Comparison of Palliative Knowledge and Self-Efficacy Expectation of German Paramedics Between a Rural and an Urban Structured Emergency Medical Service Area.

OBJECTIVE(S): Differences in the German emergency medical service (EMS) can be seen in the countryside in contrast to the city with regard to travel distances to hospitals and in the access routes of EMS-physicians. In order to investigate the success of establishment of palliative crisis cards associated with training and the rural and urban EMS structures, two urban and two rural EMS areas were compared using the Paramedic Palliative Care Test (PARPACT). Methods: The PARPACT includes test items on palliative knowledge (PK, maximum score: 15 points) and palliative self-efficacy expectations (PSE, maximum score: 18 points), as well as items on palliative attitudes in dealing with palliative care patients. We used a 4-point Likert-type scale. For data analysis, nonparametric tests (χ-test and Mann-Whitney U test) were used in addition to descriptive analysis (frequencies, means, medians, standard deviations, and ranges). Results: In total, 291 out of 750 ambulance or EMS personnel participated in the voluntary survey. Rural ambulance or EMS personnel answered the PK-questions correctly more often on average (mean: 11.19, SD: 1.85) than urban ambulance or EMS personnel (mean: 9.18, SD: 2.39; Mann-Whitney U test: U=5040.000, P=.001). In addition, ambulance or EMS personnel with the highest level of training (3-year-trained paramedics) performed better in PK (mean: 10.38, SD: 2.31) than less intensively training ambulance or EMS personnel (mean: 9.58, SD: 2.43; Mann-Whitney U-test: U=8446.500, P=.004). In terms of PSE, rural ambulance or EMS personnel also achieved higher mean PSE-scores (mean: 12.55, SD: 2.60) than urban ambulance or EMS personnel (mean: 9.77, SD: 3.41; Mann-Whitney U-test: U=5148.500, P=.001). Conclusions: Better training in the EMS is associated with improved PK compared to less qualified nonphysician EMS staff. The establishment of palliative crisis cards and the structures in the city alone do not lead to improved knowledge and PSE.

[Cancer patients in the emergency department]. / Krebspatienten in der Notaufnahme.

A growing number of patients are living with cancer or have a history of cancer leading to increasing adverse effects of treatment or disease necessitating emergency department (ED) consultation. Long-term cancer survivors are at higher risk of comorbidities causing a substantial increase in health care resource utilization. The most frequent reasons for cancer-related ED visits are dyspnea, fever, pain, gastrointestinal or neurological symptoms leading to high hospital and intensive care unit admission rates. Acute respiratory failure in cancer patients necessitates timely diagnostic testing, whereby computed tomography is superior to chest X­ray. Delay in intensive care unit (ICU) admission or mechanical ventilation increases mortality. Febrile neutropenia is an emergency with urgent need for antibiotic treatment. Treatment of neutropenic and nonneutropenic patients with sepsis does not differ. Cardiovascular disease is now the second leading cause of long-term morbidity and mortality among cancer survivors. Immunotherapy can lead to substantial and in some patients life-threatening complications that may not easily be recognized in the ED. Cancer-specific emergencies such as leukostasis, tumorlysis or hypercalcemia rarely present to ED and require interdisciplinary care. The constantly growing cancer population is likely to increase ED utilization. Knowledge about cancer treatment and disease-associated complications is crucial for emergency physicians. Palliative care education should secure appropriate end-of-life care avoiding futile interventions.

Does Prehospital Suspicion of Sepsis Shorten Time to Administration of Antibiotics in the Emergency Department? A Retrospective Study in One University Hospital.

Early treatment is the mainstay of sepsis therapy. We suspected that early recognition of sepsis by prehospital healthcare providers may shorten the time for antibiotic administration in the emergency department. We retrospectively evaluated all patients above 18 years of age who were diagnosed with sepsis or severe infection in our emergency department between 2018 and 2020. We recorded the suspected diagnosis at the time of presentation, the type of referring healthcare provider, and the time until initiation of antibiotic treatment. Differences between groups were calculated using the Kruskal-Wallis rank sum test. Of the 277 patients who were diagnosed with severe infection or sepsis in the emergency department, an infection was suspected in 124 (44.8%) patients, and sepsis was suspected in 31 (11.2%) patients by referring healthcare providers. Time to initiation of antibiotic treatment was shorter in patients where sepsis or infection had been suspected prior to arrival for both patients with severe infections (p = 0.022) and sepsis (p = 0.004). Given the well-described outcome benefits of early sepsis therapy, recognition of sepsis needs to be improved. Appropriate scores should be used as part of routine patient assessment to reduce the time to antibiotic administration and improve patient outcomes.

