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Autophagy and lysosomal pathways are involved in the cell entry of SARS-CoV-2 virus. To infect the host cell, the spike protein of SARS-CoV-2 binds to the cell surface receptor angiotensin-converting enzyme 2 (ACE2). To allow the fusion of the viral envelope with the host cell membrane, the spike protein has to be cleaved. One possible mechanism is the endocytosis of the SARS-CoV-2-ACE2 complex and subsequent cleavage of the spike protein, mainly by the lysosomal protease cathepsin L. However, detailed molecular and dynamic insights into the role of cathepsin L in viral cell entry remain elusive. To address this, HeLa cells and iPSC-derived alveolarspheres were treated with recombinant SARS-CoV-2 spike protein, and the changes in mRNA and protein levels of cathepsins L, B, and D were monitored. Additionally, we studied the effect of cathepsin L deficiency on spike protein internalization and investigated the influence of the spike protein on cathepsin L promoters in vitro. Furthermore, we analyzed variants in the genes coding for cathepsin L, B, D, and ACE2 possibly associated with disease progression using data from Regeneron's COVID Results Browser and our own cohort of 173 patients with COVID-19, exhibiting a variant of ACE2 showing significant association with COVID-19 disease progression. Our in vitro studies revealed a significant increase in cathepsin L mRNA and protein levels following exposure to the SARS-CoV-2 spike protein in HeLa cells, accompanied by elevated mRNA levels of cathepsin B and D in alveolarspheres. Moreover, an increase in cathepsin L promoter activity was detected in vitro upon spike protein treatment. Notably, the knockout of cathepsin L resulted in reduced internalization of the spike protein. The study highlights the importance of cathepsin L and lysosomal proteases in the SARS-CoV-2 spike protein internalization and suggests the potential of lysosomal proteases as possible therapeutic targets against COVID-19 and other viral infections.
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PURPOSE OF REVIEW: This review comments on the current guidelines for the treatment of wound infections under definition of acute bacterial skin and skin structure infections (ABSSSI). However, wound infections around a catheter, such as driveline infections of a left ventricular assist device (LVAD) are not specifically listed under this definition in any of the existing guidelines. RECENT FINDINGS: Definitions and classification of LVAD infections may vary across countries, and the existing guidelines and recommendations may not be equally interpreted among physicians, making it unclear if these infections can be considered as ABSSSI. Consequently, the use of certain antibiotics that are approved for ABSSSI may be considered as 'off-label' for LVAD infections, leading to rejection of reimbursement applications in some countries, affecting treatment strategies, and hence, patients' outcomes. However, we believe driveline exit site infections related to LVAD can be included within the ABSSSI definition. SUMMARY: We argue that driveline infections meet the criteria for ABSSSI which would enlarge the 'on-label' antibiotic armamentarium for treating these severe infections, thereby improving the patients' quality of life.
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Insuficiencia Cardíaca , Corazón Auxiliar , Infecciones Relacionadas con Prótesis , Enfermedades Cutáneas Infecciosas , Infecciones de los Tejidos Blandos , Infección de Heridas , Humanos , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/complicaciones , Corazón Auxiliar/efectos adversos , Calidad de Vida , Antibacterianos/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Infección de Heridas/complicaciones , Infección de Heridas/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/diagnóstico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
PURPOSE: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic. METHODS: A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers. We compared care provision and the involvement of ID specialists between ID and non-ID hospitals. Then we applied a multivariable regression model to analyse how clinical ID care influenced the mortality of COVID-19 patients in the LEOSS cohort. RESULTS: Of the 40 participating hospitals in the study, 35% (14/40) were identified as ID centers. Among those, clinical ID care structures were more commonly established, and ID specialists were always involved in pandemic management and the care of COVID-19 patients. Overall, 68% (27/40) of the hospitals involved ID specialists in the crisis management team, 78% (31/40) in normal inpatient care, and 80% (28/35) in intensive care. Multivariable analysis revealed that COVID-19 patients in ID centers had a lower mortality risk compared to those in non-ID centers (odds ratio: 0.61 (95% CI 0.40-0.93), p = 0.021). CONCLUSION: ID specialists played a crucial role in pandemic management and inpatient care.
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PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.
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PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).
