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Investigación
Respiratory viruses and Influenza
Líneas de investigación
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Virus Respiratorios y Gripe
• Gripe humana y animal. Vigilancia de su circulación. Antigripales, resistencias virales. Vacunas
• Infecciones víricas respiratorias en pacientes pediátricos • Diagnóstico, referencia y Nuevos procedimientos basados en la metagenómica viral para el estudio de virus respiratorios.
• Epidemiologia de Virus respiratorios: Gripe, Virus Respiratorio Sincitial, Adenovirus, Metapneumovirus humano, Coronavirus (MERS, 229E, OC43, HKU1, NL63), Parainfluenzavirus, Rinovirus, Bocavirus humano
• Virus respiratorios emergentes • Biodefensa y virus
Proyectos de investigación
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CURRENT PROJECTS: Award of the RETOS-COLABORATION 2019 Call for Proposals: Development of diagnostic kits using real-time multiplex PCR in liquid and gel format for the detection of viral diseases and sepsis.
Reference: RTC2019-007023-1 / MPY 292/20. Project funded by the Ministry of Science and Innovation and the State Research Agency.
PI: Inmaculada Casas and Giovanni Fedele.
Execution dates: 2020-2023.
Amount financed: 442,653 €.
Collaborator: Francisco Pozo
Publicaciones destacadas
A Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Retroviral Control.
Istvan Bartha Jonathan M Carlson, Chanson J Brumme, Paul J McLaren, Zabrina L Brumme, Mina John, David W Haas, Javier Martinez-Picado, Cecilio López Galíndez, Andri Rauch, Huldrych F Günthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Jennifer Listgarten, Nico Pfeifer, Zoltan Kutalik, Todd M Allen, Viktor Müller, P Richard Harrigan, David Heckerman, Amalio Telenti, and Jacques Fellay, for the HIV Genome-to-Genome Study and the Swiss HIV Cohort Study. A Genome-to-Genome Analysis of Associations between Human Genetic Variation, HIV-1 Sequence Diversity, and Retroviral Control. (2013). Elife. 2013;2:e01123.
PUBMED DOIPrevalence of HIV-1 dual infection in LTNP-Elite Controllers
María Pernas, Concepción Casado, Virginia Sandonis, Carolina Arcones, Carmen Rodríguez , Ezequiel Ruiz-Mateos , Eva Ramírez de Arellano , Norma Rallón , Margarita Del Val , Eulalia Grau, Mariola López-Vazquez , Manuel Leal , Jorge del Romero , Cecilio López Galíndez . Prevalence of HIV-1 dual infection in LTNP-Elite Controllers. (2013). J.of AIDS. 64, 3, 225-231. IF 4.262
PUBMED DOIEvidence of Ongoing Replication in a Human Immunodeficiency Virus Type 1 Persistently Infected Cell Line
Isabel Olivares, Carmen Sánchez-Jiménez, Catarina Reis Vieira, Víctor Toledano, Mónica Gutiérrez-Rivas, and Cecilio López-Galíndez. Evidence of Ongoing Replication in a Human Immunodeficiency Virus Type 1 Persistently Infected Cell Line. (2013). J. of General Virology. 94, 944-954.
PUBMED DOIPrevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain.
Prevalence of pSCFS7-like vectors among cfr-positive staphylococcal population in Spain. Nguyen LTT*, Román F*, Morikawa K, Trincado P, Marcos C, Rojo-Martín MD, Cafini F. Int J Antimicrob Agents. 2018 Aug;52(2):305-306.
PUBMED DOICarbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC2 or blaNDM-1
Raro OHF, da Silva RMC, Filho EMR, Sukiennik TCT, Stadnik C, Dias CAG, Oteo, Iglesias J, Pérez-Vázquez M. Carbapenemase-Producing Klebsiella pneumoniae From Transplanted Patients in Brazil: Phylogeny, Resistome, Virulome and Mobile Genetic Elements Harboring blaKPC2 or blaNDM-1.Front Microbiol. 2020 jul 15;11:1563.