Point-of-care PCR testing of SARS-CoV-2 in the emergency department: Influence on workflow and efficiency.

PROBLEM: Regarding transmissible viral diseases such as those caused by SARS-CoV-2 virus, one of the key challenges is isolation management until final diagnosis. This study investigates the influence of SARS-CoV-2 point-of-care (POC) PCR on workflow and efficiency in an emergency department (ED) of a tertiary university hospital. METHOD: An analysis of 17,875 ED patients receiving either SARS-CoV-2 POC PCR (rapid PCR, 11,686 patients) or conventional laboratory SARS-CoV-2 PCR (conventional PCR, 6,189 patients) was performed. The pathways for both groups were mapped and compared, and process times from admission to diagnosis were measured. Effects on resource management within the ED were quantified. Direct costs due to isolation, loss of capacities, and revenues were calculated for inpatients. RESULTS: The mean time from admission to result was 1.62 h with rapid PCR and 16.08 h with conventional PCR (p < 0.01), reducing the isolation time by 14.46 h. In the first 2 h after testing, test results were available for > 75% of the rapid PCR group and none of the conventional PCR group. Ninety percent of the results were available within 3 h for the rapid PCR and within 21 h for the conventional PCR group. For the conventional PCR group, an increase in direct costs of €35.74 and lost revenues of €421.06 for each inpatient case was detected. CONCLUSION: Rapid PCR significantly reduces the time-to-results and time for isolation relative to conventional PCR. Although testing costs for rapid PCR are higher, it benefits workflow, reduces total costs, and frees up ward capacity.

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).

Epicardial adipose tissue and obstructive coronary artery disease in acute chest pain: the EPIC-ACS study.

Aims: We tested the hypothesis that epicardial adipose tissue (EAT) quantification improves the prediction of the presence of obstructive coronary artery disease (CAD) in patients presenting with acute chest pain to the emergency department. Methods and results: Within this prospective observational cohort study, we included 657 consecutive patients (mean age 58.06 ± 18.04 years, 53% male) presenting to the emergency department with acute chest pain suggestive of acute coronary syndrome between December 2018 and August 2020. Patients with ST-elevation myocardial infarction, haemodynamic instability, or known CAD were excluded. As part of the initial workup, we performed bedside echocardiography for quantification of EAT thickness by a dedicated study physician, blinded to all patient characteristics. Treating physicians remained unaware of the results of the EAT assessment. The primary endpoint was defined as the presence of obstructive CAD, as detected in subsequent invasive coronary angiography. Patients reaching the primary endpoint had significantly more EAT than patients without obstructive CAD (7.90 ± 2.56 mm vs. 3.96 ± 1.91 mm, P < 0.0001). In a multivariable regression analysis, a 1 mm increase in EAT thickness was associated with a nearby two-fold increased odds of the presence of obstructive CAD [1.87 (1.64-2.12), P < 0.0001]. Adding EAT to a multivariable model of the GRACE score, cardiac biomarkers and traditional risk factors significantly improved the area under the receiver operating characteristic curve (0.759-0.901, P < 0.0001). Conclusion: Epicardial adipose tissue strongly and independently predicts the presence of obstructive CAD in patients presenting with acute chest pain to the emergency department. Our results suggest that the assessment of EAT may improve diagnostic algorithms of patients with acute chest pain.

Effect of video laryngoscopy for non-trauma out-of-hospital cardiac arrest on clinical outcome: A registry-based analysis.