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BACKGROUND: The aim of this study was to investigate whether bioactive adrenomedullin (bio-ADM) and interleukin-6 (IL-6) are related to acute kidney injury (AKI) and severe illness in COVID-19 patients. METHODS: 153 patients with COVID-19 admitted to the emergency department (ED) were included. Blood samples were collected from each patient at admission. Bio-ADM and IL-6, as well as DPP3 and routinely measured markers were evaluated regarding the endpoints AKI (22/128 hospitalized patients) and a composite endpoint of admission to intensive care unit and/or in-hospital death (n = 26/153 patients). RESULTS: Bio-ADM and IL-6 were significantly elevated in COVID-19 patients with AKI compared to COVID-19 patients without AKI (each p < 0.001). According to ROC analyses IL-6 and bio-ADM had the largest AUC (0.84 and 0.81) regarding the detection of AKI. Furthermore, bio-ADM and IL-6 were significantly elevated in COVID-19 patients reaching the composite endpoint (each p < 0.001). Regarding the composite endpoint ROC analysis showed an AUC of 0.89 for IL-6 and 0.83 for bio-ADM in COVID-19 patients. In the multivariable logistic model bio-ADM and IL-6 presented as independent significant predictors regarding both endpoints AKI and the composite endpoint in COVID-19 patients (as well as creatinine regarding the composite endpoint; each p < 0.05), opposite to leukocytes, C-reactive protein (CRP) and dipeptidyl peptidase 3 (DPP3; each p = n.s.). CONCLUSION: Elevated levels of bio-ADM and IL-6 are associated with AKI and critical illness in patients with COVID-19. Therefore, both biomarkers may be potential tools in risk stratification in COVID-19 patients at presentation in the ED.
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Lesión Renal Aguda , Biomarcadores , COVID-19 , Humanos , Lesión Renal Aguda/diagnóstico , Adrenomedulina/análisis , Biomarcadores/análisis , COVID-19/diagnóstico , Enfermedad Crítica , Mortalidad Hospitalaria , Interleucina-6/análisis , Estudios ProspectivosRESUMEN
INTRODUCTION: Face masks increase airway resistance, data on the actual extent of this effect are scarce. The aim of this study was to assess the effect of different mask types on clinical parameters during moderate exercise in healthy non-smokers, active smokers and patients with interstitial lung disease (ILD) without the need of oxygen therapy. METHODS: In a prospective observational pilot study participants performed a six-minute walk test without mask, with a surgical mask, a well-fitted FFP2 mask and with a valved FFP3 mask. Respiratory rate, blood pressure, heart rate, blood gas analysis parameters, dyspnoea and six-minute walk distance were measured. Data were analysed in an ANOVA model. RESULTS: 21 healthy participants, 17 active smokers without known pulmonary disease and 15 patients with interstitial lung disease were included. Participants with ILD had a significant lower walking distance, a higher respiratory rate and a lower pO2 when using FFP2 masks, but not with valved FFP3 masks or surgical masks compared to not wearing a mask. CONCLUSION: For patients with ILD without the need of oxygen therapy wearing an FFP2 mask had a negative impact on pO2, respiratory rate and walking distance in the six-minute walk test. This effect was not seen with valved FFP3 masks or surgical masks.
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OBJECTIVES: The use of remdesivir (RDV) as the first drug approved for coronavirus disease 2019 (COVID-19) remains controversial. Based on the Lean European Open Survey on severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infected patients (LEOSS), we aim to contribute timing-focused complementary real-world insights to its evaluation. METHODS: SARS-CoV-2 infected patients between January 2020 and December 2021 treated with RDV were matched 1:1 to controls considering sociodemographics, comorbidities and clinical status. Multiple imputations were used to account for missing data. Effects on fatal outcome were estimated using uni- and multivariable Cox regression models. RESULTS: We included 9,687 patients. For those starting RDV administration in the complicated phase, Cox regression for fatal outcome showed an adjusted hazard ratio (aHR) of 0.59 (95%CI 0.41-0.83). Positive trends could be obtained for further scenarios: an aHR of 0.51 (95%CI 0.16-1.68) when RDV was initiated in uncomplicated and of 0.76 (95% CI 0.55-1.04) in a critical phase of disease. Patients receiving RDV with concomitant steroids exhibited a further reduction in aHR in both, the complicated (aHR 0.50, 95%CI 0.29-0.88) and critical phase (aHR 0.63, 95%CI 0.39-1.02). CONCLUSION: Our study results elucidate that RDV use, in particular when initiated in the complicated phase and accompanied by steroids is associated with improved mortality. However, given the limitations of non-randomized trials in estimating the magnitude of the benefit of an intervention, further randomized trials focusing on the timing of therapy initiation seem warranted.
