Interleukin-6 drives endothelial glycocalyx damage in COVID-19 and bacterial sepsis.

Damage of the endothelial glycocalyx (eGC) plays a central role in the development of vascular hyperpermeability and organ damage during systemic inflammation. However, the specific signalling pathways for eGC damage remain poorly defined. Aim of this study was to combine sublingual video-microscopy, plasma proteomics and live cell imaging to uncover further pathways of eGC damage in patients with coronavirus disease 2019 (COVID-19) or bacterial sepsis. This secondary analysis of the prospective multicenter MICROCODE study included 22 patients with COVID-19 and 43 patients with bacterial sepsis admitted to intermediate or intensive care units and 10 healthy controls. Interleukin-6 (IL-6) was strongly associated with damaged eGC and correlated both with eGC dimensions (rs=0.36, p = 0.0015) and circulating eGC biomarkers. In vitro, IL-6 reduced eGC height and coverage, which was inhibited by blocking IL-6 signalling with the anti-IL-6 receptor antibody tocilizumab or the Janus kinase inhibitor tofacitinib. Exposure of endothelial cells to 5% serum from COVID-19 or sepsis patients resulted in a significant decrease in eGC height, which was attenuated by co-incubation with tocilizumab. In an external COVID-19 cohort of 219 patients from Massachusetts General Hospital, a previously identified proteomic eGC signature correlated with IL-6 (rs=-0.58, p < 0.0001) and predicted the combined endpoint of 28-day mortality and/or intubation (ROC-AUC: 0.86 [95% CI: 0.81-0.91], p < 0.001). The data suggest that IL-6 may significantly drive eGC damage in COVID-19 and bacterial sepsis. Our findings provide valuable insights into pathomechanisms of vascular dysfunction during systemic inflammation and highlight the need for further in vivo studies.

Analysis of Urinary Glycosaminoglycans to Predict Outcome in COVID-19 and Community-Acquired Pneumonia-A Proof-of-Concept Study.

Although coronavirus disease 2019 (COVID-19) is considered a systemic disease associated with vascular inflammation and eventual destruction of the protective endothelial glycocalyx (eGC), biomarkers of eGC damage are not yet available in the clinic. The most prominent components of eGC are sulphated glycosaminoglycans (sGAGs) attached to core proteoglycans. We hypothesised that the amount of sGAG fragments shed in urine (as a surrogate for systemic eGC damage) would correlate with disease severity and outcome. Total urinary sGAG concentration was measured using an in-house optimised 1,9-dimethylmethylene blue (DMMB) assay, which is highly accurate and insensitive to interferences. The median urinary sGAG concentration was significantly higher in 67 hospitalised patients with COVID-19 compared to 72 hospitalised patients with community-acquired pneumonia (CAP). In both groups, urinary sGAG concentrations predicted a combined endpoint (including intubation and death) with an area under the receiver operator characteristic curve of 0.72 (95% CI 0.55-0.88, p = 0.01) and 0.70 (95% CI 0.57-0.83, p = 0.007), respectively. In conclusion, the inexpensive and easy-to-perform DMMB assay provides a surrogate parameter for eGC damage that may be useful for risk stratification of patients with COVID-19 and CAP.

Impaired humoral immunity to BQ.1.1 in convalescent and vaccinated patients.

Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in a convenience sample of 1,411 patients receiving medical treatment in the emergency departments of five university hospitals in North Rhine-Westphalia, Germany, in August/September 2022. 62% reported underlying medical conditions and 67.7% were vaccinated according to German COVID-19 vaccination recommendations (13.9% fully vaccinated, 54.3% one booster, 23.4% two boosters). We detected Spike-IgG in 95.6%, Nucleocapsid-IgG in 24.0%, and neutralization against Wu01, BA.4/5 and BQ.1.1 in 94.4%, 85.0%, and 73.8% of participants, respectively. Neutralization against BA.4/5 and BQ.1.1 was 5.6- and 23.4-fold lower compared to Wu01. Accuracy of S-IgG detection for determination of neutralizing activity against BQ.1.1 was reduced substantially. We explored previous vaccinations and infections as correlates of BQ.1.1 neutralization using multivariable and Bayesian network analyses. Given a rather moderate adherence to COVID-19 vaccination recommendations, this analysis highlights the need to improve vaccine-uptake to reduce the COVID-19 risk of immune evasive variants. The study was registered as clinical trial (DRKS00029414).

