ARDS) on extracorporeal membrane oxygenation (ECMO) support. The resistance profiles of the detected Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Citrobacter freundii isolates were equipped with resistance to all four antibiotic classes including carbapenems (4MRGN) and Cefiderocol in the case of K. pneumoniae. A causal therapeutic antibiotic strategy was not available. Therefore, we measured the immune status of the patient aiming to identify a potential acquired immune deficiency. Monocyte HLA-DR expression identified by FACS analysis revealed an expression level of 34% positive monocytes and suggested severe immunosuppression. We indicated IFNγ therapy, which resulted in a rapid increase in mHLA-DR expression (96%), rapid resolution of invasive bloodstream infection, and discharge from the hospital on day 70. Discussion: Superinfection is a dangerous complication of COVID-19 pneumonia, and sepsis-induced immunosuppression is a risk factor for it. Immunosuppression is expressed by a disturbed antigen presentation of monocytes to cells of the adaptive immune system. The case presented here is remarkable as no validated antibiotic regimen existed against the detected bacterial pathogens causing bloodstream infection and severe pneumonia in a patient suffering from COVID-19 ARDS. Possible restoration of the patient's own immunity by IFNγ was a plausible option to boost the patient's immune system, eliminate the identified 4MRGNs, and allow for lung recovery. This led to the conclusion that immune status monitoring is useful in complicated COVID-19-ARDS and that concomitant IFNγ therapy may support antibiotic strategies. Conclusion: After a compromised immune system has been detected by suppressed mHLA-DR levels, the immune system can be safely reactivated by IFNγ.


Subject(s)
Bacteria/immunology , COVID-19/immunology , Drug Resistance, Multiple/immunology , HLA Antigens/immunology , Interferon-gamma/immunology , Monocytes/immunology , Respiratory Distress Syndrome/immunology , Adult , Humans , Receptors, Interferon/immunology
13.
Scand J Trauma Resusc Emerg Med ; 29(1): 155, 2021 Oct 30.
Article in English | MEDLINE | ID: covidwho-1486111

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious airborne virus inducing pandemic coronavirus disease 2019 (COVID-19). This is most relevant for medical staff working under harmful conditions in emergencies often dealing with patients and an undefined SARS-CoV-2 status. We aimed to measure the effect of high-class filtering facepieces (FFP) in emergency medical service (EMS) staff by analyzing seroprevalence and history of positive polymerase chain reaction (PCR) for SARS-CoV-2. METHOD: This observational cohort study included workers in EMS, who were compared with hospital staff (HS) and staff, which was not directly involved in patient care (NPC). All direct patient contacts of EMS workers were protected by FFP2/N95 (filtering face piece protection class 2/non-oil-based particulates filter efficiency 95%) masks, whereas HS was protected by FFP2/N95 exclusively when a patient had a proven or suspected SARS-CoV-2 infection. NPC was not protected by higher FFP. The seroprevalence of SARS-CoV-2 antibodies was analyzed by immunoassay by end of 12/2020 together with the history of a positive PCR. In addition, a self-assessment was performed regarding the quantity of SARS-CoV-2 positive contacts, about flu symptoms and personal belief of previous COVID-19 infections. RESULTS: The period in which contact to SARS-CoV-2 positive patients has been possible was 10 months (March to December 2020)-with 54,681 patient contacts documented for EMS-either emergencies (n = 33,241) or transportation services (n = 21,440). Seven hundred-thirty (n = 730) participants were included into the study (n = EMS: 325, HS: 322 and NPC: 83). The analysis of the survey showed that the exposure to patients with an unknown and consecutive positive SARS-CoV-2 result was significantly higher for EMS when compared to HS (EMS 55% vs. HS 30%, p = 0.01). The incidence of a SARS-CoV-2 infection in our cohort was 1.2% (EMS), 2.2% (HS) and 2.4% (NPC) within the three groups (ns) and lowest in EMS. Furthermore, the belief of previous COVID-19 was significant higher in EMS (19% vs. 10%), CONCLUSION: The consistent use of FFP2/N95 in EMS is able to prevent work-related SARS-CoV-2 infections in emergency situations. The significance of physical airway protection in exposed medical staff is still relevant especially under the aspect of new viral variants and unclear effectiveness of new vaccines.