AIM: Videolaryngoscopy (VL) is a promising tool to provide a safe airway during cardiopulmonary resuscitation (CPR) and to ensure early reoxygenation. Using data from the German Resuscitation Registry, we investigated the outcome of non-traumatic out-of-hospital cardiac arrest (OHCA) patients treated with VL versus direct laryngoscopy (DL) for airway management. METHODS: We analysed retrospective data of 14,387 patients from 1 January 2018 until 31 December 2021 (VL group, n = 2201; DL group, n = 12186). Primary endpoint was discharge with cerebral performance categories one and two (CPC1/2). Secondary endpoints were the rate of return of spontaneous circulation (ROSC), hospital admission, hospital admission with ongoing cardiopulmonary resuscitation, 30-day survival/ hospital discharge and airway management complications. We used multivariate binary logistic regression analysis to identify the effects on outcome of known influencing variables and of VL vs DL. RESULTS: The multivariate regression model revealed that VL was an independent predictor of CPC1/2 survival (OR = 1.34, 95% CI = 1.12-1.61, p = 0.002) and of hospital discharge/30-day survival (OR = 1.26, 95% CI = 1.08-1.47, p = 0,004). CONCLUSION: VL for endotracheal intubation (ETI) at OHCA was associated with better neurological outcome in patients with ROSC. Therefore, the use of VL for OHCA offers a promising perspective. Further prospective studies are required.

Evaluation of a new COVID-19 triage algorithm in the emergency department including combined antigen and PCR-testing: A case-control study.

The coronavirus disease 2019 (COVID-19) pandemic is a major challenge for global healthcare systems. Early and safe triage in the emergency department (ED) is crucial for proper therapy. However, differential diagnosis remains challenging. Rapid antigen testing (RAT) may help to improve early triage and patient safety. We performed a retrospective study of 234 consecutive patients with suspected COVID-19 who presented to our ED in November 2020. All underwent SARS-CoV-2-nasopharyngeal swab testing using both RAT and reverse transcription polymerase chain reaction (RT-PCR). The inpatient treatment was established according to an empirically developed triage algorithm. The accuracy of the suggested algorithm was analyzed based on the rate of outpatients returning within 7 days and inpatients staying for less than 48 hours. COVID-19 inpatients and outpatients were compared for symptoms, vital signs, and C-reactive protein levels. Of the 221 included patients with suspected COVID-19 infection, the diagnosis could be confirmed in 120 patients (54.3%) by a positive RT-PCR result, whereas only 72% of those had a positive antigen test. Of the 56 COVID-19 outpatients, three returned within 7 days with the need for hospital treatment due to clinical deterioration. Among the 64 COVID-19 inpatients, 4 were discharged within 48 hours, whereas 60 stayed longer (mean duration 10.2 days). The suggested triage algorithm was safe and efficient in the first 234 consecutive patients. RAT can confirm a diagnosis in 72% of PCR proven COVID-19 patients and allows early cohort isolation as an important way to save hospital capacity.

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.

Comparison of left double lumen tube and y-shaped and double-ended bronchial blocker for one lung ventilation in thoracic surgery-a randomised controlled clinical trial.

BACKGROUND: Double lumen tube (DLT) intubation is the most commonly used technique for one lung ventilation. Bronchial blockers (BB) are an alternative, especially for difficult airways. The EZ-bronchial blocker (EZB) is an innovative y-shaped and double-ended device of the BB family. METHODS: A randomised, controlled trial was conducted in 80 patients undergoing elective thoracic surgery using DLT or EZB for one lung ventilation (German Clinical Trial Register DRKS00014816). The objective of the study was to compare the clinical performance of EZB with DLT. Primary endpoint was total time to obtain successful one lung ventilation. Secondary endpoints were time subsections, quality of lung collapse, difficulty of intubation, any complications during the procedure, incidence of objective trauma of the oropharynx and supraglottic space and intubation-related subjective symptoms. RESULTS: 74 patients were included, DLT group (n = 38), EZB group (n = 36). Median total time to obtain one lung ventilation [IQR] in the DLT group was 234 s [207 to 294] versus 298 s [243 to 369] in the EZB group (P = 0.007). Median total time was relevantly influenced by different preparation times. Quality of lung collapse was equal in both groups, DLT group 89.5% were excellent vs. 83.3% in the EZB group (P = 0.444). Inadequate lung collapse in five patients of the EZB group resulted in unsuccessful repositioning attempts and secondary DLT placement. Endoscopic examinations revealed significantly more carina trauma (P = 0.047) and subglottic haemorrhage (P = 0.047) in the DLT group. Postoperative subjective symptoms (sore throat, hoarseness) were more common in the DLT group, as were speech problems. CONCLUSIONS: Using EZB prima facie results in prolonged time to obtain one lung ventilation with equal quality of lung collapse for the thoracic surgeon. If preparation times are omitted in the analysis, the time difference is statistically and clinically not relevant. Our data showed only little evidence for reducing objective airway trauma as well as subjective complaints. In summary both procedures were comparable in terms of times and clinical applicability. Therefore decisions for DLT or EZB should depend more on individual experience, in-house equipment and the individual patient, than on any times that are neither clinically significant nor relevant. TRIAL REGISTRATION: German Clinical Trial Register DRKS00014816 , prospectively registered on 07.06.2018.

