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1. Host-dependent editing of SARS-CoV-2 in COVID-19 patients

Author

Tomás Pumarola, Elena Sulleiro, Narcís Saubi, Mari Carmen Martin, Ariadna Rando, Juliana Esperalba, Juan Ignacio Esteban, Josep F. Abril, Joan Joseph, Josep Gregori, Francisco Rodriguez-Frias, Maria Piñana, Josep Quer, Sergi Colomer-Castell, Andrés Antón, Cristina Andrés, Carla Castillo, Carolina Campos, Damir Garcia-Cehic, Maria Francesca Cortese, Maria Gema Codina, Institut Català de la Salut, [Gregori J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Hepàtiques-Hepatitis Viral, Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Roche Diagnostics SL, Barcelona, Spain. [Cortese MF, Saubí N] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Piñana M, Andrés C, Martin MC, Castillo C] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Virus Respiratoris, Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Campos C, Garcia-Cehic D, Quer J] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Hepàtiques-Hepatitis Viral, Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. [Codina MG, Rando A, Esperalba J, Sulleiro E, Joseph J] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Colomer-Castell S, Esteban JI] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Hepàtiques-Hepatitis Viral, Unitat del Fetge, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Pumarola T] Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Rodriguez-Frias F ] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Bioquímica i Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Antón A] Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Virus Respiratoris, Servei de Microbiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Male, Virologia, Epidemiology, Protein Conformation, viruses, Genoma humà, Virus Replication, COVID-19 (Malaltia), Chemical Phenomena::Biochemical Phenomena::Molecular Structure::Amino Acid Sequence [PHENOMENA AND PROCESSES], Protein structure, Drug Discovery, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Peptide sequence, Genetics, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, Middle Aged, Infectious Diseases, Host-Pathogen Interactions, Spike Glycoprotein, Coronavirus, Female, Research Article, Adult, Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], Immunology, Viral quasispecies, Biology, Microbiology, Seqüència d'aminoàcids, Virology, Genetic variation, ADAR1, Humans, Genetic variability, Amino Acid Sequence, Human genome, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], Base Sequence, Host (biology), SARS-CoV-2, editing, Mutació (Biologia), RNA, COVID-19, Genetic Variation, quasispecies, Mutation (Biology), mutations, Viral replication, fenómenos químicos::fenómenos bioquímicos::estructura molecular::secuencia de aminoácidos [FENÓMENOS Y PROCESOS], Parasitology
Abstract

SARS-CoV-2; Mutacions; Quasiespècie SARS-CoV-2; Mutaciones; Cuasiespecie SARS-CoV-2; Mutations; Quasispecies A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 spike gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 spike variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants. This study was supported by the Direcció General de Recerca i Innovació en Salut (DGRIS) of the Catalan Health Ministry, Generalitat de Catalunya, through the Vall d’Hebron Institut de Recerca (VHIR); the European Regional Development Fund (ERDF) “A way to achieve Europe” by the Spanish Network for Research in Infectious Diseases [grant number REIPI RD16/0016/0003]; Instituto de Salud Carlos III [grant number FIS PI19/00301]; and Centro para el Desarrollo Tecnologico Industrial (CDTI) from the Ministry of Economic Affairs and Digital Transformation [grant number IDI-20200297].