Subject(s)
COVID-19 , Emergencies , Cohort Studies , Health Personnel , Humans , SARS-CoV-2 , Seroepidemiologic Studies
14.
Front Physiol ; 12: 676118, 2021.
Article in English | MEDLINE | ID: covidwho-1448801

ABSTRACT

Knowledge of gas volume, tissue mass and recruitability measured by the quantitative CT scan analysis (CT-qa) is important when setting the mechanical ventilation in acute respiratory distress syndrome (ARDS). Yet, the manual segmentation of the lung requires a considerable workload. Our goal was to provide an automatic, clinically applicable and reliable lung segmentation procedure. Therefore, a convolutional neural network (CNN) was used to train an artificial intelligence (AI) algorithm on 15 healthy subjects (1,302 slices), 100 ARDS patients (12,279 slices), and 20 COVID-19 (1,817 slices). Eighty percent of this populations was used for training, 20% for testing. The AI and manual segmentation at slice level were compared by intersection over union (IoU). The CT-qa variables were compared by regression and Bland Altman analysis. The AI-segmentation of a single patient required 5-10 s vs. 1-2 h of the manual. At slice level, the algorithm showed on the test set an IOU across all CT slices of 91.3 ± 10.0, 85.2 ± 13.9, and 84.7 ± 14.0%, and across all lung volumes of 96.3 ± 0.6, 88.9 ± 3.1, and 86.3 ± 6.5% for normal lungs, ARDS and COVID-19, respectively, with a U-shape in the performance: better in the lung middle region, worse at the apex and base. At patient level, on the test set, the total lung volume measured by AI and manual segmentation had a R 2 of 0.99 and a bias -9.8 ml [CI: +56.0/-75.7 ml]. The recruitability measured with manual and AI-segmentation, as change in non-aerated tissue fraction had a bias of +0.3% [CI: +6.2/-5.5%] and -0.5% [CI: +2.3/-3.3%] expressed as change in well-aerated tissue fraction. The AI-powered lung segmentation provided fast and clinically reliable results. It is able to segment the lungs of seriously ill ARDS patients fully automatically.

15.
Mol Med ; 27(1): 120, 2021 09 26.
Article in English | MEDLINE | ID: covidwho-1440900

ABSTRACT

BACKGROUND: Since fall 2019, SARS-CoV-2 spread world-wide, causing a major pandemic with estimated ~ 220 million subjects affected as of September 2021. Severe COVID-19 is associated with multiple organ failure, particularly of lung and kidney, but also grave neuropsychiatric manifestations. Overall mortality reaches > 2%. Vaccine development has thrived in thus far unreached dimensions and will be one prerequisite to terminate the pandemic. Despite intensive research, however, few treatment options for modifying COVID-19 course/outcome have emerged since the pandemic outbreak. Additionally, the substantial threat of serious downstream sequelae, called 'long COVID' and 'neuroCOVID', becomes increasingly evident. Among candidates that were suggested but did not yet receive appropriate funding for clinical trials is recombinant human erythropoietin. Based on accumulating experimental and clinical evidence, erythropoietin is expected to (1) improve respiration/organ function, (2) counteract overshooting inflammation, (3) act sustainably neuroprotective/neuroregenerative. Recent counterintuitive findings of decreased serum erythropoietin levels in severe COVID-19 not only support a relative deficiency of erythropoietin in this condition, which can be therapeutically addressed, but also made us coin the term 'hypoxia paradox'. As we review here, this paradox is likely due to uncoupling of physiological hypoxia signaling circuits, mediated by detrimental gene products of SARS-CoV-2 or unfavorable host responses, including microRNAs or dysfunctional mitochondria. Substitution of erythropoietin might overcome this 'hypoxia paradox' caused by deranged signaling and improve survival/functional status of COVID-19 patients and their long-term outcome. As supporting hints, embedded in this review, we present 4 male patients with severe COVID-19 and unfavorable prognosis, including predicted high lethality, who all profoundly improved upon treatment which included erythropoietin analogues. SHORT CONCLUSION: Substitution of EPO may-among other beneficial EPO effects in severe COVID-19-circumvent downstream consequences of the 'hypoxia paradox'. A double-blind, placebo-controlled, randomized clinical trial for proof-of-concept is warranted.