PUBMED DOICarbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high risk-clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2
Pérez-Vázquez M, Sola-Campoy PJ, Zurita ÁM, et al. Carbapenemase-producing Pseudomonas aeruginosa in Spain: interregional dissemination of the high risk-clones ST175 and ST244 carrying blaVIM-2, blaVIM-1, blaIMP-8, blaVIM-20 and blaKPC-2.Int J Antimicrob Agents. 2020;106026.
PUBMED DOIProspective multicenter study of carbapenemase producing Enterobacteriaceae from 83 hospitals in Spain: High in vitro susceptibility to colistin and meropenem
Oteo J*, Ortega A, Bartolomé R, Bou G, Conejo C, Fernández-Martínez M, González-López JJ, Martínez-García L, Martínez-Martínez L, Merino M, Miró E, Mora M, Navarro F, Oliver A, Pascual Á, Rodríguez-Baño J, Ruiz-Carrascoso G, Ruiz-Garbajosa P, Zamorano L, Bautista V, Pérez-Vázquez M, Campos J; GEIH-GEMARA (SEIMC) and REIPI. Prospective multicenter study of carbapenemase producing Enterobacteriaceae from 83 hospitals in Spain: High in vitro susceptibility to colistin and meropenem. Antimicrob Agents Chemother. 2015; 59(6): 3406-12.
PUBMED DOIEmergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS
Pérez-Vázquez M, Sola Campoy PJ, Ortega A, Bautista V, Monzón S, Ruiz-Carrascoso G, Mingorance J, González-Barberá EM, Gimeno C, Aracil B, Sáez D, Lara N, Fernández S, González-López JJ, Campos J, Kingsley RA, Dougan G,Oteo-Iglesias J; Spanish NDM Study Group. Emergence of NDM-producing Klebsiella pneumoniae and Escherichia coli in Spain: phylogeny, resistome, virulence and plasmids encoding blaNDM-like genes as determined by WGS. J Antimicrob Chemother. 2019 Dec 1; A 74(12):3489-3496.
PUBMED DOIZoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics
Rodriguez-Pastor, Ruth; Escudero, Raquel; Lambin, Xavier; Vidal, M Dolors; Gil, Horacio; Jado, Isabel; Rodriguez-Vargas, Manuela; Luque-Larena, Juan Jose; Mougeot, Francois. Zoonotic pathogens in fluctuating common vole (Microtus arvalis) populations: occurrence and dynamics. Parasitology. pp. 1 - 10. 24/09/2018.
PUBMED DOILong-range dispersal moved Francisella tularensis into Western Europe from the East
Dwibedi, Chinmay; Birdsell, Dawn; Larkeryd, Adrian; Myrtennas, Kerstin; Ohrman, Caroline; Nilsson, Elin; Karlsson, Edvin; Hochhalter, Christian; Rivera, Andrew; Maltinsky, Sara; Bayer, Brittany; Keim, Paul; Scholz, Holger C; Tomaso, Herbert; Wittwer, Matthias; Beuret, Christian; Schuerch, Nadia; Pilo, Paola; Hernandez Perez, Marta; Rodriguez-Lazaro, David; Escudero, Raquel; Anda, Pedro; Forsman, Mats; Wagner, David M; Larsson, Par; Johansson, Anders. Long-range dispersal moved Francisella tularensis into Western Europe from the East. Microbial genomics. 2 - 12, pp. e000100. 01/01/2016.
PUBMED DOIFrancisella species in ticks and animals, Iberian Peninsula
Lopes de Carvalho, I.; Toledo, A.; Carvalho, C. L.; Barandika, J. F.; Respicio-Kingry, L. B.; Garcia-Amil, C.; Garcia-Perez, A. L.; Olmeda, A. S.; Ze-Ze, L.; Petersen, J. M.; Anda, P.; Nuncio, M. S.; Escudero, R. Francisella species in ticks and animals, Iberian Peninsula. Ticks and Tick-Borne Diseases. 7 - 1, pp. 159 - 165. Elsevier GMBH, Urban & Fischer Verlag, 01/01/2016.
