Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Infective Endocarditis in Patients on Chronic Hemodialysis

295sinoneBackground: Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives: This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods: Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results: A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non–HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p &lt; 0.001). Cardiac surgery was less frequently performed among HD patients (30.6% vs. 46.2%; p &lt; 0.001), whereas relapses were higher (9.4% vs. 2.7%; p &lt; 0.001). Risk factors for 6-month mortality included Charlson score (hazard ratio [HR]: 1.26; 95% confidence interval [CI]: 1.11 to 1.44; p = 0.001), CNS emboli and other emboli (HR: 3.11; 95% CI: 1.84 to 5.27; p &lt; 0.001; and HR: 1.73; 95% CI: 1.02 to 2.93; p = 0.04, respectively), persistent bacteremia (HR: 1.79; 95% CI: 1.11 to 2.88; p = 0.02), and acute onset heart failure (HR: 2.37; 95% CI: 1.49 to 3.78; p &lt; 0.001). Conclusions: HD-IE is a health care–associated infection chiefly caused by S. aureus, with increasing rates of enterococcal IE. Mortality and relapses are very high and significantly larger than in non–HD-IE patients, whereas cardiac surgery is less frequently performed.nonePericas J.M.; Llopis J.; Jimenez-Exposito M.J.; Kourany W.M.; Almirante B.; Carosi G.; Durante-Mangoni E.; Fortes C.Q.; Giannitsioti E.; Lerakis S.; Montagna-Mella R.; Ambrosioni J.; Tan R.-S.; Mestres C.A.; Wray D.; Pachirat O.; Moreno A.; Chu V.H.; de Lazzari E.; Fowler V.G.; Miro J.M.; Clara L.; Sanchez M.; Casabe J.; Cortes C.; Nacinovich F.; Oses P.F.; Ronderos R.; Sucari A.; Thierer J.; Altclas J.; Kogan S.; Spelman D.; Athan E.; Harris O.; Kennedy K.; Tan R.; Gordon D.; Papanicolas L.; Korman T.; Kotsanas D.; Dever R.; Jones P.; Konecny P.; Lawrence R.; Rees D.; Ryan S.; Feneley M.P.; Harkness J.; Post J.; Reinbott P.; Gattringer R.; Wiesbauer F.; Andrade A.R.; Passos de Brito A.C.; Guimaraes A.C.; Grinberg M.; Mansur A.J.; Siciliano R.F.; Varejao Strabelli T.M.; Campos Vieira M.L.; de Medeiros Tranchesi R.A.; Paiva M.G.; de Oliveira Ramos A.; Weksler C.; Ferraiuoli G.; Golebiovski W.; Lamas C.; Karlowsky J.A.; Keynan Y.; Morris A.M.; Rubinstein E.; Jones S.B.; Garcia P.; Cereceda M.; Fica A.; Mella R.M.; Fernandez R.; Franco L.; Gonzalez J.; Jaramillo A.N.; Barsic B.; Bukovski S.; Krajinovic V.; Pangercic A.; Rudez I.; Vincelj J.; Freiberger T.; Pol J.; Zaloudikova B.; Ashour Z.; El Kholy A.; Mishaal M.; Osama D.; Rizk H.; Aissa N.; Alauzet C.; Alla F.; Campagnac C.C.; Doco-Lecompte T.; Selton-Suty C.; Casalta J.-P.; Fournier P.