Subject(s)
COVID-19/complications , COVID-19/drug therapy , Erythropoietin/genetics , Hypoxia/drug therapy , Lung/drug effects , COVID-19/genetics , COVID-19/pathology , COVID-19/virology , Erythropoietin/analogs & derivatives , Erythropoietin/therapeutic use , Humans , Hypoxia/genetics , Hypoxia/pathology , Hypoxia/virology , Lung/pathology , Lung/virology , Pandemics , Recombinant Proteins/genetics , Recombinant Proteins/therapeutic use , SARS-CoV-2/drug effects
16.
BMC Infect Dis ; 21(1): 736, 2021 Aug 03.
Article in English | MEDLINE | ID: covidwho-1435224

ABSTRACT

BACKGROUND: Capnocytophaga canimorsus (C. canimorsus) infections are rare and usually present with unspecific symptoms, which can eventually end in fatal septic shock and multiorgan failure. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) related coronavirus disease 2019 (COVID-19), on the other hand, is predominantly characterized by acute respiratory failure, although other organ complications can occur. Both infectious diseases have in common that hyperinflammation with a cytokine storm can occur. While microbial detection of C. canimorsus in blood cultures can take over 48 h, diagnosis of SARS-CoV-2 is facilitated by a widely available rapid antigen diagnostic test (Ag-RDT) the results of which are available within half an hour. These Ag-RDT results are commonly verified by a nucleic acid amplification test (NAAT), whose results are only available after a further 24 h. CASE PRESENTATION: A 68-year-old male patient with the diagnosis of COVID-19 pneumonia was referred to our Intensive Care Unit (ICU) from another hospital after testing positive on an Ag-RDT. While the initial therapy was focused on COVID-19, the patient developed a fulminant septic shock within a few hours after admission to the ICU, unresponsive to maximum treatment. SARS-CoV-2 NAATs were negative, but bacteremia of C. canimorsus was diagnosed post-mortem. Further anamnestic information suggest that a small skin injury caused by a dog leash or the subsequent contact of this injury with the patient's dog could be the possible point of entry for these bacteria. CONCLUSION: During the acute phase of hyperinflammation and cytokine storm, laboratory results can resemble both, sepsis of bacterial origin or SARS-CoV-2. This means that even in the light of a global SARS-CoV-2 pandemic, where this diagnosis provides the most salient train of thoughts, differential diagnoses must be considered. Ag-RDT can contribute to early detection of a SARS-CoV-2 infection, but false-positive results may cause fixation errors with severe consequences for patient outcome.


Subject(s)
Bacteremia , COVID-19 , Shock, Septic , Capnocytophaga , Fatal Outcome , Humans , Male , SARS-CoV-2 , Shock, Septic/diagnosis
17.
Anaesthesist ; 71(4): 281-290, 2022 Apr.
Article in German | MEDLINE | ID: covidwho-1427225

ABSTRACT

BACKGROUND: In the context of COVID-19, the German CEOsys project (COVID-19 Evidenz Ökosystem, www.covid-evidenz.de ) identifies, evaluates and summarizes the results of scientific studies to obtain evidence on this disease. The evidence syntheses are used to derive specific recommendations for clinical practice and to contribute to national guidelines. Besides the necessity of conducting good quality evidence syntheses during a pandemic, just as important is that the dissemination of evidence needs to be quick and efficient, especially in a health crisis. The CEOsys project has set itself this challenge. OBJECTIVE: Preparing the most suitable distribution of evidence syntheses as part of the CEOsys project tasks. METHODS: Intensive care unit (ICU) personnel in Germany were surveyed via categorical and free text questions. The survey focused on the following topics: evidence syntheses, channels and strategies of distribution, possibility of feedback, structure and barriers of dissemination and trustworthiness of various organizations. Profession, qualification, setting and size of the facility were recorded. Questionnaires were pretested throughout the queried professions (physician, nurse, others). The survey was anonymously carried out online through SosciSurvey® and an e­mail was sent directly to 940 addresses. The survey was launched on 3 December, a reminder was sent after 14 days and it ended on 31 December. The survey was also announced via e­mail through DIVI. RESULTS: Of 317 respondents 200 completed the questionnaire. All information was analyzed including the responses from incomplete questionnaires. The most stated barriers were lack of time and access. Especially residents and nurses without specialization in intensive care mentioned uncertainty or insufficient experience in dealing with evidence syntheses as a barrier. Active distribution of evidence syntheses was clearly preferred. More than half of the participants chose websites of public institutions, medical journals, professional societies and e­mail newsletters for drawing attention to new evidence syntheses. Short versions, algorithms and webinars were the most preferred strategies for dissemination. Trust in organizations supplying information on the COVID-19 pandemic was given to professional societies and the Robert Koch Institute (RKI) as the German governmental institute for infections and public health. The respondents' prioritized topics are long-term consequences of the disease, protection of medical personnel against infection and possibilities of ventilation treatment. CONCLUSION: Even though universally valid, evidence syntheses should be actively brought to the target audience, especially during a health crisis such as the COVID-19 pandemic with its exceptional challenges including lack of time and uncertainties in patient care. The contents should be clear, short (short versions, algorithms) and with free access. E­mail newsletters, websites or medical journals should continuously report on new evidence syntheses. Professional societies and the governmental institute for infections and public health should be involved in dissemination due to their obvious trustworthiness.


