RT info:eu-repo/semantics/article T1 Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19 A1 Bermejo-Martin, Jesús F. A1 González-Rivera, Milagros A1 Almansa, Raquel A1 Micheloud, Dariela A1 Tedim, Ana P. A1 Domínguez-Gil, Marta A1 Resino, Salvador A1 Martín-Fernández, Marta A1 Ryan Murua, Pablo A1 Pérez-García, Felipe A1 Tamayo, Luis A1 López Izquierdo, Raúl A1 Bustamante, Elena A1 Aldecoa, César A1 Gómez, José Manuel A1 Rico-Feijoo, Jesús A1 Orduña, Antonio A1 Méndez, Raúl A1 Fernández Natal, Isabel A1 Megías, Gregoria A1 González-Estecha, Montserrat A1 Carriedo, Demetrio A1 Doncel, Cristina A1 Jorge, Noelia A1 Ortega, Alicia A1 de la Fuente, Amanda A1 del Campo, Félix A1 Fernández-Ratero, José Antonio A1 Trapiello, Wysali A1 González-Jiménez, Paula A1 Ruiz, Guadalupe A1 Kelvin, Alyson A. A1 Ostadgavahi, Ali Toloue A1 Oneizat, Ruth A1 Ruiz, Luz María A1 Miguéns, Iria A1 Gargallo, Esther A1 Muñoz, Ioana A1 Pelegrin, Sara A1 Martín, Silvia A1 García Olivares, Pablo A1 Cedeño, Jamil Antonio A1 Ruiz Albi, Tomás A1 Puertas, Carolina A1 Berezo, Jose Ángel A1 Renedo, Gloria A1 Herrán, Rubén A1 Bustamante-Munguira, Juan A1 Enríquez, Pedro A1 Cicuendez, Ramón A1 Blanco, Jesús A1 Abadia, Jesica A1 Gómez Barquero, Julia A1 Mamolar, Nuria A1 Blanca-López, Natalia A1 Valdivia, Luis Jorge A1 Fernández Caso, Belén A1 Mantecón, María Ángeles A1 Motos, Anna A1 Fernandez-Barat, Laia A1 Ferrer, Ricard A1 Barbé, Ferrán A1 Torres, Antoni A1 Menéndez, Rosario A1 Eiros Bouza, José María A1 Kelvin, David J. AB 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. YR 2020 FD 2020 LK https://uvadoc.uva.es/handle/10324/65432 UL https://uvadoc.uva.es/handle/10324/65432 LA eng NO Crit Care. 2020 Dec 14;24(1):691. NO Producción Científica DS UVaDOC RD 11-jul-2024