Published
2021

2. Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol

Author

Victor Arévalos, Luis Ortega-Paz, Diego Fernandez-Rodríguez, Víctor Alfonso Jiménez-Díaz, Jordi Bañeras Rius, Gianluca Campo, Miguel Rodríguez-Santamarta, Armando Pérez de Prado, Antonio Gómez-Menchero, José Francisco Díaz Fernández, Claudia Scardino, Nieves Gonzalo, Alberto Pernigotti, Fernando Alfonso, Ignacio Jesús Amat-Santos, Antonio Silvestro, Alfonso Ielasi, José María de la Torre, Gabriela Bastidas, Josep Gómez-Lara, Manel Sabaté, Salvatore Brugaletta, CV COVID-19 Registry Investigators, Institut Català de la Salut, [Arévalos V, Ortega-Paz L] Department of Cardiology, Clinic Cardiovascular Institute, Hospital Universitari Clinic, Barcelona, Spain. [Fernandez-Rodríguez D] Department of Cardiology, Hospital Universitari Arnau de Vilanova, Lérida, Spain. [Jiménez-Díaz VA] Department of Cardiology, Hospital Universitario de Vigo, Vigo, Spain. [Rius JB] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [Campo G] Department of Cardiology, Azienda Ospedaliero-Universitaria di Ferrara, Ferrara, Italy, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, RNA viruses, Male, Viral Diseases, Virologia, Time Factors, Coronaviruses, Myocardial Infarction, Artificial Gene Amplification and Extension, Disease, 030204 cardiovascular system & hematology, Sistema cardiovascular - Malalties, Cardiac Arrhythmias, Cardiovascular System, COVID-19, Myocardial Infarction, Heart Failure, Pulmonary Embolism, Registries, Stroke, Polymerase Chain Reaction, Vascular Medicine, Cardiovascular System, Study Protocol, Otros calificadores::Otros calificadores::/complicaciones [Otros calificadores], 0302 clinical medicine, Medical Conditions, Cardiac Arrhythmias, Medicine and Health Sciences, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, Myocardial infarction, Registries, Stroke, Pathology and laboratory medicine, Statistical Data, COVID-19 (Malaltia) - Complicacions, Multidisciplinary, Statistics, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Medical microbiology, Prognosis, Pulmonary embolism, Cardiovascular system, Infectious Diseases, Treatment Outcome, Neurology, Italy, Viruses, Physical Sciences, Female, SARS CoV 2, Pathogens, medicine.medical_specialty, SARS coronavirus, Cerebrovascular Diseases, Science, Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], Cardiology, Research and Analysis Methods, Microbiology, Cardiovascular System [ANATOMY], NO, 03 medical and health sciences, Diagnostic Medicine, Humans, Adverse effect, Molecular Biology Techniques, Molecular Biology, sistema cardiovascular [ANATOMÍA], Retrospective Studies, Sistema cardiovascular, Heart Failure, Biology and life sciences, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], business.industry, Organisms, Viral pathogens, COVID-19, Retrospective cohort study, Covid 19, Arrhythmias, Cardiac, Reverse Transcriptase-Polymerase Chain Reaction, medicine.disease, Microbial pathogens, 030104 developmental biology, Spain, Heart failure, Emergency medicine, Observational study, business, Pulmonary Embolism, Mathematics, Other subheadings::Other subheadings::/complications [Other subheadings]
Abstract

Background Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. Study and design This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. Conclusion The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.

Published
2021

3. Population Disequilibrium as Promoter of Adaptive Explorations in Hepatitis C Virus

Author

Lucía Vázquez-Sirvent, Rebeca Lobo-Vega, Brenda Martínez-González, Celia Perales, María Eugenia Soria, Josep Quer, Ana Isabel de Ávila, Carlos Briones, Esteban Domingo, Jordi Gómez, Josep Gregori, Isabel Gallego, Elena Moreno, Carlos García-Crespo, Institut Català de la Salut, [García-Crespo C, Ávila AI] Centro de Biología Molecular 'Severo Ochoa' (CBMSO) (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain. [Gallego I] Centro de Biología Molecular 'Severo Ochoa' (CBMSO) (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain. [Soria ME] Centro de Biología Molecular 'Severo Ochoa' (CBMSO) (CSIC-UAM), Consejo Superior de Investigaciones Científicas (CSIC), Campus de Cantoblanco, 28049 Madrid, Spain. Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain. [Martínez-González B, Vázquez-Sirvent L] Department of Clinical Microbiology, Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), 28040 Madrid, Spain. [Gregori J] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain. Unitat del Fetge, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Roche Diagnostics, S.L., Sant Cugat del Vallés, 08174 Barcelona, Spain. [Quer J] Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, 28029 Madrid, Spain. Unitat del Fetge, Servei de Medicina Interna, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Unidad de Excelencia Científica María de Maeztu Centro de Astrobiología del Instituto Nacional de Técnica Aeroespacial y CSIC, MDM-2017-0737, García Crespo, C. [0000-0001-6561-5389], Martínez González, B. [0000-0002-4482-5181], Moreno, E. [0000-0002-2301-4558], Briones, C. [0000-0003-2213-8353], Quer, J. [0000-0003-0014-084X], Banco Santander, Fundación Ramón Areces, Instituto de Salud Carlos III (ISCIII), Agencia Estatal de Investigación (AEI), Ministerio de Economía y Competitividad (MINECO), Ministerio de Ciencia, SAF2017-87846-R and BFU2017-91384-EXP Innovación y Universidades (MCIU), Miguel Servet program of the Instituto de Salud Carlos III, CPII19/00001, Instituto de Salud Carlos III, PI18/00210, European Regional Development Fund (ERDF), PI19/00301, Centro para el Desarrollo Tecnológico Industrial (CDTI), IDI-20200297, Predoctoral contract MCIU, PRE2018-083422, Predoctoral contract PFIS Instituto de Salud Carlos III, FI19/00119, Ministerio de Economía y Competitividad (España), Ministerio de Ciencia, Innovación y Universidades (España), Instituto de Salud Carlos III, European Commission, Global Virus Network, CSIC-INTA - Centro de Astrobiología (CAB), Fundación Banco Santander, and Agencia Estatal de Investigación (España)