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COVID-19 , Humanos , SARS-CoV-2 , Tratamiento Farmacológico de COVID-19 , Estudios de Cohortes , AntiviralesRESUMEN
INTRODUCTION: The ongoing COVID-19 pandemic is placing an extraordinary burden on our health care system with its limited resources. Accurate triage of patients is necessary to ensure medical care for those most severely affected. In this regard, biomarkers could contribute to risk evaluation. The aim of this prospective observational clinical study was to assess the relationship between urinary N-terminal pro-brain natriuretic peptide (NT-proBNP) and acute kidney injury (AKI) as well as severe disease in patients with COVID-19. METHODS: 125 patients treated with an acute respiratory infection in the emergency department of the University Hospital Regensburg were analyzed. These patients were divided into a COVID-19 cohort (n = 91) and a cohort with infections not caused by severe acute respiratory syndrome-coronavirus-2 (n = 34). NT-proBNP was determined from serum and fresh urine samples collected in the emergency department. Clinical endpoints were the development of AKI and a composite one consisting of AKI, intensive care unit admission, and in-hospital death. RESULTS: 11 (12.1%) COVID-19 patients developed AKI during hospitalization, whereas 15 (16.5%) reached the composite endpoint. Urinary NT-proBNP was significantly elevated in COVID-19 patients who suffered AKI or reached the composite endpoint (each p < 0.005). In a multivariate regression analysis adjusted for age, chronic kidney disease, chronic heart failure, and arterial hypertension, urinary NT-proBNP was identified as independent predictor of AKI (p = 0.017, OR = 3.91 [CI: 1.28-11.97] per standard deviation [SD]), as well as of the composite endpoint (p = 0.026, OR 2.66 [CI: 1.13-6.28] per SD). CONCLUSION: Urinary NT-proBNP might help identify patients at risk for AKI and severe disease progression in COVID-19.
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Lesión Renal Aguda , COVID-19 , Insuficiencia Cardíaca , Humanos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Biomarcadores , COVID-19/complicaciones , Insuficiencia Cardíaca/complicaciones , Mortalidad Hospitalaria , Péptido Natriurético Encefálico , Pandemias , Fragmentos de Péptidos , Pronóstico , Estudios ProspectivosRESUMEN
The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results.
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COVID-19 , Triaje , Humanos , Triaje/métodos , Vías Clínicas , Pandemias , Algoritmos , Servicio de Urgencia en Hospital , Inteligencia ArtificialRESUMEN
INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.
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Pacientes Internos , Pandemias , Humanos , Técnica Delphi , Alemania/epidemiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.
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COVID-19/diagnóstico , SARS-CoV-2 , Seroconversión , Carga Viral , Adulto , Anticuerpos Antivirales , Antígenos Virales , COVID-19/inmunología , Femenino , Humanos , Masculino , Salud Pública , ARN Viral , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/patogenicidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE). METHODS: We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT. RESULTS: Final analysis included 29 patients, whereof 28 patients had surgically proven IE. FDG PET/CT scan was true-positive in 15 patients (sensitivity (SEN) 56%) and false-negative in 12 patients. Combination of Duke criteria (DC) with FDG PET/CT scan resulted in gain of SEN for all patients with confirmed IE (SEN of DC 79% vs SEN of combination DC and FDG PET/CT 89%), driven by a relevant gain in PVE patients only (SEN of DC 78% vs SEN of combination DC and FDG PET/CT 94%). Interestingly, higher prosthesis age was observed in patients with false-negative scans. CONCLUSIONS: We found a SEN of 56% for FDG PET/CT in a real-world cohort of patients with surgically proven IE which was associated with a 16% gain of IE diagnosis in patients with PVE when combined with DC.