[Wave riding - 12 months of COVID-19 in a German tertiary care center]. / Wellenreiten ­ 12 Monate COVID-19 im Maximalversorger.

INTRODUCTION: With more than 1400 COVID-19 inpatients, the university hospital of Essen is the main regional caregiver during COVID-19 pandemic. We present outcome data of our inpatients during the first 12 months of pandemic and our derived clinical care concepts. METHODS: Retrospective analysis of all 1396 COVID-19 inpatients presenting between March, 1st of 2020 and February, 28th of 2021 for comorbidities, survival and complications. Group comparison between patients receiving standard care and those requiring intermediate/ intensive care. RESULTS: Mortality rate of all inpatients was 19,8 % (277/ 1396), whereas 10.6 % (93/877) of the patients with standard care and 35.5 % (184/519) of those with intermediate/intensive care died during hospital stay. Age above 60 years, obesity, need for mechanical ventilation, nitric oxide therapy, ECMO and acute renal failure as well as stroke during the clinical course were independent predictors of mortality. CONCLUSIONS: The mortality of both patient groups ranges within the numbers published by other international groups. The vast impact of usual comorbidities could be observed as well as the high rate of complications in serious ill COVID-19 patients. The mean age of both patient groups was lower than expected (60 years standard care versus 63 years intermediate/ intensive care). A maximum of patient and staff protection measures, a fast and efficient testing strategy during primary triage, standardized concepts from emergency department to intensive care units and dynamic adjustment of resources to daily changing needs can ensure a high quality of care even during peak of pandemic.

[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.

[Risk management in the triage of emergency room patients to outpatient care : Manchester Triage System and CEReCo-blue as a tool for low-risk patient management in integrated emergency centers]. / Risikomanagement in der Triage ambulanter Notfallpatienten : Manchester Triage System und CEReCo-blue als Instrument zur risikoarmen Patientensteuerung in integrierten Notfallzentren.

BACKGROUND: So-called "integrated emergency centers (IEC)" are going to be implemented in German hospitals and will be the first contact point in the emergency care setting. For early decision-making whether outpatient care or inpatient admission in the emergency department is indicated, it would be helpful to have a system to identify patients for outpatient treatment. In this study, we investigated whether the Manchester Triage System (MTS) is suitable for identifying patients who can be safely referred to emergency room patients to outpatient care. METHODS: Patients in the emergency department of the "blue" MTS level were examined for the endpoint inpatient admission and were compared with the next higher MTS category "green". In a second step, the "blue" MTS category was examined for the most common criteria leading to inpatient admission. RESULTS: After excluding patients who were presented by the emergency medical services (EMS) or after prior medical consultation, the rate of inpatient admissions in the blue MTS category was significantly lower than in the green category (10.8% vs 29.0%). The rate could be reduced to 0.9% by establishing a subgroup with the additional exclusion criteria chronic disorder and readmission after prior inpatient treatment (CEReCo-blue group: Chronic Disorder (C), Emergency Medical Service (E), Readmission (R), Prior Medical Consultation (Co)). CONCLUSION: The blue MTS category does not appear to be suitable for the selection of patients with indication for outpatient treatment. We propose the introduction of a subgroup, the so-called CEReCo-blue group, which could be helpful for the selection of this patient group.

FAST-ED scale smartphone app-based prediction of large vessel occlusion in suspected stroke by emergency medical service.