PUBMED DOIStable levels of Coxiella burnetii prevalence in dairy sheep flocks but changes in genotype distribution after a 10-year period in northern Spain
Álvarez-Alonso R, Barandika JF, Ruiz-Fons F, Ortega-Araiztegi I, Jado I, Hurtado A, García-Pérez AL. Stable levels of Coxiella burnetii prevalence in dairy sheep flocks but changes in genotype distribution after a 10-year period in northern Spain. Acta Vet Scand. 2018 Nov 20;60(1):75.
PUBMED DOIEvidence for Suppression of Onchocerciasis Transmission in Bioko Island, Equatorial Guinea
Moya L, Herrador Z, Ta-Tang TH, Rubio JM, Perteguer MJ, Hernandez-González A, García B, Nguema R, Nguema J, Ncog P, Garate T, Benito A, Sima A and Aparicio P. Evidence for Suppression of Onchocerciasis Transmission in Bioko Island, Equatorial Guinea.PLoS Negl Trop Dis, 2016; 10(7): e0004829.
PUBMED DOILAMP kit for diagnosis of non-falciparum malaria in Plasmodium ovale infected patients
Cuadros J, Martin Ramírez A, González IJ, Ding XC, Perez Tanoira R, Rojo-Marcos G, Gómez-Herruz P, Rubio JM. LAMP kit for diagnosis of non-falciparum malaria in Plasmodium ovale infected patients. Malar J. 2017 Jan 7;16(1):20.
PUBMED DOIPlasmodium species differentiation by non-expert on-line volunteers for remote malaria field diagnosis
Ortiz-Ruiz A, Postigo M, Gil-Casanova S, Cuadrado D, Bautista JM, Rubio JM, Luengo-Oroz M, Linares M. Plasmodium species differentiation by non-expert on-line volunteers for remote malaria field diagnosis. Malar J. 2018 Jan 30;17(1):54.
PUBMED DOIStudy of the diagnostic accuracy of microbiological techniques in the diagnosis of malaria in the immigrant population in Madrid
Martín-Díaz A, Rubio JM, Herrero-Martínez JM, Lizasoain M, Ruiz-Giardin JM, Jaqueti J, Cuadros J, Rojo-Marcos G, Martín-Rabadán P, Calderón M, Campelo C, Velasco M, Pérez-Ayala A. Study of the diagnostic accuracy of microbiological techniques in the diagnosis of malaria in the immigrant population in Madrid. Malar J. 2018 Aug 29;17(1):314.
PUBMED DOIpective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections.
Rojo-Marcos G, Rubio-Muñoz JM, Angheben A, Jaureguiberry S, García-Bujalance S, Tomasoni LR, Rodríguez-Valero N, Ruiz-Giardín JM, Salas-Coronas J, Cuadros-González J, García-Rodríguez M, Molina-Romero I, López-Vélez R, Gobbi F, Calderón-Moreno M, Martin-Echevarría E, Elía-López M, Llovo-Taboada J; TropNet Plasmodium ovale investigator group. Prospective comparative multi-centre study on imported Plasmodium ovale wallikeri and Plasmodium ovale curtisi infections. Malar J. 2018 Oct 30;17(1):399.
PUBMED DOIImported and autochthonous malaria in West Saudi Arabia: results from a reference hospital
Soliman RH, Garcia-Aranda P, Elzagawy SM, Hussein BE, Mayah WW, Martin Ramirez A, Ta-Tang TH, Rubio JM. Imported and autochthonous malaria in West Saudi Arabia: results from a reference hospital. Malar J. 2018 Aug 7;17(1):286.