-E.; Habib G.; Raoult D.; Thuny F.; Delahaye F.; Delahaye A.; Vandenesch F.; Donal E.; Donnio P.Y.; Flecher E.; Michelet C.; Revest M.; Tattevin P.; Chevalier F.; Jeu A.; Remadi J.P.; Rusinaru D.; Tribouilloy C.; Bernard Y.; Chirouze C.; Hoen B.; Leroy J.; Plesiat P.; Naber C.; Neuerburg C.; Mazaheri B.; Sophia Athanasia C.N.; Deliolanis I.; Giamarellou H.; Thomas T.; Mylona E.; Paniara O.; Papanicolaou K.; Pyros J.; Skoutelis A.; Papanikolaou K.; Sharma G.; Francis J.; Nair L.; Thomas V.; Venugopal K.; Hannan M.M.; Hurley J.P.; Wanounou M.; Gilon D.; Israel S.; Korem M.; Strahilevitz J.; Iossa D.; Orlando S.; Ursi M.P.; Pafundi P.C.; D'Amico F.; Bernardo M.; Cuccurullo S.; Dialetto G.; Covino F.E.; Manduca S.; Della Corte A.; De Feo M.; Tripodi M.F.; Cecchi E.; De Rosa F.; Forno D.; Imazio M.; Trinchero R.; Grossi P.; Lattanzio M.; Toniolo A.; Goglio A.; Raglio A.; Ravasio V.; Rizzi M.; Suter F.; Magri S.; Signorini L.; Kanafani Z.; Kanj S.S.; Sharif-Yakan A.; Abidin I.; Tamin S.S.; Martinez E.R.; Soto Nieto G.I.; van der Meer J.T.M.; Chambers S.; Holland D.; Morris A.; Raymond N.; Read K.; Murdoch D.R.; Dragulescu S.; Ionac A.; Mornos C.; Butkevich O.M.; Chipigina N.; Kirill O.; Vadim K.; Vinogradova T.; Edathodu J.; Halim M.; Liew Y.-Y.; Lejko-Zupanc T.; Logar M.; Mueller-Premru M.; Commerford P.; Commerford A.; Deetlefs E.; Hansa C.; Ntsekhe M.; Almela M.; Azqueta M.; Brunet M.; Castro P.; Falces C.; Fuster D.; Fita G.; Garcia- de- la- Maria C.; Garcia-Gonzalez J.; Gatell J.M.; Marco F.; Miro J.M.; Ortiz J.; Ninot S.; Pare J.C.; Pericas J.M.; Quintana E.; Ramirez J.; Rovira I.; Sandoval E.; Sitges M.; Tellez A.; Tolosana J.M.; Vidal B.; Vila J.; Anguera I.; Font B.; Guma J.R.; Bermejo J.; Bouza E.; Garcia Fernandez M.A.; Gonzalez-Ramallo V.; Marin M.; Munoz P.; Pedromingo M.; Roda J.; Rodriguez-Creixems M.; Solis J.; Fernandez-Hidalgo N.; Tornos P.; de Alarcon A.; Parra R.; Alestig E.; Johansson M.; Olaison L.; Snygg-Martin U.; Pachirat P.; Pussadhamma B.; Senthong V.; Casey A.; Elliott T.; Lambert P.; Watkin R.; Eyton C.; Klein J.L.; Bradley S.; Kauffman C.; Bedimo R.; Corey G.R.; Crowley A.L.; Douglas P.; Drew L.; Holland T.; Lalani T.; Mudrick D.; Samad Z.; Sexton D.; Stryjewski M.; Wang A.; Woods C.W.; Cantey R.; Steed L.; Dickerman S.A.; Bonilla H.; DiPersio J.; Salstrom S.-J.; Baddley J.; Patel M.; Peterson G.; Stancoven A.; Levine D.; Riddle J.; Rybak M.; Cabell C.H.Pericas, J. M.; Llopis, J.; Jimenez-Exposito, M. J.; Kourany, W. M.; Almirante, B.; Carosi, G.; Durante-Mangoni, E.; Fortes, C. Q.; Giannitsioti, E.; Lerakis, S.; Montagna-Mella, R.; Ambrosioni, J.; Tan, R. -S.; Mestres, C. A.; Wray, D.; Pachirat, O.; Moreno, A.; Chu, V. H.; de Lazzari, E.; Fowler, V. G.; Miro, J. M.; Clara, L.; Sanchez, M.; Casabe, J.; Cortes, C.; Nacinovich, F.; Oses, P. F.; Ronderos, R.; Sucari, A.; Thierer, J.; Altclas, J.; Kogan, S.; Spelman, D.; Athan, E.; Harris, O.; Kennedy, K.; Tan, R.; Gordon, D.; Papanicolas, L.; Korman, T.; Kotsanas, D.; Dever, R.; Jones, P.; Konecny, P.; Lawrence, R.; Rees, D.; Ryan, S.; Feneley, M. P.; Harkness, J.; Post, J.; Reinbott, P.; Gattringer, R.; Wiesbauer, F.; Andrade, A. R.; Passos de Brito, A. C.; Guimaraes, A. C.; Grinberg, M.; Mansur, A. J.; Siciliano, R. F.; Varejao Strabelli, T. M.; Campos Vieira, M. L.; de Medeiros Tranchesi, R. A.; Paiva, M. G.; de Oliveira