Subjects
hepatitis C virus, viruses, lcsh:QR1-502, Residue conservation, Hepacivirus, Review, Viral Nonstructural Proteins, medicine.disease_cause, Virus Replication, Antiviral drug resistance, lcsh:Microbiology, Viral quasispecies, Genetics, Mutation, education.field_of_study, Hepatitis C virus, antiviral drug resistance, virosis::hepatitis viral humana::hepatitis C [ENFERMEDADES], Virus Diseases::Hepatitis, Viral, Human::Hepatitis C [DISEASES], Hepatitis C, Microbiological Phenomena::Virus Physiological Phenomena::Virus Replication [PHENOMENA AND PROCESSES], Infectious Diseases, sequence space, residue conservation, RNA, Viral, Sequence Analysis, Mutational waves, fenómenos microbiológicos::farmacorresistencia microbiana::farmacorresistencia viral [FENÓMENOS Y PROCESOS], Population, Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], Biology, Favipiravir, Antiviral Agents, Virus, Cell Line, universal vaccines, Virology, Drug Resistance, Viral, Ribavirin, medicine, Microbiological Phenomena::Drug Resistance, Microbial::Drug Resistance, Viral [PHENOMENA AND PROCESSES], Humans, Sequence space, education, Resistència als medicaments, NS3, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], mutational waves, Virus - Reproducció, fenómenos microbiológicos::fenómenos fisiológicos de los virus::replicación viral [FENÓMENOS Y PROCESOS], COVID-19, Universal vaccines, Viral replication, Covis 19, Virus de l'hepatitis C, viral quasispecies
Abstract

Replication of RNA viruses is characterized by exploration of sequence space which facilitates their adaptation to changing environments. It is generally accepted that such exploration takes place mainly in response to positive selection, and that further diversification is boosted by modifications of virus population size, particularly bottleneck events. Our recent results with hepatitis C virus (HCV) have shown that the expansion in sequence space of a viral clone continues despite prolonged replication in a stable cell culture environment. Diagnosis of the expansion was based on the quantification of diversity indices, the occurrence of intra-population mutational waves (variations in mutant frequencies), and greater individual residue variations in mutant spectra than those anticipated from sequence alignments in data banks. In the present report, we review our previous results, and show additionally that mutational waves in amplicons from the NS5A-NS5B-coding region are equally prominent during HCV passage in the absence or presence of the mutagenic nucleotide analogues favipiravir or ribavirin. In addition, by extending our previous analysis to amplicons of the NS3- and NS5A-coding region, we provide further evidence of the incongruence between amino acid conservation scores in mutant spectra from infected patients and in the Los Alamos National Laboratory HCV data banks. We hypothesize that these observations have as a common origin a permanent state of HCV population disequilibrium even upon extensive viral replication in the absence of external selective constraints or changes in population size. Such a persistent disequilibrium¿revealed by the changing composition of the mutant spectrum¿may facilitate finding alternative mutational pathways for HCV antiviral resistance. The possible significance of our model for other genetically variable viruses is discussed., The work at CBMSO was supported by grants SAF2014-52400-R from Ministerio de Economía y Competitividad (MINECO), SAF2017-87846-R and BFU2017-91384-EXP from Ministerio de Ciencia, Innovación y Universidades (MCIU), PI18/00210 from Instituto de Salud Carlos III, S2013/ABI-2906 (PLATESA from Comunidad de Madrid/FEDER), and S2018/BAA-4370 (PLATESA2 from Comunidad de Madrid/FEDER). C.P. is supported by the Miguel Servet program of the Instituto de Salud Carlos III (CPII19/00001), cofinanced by the European Regional Development Fund (ERDF). CIBERehd (Centro de Investigación en Red de Enfermedades Hepáticas y Digestivas) is funded by Instituto de Salud Carlos III. Institutional grants from the Fundación Ramón Areces and Banco Santander to the CBMSO are also acknowledged. The team at CBMSO belongs to the Global Virus Network (GVN). The work in Barcelona was supported by Instituto de Salud Carlos III, cofinanced by the European Regional Development Fund (ERDF) Grant No. PI19/00301 and by the Centro para el Desarrollo Tecnológico Industrial (CDTI) from the MICIU, Grant No. IDI-20200297. Work at CAB was supported by MINECO grant BIO2016-79618R and PID2019-104903RB-I00 (funded by the EU under the FEDER program) and by the Spanish State research agency (AEI) through project number MDM-2017-0737 Unidad de Excelencia “María de Maeztu”-Centro de Astrobiología (CSIC-INTA). C.G.-C. is supported by predoctoral contract PRE2018-083422 from MCIU. B.M.-G. is supported by predoctoral contract PFIS FI19/00119 from Instituto de Salud Carlos III (Ministerio de Sanidad y Consumo), cofinanced by Fondo Social Europeo (FSE).

