ORCID Profile
0000-0001-6970-2869
Current Organisations
University Hospital of Geneva
,
University of St Andrews
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Publisher: Wiley
Date: 18-12-2011
Publisher: American Geophysical Union (AGU)
Date: 04-06-2019
DOI: 10.1029/2018GL081339
Publisher: Elsevier BV
Date: 04-2023
Publisher: Elsevier BV
Date: 10-2019
Publisher: Elsevier BV
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 07-03-2022
DOI: 10.1038/S41586-022-04576-6
Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from in iduals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill in iduals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling ( IL10RB and PLSCR1 ), leucocyte differentiation ( BCL11A ) and blood-type antigen secretor status ( FUT2 ). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase ( ATP11A ), and increased expression of a mucin ( MUC1 )—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules ( SELE , ICAM5 and CD209 ) and the coagulation factor F8 , all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
Publisher: Oxford University Press (OUP)
Date: 29-07-2021
DOI: 10.1093/JAC/DKAB259
Abstract: To evaluate the safety and efficacy of cidofovir for the treatment of double-stranded DNA (dsDNA) viral infections following allogeneic haematopoietic cell transplant (HCT). This was a retrospective multicentre cohort study including adult HCT recipients who received ≥1 dose of IV-administered cidofovir for any dsDNA viral infection from 2006 to 2019. The objectives were to describe the rate of and risk factors for nephrotoxicity and virological response by the end of treatment (EOT). We included 165 patients from nine centres. Cidofovir was administered at 5 mg/kg/week (N = 115 69.7%), 1 mg/kg/week (18 10.9%), 3 mg/kg/week (12 7.3%) or 1 mg/kg three times/week (11 6.7%). Cidofovir was administered for adenovirus, cytomegalovirus (CMV) and BK virus infection in 75 (45.5%), 64 (38.8%) and 51 (30.9%) patients, respectively. Among 158 patients with renal function data at baseline and EOT, 40 (25.3%) developed nephrotoxicity. In multivariable analyses, age (OR 1.04 P = 0.05), weight (OR 1.05 P = 0.01), CMV infection (OR 3.6 P = 0.02), liposomal hotericin B (OR 8.06 P = 0.05) and IV voriconazole osaconazole (OR 13.0 P = 0.003) were predictors of nephrotoxicity. Creatinine concentration was significantly higher at EOT (1.16 ± 0.95 mg/dL) compared with baseline (0.91 ± 0.39 mg/dL P & 0.001), but improved by 2 weeks (0.91 ± 0.84 mg/dL P = 0.007) and 4 weeks (0.96 ± 0.89 mg/dL P = 0.03) post-EOT. Median viral load significantly declined for patients with adenovirus DNAaemia by EOT (P & 0.0001) and for patients with CMV DNAaemia by EOT + 4 weeks (P = 0.003), but not for patients with BK virus DNAaemia. One in four HCT recipients treated with IV cidofovir developed largely reversible nephrotoxicity. Careful selection of patients and close follow-up of renal function may minimize toxicity.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Wiley
Date: 18-06-2021
DOI: 10.1111/GBI.12459
Abstract: Due to their potential to support chemolithotrophic life, relic hydrothermal systems on Mars are a key target for astrobiological exploration. We analysed water and sediments at six geothermal pools from the rhyolitic Kerlingarfjöll and basaltic Kverkfjöll volcanoes in Iceland, to investigate the localised controls on the habitability of these systems in terms of microbial community function. Our results show that host lithology plays a minor role in pool geochemistry and authigenic mineralogy, with the system geochemistry primarily controlled by deep volcanic processes. We find that by dictating pool water pH and redox conditions, deep volcanic processes are the primary control on microbial community structure and function, with water input from the proximal glacier acting as a secondary control by regulating pool temperatures. Kerlingarfjöll pools have reduced, circum‐neutral CO 2 ‐rich waters with authigenic calcite‐, pyrite‐ and kaolinite‐bearing sediments. The dominant metabolisms inferred from community profiles obtained by 16S rRNA gene sequencing are methanogenesis, respiration of sulphate and sulphur (S 0 ) oxidation. In contrast, Kverkfjöll pools have oxidised, acidic (pH 3) waters with high concentrations of SO 4 2‐ and high argillic alteration, resulting in Al‐phyllosilicate‐rich sediments. The prevailing metabolisms here are iron oxidation, sulphur oxidation and nitrification. Where analogous ice‐fed hydrothermal systems existed on early Mars, similar volcanic processes would likely have controlled localised metabolic potential and thus habitability. Moreover, such systems offer several habitability advantages, including a localised source of metabolic redox pairs for chemolithotrophic microorganisms and accessible trace metals. Similar pools could have provided transient environments for life on Mars when paired with surface or near‐surface ice, these habitability niches could have persisted into the Amazonian. Additionally, they offer a confined site for biosignature formation and deposition that lends itself well to in situ robotic exploration.
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 08-07-2021
DOI: 10.1038/S41586-021-03767-X
Abstract: The genetic make-up of an in idual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United States of America
Location: Greece
Location: United States of America
No related grants have been discovered for Dionysios Neofytos.