Resuscitation room management of patients with non-traumatic critical illness in the emergency department (OBSERvE-DUS-study).

BACKGROUND: Few studies address the care of critically ill non-traumatic patients in the emergency department (ED). The aim of this study was to assess the epidemiology, management, and outcome of these patients. METHODS: In this retrospective study, we identified and analyzed data from all consecutive adult critically ill non-traumatic ED patients treated from March 2018 to February 2019. Patient characteristics, major complaint leading to admission, out-of-hospital, and in-hospital interventions and 30-day mortality were extracted from medical records of the electronic patient data management system. RESULTS: During the study period, we analyzed 40,764 patients admitted to the ED. Of these, 621 (1.5%) critically ill non-traumatic patients were admitted for life-threatening emergencies to the resuscitation room (age: 70 ± 16 years, 52% male). Leading problem on admission was disability/unconsciousness (D), shock (C), respiratory failure (B), airway obstruction (A), and environment problems (E) in 41%, 31%, 25%, 2%, and 1%, respectively. Out-of-hospital and in-hospital measures included: intravenous access (61% vs. 99%), 12-lead ECG (55% vs. 87%), invasive airway management (21% vs. 34%) invasive ventilation (21% vs. 34%), catecholamines (9% vs. 30%), arterial access (0% vs. 52%), and cardiopulmonary resuscitation (11% vs. 6%). The underlying diagnoses were mainly neurological (29%), followed by cardiological (28%), and pulmonological (20%) emergencies. The mean length of stay (LOS) in the resuscitation room and ED was 123 ± 122 and 415 ± 479 min, respectively. The 30-day mortality was 18.5%. CONCLUSION: The data describe the care of critically ill non-traumatic patients in the resuscitation room. Based on these data, algorithms for the structured care of critically ill non-traumatic patients need to be developed.

["B problems" in non-traumatic resuscitation room management]. / "B-Probleme" des nichttraumatologischen Schockraummanagements.

In the primary survey of resuscitation room management in critically ill nontrauma patients, the ABCDE (airway, breathing, circulation, disability, exposure) approach is used for immediate recognition and treatment of life-threatening conditions. "B problems" are associated with respiratory failure and require immediate treatment. The pathogenesis is diverse, especially in the nontrauma resuscitation room. Clinical examination, emergency sonography and knowledge of oxygenation techniques and ventilation are important components of diagnosis and therapy. Standardized procedures and regular training in the emergency room are of fundamental importance.

Persistent capillary rarefication in long COVID syndrome.

BACKGROUND: Recent studies have highlighted Coronavirus disease 2019 (COVID-19) as a multisystemic vascular disease. Up to 60% of the patients suffer from long-term sequelae and persistent symptoms even 6 months after the initial infection. METHODS: This prospective, observational study included 58 participants, 27 of whom were long COVID patients with persistent symptoms > 12 weeks after recovery from PCR-confirmed SARS-CoV-2 infection. Fifteen healthy volunteers and a historical cohort of critically ill COVID-19 patients (n = 16) served as controls. All participants underwent sublingual videomicroscopy using sidestream dark field imaging. A newly developed version of Glycocheck™ software was used to quantify vascular density, perfused boundary region (PBR-an inverse variable of endothelial glycocalyx dimensions), red blood cell velocity (VRBC) and the microvascular health score (MVHS™) in sublingual microvessels with diameters 4-25 µm. MEASUREMENTS AND MAIN RESULTS: Although dimensions of the glycocalyx were comparable to those of healthy controls, a µm-precise analysis showed a significant decrease of vascular density, that exclusively affected very small capillaries (D5: - 45.16%; D6: - 35.60%; D7: - 22.79%). Plotting VRBC of capillaries and feed vessels showed that the number of capillaries perfused in long COVID patients was comparable to that of critically ill COVID-19 patients and did not respond adequately to local variations of tissue metabolic demand. MVHS was markedly reduced in the long COVID cohort (healthy 3.87 vs. long COVID 2.72 points; p = 0.002). CONCLUSIONS: Our current data strongly suggest that COVID-19 leaves a persistent capillary rarefication even 18 months after infection. Whether, to what extent, and when the observed damage might be reversible remains unclear.

A Dietary Supplement Containing Fucoidan Preserves Endothelial Glycocalyx through ERK/MAPK Signaling and Protects against Damage Induced by CKD Serum.