PUBMED DOICryptosporidium hominis genotypes involved in increased incidence and clusters of cases, Navarra, Spain, 2012.
Fuentes, I., Martín, C., Beristain, X; Mazón,A, Saugar, JM, Blanco, A; García M, Cenoz, Valle-Cristia, Ezpeleta, C., Castilla, J. 2015. Cryptosporidium hominis genotypes involved in increased incidence and clusters of cases, Navarra, Spain, 2012. Epidemiology and Infection; 143:1033-6
PUBMED DOIMolecular genotyping of Giardia duodenalis isolates from symptomatic individuals attending two major public hospitals in Madrid, Spain.
Lucio A, Martínez-Ruiz R, Merino FJ, Bailo B, Aguilera M, Fuentes I, Carmena D. 2015. Molecular genotyping of Giardia duodenalis isolates from symptomatic individuals attending two major public hospitals in Madrid, Spain. PLoS One. 10 (12): e0143981.
PUBMED DOIOccurrence and subtype distribution of Blastocystis sp. in humans, dogs, and cats sharing household in northern Spain and assessment of zoonotic transmission risk.
Paulos S, Köster PC, de Lucio A, Hernández-de-Mingo M, Cardona GA, Fernández-Crespo JC, Stensvold RC, Carmena D. 2018. Occurrence and subtype distribution of Blastocystis sp. in humans, dogs, and cats sharing household in northern Spain and assessment of zoonotic transmission risk. Zoonoses and Public Health, 65:993-1002.
PUBMED DOIPhlebotomine sand fly survey in the focus of leishmaniasis of Madrid, Spain (2012–2014): seasonal dynamics, Leishmania infantum infection rates and blood meal preferences.
González E, Jiménez M, Hernández S, Martín-Martín I, Molina R. Phlebotomine sand fly survey in the focus of leishmaniasis of Madrid, Spain (2012–2014): seasonal dynamics, Leishmania infantum infection rates and blood meal preferences. Parasit Vectors 2017, 10:368.
PUBMED DOIMethods in Sand Fly Research
Molina R, Jiménez M, Alvar J, González E, Hernández-Taberna S, Martín-Martín Inés. 2017. Methods in Sand Fly Research (R. Molina, M. Jiménez & J. Alvar, edits.). Servicio de Publicaciones Universidad de Alcalá de Henares. ISBN: 978-84-16978-28-1
Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia
Custodio E, Gadisa E, Sordo L, Cruz I, Moreno J, Nieto J, Chicharro C, Aseffa A, Abraham Z, Hailu T, Cañavate C. Factors associated with Leishmania asymptomatic infection: results from a cross-sectional survey in highland northern Ethiopia. PLoS Negl Trop Dis. 2012;6(9):e1813.
PUBMED DOICytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients.
Carrillo E, Carrasco-Antón N, López-Medrano F, Salto E, Fernández L, San Martín JV, Alvar J, Aguado JM, Moreno J. Cytokine Release Assays as Tests for Exposure to Leishmania, and for Confirming Cure from Leishmaniasis, in Solid Organ Transplant Recipients. PLoS Negl Trop Dis. 2015 Oct 23;9(10):e0004179.
PUBMED DOIChemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum
Ibarra-Meneses AV, Sanchez C, Alvar J, Moreno J, Carrillo E. Monocyte Chemotactic Protein 1 in Plasma from Soluble Leishmania Antigen-Stimulated Whole Blood as a Potential Biomarker of the Cellular Immune Response to Leishmania infantum. Front Immunol. 2017 Sep 29;8:1208.
PUBMED DOICytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection.
Ibarra-Meneses AV, Mondal D, Alvar J, Moreno J, Carrillo E. Cytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection. Sci Rep. 2017 Dec 8;7(1):17266.
PUBMED DOICellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease.
