Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/12031
Título
Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19
Autor(es)
Bermejo-Martin, Jesús F. | González-Rivera, Milagros | Almansa, Raquel | Micheloud, Dariela | Domínguez-Gil, Marta | Resino, Salvador ISCIII | Martín-Fernández, Marta | Ryan Murúa, Pablo | Peréz-García, Felipe | Tamayo, Luis | Lopez-Izquierdo, Raúl | Bustamante, Elena | Aldecoa, César | Gómez, José Manuel | Rico-Feijoo, Jesús | Orduña, Antonio | Méndez, Raúl | Fernández Natal, Isabel | Megías, Gregoria | González-Estecha, Montserrat | Carriedo, Demetrio | Doncel, Cristina | Jorge, Noelia | Ortega, Alicia | de la Fuente, Amanda | del Campo, Félix | Fernández-Ratero, José Antonio | Trapiello, Wysali | González-Jiménez, Paula | Ruiz, Guadalupe | Kelvin, Alyson A. | Ostadgavahi, Ali Toloue | Oneizat, Ruth | Ruiz, Luz María | Miguéns, Iria | Gargallo, Esther | Muñoz, Ioana | Pelegrin, Sara | Martín, Silvia | García Olivares, Pablo | Cedeño, Jamil Antonio | Ruiz Albi, Tomás | Puertas, Carolina | Berezo, Jose Ángel | Renedo, Gloria | Herrán, Rubén | Bustamante-Munguira, Juan | Enríquez, Pedro | Cicuendez, Ramón | Blanco, Jesús | Abadia, Jesica | Gómez Barquero, Julia | Mamolar, Nuria | Blanca-López, Natalia | Valdivia, Luis Jorge | Fernández Caso, Belén | Mantecón, María Ángeles | Motos, Anna | Fernandez-Barat, Laia | Ferrer, Ricard | Barbé, Ferrán | Torres, Antoni | Menéndez, Rosario | Eiros, José María | Kelvin, David J. | Bermejo-Martin, Jesús F | Tedim, Ana P | Del Campo, Félix | Kelvin, Alyson A | Kelvin, David J | Group of Biomedical Research in Critical Care Medicine (BioCritic) | Martinez, Isidoro ISCIII
Fecha de publicación
2020-12-14
Cita
Crit Care. 2020; 24: 691.
Idioma
Inglés
Tipo de documento
journal article
Resumen
Background: 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.
Palabras clave
MESH
Adult | Aged | Biomarkers | Chi-Square Distribution | Critical Illness | Female | Humans | Male | Middle Aged | Multivariate Analysis | Polymerase Chain Reaction | RNA, Viral | Statistics, Nonparametric | Viral Load | COVID-19
Versión en línea
DOI
Aparece en las colecciones
- Investigación > IIS > IRB LÉRIDA - Instituto de Investigación Biomédica de Lérida (Cataluña)
- Investigación > IIS > IDIBAPS - Instituto de Investigaciones Biomédicas August Pi i Sunyer (Cataluña)
- Investigación > ISCIII > Centro Nacional de Microbiología (CNM)
- Investigación > IIS > IBSAL - Instituto de Investigación Biómedica de Salamanca (Castilla y León)
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