(1) Damage to the endothelial glycocalyx (eGC), a protective layer lining the endothelial luminal surface, is associated with chronic kidney disease (CKD), which leads to a worsening of cardiovascular outcomes in these patients. Currently, there are no targeted therapeutic approaches. Whether the dietary supplement EndocalyxTM (ECX) protects against endothelial damage caused by uremic toxins is unknown. (2) We addressed this question by performing atomic force microscopy measurements on living endothelial cells. We examined the effect of ECX on eGC thickness at baseline and with pooled serum from hemodialysis patients. ECX was also successfully administered in vivo in mice, in which eGC was assessed using perfused boundary region measurements by intravital microscopy of cremasteric vessels. (3) Both ECX and fucoidan significantly improved baseline eGC thickness. Our data indicate that these effects are dependent on ERK/MAPK and PI3K signaling. After incubation with eGC damaging serum from dialysis patients, ECX increased eGC height. Intravital microscopy in mice revealed a relevant increase in baseline eGC dimensions after feeding with ECX. (4) We identified a dietary supplement containing glycocalyx substrates and fucoidan as potential mediators of eGC preservation in vitro and in vivo. Our findings suggest that fucoidan may be an essential component responsible for protecting the eGC in acute settings. Moreover, ECX might contribute to both protection and rebuilding of the eGC in the context of CKD.

Epidemiology, management, and outcome of infection, sepsis, and septic shock in a German emergency department (EpiSEP study).

Background: The adjacent conditions infection, sepsis, and septic shock are among the most common causes of treatment in the emergency department (ED). Most available data come from intensive care units (ICU) and include nosocomial infections acquired during hospitalization. Epidemiological data from German EDs are not yet available, although the ED is one of the first points of contact for patients. The aim of this study was to investigate the epidemiology, causes, diagnosis, mortality, and treatment of patients with infections in the ED. Materials and methods: In this retrospective, single-center observational study, routinely collected data from the patient data management system and from the hospital information system were analyzed. All adult patients who presented to the ED in connection with an infection during the study period from 01/01 to 28/02/2019 were included. Exclusion criteria were age ≤ 17 years and incomplete records. Three groups (I. Infection, II. Sepsis, and III. Septic shock) were defined according to SEPSIS-3 definitions. Results: During the study period, a total of 6,607 patients were treated in the ED. Of these patients, 19.3% (n = 1,278) had an infection (mean age 56 ± 23 years, 50% female). The sites of infection were distributed as follows: Respiratory tract 35%, genitourinary tract 18%, maxillofacial/ears/nose/throat 14%, intraabdominal 13%, soft tissues 10%, central nervous system 1%, other cause 3%, or unknown cause 6%. Infection only, sepsis and septic shock were present in 86, 10, and 3%, respectively. There were significant differences in vital signs as well as in the various emergency sepsis scores across the predefined groups [I vs. II vs. III: SOFA (pts.): 1 ± 1 vs. 4 ± 2 vs. 7 ± 3 (p < 0.0001), systolic blood pressure (mmHg): 137 ± 25 vs. 128 ± 32 vs. 107 ± 34 (p < 0.05), heart rate (bpm): 92 ± 18 vs. 99 ± 23 vs. 113 ± 30 (p < 0.05), respiratory rate (min-1): 18 ± 4 vs. 20 ± 7 vs. 24 ± 10 (p < 0.05)]. In the three groups, blood cultures were obtained in 34, 81, and 86%, of cases, respectively and antibiotics were administered in the ED in 50, 89, and 86%, of cases respectively. The 30-day mortality rate in the three groups was 1.6, 12.0, and 38.1%, respectively. Conclusion: This study is the first to show the incidence, management, and outcome of patients classified as infection, sepsis, and septic shock in a German ED. The findings of our real-world data are important for quality management and enable the optimization of treatment pathways for patients with infectious diseases.

Development of the Interdisciplinary and Interprofessional Course Concept "Advanced Critical Illness Life Support".

The Advanced Critical Illness Life Support (ACiLS) course was developed on behalf of the German Society for Interdisciplinary Emergency and Acute Medicine (DGINA). The goal of the ACiLS course is to provide a nationally recognized and certified life support course that teaches medical professionals the key principles of initial care of critically ill patients in the emergency department, including the (PR_E-)AUD2IT-algorithm. It is designed for interdisciplinary and multi-professional staff in the resuscitation room to optimize patient safety and outcome. ACiLS includes a new blended learning concept with a theoretical part as comprehensive e-learning and a two-day practical part with strong focus on team training in scenarios and workshops. The course format was conceived to balance best teaching practices within the limited instructional time and resources available. This article describes the development of the ACiLS course and provides an overview of its future implementation.

