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dc.contributor.authorBermejo-Martin, Jesús F.
dc.contributor.authorGonzález-Rivera, Milagros
dc.contributor.authorAlmansa, Raquel
dc.contributor.authorMicheloud, Dariela
dc.contributor.authorDomínguez-Gil, Marta
dc.contributor.authorResino, Salvador 
dc.contributor.authorMartín-Fernández, Marta
dc.contributor.authorRyan Murúa, Pablo
dc.contributor.authorPeréz-García, Felipe
dc.contributor.authorTamayo, Luis
dc.contributor.authorLopez-Izquierdo, Raúl
dc.contributor.authorBustamante, Elena
dc.contributor.authorAldecoa, César
dc.contributor.authorGómez, José Manuel
dc.contributor.authorRico-Feijoo, Jesús
dc.contributor.authorOrduña, Antonio
dc.contributor.authorMéndez, Raúl
dc.contributor.authorFernández Natal, Isabel
dc.contributor.authorMegías, Gregoria
dc.contributor.authorGonzález-Estecha, Montserrat
dc.contributor.authorCarriedo, Demetrio
dc.contributor.authorDoncel, Cristina
dc.contributor.authorJorge, Noelia
dc.contributor.authorOrtega, Alicia
dc.contributor.authorde la Fuente, Amanda
dc.contributor.authordel Campo, Félix
dc.contributor.authorFernández-Ratero, José Antonio
dc.contributor.authorTrapiello, Wysali
dc.contributor.authorGonzález-Jiménez, Paula
dc.contributor.authorRuiz, Guadalupe
dc.contributor.authorKelvin, Alyson A.
dc.contributor.authorOstadgavahi, Ali Toloue
dc.contributor.authorOneizat, Ruth
dc.contributor.authorRuiz, Luz María
dc.contributor.authorMiguéns, Iria
dc.contributor.authorGargallo, Esther
dc.contributor.authorMuñoz, Ioana
dc.contributor.authorPelegrin, Sara
dc.contributor.authorMartín, Silvia
dc.contributor.authorGarcía Olivares, Pablo
dc.contributor.authorCedeño, Jamil Antonio
dc.contributor.authorRuiz Albi, Tomás
dc.contributor.authorPuertas, Carolina
dc.contributor.authorBerezo, Jose Ángel
dc.contributor.authorRenedo, Gloria
dc.contributor.authorHerrán, Rubén
dc.contributor.authorBustamante-Munguira, Juan
dc.contributor.authorEnríquez, Pedro
dc.contributor.authorCicuendez, Ramón
dc.contributor.authorBlanco, Jesús
dc.contributor.authorAbadia, Jesica
dc.contributor.authorGómez Barquero, Julia
dc.contributor.authorMamolar, Nuria
dc.contributor.authorBlanca-López, Natalia
dc.contributor.authorValdivia, Luis Jorge
dc.contributor.authorFernández Caso, Belén
dc.contributor.authorMantecón, María Ángeles
dc.contributor.authorMotos, Anna
dc.contributor.authorFernandez-Barat, Laia
dc.contributor.authorFerrer, Ricard
dc.contributor.authorBarbé, Ferrán
dc.contributor.authorTorres, Antoni
dc.contributor.authorMenéndez, Rosario
dc.contributor.authorEiros, José María
dc.contributor.authorKelvin, David J.
dc.contributor.authorBermejo-Martin, Jesús F
dc.contributor.authorTedim, Ana P
dc.contributor.authorDel Campo, Félix
dc.contributor.authorKelvin, Alyson A
dc.contributor.authorKelvin, David J
dc.contributor.authorGroup of Biomedical Research in Critical Care Medicine (BioCritic)
dc.contributor.authorMartinez, Isidoro 
dc.date.accessioned2021-02-26T20:05:05Z
dc.date.available2021-02-26T20:05:05Z
dc.date.issued2020-12-14
dc.identifier.citationCrit Care. 2020; 24: 691.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/12031
dc.description.abstractBackground: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. Methods: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. Results: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). Conclusions: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.es_ES
dc.description.sponsorshipThis work was supported by awards from the Canadian Institutes of Health Research, the Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative (CIHR OV2 – 170357), Research Nova Scotia (DJK), Atlantic Genome/Genome Canada (DJK), Li-Ka Shing Foundation (DJK), Dalhousie Medical Research Foundation (DJK), the “Subvenciones de concesión directa para proyectos y programas de investigación del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la financiación de proyectos de investigación en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Inflammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-financed by the European Development Regional Fund (A Way to Achieve Europe programme).es_ES
dc.language.isoenges_ES
dc.publisherBioMed Central (BMC) es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSARS-CoV-2es_ES
dc.subjectCytokinees_ES
dc.subjectSepsises_ES
dc.subjectCOVID-19es_ES
dc.subjectPlasmaes_ES
dc.subjectRnaemiaes_ES
dc.subjectViral RNA loades_ES
dc.subjectICUes_ES
dc.subject.meshAdult es_ES
dc.subject.meshAged es_ES
dc.subject.meshBiomarkers es_ES
dc.subject.meshChi-Square Distribution es_ES
dc.subject.meshCritical Illness es_ES
dc.subject.meshFemale es_ES
dc.subject.meshHumans es_ES
dc.subject.meshMale es_ES
dc.subject.meshMiddle Aged es_ES
dc.subject.meshMultivariate Analysis es_ES
dc.subject.meshPolymerase Chain Reaction es_ES
dc.subject.meshRNA, Viral es_ES
dc.subject.meshStatistics, Nonparametric es_ES
dc.subject.meshViral Load es_ES
dc.subject.meshCOVID-19es_ES
dc.titleViral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID33317616es_ES
dc.format.volume24es_ES
dc.format.number1es_ES
dc.format.page691es_ES
dc.identifier.doi10.1186/s13054-020-03398-0es_ES
dc.contributor.funderInstituto de Salud Carlos III 
dc.contributor.funderCanadian Institutes of Health Research 
dc.contributor.funderThe Canadian 2019 Novel Coronavirus (COVID-19) Rapid Research Funding initiative
dc.contributor.funderResearch Nova Scotia
dc.contributor.funderAtlantic Genome/Genome Canada
dc.contributor.funderLi Ka Shing Foundation 
dc.contributor.funderDalhousie Medical Research Foundation 
dc.contributor.funderJunta de Castilla y León (España) 
dc.description.peerreviewedes_ES
dc.identifier.e-issn1364-8535es_ES
dc.relation.publisherversionhttps://doi.org/10.1186/s13054-020-03398-0es_ES
dc.identifier.journalCritical Carees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES
dc.repisalud.institucionISCIIIes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/ES/COV20/00110es_ES
dc.rights.accessRightsopen accesses_ES


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Atribución 4.0 Internacional
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