Harald Brüssow

Bio: Harald Brüssow is an academic researcher from Katholieke Universiteit Leuven. The author has contributed to research in topics: Prophage & Negativicutes. The author has an hindex of 10, co-authored 36 publications receiving 369 citations.

Problems with the concept of gut microbiota dysbiosis.

Abstract: The human microbiome research is with the notable exception of fecal transplantation still mostly in a descriptive phase. Part of the difficulty for translating research into medical interventions is due to the large compositional complexity of the microbiome resulting in datasets that need sophisticated statistical methods for their analysis and do not lend to industrial applications. Another part of the difficulty might be due to logical flaws in terminology particularly concerning 'dysbiosis' that avoids circular conclusions and is based on sound ecological and evolutionary reasoning. Many case-control studies are underpowered necessitating more meta-analyses that sort out consistent from spurious dysbiosis-disease associations. We also need for the microbiome a transition from statistical associations to causal relationships with diseases that fulfil a set of modified Koch's postulates for commensals. Disturbingly, the most sophisticated statistical analyses explain only a small percentage of the variance in the microbiome. Microbe-microbe interactions irrelevant to the host and stochastic processes might play a greater role than anticipated. To satisfy the concept of Karl Popper about conjectures and refutations in the scientific process, we should also conduct more experiments that try to refute the role of the commensal gut microbiota for human health and disease.

Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo-controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers

Abstract: Bacteriophage therapy is a commonly used treatment for Staphylococcus aureus infections in countries of the former Soviet Union, using both single phages and phage cocktails. The scarce data available on Eastern phage cocktails prompted an investigation into commercially-available Pyophage cocktails from two different manufacturers used to treat skin and wound infections. Comparison of the metagenomic composition of two Pyophage products from Georgia and Russia revealed substantial differences in phage-types targeting Escherichia, Enterococcus, Salmonella, Pseudomonas aeruginosa and Proteus, therefore indicating multiple strategies for composing phage cocktails against these bacterial pathogens. Closely-related Kayvirus-like Myoviruses were, however, a shared component against S. aureus within all products, except for the inclusion of a secondary S. aureus Podovirus in one Microgen cocktail. Metagenomic analysis also revealed the presence of several probable prophage sequences but detected no genetic safety risks in terms of virulence factors or antibiotic resistance genes. The safety of broad-spectrum cocktails was tested by comparing the effects of nasal and oral exposure to Eliava Pyophage, a monospecies counterpart and placebo in healthy human carriers of S. aureus. The lack of adverse effects in any treatment groups supports the clinical safety of S. aureus phages administered as a single phage or as phage cocktail.

The Novel Coronavirus - A Snapshot of Current Knowledge.

Abstract: Another animal to human transmission of a coronavirus occurred in December 2019 on a live animal market in the Chinese city of Wuhan causing an epidemic in China, reaching now different continents. This minireview summarizes the research literature on the virological, clinical and epidemiological aspects of this epidemic published until end of February 2020.

Clinical evidence that the pandemic from 1889 to 1891 commonly called the Russian flu might have been an earlier coronavirus pandemic.

Abstract: Contemporary medical reports from Britain and Germany on patients suffering from a pandemic infection between 1889 and 1891, which was historically referred to as the Russian flu, share a number of characteristics with COVID-19. Most notable are aspects of multisystem affections comprising respiratory, gastrointestinal and neurological symptoms including loss of taste and smell perception; a protracted recovery resembling long covid and pathology observations of thrombosis in multiple organs, inflammation and rheumatic affections. As in COVID-19 and unlike in influenza, mortality was seen in elderly subjects while children were only weakly affected. Contemporary reports noted trans-species infection between pet animals or horses and humans, which would concur with a cross-infection by a broad host range bovine coronavirus dated by molecular clock arguments to an about 1890 cross-species infection event.

Immunology of COVID-19.

Abstract: The immune response to SARS-CoV-2 reveals a delicate balance between protective effects and harmful pathological reactions and can possibly explain the highly variable disease manifestations in subjects infected with this novel coronavirus. A better understanding of the anti-viral immune response is not only critical for vaccine development but might also provide targets for pharmaceutical and immunological treatment options. Recent research literature on immune aspects of COVID-19 is summarized in this review with an outlook how bats have evolved to live with these viral infections.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Abstract: The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

SARS-CoV-2 receptor ACE2 and TMPRSS2 are primarily expressed in bronchial transient secretory cells.

Abstract: The SARS-CoV-2 pandemic affecting the human respiratory system severely challenges public health and urgently demands for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and replication. SARS-CoV-2 was reported to enter cells via binding to ACE2, followed by its priming by TMPRSS2. Here, we investigate ACE2 and TMPRSS2 expression levels and their distribution across cell types in lung tissue (twelve donors, 39,778 cells) and in cells derived from subsegmental bronchial branches (four donors, 17,521 cells) by single nuclei and single cell RNA sequencing, respectively. While TMPRSS2 is strongly expressed in both tissues, in the subsegmental bronchial branches ACE2 is predominantly expressed in a transient secretory cell type. Interestingly, these transiently differentiating cells show an enrichment for pathways related to RHO GTPase function and viral processes suggesting increased vulnerability for SARS-CoV-2 infection. Our data provide a rich resource for future investigations of COVID-19 infection and pathogenesis.

Microbiome definition re-visited: old concepts and new challenges

Abstract: The field of microbiome research has evolved rapidly over the past few decades and has become a topic of great scientific and public interest. As a result of this rapid growth in interest covering different fields, we are lacking a clear commonly agreed definition of the term “microbiome.” Moreover, a consensus on best practices in microbiome research is missing. Recently, a panel of international experts discussed the current gaps in the frame of the European-funded MicrobiomeSupport project. The meeting brought together about 40 leaders from diverse microbiome areas, while more than a hundred experts from all over the world took part in an online survey accompanying the workshop. This article excerpts the outcomes of the workshop and the corresponding online survey embedded in a short historical introduction and future outlook. We propose a definition of microbiome based on the compact, clear, and comprehensive description of the term provided by Whipps et al. in 1988, amended with a set of novel recommendations considering the latest technological developments and research findings. We clearly separate the terms microbiome and microbiota and provide a comprehensive discussion considering the composition of microbiota, the heterogeneity and dynamics of microbiomes in time and space, the stability and resilience of microbial networks, the definition of core microbiomes, and functionally relevant keystone species as well as co-evolutionary principles of microbe-host and inter-species interactions within the microbiome. These broad definitions together with the suggested unifying concepts will help to improve standardization of microbiome studies in the future, and could be the starting point for an integrated assessment of data resulting in a more rapid transfer of knowledge from basic science into practice. Furthermore, microbiome standards are important for solving new challenges associated with anthropogenic-driven changes in the field of planetary health, for which the understanding of microbiomes might play a key role.