Lethal Waterhouse-Friderichsen syndrome caused by Capnocytophaga canimorsus in an asplenic patient.

BACKGROUND: Capnocytophaga canimorsus, a Gram-negative rod, belongs to the Flavobacteriaceae family and colonizes the oropharynx of dogs and cats. Infections with C. canimorsus are rare and can induce a systemic infection with a severe course of the disease. So far, only five case reports of C. canimorsus infections associated with Waterhouse-Friderichsen Syndrome (WFS) have been reported with only two of the patients having a history of splenectomy. CASE PRESENTATION: Here, we report a fatal case of WFS due to C. canimorsus bacteremia and mycetal superinfection in a 61-year-old female asplenic patient. Despite extensive therapy including mechanical ventilation, antibiotic coverage with meropenem, systemic corticosteroids medication, vasopressor therapy, continuous renal replacement therapy, therapeutic plasma exchange, multiple transfusions of blood products and implantation of a veno-arterial extracorporeal membrane oxygenation the patient died 10 days after a dog bite. The autopsy showed bilateral hemorrhagic necrosis of the adrenal cortex and septic embolism to heart, kidneys, and liver. Diagnosis of C. canimorsus was prolonged due to the fastidious growth of the bacteria. CONCLUSIONS: The occurrence of a severe sepsis after dog bite should always urge the attending physician to consider C. canimorsus as the disease-causing pathogen. A therapeutic regimen covering C. canimorsus such as aminopenicillins or carbapenems should be chosen. However, despite maximum therapy, the prognosis of C. canimorsus-induced septic shock remains very poor. Asplenic or otherwise immunocompromised patients are at higher risk for a severe course of disease and should avoid exposure to dogs and cats and consider antibiotic prophylaxis after animal bite.

Medical and cardio-vascular emergency department visits during the COVID-19 pandemic in 2020: is there a collateral damage? A retrospective routine data analysis.

BACKGROUND: In this retrospective routine data analysis, we investigate the number of emergency department (ED) consultations during the COVID-19 pandemic of 2020 in Germany compared to the previous year with a special focus on numbers of myocardial infarction and acute heart failure. METHODS: Aggregated case numbers for the two consecutive years 2019 and 2020 were obtained from 24 university hospitals and 9 non-university hospitals in Germany and assessed by age, gender, triage scores, disposition, care level and by ICD-10 codes including the tracer diagnoses myocardial infarction (I21) and heart failure (I50). RESULTS: A total of 2,216,627 ED consultations were analyzed, of which 1,178,470 occurred in 2019 and 1,038,157 in 2020. The median deviation in case numbers between 2019 and 2020 was - 14% [CI (- 11)-(- 16)]. After a marked drop in all cases in the first COVID-19 wave in spring 2020, case numbers normalized during the summer. Thereafter starting in calendar week 39 case numbers constantly declined until the end of the year 2020. The decline in case numbers predominantly concerned younger [- 16%; CI (- 13)-(- 19)], less urgent [- 18%; CI (- 12)-(- 22)] and non-admitted cases [- 17%; CI (- 13)-(- 20)] in particular during the second wave. During the entire observation period admissions for chest pain [- 13%; CI (- 21)-2], myocardial infarction [- 2%; CI (- 9)-11] and heart failure [- 2%; CI (- 10)-6] were less affected and remained comparable to the previous year. CONCLUSIONS: ED visits were noticeably reduced during both SARS-CoV-2 pandemic waves in Germany but cardiovascular diagnoses were less affected and no refractory increase was noted. However, long-term effects cannot be ruled out and need to be analysed in future studies.

Heparanase Is a Putative Mediator of Endothelial Glycocalyx Damage in COVID-19 - A Proof-of-Concept Study.

Coronavirus disease 2019 (COVID-19) is a systemic disease associated with injury (thinning) of the endothelial glycocalyx (eGC), a protective layer on the vascular endothelium. The aim of this translational study was to investigate the role of the eGC-degrading enzyme heparanase (HPSE), which is known to play a central role in the destruction of the eGC in bacterial sepsis. Excess activity of HPSE in plasma from COVID-19 patients correlated with several markers of eGC damage and perfused boundary region (PBR, an inverse estimate of glycocalyx dimensions of vessels with a diameter 4-25 µm). In a series of translational experiments, we demonstrate that the changes in eGC thickness of cultured cells exposed to COVID-19 serum correlated closely with HPSE activity in concordant plasma samples (R = 0.82, P = 0.003). Inhibition of HPSE by a nonanticoagulant heparin fragment prevented eGC injury in response to COVID-19 serum, as shown by atomic force microscopy and immunofluorescence imaging. Our results suggest that the protective effect of heparin in COVID-19 may be due to an eGC-protective off-target effect.

