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

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 plas...

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Published in:Critical care (London, England) Vol. 24; no. 1; pp. 691 - 13
Main Authors: Bermejo-Martin, Jesús F., González-Rivera, Milagros, Almansa, Raquel, Micheloud, Dariela, Tedim, Ana P., Domínguez-Gil, Marta, Resino, Salvador, Martín-Fernández, Marta, Ryan Murua, Pablo, Pérez-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.
Format: Journal Article
Language:English
Published: London BioMed Central 14.12.2020
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
Adult
Aged
Biomarkers
Biomarkers - analysis
Biomarkers - blood
Blood plasma
Chi-Square Distribution
Coronaviruses
COVID-19
COVID-19 - blood
COVID-19 - complications
Critical care
Critical Care Medicine
Critical Illness
Critically ill
Cytokine
Emergency medical care
Emergency Medicine
Female
Genetic aspects
Host-virus relationships
Humans
Intensive
Male
Medicine
Medicine & Public Health
Middle Aged
Multivariate Analysis
Physiological aspects
Plasma
Polymerase Chain Reaction - methods
RNA
RNA, Viral - analysis
RNA, Viral - blood
Rnaemia
SARS-CoV-2
Sepsis
Severe acute respiratory syndrome coronavirus 2
Statistics, Nonparametric
Viral Load - immunology
United States
United States > US
COVID-19
Plasma
SARS-CoV-2
Viral RNA load
Cytokine
Sepsis
ICU
Rnaemia
ISSN:1364-8535, 1466-609X, 1364-8535, 1466-609X, 1366-609X
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Summary: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.
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ISSN:1364-8535
1466-609X
1364-8535
1466-609X
1366-609X
DOI:10.1186/s13054-020-03398-0