Botana L, Matía B, San Martin JV, Romero-Maté A, Castro A, Molina L, Fernandez L, Ibarra-Meneses A, Aguado M, Sánchez C, Horrillo L, Chicharro C, Nieto J, Ortega S, Ruiz-Giardin JM, Carrillo E, Moreno J. Cellular Markers of Active Disease and Cure in Different Forms of Leishmania infantum-Induced Disease. Front Cell Infect Microbiol. 2018 Nov 13;8:381.
PUBMED DOICarroll MW et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature.
Carroll MW et al. Temporal and spatial analysis of the 2014-2015 Ebola virus outbreak in West Africa. Nature. 2015 Aug 6;524(7563):97-101. doi: 10.1038/nature14594. Epub 2015 Jun 17. PMID: 26083749.
Fernandez-Garcia MD, Meertens L, Chazal M, Hafirassou ML, Dejarnac O, Zamborlini A, Despres P, Sauvonnet N, Arenzana-Seisdedos F, Jouvenet N, Amara A. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses.
Fernandez-Garcia MD, Meertens L, Chazal M, Hafirassou ML, Dejarnac O, Zamborlini A, Despres P, Sauvonnet N, Arenzana-Seisdedos F, Jouvenet N, Amara A. Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses. mBio. 2016 Feb 9;7(1):e01956-15. doi: 10.1128/mBio.01956-15. PMID: 26861019; PMCID:PMC4752603.
Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015
Fernandez-Garcia MD, Majumdar M, Kebe O, Ndiaye K, Martin J. Identification and whole-genome characterization of a recombinant Enterovirus B69 isolated from a patient with Acute Flaccid Paralysis in Niger, 2015. Sci Rep. 2018 Feb 1;8(1):2181. doi: 10.1038/s41598-018-20346-9. PMID: 29391547; PMCID: PMC5795009.
Majumdar M, Sharif S, Klapsa D, Wilton T, Alam MM, Fernandez-Garcia MD, Rehman L, Mujtaba G, McAllister G, Harvala H, Templeton K, Mee ET, Asghar H, Ndiaye K, Minor PD, Martin J. Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations. Open Forum Infect Dis. 2018
Majumdar M, Sharif S, Klapsa D, Wilton T, Alam MM, Fernandez-Garcia MD, Rehman L, Mujtaba G, McAllister G, Harvala H, Templeton K, Mee ET, Asghar H, Ndiaye K, Minor PD, Martin J. Environmental Surveillance Reveals Complex Enterovirus Circulation Patterns in Human Populations. Open Forum Infect Dis. 2018 Oct 1;5(10):ofy250. doi: 10.1093/ofid/ofy250. PMID: 30377626; PMCID: PMC6201154.
Fernandez-Garcia MD, Majumdar M, Kebe O, Fall AD, Kone M, Kande M, Dabo M, Sylla MS, Sompare D, Howard W, Faye O, Martin J, Ndiaye K. Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014-2015.
Fernandez-Garcia MD, Majumdar M, Kebe O, Fall AD, Kone M, Kande M, Dabo M, Sylla MS, Sompare D, Howard W, Faye O, Martin J, Ndiaye K. Emergence of Vaccine-Derived Polioviruses during Ebola Virus Disease Outbreak, Guinea, 2014-2015. Emerg Infect Dis. 2018 Jan;24(1):65-74. doi: 10.3201/eid2401.171174. PMID:29260690; PMCID: PMC5749474.
Tarragó, D.; Mateos, M.-L.; Avellón, A.; Pérez-Vázquez, M.-D.; Tenorio, A.2004
Tarragó, D.; Mateos, M.-L.; Avellón, A.; Pérez-Vázquez, M.-D.; Tenorio, A.2004. Quantitation of Cytomegalovirus DNA in Cerebrospinal Fluid and Serum Specimens from AIDS Patients Using a Novel Highly Sensitive Nested Competitive PCR and the Cobas Amplicor CMV Monitor™ Journal of Medical Virology. 72-2, pp.249-256. ISSN 01466615. 10. Tarragó, D.; Quereda, C.; Tenorio, A.2003. Different cytomegalovirus glycoprotein B genotype distribution in serum and cerebrospinal fluid specimens determined by a novel multiplex nested PCR Journal of Clinical Microbiology. 41-7, pp.2872-2877. ISSN 00951137.