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Endocarditis Bacteriana , Endocarditis , Prótesis Valvulares Cardíacas , Endocarditis/diagnóstico por imagen , Endocarditis/cirugía , Endocarditis Bacteriana/diagnóstico , Fluorodesoxiglucosa F18 , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Radiofármacos , Estudios RetrospectivosRESUMEN
PURPOSE: Reported antibiotic use in coronavirus disease 2019 (COVID-19) is far higher than the actual rate of reported bacterial co- and superinfection. A better understanding of antibiotic therapy in COVID-19 is necessary. METHODS: 6457 SARS-CoV-2-infected cases, documented from March 18, 2020, until February 16, 2021, in the LEOSS cohort were analyzed. As primary endpoint, the correlation between any antibiotic treatment and all-cause mortality/progression to the next more advanced phase of disease was calculated for adult patients in the complicated phase of disease and procalcitonin (PCT) ≤ 0.5 ng/ml. The analysis took the confounders gender, age, and comorbidities into account. RESULTS: Three thousand, six hundred twenty-seven cases matched all inclusion criteria for analyses. For the primary endpoint, antibiotic treatment was not correlated with lower all-cause mortality or progression to the next more advanced (critical) phase (n = 996) (both p > 0.05). For the secondary endpoints, patients in the uncomplicated phase (n = 1195), regardless of PCT level, had no lower all-cause mortality and did not progress less to the next more advanced (complicated) phase when treated with antibiotics (p > 0.05). Patients in the complicated phase with PCT > 0.5 ng/ml and antibiotic treatment (n = 286) had a significantly increased all-cause mortality (p = 0.029) but no significantly different probability of progression to the critical phase (p > 0.05). CONCLUSION: In this cohort, antibiotics in SARS-CoV-2-infected patients were not associated with positive effects on all-cause mortality or disease progression. Additional studies are needed. Advice of local antibiotic stewardship- (ABS-) teams and local educational campaigns should be sought to improve rational antibiotic use in COVID-19 patients.
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Programas de Optimización del Uso de los Antimicrobianos , Tratamiento Farmacológico de COVID-19 , Adulto , Antibacterianos/uso terapéutico , Progresión de la Enfermedad , Humanos , SARS-CoV-2RESUMEN
PURPOSE: While more advanced COVID-19 necessitates medical interventions and hospitalization, patients with mild COVID-19 do not require this. Identifying patients at risk of progressing to advanced COVID-19 might guide treatment decisions, particularly for better prioritizing patients in need for hospitalization. METHODS: We developed a machine learning-based predictor for deriving a clinical score identifying patients with asymptomatic/mild COVID-19 at risk of progressing to advanced COVID-19. Clinical data from SARS-CoV-2 positive patients from the multicenter Lean European Open Survey on SARS-CoV-2 Infected Patients (LEOSS) were used for discovery (2020-03-16 to 2020-07-14) and validation (data from 2020-07-15 to 2021-02-16). RESULTS: The LEOSS dataset contains 473 baseline patient parameters measured at the first patient contact. After training the predictor model on a training dataset comprising 1233 patients, 20 of the 473 parameters were selected for the predictor model. From the predictor model, we delineated a composite predictive score (SACOV-19, Score for the prediction of an Advanced stage of COVID-19) with eleven variables. In the validation cohort (n = 2264 patients), we observed good prediction performance with an area under the curve (AUC) of 0.73 ± 0.01. Besides temperature, age, body mass index and smoking habit, variables indicating pulmonary involvement (respiration rate, oxygen saturation, dyspnea), inflammation (CRP, LDH, lymphocyte counts), and acute kidney injury at diagnosis were identified. For better interpretability, the predictor was translated into a web interface. CONCLUSION: We present a machine learning-based predictor model and a clinical score for identifying patients at risk of developing advanced COVID-19.
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COVID-19 , Puntuación de Alerta Temprana , Área Bajo la Curva , COVID-19/diagnóstico , Humanos , Aprendizaje Automático , Estudios Retrospectivos , SARS-CoV-2RESUMEN
The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.
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COVID-19 , Pandemias , Adulto , COVID-19/epidemiología , Niño , Ensayos Clínicos como Asunto , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Proyectos de Investigación , SARS-CoV-2RESUMEN
Pneumonia caused by severe acute respiratory syndrome coronavirus 2 emerged in China at the end of 2019. Because of the severe immunomodulation and lymphocyte depletion caused by this virus and the subsequent administration of drugs directed at the immune system, we anticipated that patients might experience fungal superinfection. We collected data from 186 patients who had coronavirus disease-associated pulmonary aspergillosis (CAPA) worldwide during March-August 2020. Overall, 182 patients were admitted to the intensive care unit (ICU), including 180 with acute respiratory distress syndrome and 175 who received mechanical ventilation. CAPA was diagnosed a median of 10 days after coronavirus disease diagnosis. Aspergillus fumigatus was identified in 80.3% of patient cultures, 4 of which were azole-resistant. Most (52.7%) patients received voriconazole. In total, 52.2% of patients died; of the deaths, 33.0% were attributed to CAPA. We found that the cumulative incidence of CAPA in the ICU ranged from 1.0% to 39.1%.
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Aspergillus fumigatus/aislamiento & purificación , COVID-19 , Unidades de Cuidados Intensivos/estadística & datos numéricos , Aspergilosis Pulmonar , Voriconazol/uso terapéutico , Anciano , Antifúngicos/uso terapéutico , COVID-19/complicaciones , COVID-19/inmunología , COVID-19/mortalidad , COVID-19/terapia , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/efectos adversos , Incidencia , Cooperación Internacional , Masculino , Evaluación de Procesos y Resultados en Atención de Salud , Aspergilosis Pulmonar/diagnóstico , Aspergilosis Pulmonar/tratamiento farmacológico , Aspergilosis Pulmonar/mortalidad , Sistema de Registros , Respiración Artificial/métodos , Factores de Riesgo , SARS-CoV-2/aislamiento & purificaciónRESUMEN
BACKGROUND AND PURPOSE: During acute coronavirus disease 2019 (COVID-19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real-world data from a multinational registry. METHODS: We analyzed COVID-19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS-Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. RESULTS: A total of 6537 COVID-19 patients (97.7% PCR-confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20-1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07-1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short-term outcome of COVID-19. CONCLUSION: Our data on mostly hospitalized COVID-19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short-term outcome. ICB in critical COVID-19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life-threatening systemic viral infection.
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COVID-19 , Enfermedades Neurodegenerativas , Accidente Cerebrovascular , Cefalea , Humanos , SARS-CoV-2RESUMEN
We present four cases with Gram-positive bacteremia (pathogens: MRSA n = 1, Enterococcus spp. n = 3) due to an intravascular source (left ventricular assist device: n = 2, transfemoral aortic valve implantation n = 1, prosthetic aortic valve: n = 1) where no curative treatment was available. These patients received indefinite, chronic suppressive (palliative) therapy with dalbavancin (500 mg weekly or 1000 mg biweekly regimens). Outcomes and clinical characteristics are described; treatment was effective in suppression of bacteremia in all patients over several months (range: 1 to more than 12 months), we observed no relevant side effects.
Asunto(s)
Antibacterianos , Bacteriemia/tratamiento farmacológico , Endocarditis Bacteriana/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Teicoplanina/análogos & derivados , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias Grampositivas/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Teicoplanina/administración & dosificación , Teicoplanina/farmacología , Teicoplanina/uso terapéuticoRESUMEN
PURPOSE: SARS-CoV-2 is a recently emerged ß-coronavirus. Here we present the current knowledge on its epidemiologic features. METHODS: Non-systematic review. RESULTS: SARS-CoV-2 replicates in the upper and lower respiratory tract. It is mainly transmitted by droplets and aerosols from asymptomatic and symptomatic infected subjects. The consensus estimate for the basis reproduction number (R0) is between 2 and 3, and the median incubation period is 5.7 (range 2-14) days. Similar to SARS and MERS, superspreading events have been reported, the dispersion parameter (kappa) is estimated at 0.1. Most infections are uncomplicated, and 5-10% of patients are hospitalized, mainly due to pneumonia with severe inflammation. Complications are respiratory and multiorgan failure; risk factors for complicated disease are higher age, hypertension, diabetes, chronic cardiovascular, chronic pulmonary disease and immunodeficiency. Nosocomial and infections in medical personnel have been reported. Drastic reductions of social contacts have been implemented in many countries with outbreaks of SARS-CoV-2, leading to rapid reductions. Most interventions have used bundles, but which of the measures have been more or less effective is still unknown. The current estimate for the infection's fatality rate is 0.5-1%. Using current models of age-dependent infection fatality rates, upper and lower limits for the attack rate in Germany can be estimated between 0.4 and 1.6%, lower than in most European countries. CONCLUSIONS: Despite a rapid worldwide spread, attack rates have been low in most regions, demonstrating the efficacy of control measures.