Microvascular and proteomic signatures overlap in COVID-19 and bacterial sepsis: the MICROCODE study.

AIMS: Although coronavirus disease 2019 (COVID-19) and bacterial sepsis are distinct conditions, both are known to trigger endothelial dysfunction with corresponding microcirculatory impairment. The purpose of this study was to compare microvascular injury patterns and proteomic signatures in COVID-19 and bacterial sepsis patients. METHODS AND RESULTS: This multi-center, observational study included 22 hospitalized adult COVID-19 patients, 43 hospitalized bacterial sepsis patients, and 10 healthy controls from 4 hospitals. Microcirculation and glycocalyx dimensions were quantified via intravital sublingual microscopy. Plasma proteins were measured using targeted proteomics (Olink). Coregulation and cluster analysis of plasma proteins was performed using a training-set and confirmed in a test-set. An independent external cohort of 219 COVID-19 patients was used for validation and outcome analysis. Microcirculation and plasma proteome analysis found substantial overlap between COVID-19 and bacterial sepsis. Severity, but not disease entity explained most data variation. Unsupervised correlation analysis identified two main coregulated plasma protein signatures in both diseases that strictly counteract each other. They were associated with microvascular dysfunction and several established markers of clinical severity. The signatures were used to derive new composite biomarkers of microvascular injury that allow to predict 28-day mortality or/and intubation (area under the curve 0.90, p < 0.0001) in COVID-19. CONCLUSION: Our data imply a common biological host response of microvascular injury in both bacterial sepsis and COVID-19. A distinct plasma signature correlates with endothelial health and improved outcomes, while a counteracting response is associated with glycocalyx breakdown and high mortality. Microvascular health biomarkers are powerful predictors of clinical outcomes.

Safety and efficacy of the Seraph® 100 Microbind® Affinity Blood Filter to remove bacteria from the blood stream: results of the first in human study.

BACKGROUND: Bacterial burden as well as duration of bacteremia influence the outcome of patients with bloodstream infections. Promptly decreasing bacterial load in the blood by using extracorporeal devices in addition to anti-infective therapy has recently been explored. Preclinical studies with the Seraph® 100 Microbind® Affinity Blood Filter (Seraph® 100), which consists of heparin that is covalently bound to polymer beads, have demonstrated an effective binding of bacteria and viruses. Pathogens adhere to the heparin coated polymer beads in the adsorber as they would normally do to heparan sulfate on cell surfaces. Using this biomimetic principle, the Seraph® 100 could help to decrease bacterial burden in vivo. METHODS: This first in human, prospective, multicenter, non-randomized interventional study included patients with blood culture positive bloodstream infection and the need for kidney replacement therapy as an adjunctive treatment for bloodstream infections. We performed a single four-hour hemoperfusion treatment with the Seraph® 100 in conjunction with a dialysis procedure. Post procedure follow up was 14 days. RESULTS: Fifteen hemodialysis patients (3F/12 M, age 74.0 [68.0-78.5] years, dialysis vintage 28.0 [11.0-45.0] months) were enrolled. Seraph® 100 treatment started 66.4 [45.7-80.6] hours after the initial positive blood culture was drawn. During the treatment with the Seraph® 100 with a median blood flow of 285 [225-300] ml/min no device or treatment related adverse events were reported. Blood pressure and heart rate remained stable while peripheral oxygen saturation improved during the treatment from 98.0 [92.5-98.0] to 99.0 [98.0-99.5] %; p = 0.0184. Four patients still had positive blood culture at the start of Seraph® 100 treatment. In one patient blood cultures turned negative during treatment. The time to positivity (TTP) was increased between inflow and outflow blood cultures by 36 [- 7.2 to 96.3] minutes. However, overall TTP increase was not statistical significant. CONCLUSIONS: Seraph® 100 treatment was well tolerated. Adding Seraph® 100 to antibiotics early in the course of bacteremia might result in a faster resolution of bloodstream infections, which has to be evaluated in further studies. TRAIL REGISTRATION: ClinicalTrials.gov Identifier: NCT02914132 , first posted September 26, 2016.

