Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19

dc.contributor.authorBermejo Martin, Jesús F.
dc.contributor.authorGonzález Rivera, Milagros
dc.contributor.authorAlmansa, Raquel
dc.contributor.authorMicheloud, Dariela
dc.contributor.authorTedim, Ana P.
dc.contributor.authorDomínguez Gil, Marta
dc.contributor.authorResino, Salvador
dc.contributor.authorMartín Fernández, Marta
dc.contributor.authorMurua, Pablo Ryan
dc.contributor.authorPérez García, Felipe
dc.contributor.authorTamayo Lomas, Luis
dc.contributor.authorLópez Izquierdo, Raúl
dc.contributor.authorBustamante Munguira, 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.authorFuente, Amanda de la
dc.contributor.authorCampo, Félix del
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.authorToloue Ostadgavahi, Ali
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.authorFernández Barat, Laia
dc.contributor.authorFerrer, Ricard
dc.contributor.authorBarbé Illa, Ferran
dc.contributor.authorTorres, Antoni
dc.contributor.authorMenéndez, Rosario
dc.contributor.authorEiros, José María
dc.contributor.authorKelvin, David J.
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.ca_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 fnally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la fnanciación 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 Infammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-fnanced by the European Development Regional Fund (A Way to Achieve Europe programme). The funding sources did not play any role neither in the design of the study and collection, not in the analysis, in the interpretation of data or in writing the manuscript.ca_ES
dc.relation.isformatofReproducció del document publicat a:
dc.relation.ispartofCritical Care, 2020, vol. 24ca_ES
dc.rightscc-by (c) Authors, 2020ca_ES
dc.subjectViral RNA loadca_ES
dc.titleViral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID‑19ca_ES
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