Fernandez-Garcia, Maria Dolores (AC); Kebe, Ousmane; Fall, Aichatou D.; Dia, Hamet; Diop, Ousmane M.; Delpeyroux, Francis; Ndiaye, Kader. 2016.
Fernandez-Garcia, Maria Dolores (AC); Kebe, Ousmane; Fall, Aichatou D.; Dia, Hamet; Diop, Ousmane M.; Delpeyroux, Francis; Ndiaye, Kader. (1/ 7). 2016. Enterovirus A71 Genogroups C and E in Children with Acute Flaccid Paralysis, West Africa EMERGING INFECTIOUS DISEASES. 22-4, pp.753-755. ISSN 1080-6040.
Molecular epidemiology of coxsackievirus B3 infection in Spain, 2004-2015.
K Calderón, M Díaz-de Cerio, C Muñoz-Almagro, N Rabella, I Martínez-Rienda, A Moreno-Docón, G Trallero, M Cabrerizo*. Molecular epidemiology of coxsackievirus B3 infection in Spain, 2004-2015. Arch Virol 161: 1365-1370 (2016).
PUBMED DOIContent with Investigacion .
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Inmaculada Casas
Jefe de Grupo. Científico Titular de OPIs
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Francisco Pozo
Científico Titular de OPIs
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Mónica González-Esguevillas
Colaborador I+D+I de OPIs
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Mar Molinero Calamita
Colaborador I+D+I de OPIs
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María de la Montaña Iglesias Caballero
Contratado Predoctoral PFIS
List of staff
Información adicional
The Respiratory Viruses and Influenza Unit is the oldest WHO Influenza Center in our country (1968), designated as the National Influenza Center by the Ministry of Health in 1971, and is the national coordinator of the CCAA laboratories in the National Influenza Surveillance Network of the Influenza Surveillance System in Spain.
Its general objective is virological surveillance, detection and control of influenza in Spain. Since 1992, together with the Pediatric Service of the Severo Ochoa Hospital, a line of research has been developed based on the etiological study of viral respiratory infections in hospitalized children.
Since 2015, the La Paz Children's University Hospital and the Immunology Laboratory of the IIS-Fundación Jiménez Díaz have also participated, expanding the study to newborns and neonatal units.
To comprehensively study respiratory viruses and the response of the immune system in viral respiratory infections that affect newborns and pediatric patients.
Deepen the knowledge of the biological properties of the viruses involved in the disease: dependency/facilitation, balance between viruses and their adaptation in multiple infections, relationship with severity, existence of virome imbalance.
The Respiratory Viruses and Influenza Unit is the oldest WHO Influenza Center in our country (1968), designated as the National Influenza Center by the Ministry of Health in 1971, and is the national coordinator of the CCAA laboratories in the National Influenza Surveillance Network of the Influenza Surveillance System in Spain.
Its general objective is virological surveillance, detection and control of influenza in Spain. Since 1992, together with the Pediatric Service of the Severo Ochoa Hospital, a line of research has been developed based on the etiological study of viral respiratory infections in hospitalized children.
Since 2015, the La Paz Children's University Hospital and the Immunology Laboratory of the IIS-Fundación Jiménez Díaz have also participated, expanding the study to newborns and neonatal units.
To comprehensively study respiratory viruses and the response of the immune system in viral respiratory infections that affect newborns and pediatric patients.
Deepen the knowledge of the biological properties of the viruses involved in the disease: dependency/facilitation, balance between viruses and their adaptation in multiple infections, relationship with severity, existence of virome imbalance.