Investigating Morphological Changes of T-lymphocytes after Exposure with Bacterial Determinants for Early Detection of Septic Conditions.

Sepsis is a leading cause of morbidity and mortality, annually affecting millions of people worldwide. Immediate treatment initiation is crucial to improve the outcome but despite great progress, early identification of septic patients remains a challenge. Recently, white blood cell morphology was proposed as a new biomarker for sepsis diagnosis. In this proof-of-concept study, we aimed to investigate the effect of different bacteria and their determinants on T-lymphocytes by digital holographic microscopy (DHM). We hypothesize that species- and strain-specific morphological changes occur, which may offer a new approach for early sepsis diagnosis and identification of the causative agent. Jurkat cells as a model system were exposed to different S. aureus or E. coli strains either using sterile determinants or living bacteria. Time-lapse DHM was applied to analyze cellular morphological changes. There were not only living bacteria but also membrane vesicles and sterile culture supernatant-induced changes of cell area, circularity, and mean phase contrast. Interestingly, different cellular responses occurred depending on both the species and strain of the causative bacteria. Our findings suggest that investigation of T-lymphocyte morphology might provide a promising tool for the early identification of bacterial infections and possibly discrimination between different causative agents. Distinguishing gram-positive from gram-negative infection would already offer a great benefit for the proper administration of antibiotics.

[Epidemiology and Causes of Acute Renal Failure and Transition to Chronic Kidney Disease]. / Epidemiologie und Ursachen für ein akutes Nierenversagen ­ Übergang in eine chronische Nierenschädigung.

Acute kidney injury (AKI) refers to an acute functional deterioration of the kidneys, which leads to retention of urinary substances, dysregulation of the electrolyte and acid-base balance, and disturbance of fluids. Although didactically helpful, the oversimplified AKI classification of prerenal/renal/postrenal is currently considered obsolete. Indeed, the boundaries blur quite quickly, particularly between prerenal and renal causes. Based on the AKI pathophysiology, it can be etiologically divided into decreased renal perfusion, postrenal obstruction and kidney specific injury or unspecific injury. AKI is a common event in hospitalized patients and associates strongly with mortality and chronic kidney disease (CKD). Today it is accepted that AKI and CKD are rather an individually variable continuum, than 2 distinct entities. If AKI has not regressed after 7 days, it is referred to as acute kidney disease (AKD). Persisting AKD for > 90 days is classified as CKD. The transition from AKD to CKD is the result of an incomplete and maladaptive repair process. Although follow-up of post-AKI patients is essential, optimal concepts still need to be developed.

[University emergency departments in the corona pandemic-Results from the ReCovER registry]. / Universitäre Notaufnahmen in der Coronapandemie ­ Ergebnisse des ReCovER-Registers.

BACKGROUND: The current COVID-19 pandemic, despite the availability of rapid tests and the start of the vaccination campaign, continues to pose major challenges to emergency departments (ED). Structured collection of demographic, clinical, as well as treatment-related data provides the basis for establishing evidence-based processes and treatment concepts. AIM OF THE WORK: To present the systematic collection of clinical parameters in patients with suspected COVID-19 in the Registry for COVID-19 in the Emergency Room (ReCovER) and descriptive presentation of the first 1000 patients. MATERIALS AND METHODS: Data from patients with suspected COVID-19, regardless of evidence of SARS-CoV­2 infection, are continuously entered into a web-based, anonymized registry in ED at six university hospitals. RESULTS: Between 19 May 2020 and 13 January 2021, 1000 patients were entered into the registry, of whom 594 patients (59.4%) were in the SARS-CoV­2 positive group (PG) and 406 patients (40.6%) were in the negative group (NG). Patients of the PG had significantly fewer pre-existing conditions and a significantly longer latency between symptom onset and presentation to the ED (median 5 vs. 3 days), were more likely to suffer from cough, myalgia, fatigue, and loss of smell/taste and had significantly higher oxygen requirements than NG patients. The rate of severe disease progression was significantly higher in the PG, and persistent symptoms were more common after discharge (11.1 vs. 4.6%). CONCLUSIONS: The multicenter collection of comprehensive clinical data on COVID-19 suspected cases in the ED allows analysis of aspects specific to the situation in Germany in particular. This is essential for a targeted review and adaptation of internationally published strategies.