Published
2021

4. Intraventricular Conundrum in a SARS-CoV-2-Positive Patient With Elevated Biomarkers of Myocardial Injury

Author

Servato, María L., Valente, Filipa, García-Moreno, Laura Gutiérrez, Casas, Guillem, Fernández-Galera, Ruben, Burcet, Gemma, Teixidó-Tura, Gisela, Calabria, Hug Cuéllar, González, Ignacio Ferreira, Rodríguez-Palomares, José F., Universitat Autònoma de Barcelona, Institut Català de la Salut, [Servato ML, Valente FX, García-Moreno LG, Casas G, Fernández-Galera R, Teixidó-Tura G, Rodríguez-Palomares JF] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Center for Biomedical Investigation Cardiovascular Consortium, Madrid, Spain. [Burcet G, Calabria HC] Servei de Radiologia, Institut d’Imatge per al Diagnòstic, Vall d’Hebron Hospital Universitari, Barcelona, Spain. [González IF] Servei de Cardiologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Center for Biomedical Investigation Epidemiology and Public Health Consortium, Madrid, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, viruses, enfermedades cardiovasculares::enfermedades cardíacas::miocardiopatías::miocarditis [ENFERMEDADES], Case Report, 030105 genetics & heredity, COVID-19 (Malaltia), 0302 clinical medicine, CMR, cardiac magnetic resonance, LVEF, left ventricular ejection fraction, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Medicine, echocardiography, Fio2, fraction of inspired oxygen, Computed tomography, Pneumònia vírica, COVID-19, coronavirus disease-2019, NT-proBNP, N-terminal pro-B-type natriuretic peptide, SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2, virus diseases, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], enfermedades respiratorias::enfermedades respiratorias::infecciones del tracto respiratorio::neumonía::neumonía vírica [ENFERMEDADES], Positive patient, Thrombosis, Fi, fraction of inspired oxygen, Myocarditis, thrombus, Echocardiography, Cardiology, cardiovascular system, Cardiology and Cardiovascular Medicine, cardiovascular magnetic resonance (CMR), Thrombus, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], Miocarditis - Tractament, 03 medical and health sciences, Clinical Case, Internal medicine, Diseases of the circulatory (Cardiovascular) system, cardiovascular diseases, LV, left ventricular, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], business.industry, COVID-19, computed tomography, medicine.disease, Atypical pneumonia, RC666-701, Heart failure, NT-proBNP, N-terminal pro–B-type natriuretic peptide, myocarditis, Respiratory Tract Diseases::Respiratory Tract Diseases::Respiratory Tract Infections::Pneumonia::Pneumonia, Viral [DISEASES], business, Cardiovascular Diseases::Heart Diseases::Cardiomyopathies::Myocarditis [DISEASES], 030217 neurology & neurosurgery, Cardiovascular magnetic resonance (CMR)
Abstract

We present a case of acute myocarditis with left ventricular dysfunction and intracavitary thrombosis in a 55-year-old man with severe acute respiratory syndrome coronavirus 2 infection (coronavirus disease 2019) who was admitted with bilateral atypical pneumonia. The patient was treated with anticoagulation and optimal heart failure therapy and had an improvement of left ventricular function and thrombus resolution. (Level of Difficulty: Intermediate.), Graphical abstract