BACKGROUND AND PURPOSE: Considering the highly time-dependent therapeutic effect of endovascular treatment in patients with large vessel occlusion-associated acute ischemic stroke, prehospital identification of large vessel occlusion and subsequent triage for direct transport to a comprehensive stroke center offers an intriguing option for optimizing patient pathways. METHODS: This prospective in-field validation study included 200 patients with suspected acute ischemic stroke who were admitted by emergency medical service to a comprehensive stroke center. Ambulances were equipped with smartphones running an app-based Field Assessment Stroke Triage for Emergency Destination scale for transmission prior to admission. The primary measure was the predictive accuracy of the transmitted Field Assessment Stroke Triage for Emergency Destination for large vessel occlusion and the secondary measure the predictive accuracy for endovascular treatment. RESULTS: A Field Assessment Stroke Triage for Emergency Destination ⩾4 revealed very good accuracy to detect large vessel occlusion-related acute ischemic stroke with a sensitivity of 82.4% (95% confidence interval = 65.5-93.2), specificity of 78.3% (95% confidence interval = 71.3-84.3), and an area under the curve c-statistics of 0.89 (95% confidence interval = 0.85-0.94). Field Assessment Stroke Triage for Emergency Destination ⩾4 correctly identified 84% of patients who received endovascular treatment [73.5% specificity (95% confidence interval = 66.4-79.8)] with an area under the curve c-statistics of 0.82 (95% confidence interval = 0.74-0.89). In a hypothetical triage model of an urban setting, one secondary transportation would be avoided with every fifth patient screened. CONCLUSION: A smartphone app-based stroke triage completed by emergency medical service personnel showed adequate quality for the Field Assessment Stroke Triage for Emergency Destination to identify large vessel occlusion-associated acute ischemic stroke. We demonstrate feasibility of the use of a medical messaging service in prehospital stroke care. Based on these first results, a randomized trial evaluating the clinical benefit of such a triage system in an urban setting is currently in preparation.Clinical Trial Registration: https://clinicaltrials.gov Unique identifier: NCT04404504.

What about the others: differential diagnosis of COVID-19 in a German emergency department.

BACKGROUND: The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging. METHOD: We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs. RESULTS: Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014). CONCLUSION: For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections. TRIAL REGISTRATION: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.

Transmembrane serine protease 2 Polymorphisms and Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Type 2 Infection: A German Case-Control Study.

The transmembrane serine protease 2 (TMPRSS2) is the major host protease that enables entry of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) into host cells by spike (S) protein priming. Single nucleotide polymorphisms (SNPs) in the gene TMPRSS2 have been associated with susceptibility to and severity of H1N1 or H1N9 influenza A virus infections. Functional variants may influence SARS-CoV-2 infection risk and severity of Coronavirus disease 2019 (COVID-19) as well. Therefore, we analyzed the role of SNPs in the gene TMPRSS2 in a German case-control study. We performed genotyping of the SNPs rs2070788, rs383510, and rs12329760 in the gene TMPRSS2 in 239 SARS-CoV-2-positive and 253 SARS-CoV-2-negative patients. We analyzed the association of the SNPs with susceptibility to SARS-CoV-2 infection and severity of COVID-19. SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding their demographics. The CC genotype of TMPRSS2 rs383510 was associated with a 1.73-fold increased SARS-CoV-2 infection risk, but was not correlated to severity of COVID-19. Neither TMPRSS2 rs2070788 nor rs12329760 polymorphisms were related to SARS-CoV-2 infection risk or severity of COVID-19. In a multivariable analysis (MVA), the rs383510 CC genotype remained an independent predictor for a 2-fold increased SARS-CoV-2 infection risk. In summary, our report appears to be the first showing that the intron variant rs383510 in the gene TMPRSS2 is associated with an increased risk to SARS-CoV-2 infection in a German cohort.

SARS-CoV-2 rapid antigen test: Fast-safe or dangerous? An analysis in the emergency department of an university hospital.