Ramos, A.; Weksler, C.; Ferraiuoli, G.; Golebiovski, W.; Lamas, C.; Karlowsky, J. A.; Keynan, Y.; Morris, A. M.; Rubinstein, E.; Jones, S. B.; Garcia, P.; Cereceda, M.; Fica, A.; Mella, R. M.; Fernandez, R.; Franco, L.; Gonzalez, J.; Jaramillo, A. N.; Barsic, B.; Bukovski, S.; Krajinovic, V.; Pangercic, A.; Rudez, I.; Vincelj, J.; Freiberger, T.; Pol, J.; Zaloudikova, B.; Ashour, Z.; El Kholy, A.; Mishaal, M.; Osama, D.; Rizk, H.; Aissa, N.; Alauzet, C.; Alla, F.; Campagnac, C. C.; Doco-Lecompte, T.; Selton-Suty, C.; Casalta, J. -P.; Fournier, P. -E.; Habib, G.; Raoult, D.; Thuny, F.; Delahaye, F.; Delahaye, A.; Vandenesch, F.; Donal, E.; Donnio, P. Y.; Flecher, E.; Michelet, C.; Revest, M.; Tattevin, P.; Chevalier, F.; Jeu, A.; Remadi, J. P.; Rusinaru, D.; Tribouilloy, C.; Bernard, Y.; Chirouze, C.; Hoen, B.; Leroy, J.; Plesiat, P.; Naber, C.; Neuerburg, C.; Mazaheri, B.; Sophia Athanasia, C. N.; Deliolanis, I.; Giamarellou, H.; Thomas, T.; Mylona, E.; Paniara, O.; Papanicolaou, K.; Pyros, J.; Skoutelis, A.; Papanikolaou, K.; Sharma, G.; Francis, J.; Nair, L.; Thomas, V.; Venugopal, K.; Hannan, M. M.; Hurley, J. P.; Wanounou, M.; Gilon, D.; Israel, S.; Korem, M.; Strahilevitz, J.; Iossa, D.; Orlando, S.; Ursi, M. P.; Pafundi, P. C.; D'Amico, F.; Bernardo, M.; Cuccurullo, S.; Dialetto, G.; Covino, F. E.; Manduca, S.; Della Corte, A.; De Feo, M.; Tripodi, M. F.; Cecchi, E.; De Rosa, F.; Forno, D.; Imazio, M.; Trinchero, R.; Grossi, P.; Lattanzio, M.; Toniolo, A.; Goglio, A.; Raglio, A.; Ravasio, V.; Rizzi, M.; Suter, F.; Magri, S.; Signorini, L.; Kanafani, Z.; Kanj, S. S.; Sharif-Yakan, A.; Abidin, I.; Tamin, S. S.; Martinez, E. R.; Soto Nieto, G. I.; van der Meer, J. T. M.; Chambers, S.; Holland, D.; Morris, A.; Raymond, N.; Read, K.; Murdoch, D. R.; Dragulescu, S.; Ionac, A.; Mornos, C.; Butkevich, O. M.; Chipigina, N.; Kirill, O.; Vadim, K.; Vinogradova, T.; Edathodu, J.; Halim, M.; Liew, Y. -Y.; Lejko-Zupanc, T.; Logar, M.; Mueller-Premru, M.; Commerford, P.; Commerford, A.; Deetlefs, E.; Hansa, C.; Ntsekhe, M.; Almela, M.; Azqueta, M.; Brunet, M.; Castro, P.; Falces, C.; Fuster, D.; Fita, G.; Garcia- de- la- Maria, C.; Garcia-Gonzalez, J.; Gatell, J. M.; Marco, F.; Miro, J. M.; Ortiz, J.; Ninot, S.; Pare, J. C.; Pericas, J. M.; Quintana, E.; Ramirez, J.; Rovira, I.; Sandoval, E.; Sitges, M.; Tellez, A.; Tolosana, J. M.; Vidal, B.; Vila, J.; Anguera, I.; Font, B.; Guma, J. R.; Bermejo, J.; Bouza, E.; Garcia Fernandez, M. A.; Gonzalez-Ramallo, V.; Marin, M.; Munoz, P.; Pedromingo, M.; Roda, J.; Rodriguez-Creixems, M.; Solis, J.; Fernandez-Hidalgo, N.; Tornos, P.; de Alarcon, A.; Parra, R.; Alestig, E.; Johansson, M.; Olaison, L.; Snygg-Martin, U.; Pachirat, P.; Pussadhamma, B.; Senthong, V.; Casey, A.; Elliott, T.; Lambert, P.; Watkin, R.; Eyton, C.; Klein, J. L.; Bradley, S.; Kauffman, C.; Bedimo, R.; Corey, G. R.; Crowley, A. L.; Douglas, P.; Drew, L.; Holland, T.; Lalani, T.; Mudrick, D.; Samad, Z.; Sexton, D.; Stryjewski, M.; Wang, A.; Woods, C. W.; Cantey, R.; Steed, L.; Dickerman, S. A.; Bonilla, H.; Dipersio, J.; Salstrom, S. -J.; Baddley, J.; Patel, M.; Peterson, G.; Stancoven, A.; Levine, D.; Riddle, J.; Rybak, M.; Cabell, C. H

