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00925njm 22002777a 4500 dc Bermejo-Martin, Jesús F author González-Rivera, Milagros author Almansa, Raquel author Micheloud, Dariela author Domínguez-Gil, Marta author Resino, Salvador author Martín-Fernández, Marta author Ryan Murúa, Pablo author Perez-Garcia, Felipe author Tamayo, Luis author Lopez-Izquierdo, Raúl author Bustamante, Elena author Aldecoa, César author Gómez, José Manuel author Rico-Feijoo, Jesús author Orduña, Antonio author Méndez, Raúl author Fernández Natal, Isabel author Megías, Gregoria author González-Estecha, Montserrat author Carriedo, Demetrio author Doncel, Cristina author Jorge, Noelia author Ortega, Alicia author de la Fuente, Amanda author Del Campo, Félix author Fernández-Ratero, José Antonio author Trapiello, Wysali author González-Jiménez, Paula author Ruiz, Guadalupe author Kelvin, Alyson A author Ostadgavahi, Ali Toloue author Oneizat, Ruth author Ruiz, Luz María author Miguéns, Iria author Gargallo, Esther author Muñoz, Ioana author Pelegrin, Sara author Martín, Silvia author García Olivares, Pablo author Cedeño, Jamil Antonio author Ruiz Albi, Tomás author Puertas, Carolina author Berezo, Jose Ángel author Renedo, Gloria author Herrán, Rubén author Bustamante-Munguira, Juan author Enríquez, Pedro author Cicuendez, Ramón author Blanco, Jesús author Abadia, Jesica author Gómez Barquero, Julia author Mamolar, Nuria author Blanca-López, Natalia author Valdivia, Luis Jorge author Fernández Caso, Belén author Mantecón, María Ángeles author Motos, Anna author Fernandez-Barat, Laia author Ferrer, Ricard author Barbé, Ferrán author Torres, Antoni author Menéndez, Rosario author Eiros, José María author Kelvin, David J author Bermejo-Martin, Jesús F author Tedim, Ana P author Del Campo, Félix author Kelvin, Alyson A author Kelvin, David J author Group of Biomedical Research in Critical Care Medicine (BioCritic) author Martinez, Isidoro author 2020-12-14 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. Crit Care. 2020; 24: 691. 10.1186/s13054-020-03398-0 1364-8535 Critical Care 33317616 http://hdl.handle.net/20.500.12105/12031 SARS-CoV-2 Cytokine Sepsis COVID-19 Plasma Rnaemia Viral RNA load ICU Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19