The use of Antigen point of care tests (AgPOCT) might be an essential tool to fight the coronavirus disease 2019 (COVID-19) pandemic. Manufacturer information indicates a specificity of about 95% and there is a growing interest to use these tests area-wide. Therefore, it is necessary to clarify whether AgPOCT can be used safely for "rule-in" (detection of positive patients) and for "rule-out" (valid negative testing). Two thousand three hundred and seventy-five patients received polymerase chain reaction (PCR) testing and AgPOCT for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) regardless of symptoms. The positive predictive value of symptomatic and asymptomatic patients was compared with a cut-off threshold cycle (C t ) value of ≤30 and in total. Five hundrded and fifty-one patients tested positive for the SARS-CoV-2 virus by PCR, of whom 35.2% presented without symptoms. In all patients, regardless of their symptoms or C t values, a sensitivity of 68.9% and a specificity of 99.6% were calculated for AgPOCT. In patients with C t values ≤30, a sensitivity of 80.5% (95% confidence interval: ±1.62) and a specificity of 99.6% were shown for all tests (symptomatic/asymptomatic). Highly infectious patients (C t ≤ 20), regardless of symptoms, were reliably detected by the AgPOCT. In infectious patients with C t values ≤30, the test has a sensitivity of about 80% regardless of COVID-19 typical symptoms, which is apparently less than the 96.52% specificity indicated by the manufacturer. Relevant improvement in test sensitivity by querying the patients who are symptomatic and asymptomatic is also not feasible. We strongly suggest that we critically question the use of AgPOCT for "rule-out," as they only provide a supposed safety.

ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.

OBJECTIVES: The RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for coronavirus disease 2019 (COVID-19). Cell entry is mediated by the human angiotensin-converting enzyme II (ACE2). ACE2 and its close homolog angiotensin-converting enzyme I (ACE) are currently discussed candidate genes, in which single-nucleotide polymorphisms (SNPs) could alter binding or entry of SARS-CoV-2 and enhance tissue damage in the lung or other organs. This could increase the susceptibility for SARS-CoV-2 infection and the severity of COVID-19. PATIENTS AND METHODS: We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. RESULTS: SARS-CoV-2-positive and SARS-CoV-2-negative patients did not differ regarding demographics and clinical characteristics. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease. In a multivariable analysis, the ACE2 rs2285666 G-allele remained as an independent risk factor for serious disease besides the known risk factors male gender and cardiovascular disease. CONCLUSIONS: In summary, our report appears to be the first showing that a common ACE2 polymorphism impacts the risk for SARS-CoV-2 infection and the course of COVID-19 independently from previously described risk factors.

Which parameters support disposition decision in suspected COVID-19 cases in the emergency department (ED): a German clinical cohort study.

OBJECTIVES: One major goal of the emergency department (ED) is to decide, whether patients need to be hospitalised or can be sent home safely. We aim at providing criteria for these decisions without knowing the SARS-CoV-2 test result in suspected cases. SETTING: Tertiary emergency medicine. PARTICIPANTS: All patients were treated at the ED of the Charité during the pandemic peak and underwent SARS-CoV-2 testing. Patients with positive test results were characterised in detail and underwent a 14-day-follow-up. PRIMARY AND SECONDARY OUTCOME MEASURES: Logistic regression and classification and regression tree (CART) analyses were performed to identify predictors (primary endpoint), which confirm safe discharge. The clinical endpoint was all-cause mortality or need for mechanical ventilation during index stay or after readmission. RESULTS: The primary test population of suspected COVID-19 consisted of n=1255 cases, 45.2% were women (n=567). Of these, n=110 tested positive for SARS-CoV-2 (8.8%). The median age of SARS-CoV-2-positive cases was 45 years (IQR: 33-66 years), whereas the median age of the group tested negative for SARS-CoV-2 was 42 years (IQR: 30-60 years) (p=0.096). 43.6% were directly admitted to hospital care.CART analysis identified the variables oxygen saturation (<95%), dyspnoea and history of cardiovascular (CV) disease to distinguish between high and low-risk groups. If all three variables were negative, most patients were discharged from ED, and the incidence of the clinical endpoint was 0%. The validation cohort confirmed the safety of discharge using these variables and revealed an incidence of the clinical endpoint from 14.3% in patients with CV disease, 9.4% in patients with dyspnoea and 18.2% in patients with O2 satuaration below 95%. CONCLUSIONS: Based on easily available variables like dyspnoea, oxygen saturation, history of CV disease, approximately 25% of patients subsequently confirmed with COVID-19 can be identified for safe discharge. TRIAL REGISTRATION NUMBER: DRKS00023117.