Subject(s)
COVID-19 , Pandemics , Critical Care , Germany/epidemiology , Humans , Pandemics/prevention & control , Surveys and Questionnaires
18.
Crit Care ; 25(1): 295, 2021 Aug 17.
Article in English | MEDLINE | ID: covidwho-1362062

ABSTRACT

BACKGROUND: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. METHODS: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. RESULTS: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. CONCLUSIONS: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.


Subject(s)
COVID-19/epidemiology , Critical Illness/epidemiology , Electronic Health Records/statistics & numerical data , Intensive Care Units , Machine Learning , Adult , Aged , COVID-19/therapy , Cohort Studies , Critical Illness/therapy , Emergency Service, Hospital , Female , Germany , Humans , Male , Middle Aged , Outcome Assessment, Health Care
19.
J Clin Med ; 10(15)2021 Jul 29.
Article in English | MEDLINE | ID: covidwho-1335124

ABSTRACT

INTRODUCTION: Coronavirus disease (COVID-19) has recently dominated scientific literature. Incomplete understanding and a lack of data concerning the pathophysiology, epidemiology, and optimal treatment of the disease has resulted in conflicting recommendations. Adherence to existing guidelines and actual treatment strategies have thus far not been studied systematically. We hypothesized that capturing the variance in care would lead to the discovery of aspects that need further research and-in case of proven benefits of interventions not being performed-better communication to care providers. METHODS: This article is based on a quantitative and qualitative cross-sectional mixed-methods online survey among intensive-care physicians in Germany during the COVID-19 pandemic by the CEOsys (COVID-19 Evidence Ecosystem) network, endorsed by the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) conducted from December 3 to 31 December 2020. RESULTS: We identified several areas of care with an especially high variance in treatment among hospitals in Germany. Crucially, 51.5% of the participating ICUs (n = 205) reported using intubation as a last resort for respiratory failure in COVID-19 patients, while 21.8% used intubation early after admission. Furthermore, 11.5% considered extracorporeal membrane oxygenation (ECMO) in awake patients. Finally, 72.3% of respondents used the ARDS-network-table to titrate positive end-expiratory-pressure (PEEP) levels, with 36.9% choosing the low-PEEP table and 41.8% the high-PEEP table. CONCLUSIONS: We found that significant differences exist between reported treatment strategies and that adherence to published guidelines is variable. We describe necessary steps for future research based on our results highlighting significant clinical variability in care.

20.
J Clin Med ; 10(14)2021 Jul 09.
Article in English | MEDLINE | ID: covidwho-1308366

ABSTRACT

In COVID-19, guidelines recommend a urinalysis on hospital admission as SARS-CoV-2 renal tropism, post-mortem, was associated with disease severity and mortality. Following the hypothesis from our pilot study, we now validate an algorithm harnessing urinalysis to predict the outcome and the need for ICU resources on admission to hospital. Patients were screened for urinalysis, serum albumin (SA) and antithrombin III activity (AT-III) obtained prospectively on admission. The risk for an unfavorable course was categorized as (1) "low", (2) "intermediate" or (3) "high", depending on (1) normal urinalysis, (2) abnormal urinalysis with SA ≥ 2 g/dL and AT-III ≥ 70%, or (3) abnormal urinalysis with SA or AT-III abnormality. Time to ICU admission or death served as the primary endpoint. Among 223 screened patients, 145 were eligible for enrollment, 43 falling into the low, 84 intermediate, and 18 into high-risk categories. An abnormal urinalysis significantly elevated the risk for ICU admission or death (63.7% vs. 27.9%; HR 2.6; 95%-CI 1.4 to 4.9; p = 0.0020) and was 100% in the high-risk group. Having an abnormal urinalysis was associated with mortality, a need for mechanical ventilation, extra-corporeal membrane oxygenation or renal replacement therapy. In conclusion, our data confirm that COVID-19-associated urine abnormalities on admission predict disease aggravation and the need for ICU (ClinicalTrials.gov number NCT04347824).

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