Impact of early valve surgery on outcome of Staphylococcus aureus prosthetic valve infective endocarditis: analysis in the international collaboration of Endocarditis-Prospective Cohort Study

Background. The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis–Prospective Cohort Study. Methods. Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results. EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non–S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39–1.15]; P = .15). Conclusions. In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE

GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19

Data availability: Downloadable summary data are available through the GenOMICC data site (https://genomicc.org/data). Summary statistics are available, but without the 23andMe summary statistics, except for the 10,000 most significant hits, for which full summary statistics are available. The full GWAS summary statistics for the 23andMe discovery dataset will be made available through 23andMe to qualified researchers under an agreement with 23andMe that protects the privacy of the 23andMe participants. For further information and to apply for access to the data, see the 23andMe website (https://research.23andMe.com/dataset-access/). All individual-level genotype and whole-genome sequencing data (for both academic and commercial uses) can be accessed through the UKRI/HDR UK Outbreak Data Analysis Platform (https://odap.ac.uk). A restricted dataset for a subset of GenOMICC participants is also available through the Genomics England data service. Monocyte RNA-seq data are available under the title ‘Monocyte gene expression data’ within the Oxford University Research Archives (https://doi.org/10.5287/ora-ko7q2nq66). Sequencing data will be made freely available to organizations and researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research through a data access agreement. Sequencing data have been deposited at the European Genome–Phenome Archive (EGA), which is hosted by the EBI and the CRG, under accession number EGAS00001007111.Extended data figures and tables are available online at https://www.nature.com/articles/s41586-023-06034-3#Sec21 .Supplementary information is available online at https://www.nature.com/articles/s41586-023-06034-3#Sec22 .Code availability: Code to calculate the imputation of P values on the basis of SNPs in linkage disequilibrium is available at GitHub (https://github.com/baillielab/GenOMICC_GWAS).Acknowledgements: We thank the members of the Banco Nacional de ADN and the GRA@CE cohort group; and the research participants and employees of 23andMe for making this work possible. A full list of contributors who have provided data that were collated in the HGI project, including previous iterations, is available online (https://www.covid19hg.org/acknowledgements).Change history: 11 July 2023: A Correction to this paper has been published at: https://doi.org/10.1038/s41586-023-06383-z. -- In the version of this article initially published, the name of Ana Margarita Baldión-Elorza, of the SCOURGE Consortium, appeared incorrectly (as Ana María Baldion) and has now been amended in the HTML and PDF versions of the article.Copyright © The Author(s) 2023, Critical illness in COVID-19 is an extreme and clinically homogeneous disease phenotype that we have previously shown1 to be highly efficient for discovery of genetic associations2. Despite the advanced stage of illness at presentation, we have shown that host genetics in patients who are critically ill with COVID-19 can identify immunomodulatory therapies with strong beneficial effects in this group3. Here we analyse 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously. To investigate the therapeutic implications of these findings, we infer the structural consequences of protein-coding variants, and combine our GWAS results with gene expression data using a monocyte transcriptome-wide association study (TWAS) model, as well as gene and protein expression using Mendelian randomization. We identify potentially druggable targets in multiple systems, including inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).GenOMICC was funded by Sepsis Research (the Fiona Elizabeth Agnew Trust), the Intensive Care Society, a Wellcome Trust Senior Research Fellowship (to J.K.B., 223164/Z/21/Z), the Department of Health and Social Care (DHSC), Illumina, LifeArc, the Medical Research Council, UKRI, a BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070 and BBS/E/D/30002275) and UKRI grants MC_PC_20004, MC_PC_19025, MC_PC_1905 and MRNO2995X/1. A.D.B. acknowledges funding from the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z), the Edinburgh Clinical Academic Track (ECAT) programme. This research is supported in part by the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20029). Laboratory work was funded by a Wellcome Intermediate Clinical Fellowship to B.F. (201488/Z/16/Z). We acknowledge the staff at NHS Digital, Public Health England and the Intensive Care National Audit and Research Centre who provided clinical data on the participants; and the National Institute for Healthcare Research Clinical Research Network (NIHR CRN) and the Chief Scientist’s Office (Scotland), who facilitate recruitment into research studies in NHS hospitals, and to the global ISARIC and InFACT consortia. GenOMICC genotype controls were obtained using UK Biobank Resource under project 788 funded by Roslin Institute Strategic Programme Grants from the BBSRC (BBS/E/D/10002070 and BBS/E/D/30002275) and Health Data Research UK (HDR-9004 and HDR-9003). UK Biobank data were used in the GSMR analyses presented here under project 66982. The UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. The work of L.K. was supported by an RCUK Innovation Fellowship from the National Productivity Investment Fund (MR/R026408/1). J.Y. is supported by the Westlake Education Foundation. SCOURGE is funded by the Instituto de Salud Carlos III (COV20_00622 to A.C., PI20/00876 to C.F.), European Union (ERDF) ‘A way of making Europe’, Fundación Amancio Ortega, Banco de Santander (to A.C.), Cabildo Insular de Tenerife (CGIEU0000219140 ‘Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19’ to C.F.) and Fundación Canaria Instituto de Investigación Sanitaria de Canarias (PIFIISC20/57 to C.F.). We also acknowledge the contribution of the Centro National de Genotipado (CEGEN) and Centro de Supercomputación de Galicia (CESGA) for funding this project by providing supercomputing infrastructures. A.D.L. is a recipient of fellowships from the National Council for Scientific and Technological Development (CNPq)-Brazil (309173/2019-1 and 201527/2020-0)

Impact of early valve surgery on outcome of staphylococcus aureus prosthetic valve infective endocarditis: Analysis in the international collaboration of endocarditis-prospective cohort study

Background. The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods. Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results. EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions. In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE

Impact of early valve surgery on outcome of staphylococcus aureus prosthetic valve infective endocarditis: Analysis in the international collaboration of endocarditis-prospective cohort study

Background. The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods. Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results. EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions. In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE

HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort.

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p&lt;0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p&lt;0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p&lt;0.01) and younger age (OR 0.62; CI 0.49-0.90; p&lt;0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p&lt;0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences

Influence of the timing of cardiac surgery on the outcome of patients with infective endocarditis and stroke.

BACKGROUND: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. METHODS: Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. RESULTS: Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308; 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328; adjusted hazard ratio, 1.138; 95% CI, .802-1.650). CONCLUSIONS: There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes

Infective Endocarditis in Patients on Chronic Hemodialysis

International audienceInfective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD)