ORCID Profile
0000-0003-0883-0423
Current Organisations
University Hospital of Basel
,
University of Basel
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Publisher: Oxford University Press (OUP)
Date: 08-09-2017
DOI: 10.1093/JAC/DKX324
Abstract: To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT. Review of English literature and evidence-based recommendations by expert consensus. BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use. BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-10-2012
Publisher: American Association for the Advancement of Science (AAAS)
Date: 04-02-2022
Abstract: We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine in iduals with this variant had a 0.54 to 0.74 log
Publisher: SMW Supporting Association
Date: 10-08-2021
Abstract: OBJECTIVES Patients with severe COVID-19 may be at risk of longer term sequelae. Long-term clinical, immunological, pulmonary and radiological outcomes of patients treated with anti-inflammatory drugs are lacking. METHODS In this single-centre prospective cohort study, we assessed 90-day clinical, immunological, pulmonary and radiological outcomes of hospitalised patients with severe COVID-19 treated with tocilizumab from March 2020 to May 2020. Criteria for tocilizumab administration were oxygen saturation %, respiratory rate /min, C-reactive protein levels mg/l, extensive area of ground-glass opacities or progression on computed tomography (CT). Descriptive analyses were performed using StataIC 16. RESULTS Between March 2020 and May 2020, 50 (27%) of 186 hospitalised patients had severe COVID-19 and were treated with tocilizumab. Of these, 52% were hospitalised on the intensive care unit (ICU) and 12% died. Eleven (22%) patients developed at least one microbiologically confirmed super-infection, of which 91% occurred on ICU. Median duration of hospitalisation was 15 days (interquartile range [IQR] 10–24) with 24 days (IQR 14–32) in ICU patients and 10 days (IQR 7–15) in non-ICU patients. At day 90, 41 of 44 survivors (93%) were outpatients. No long-term adverse events or late-onset infections were identified after acute hospital care. High SARS-CoV-2 antibody titres were found in all but one patient, who was pretreated with rituximab. Pulmonary function tests showed no obstructive patterns, but restrictive patterns in two (5.7%) and impaired diffusion capacities for carbon monoxide in 11 (31%) of 35 patients, which predominated in prior ICU patients. Twenty-one of 35 (60%) CT-scans at day 90 showed residual abnormalities, with similar distributions between prior ICU and non-ICU patients. CONCLUSIONS In this cohort of severe COVID-19 patients, no tocilizumab-related long-term adverse events or late-onset infections were identified. Although chest CT abnormalities were highly prevalent at day 90, the majority of patients showed normal lung function. Trial registration ClinicalTrials.gov NCT04351503
Publisher: Public Library of Science (PLoS)
Date: 06-11-2201
Publisher: Public Library of Science (PLoS)
Date: 19-03-2021
DOI: 10.1371/JOURNAL.PPAT.1009374
Abstract: The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26 th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26 th until March 23 rd . We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic ersity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2 nd , although the first s le identified belonged to B.1.1. Within B.1, 68·2% of our s les fall within a clade defined by the SNP C15324T (‘Basel cluster’), including 157 identical sequences at the root of the ‘Basel cluster’, some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503 .
Publisher: Cold Spring Harbor Laboratory
Date: 05-09-2020
DOI: 10.1101/2020.09.01.20186155
Abstract: The first case of SARS-CoV-2 in Basel, Switzerland, was detected on February 26 th 2020. We present a phylogenetic longitudinal study and explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26 th until March 23 rd . We sequenced SARS-CoV-2 from naso-oropharyngeal swabs, generated 468 high quality genomes, and called variants with our COVID-19 Pipeline (COVGAP). We analysed viral genetic ersity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected from March 2 nd , although the first lineage identified was B.1.1. Within B.1, a clade containing 68·2% of our s les, defined by the SNP C15324T, suggests local spreading events. We infer the geographic origin of this mutation to our tri-national region. The remaining genomes map broadly over the global phylogenetic tree, evidencing several events of introduction from and/or dissemination to other regions of the world. We also observe family transmission events. A single lineage dominated the outbreak in the City of Basel while other lineages such as the first (B1.1) did not propagate. Thus spreading events seem to have contributed most to viral spread, while travel returners and family transmissions were better controlled by the recommended measures. This phylogenetic analysis enriches epidemiological and contact tracing data, allowing connection of seemingly unconnected events, and can inform public health interventions. No dedicated funding was used for this work.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2011
Publisher: Cold Spring Harbor Laboratory
Date: 04-01-2021
DOI: 10.1101/2020.12.28.20248663
Abstract: Antiviral treatments for COVID-19 have involved many repurposed drugs. Currently, SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8 ) has been targeted by numerous inhibitors with debated clinical impact. Among these, remdesivir has been conditionally approved for the treatment of COVID-19 patients. Although the emergence of antiviral resistance, an indirect proxy for antiviral efficacy, poses a considerable healthcare threat, an evolutionary perspective on emerging resistant mutants is still lacking. Here we show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare, and unlikely to lead to viral fitness loss. In more than 56,000 viral genomes from 105 countries dating from December 2019 to July 2020 we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Those affected known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations found globally, in silico structural models show that this rarely implies loss of stability in RdRp. No potential escape mutation were found in our local cohort of remdesivir treated patients from the first wave (n=8). Our results indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. Our study could be the starting point of a larger monitoring effort of drug resistance throughout the COVID-19 pandemic. We recommend the application of repetitive genome sequencing of SARS-CoV-2 from patients treated with antivirals to provide early insights into the evolution or antiviral resistance.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-09-2010
Publisher: MDPI AG
Date: 19-05-2021
DOI: 10.3390/MICROORGANISMS9051094
Abstract: A variety of antiviral treatments for COVID-19 have been investigated, involving many repurposed drugs. Currently, the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp, encoded by nsp12-nsp7-nsp8) has been targeted by numerous inhibitors, e.g., remdesivir, the only provisionally approved treatment to-date, although the clinical impact of these interventions remains inconclusive. However, the potential emergence of antiviral resistance poses a threat to the efficacy of any successful therapies on a wide scale. Here, we propose a framework to monitor the emergence of antiviral resistance, and as a proof of concept, we address the interaction between RdRp and remdesivir. We show that SARS-CoV-2 RdRp is under purifying selection, that potential escape mutations are rare in circulating lineages, and that those mutations, where present, do not destabilise RdRp. In more than 56,000 viral genomes from 105 countries from the first pandemic wave, we found negative selective pressure affecting nsp12 (Tajima’s D = −2.62), with potential antiviral escape mutations in only 0.3% of sequenced genomes. Potential escape mutations included known key residues, such as Nsp12:Val473 and Nsp12:Arg555. Of the potential escape mutations involved globally, in silico structural models found that they were unlikely to be associated with loss of stability in RdRp. No potential escape mutation was found in a local cohort of remdesivir treated patients. Collectively, these findings indicate that RdRp is a suitable drug target, and that remdesivir does not seem to exert high selective pressure. We anticipate our framework to be the starting point of a larger effort for a global monitoring of drug resistance throughout the COVID-19 pandemic.
Publisher: Elsevier BV
Date: 08-2014
Abstract: B cells in airways and lung parenchyma may be involved in COPD evolution however, whether their pathogenic role is beneficial or harmful remains controversial. The objective of this study was to investigate the maturation of adenovirus-specific immunoglobulins in patients with COPD with respect to clinical outcome. The presence of adenovirus-specific immunoglobulins during acute exacerbation of COPD (AECOPD) was analyzed at exacerbation and 2 to 3 weeks later. Patients with detectable adenovirus-specific IgM and low IgG avidity were grouped into fast and delayed IgG maturation. The clinical outcome of both groups was evaluated. Of 208 patients, 43 (20.7%) had serologic evidence of recent adenovirus infection and were grouped by fast IgG maturation (26 patients) and delayed IgG maturation (17 patients). Baseline characteristics, AECOPD therapy, and duration of hospitalization were similar in both groups, but the AECOPD recurrence rate within 6 months was higher (P = .003), and there was a trend for earlier AECOPD-related rehospitalizations (P = .061) in the delayed IgG maturation group. The time to rehospitalization or death within 2 years was shorter in patients with delayed IgG maturation (P = .003). Adenovirus-specific IgG maturation was an independent predictor of the number of AECOPD recurrences within 6 months (P = .001) and the occurrence of hospitalization or death within 2 years (P = .005). Delayed immunoglobulin avidity maturation following COPD exacerbation is associated with worse outcomes. ISRCTN Register No.: ISRCTN77261143 URL: www.isrctn.org.
No related grants have been discovered for Hans H. Hirsch.