Published
2021

5. Sensitive quantification of the HIV-1 reservoir in gut-associated lymphoid tissue

Author

Cristina Gálvez, Sara Morón-López, Maria Esteve, Javier Martinez-Picado, J. Manyé, Anna Carrasco, Maria C. Puertas, Jordi Navarro, Manel Crespo, Maria Salgado, Institut Català de la Salut, [Morón-López S, Puertas MC, Gálvez C] AIDS Research Institute IrsiCaixa, Institut d'Investigació en Cièncias de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Navarro J, Crespo M] Servei de Malalties Infeccioses, Vall d'Hebron Hospital Universitari, Barcelona, Spain. [Carrasco A, Esteve M] Department of Gastroenterology, Hospital Universitari Mutua de Terrassa, University of Barcelona, Research Foundation Mutua de Terrassa, Terrassa, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas [CIBERehd], Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
0301 basic medicine, Male, RNA viruses, Sistema limfàtic, Gut-associated lymphoid tissue, Biopsy, lcsh:Medicine, HIV Infections, Artificial Gene Amplification and Extension, Virus Replication, Pathology and Laboratory Medicine, Polymerase Chain Reaction, White Blood Cells, Intestinal mucosa, Immunodeficiency Viruses, Animal Cells, Medicine and Health Sciences, Digital polymerase chain reaction, enfermedades del sistema inmune::síndromes de inmunodeficiencia::infecciones por VIH [ENFERMEDADES], Intestinal Mucosa, lcsh:Science, Multidisciplinary, T Cells, Middle Aged, Viral Load, Lymphatic system, medicine.anatomical_structure, Cèl·lules T, Medical Microbiology, Viral Pathogens, Viruses, Female, Pathogens, Cellular Types, Anatomy, Biòpsia, Viral load, sistemas sanguíneo e inmunológico::sistema inmunológico::sistema linfático::tejido linfoide [ANATOMÍA], Research Article, Lymphoid Tissue, Immune Cells, Other subheadings::Other subheadings::Other subheadings::/virology [Other subheadings], Immunology, T cells, Surgical and Invasive Medical Procedures, Biology, Research and Analysis Methods, Peripheral blood mononuclear cell, Microbiology, Lymphatic System, 03 medical and health sciences, Ileum, Retroviruses, medicine, VIH (Virus), Humans, Molecular Biology Techniques, Microbial Pathogens, Molecular Biology, Lamina propria, Blood Cells, Otros calificadores::Otros calificadores::Otros calificadores::/virología [Otros calificadores], HIV (Viruses), lcsh:R, Lentivirus, Organisms, Biology and Life Sciences, HIV, Hemic and Immune Systems::Immune System::Lymphatic System::Lymphoid Tissue [ANATOMY], Cell Biology, Virology, Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [DISEASES], Gastrointestinal Tract, 030104 developmental biology, Viral replication, DNA, Viral, HIV-1, Leukocytes, Mononuclear, lcsh:Q, Infeccions per VIH, Digestive System
Abstract

Biòpsia; VIH-1; Teixit limfoide Biopsia; VIH-1; Tejido linfoide Biopsy; HIV-1; Lymphoid tissue Background The implementation of successful strategies to achieve an HIV cure has become a priority in HIV research. However, the current location and size of HIV reservoirs is still unknown since there are limited tools to evaluate HIV latency in viral sanctuaries such as gut-associated lymphoid tissue (GALT). As reported in the so called “Boston Patients”, despite undetectable levels of proviral HIV-1 DNA in blood and GALT, viral rebound happens in just few months after ART interruption. This fact might imply that current methods are not sensitive enough to detect residual reservoirs. Showing that, it is imperative to improve the detection and quantification of HIV-1 reservoir in tissue samples. Herein, we propose a novel non-enzymatic protocol for purification of Lamina Propria Leukocytes (LPL) from gut biopsies combined to viral HIV DNA (vDNA) quantification by droplet digital PCR (ddPCR) to improve the sensitivity and accuracy of viral reservoir measurements (LPL-vDNA assay). Methods Endoscopic ileum biopsies were sampled from 12 HIV-1-infected cART-suppressed subjects. We performed a DTT/EDTA-based treatment for epithelial layer removal followed by non-enzymatic disruption of the tissue to obtain lamina propria cell suspension (LP). CD45+ cells were subsequently purified by flow sorting and vDNA was determined by ddPCR. Results vDNA quantification levels were significantly higher in purified LPLs (CD45+) than in bulk LPs (p

Published
2017

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