Publications by authors named "Leif E Sander"

Background: COVID-19 vaccines are well tolerated and effective but may have adverse effects on the cardiovascular system. Vaccine-associated myocardial injury was analysed by measuring high-sensitive troponin T (hsTnT); mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction.

Methods: This was a prospective study with a vulnerable population of healthcare workers (HCWs) and elderly patients (>70 years) who were vaccinated with either one dose of ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) followed by one dose of the BNT162b2 messenger RNA vaccine (BNT), or with two doses of BNT (12th of January - 30th of November 2021).

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Rsv (respiratory Syncytial Virus): RSV is a common cause of respiratory tract infections, posing a risk of severe disease, particularly for newborns and infants, as well as in older individuals with pre-existing conditions. Two safe and effective RSV vaccines were approved in 2023. These vaccines elicit protective antibodies and offer robust protection with no additional benefit from annual boosters.

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Background: Patients with post-COVID-19 condition frequently suffer from chronic dyspnoea. The causes and mechanism for dyspnoea in these patients without evidence of structural lung disease are unclear.

Methods: Patients treated for COVID-19 at Charité University Hospital in Berlin received pulmonary function testing including respiratory muscle strength tests and completed health-related quality-of-life questionnaires during follow-up.

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Purpose: Infective endocarditis caused by non-HACEK gram-negative bacilli (GNB-IE) is rare but associated with significant morbidity and case fatality. Evidence on optimal treatment and management is limited. We aimed to describe the characteristics and management of GNB-IE patients, investigating factors associated with disease acquisition and unfavorable outcomes.

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SARS-COV-2 : During the COVID-19 pandemic, mRNA-based vaccines were approved for the first time. The mRNA encodes for the viral spike protein, leading to the development of specific antibodies and T-cells, providing effective protection against severe illness and death from COVID-19. New variants regularly emerge due to rapid viral evolution.

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The clinical course of COVID-19 is variable and often unpredictable. To test the hypothesis that disease progression and inflammatory responses associate with alterations in the microbiome and metabolome, we analyzed metagenome, metabolome, cytokine, and transcriptome profiles of repeated samples from hospitalized COVID-19 patients and uninfected controls, and leveraged clinical information and post-hoc confounder analysis. Severe COVID-19 was associated with a depletion of beneficial intestinal microbes, whereas oropharyngeal microbiota disturbance was mainly linked to antibiotic use.

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Dexamethasone is a life-saving treatment for severe COVID-19, yet its mechanism of action is unknown, and many patients deteriorate or die despite timely treatment initiation. Here, we identify dexamethasone treatment-induced cellular and molecular changes associated with improved survival in COVID-19 patients. We observed a reversal of transcriptional hallmark signatures in monocytes associated with severe COVID-19 and the induction of a monocyte substate characterized by the expression of glucocorticoid-response genes.

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Medicine in Germany is currently facing major structural and economic challenges. Infectious Diseases, with the recent introduction of a new specialty in "Internal Medicine and Infectious Diseases" and with the existing additional training for almost all specializations, will make an important contribution to overcoming these challenges. Expertise in infectious diseases has to be very broad and requires high interdisciplinarity, which makes infectious diseases an attractive and demanding specialty.

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Identifying immune modulators that impact neutralizing antibody responses against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is of great relevance. We postulated that high serum concentrations of soluble angiotensin-converting enzyme 2 (sACE2) might mask the spike and interfere with antibody maturation toward the SARS-CoV-2-receptor-binding motif (RBM). We tested 717 longitudinal samples from 295 COVID-19 patients and showed a 2- to 10-fold increase of enzymatically active sACE2 (a-sACE2), with up to 1 μg/mL total sACE2 in moderate and severe patients.

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Background: Cases of mpox have been reported worldwide since May 2022. Limited knowledge exists regarding the long-term course of this disease. To assess sequelae in terms of scarring and quality of life (QoL) in mpox patients 4-6 months after initial infection.

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Pandemics and epidemic outbreaks caused by emerging pathogens can usually only be curbed in the longterm through establishment of protective population-wide immunity. With the unprecedented rapid development and supply of highly effective vaccines against COVID-19, science and industry delivered the critical medical breakthrough for the successful management of the COVID-19 pandemic. By May 2023, WHO could end the public health emergency.

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Disease-modifying therapies (DMTs) are widely used in neuroimmunological diseases such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Although these treatments are known to predispose patients to infections and affect their responses to vaccination, little is known about the impact of DMTs on the myeloid cell compartment. In this study, we use mass cytometry to examine DMT-associated changes in the innate immune system in untreated and treated patients with MS (n = 39) or NMOSD (n = 23).

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The COVID-19 pandemic has spurred large-scale, interinstitutional research efforts. To enable these efforts, researchers must agree on data set definitions that not only cover all elements relevant to the respective medical specialty but also are syntactically and semantically interoperable. Therefore, the German Corona Consensus (GECCO) data set was developed as a harmonized, interoperable collection of the most relevant data elements for COVID-19-related patient research.

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The structure-based design of antigens holds promise for developing vaccines with higher efficacy and improved safety profiles. We postulate that abrogation of host receptor interaction bears potential for the improvement of vaccines by preventing antigen-induced modification of receptor function as well as the displacement or masking of the immunogen. Antigen modifications may yet destroy epitopes crucial for antibody neutralization.

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Background: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19).

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Clinical expertise in infectious diseases is crucial in treating patients with infectious complications. The new board certification in infectious diseases will establish this expertise in Germany. The role of the specialty of infectious diseases in German hospitals and the definition for clinical services in hospitals (levels 2 and 3) are outlined here.

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The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms. However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS.

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Antiviral CD8 T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4 T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/β or CD40 alone.

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Background: Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors.

Methods: This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients.

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Introduction: The SARS-CoV-2 pandemic remains a threat to public health. Soon after its outbreak, it became apparent that children are less severely affected. Indeed, opposing clinical manifestations between children and adults are observed for other infections.

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The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study.

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BACKGROUNDAfter its introduction as standard-of-care for severe COVID-19, dexamethasone has been administered to a large number of patients globally. Detailed knowledge of its impact on the cellular and humoral immune response to SARS-CoV-2 remains scarce.METHODSWe included immunocompetent individuals with (a) mild COVID-19, (b) severe COVID-19 before introduction of dexamethasone treatment, and (c) severe COVID-19 infection treated with dexamethasone from prospective observational cohort studies at Charité-Universitätsmedizin Berlin, Germany.

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Article Synopsis
  • * Researchers found elevated levels of soluble ACE2 (sACE2) and anti-ACE2 IgG in critically ill COVID-19 patients, but these levels did not correlate well with each other.
  • * The findings suggest that many autoantibodies may show broad reactivity without significantly impacting key viral proteins or immune functions, challenging the interpretation of autoimmunity in COVID-19.
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