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

Jesús F. Bermejo-Martin; Milagros González-Rivera; Raquel Almansa; Dariela Micheloud; Ana P. Tedim; Marta Domínguez-Gil; Salvador Resino; Marta Martín-Fernández; Pablo Ryan Murua; Felipe Pérez-García; Luis Tamayo; Raúl Lopez-Izquierdo; Elena Bustamante; César Aldecoa; José Manuel Gómez; Jesús Rico-Feijoo; Antonio Orduña; Raúl Méndez; Isabel Fernández Natal; Gregoria Megías; Montserrat González-Estecha; Demetrio Carriedo; Cristina Doncel; Noelia Jorge; Alicia Ortega; Amanda de la Fuente; Félix del Campo; José Antonio Fernández-Ratero; Wysali Trapiello; Paula González-Jiménez; Guadalupe Ruiz; Alyson A. Kelvin; Ali Toloue Ostadgavahi; Ruth Oneizat; Luz María Ruiz; Iria Miguéns; Esther Gargallo; Ioana Muñoz; Sara Pelegrin; Silvia Martín; Pablo García Olivares; Jamil Antonio Cedeño; Tomás Ruiz Albi; Carolina Puertas; Jose Ángel Berezo; Gloria Renedo; Rubén Herrán; Juan Bustamante-Munguira; Pedro Enríquez; Ramón Cicuendez; Jesús Blanco; Jesica Abadia; Julia Gómez Barquero; Nuria Mamolar; Natalia Blanca-López; Luis Jorge Valdivia; Belén Fernández Caso; María Ángeles Mantecón; Anna Motos; Laia Fernandez-Barat; Ricard Ferrer; Ferrán Barbé; Antoni Torres; Rosario Menéndez; José María Eiros; David J. Kelvin

doi:10.1186/s13054-020-03398-0

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

Jesús F. Bermejo-Martin, Milagros González-Rivera, Raquel Almansa, Dariela Micheloud, Ana P. Tedim, Marta Domínguez-Gil, Salvador Resino, Marta Martín-Fernández, Pablo Ryan Murua, Felipe Pérez-García, Luis Tamayo, Raúl Lopez-Izquierdo, Elena Bustamante, César Aldecoa, José Manuel Gómez, Jesús Rico-Feijoo, Antonio Orduña, Raúl Méndez, Isabel Fernández Natal, Gregoria MegíasMontserrat González-Estecha, Demetrio Carriedo, Cristina Doncel, Noelia Jorge, Alicia Ortega, Amanda de la Fuente, Félix del Campo, José Antonio Fernández-Ratero, Wysali Trapiello, Paula González-Jiménez, Guadalupe Ruiz, Alyson A. Kelvin, Ali Toloue Ostadgavahi, Ruth Oneizat, Luz María Ruiz, Iria Miguéns, Esther Gargallo, Ioana Muñoz, Sara Pelegrin, Silvia Martín, Pablo García Olivares, Jamil Antonio Cedeño, Tomás Ruiz Albi, Carolina Puertas, Jose Ángel Berezo, Gloria Renedo, Rubén Herrán, Juan Bustamante-Munguira, Pedro Enríquez, Ramón Cicuendez, Jesús Blanco, Jesica Abadia, Julia Gómez Barquero, Nuria Mamolar, Natalia Blanca-López, Luis Jorge Valdivia, Belén Fernández Caso, María Ángeles Mantecón, Anna Motos, Laia Fernandez-Barat, Ricard Ferrer, Ferrán Barbé, Antoni Torres, Rosario Menéndez, José María Eiros, David J. Kelvin

Medicine

Research output: Contribution to journal › Article › peer-review

188 Citations (Scopus)

Abstract

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.[Figure not available: see fulltext.]

Original language	English
Article number	691
Journal	Critical Care
Volume	24
Issue number	1
DOIs	https://doi.org/10.1186/s13054-020-03398-0
Publication status	Published - Dec 2020

Bibliographical note

Funding Information:
We thank SEIMC-GESIDA Foundation for the scientific sponsoring of this project. We thank also the “Biobanco del Centro de Hemoterapia y Hemodonación de Castilla y León”, which provided the plasma simples used in the healthy control group.

Funding Information:
This 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 finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la financiación 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 Inflammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-financed 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.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus Subject Areas

Critical Care and Intensive Care Medicine

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1186/s13054-020-03398-0

Cite this

Bermejo-Martin, J. F., González-Rivera, M., Almansa, R., Micheloud, D., Tedim, A. P., Domínguez-Gil, M., Resino, S., Martín-Fernández, M., Ryan Murua, P., Pérez-García, F., Tamayo, L., Lopez-Izquierdo, R., Bustamante, E., Aldecoa, C., Gómez, J. M., Rico-Feijoo, J., Orduña, A., Méndez, R., Fernández Natal, I., ... Kelvin, D. J. (2020). Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19. Critical Care, 24(1), Article 691. https://doi.org/10.1186/s13054-020-03398-0

Bermejo-Martin, JF, González-Rivera, M, Almansa, R, Micheloud, D, Tedim, AP, Domínguez-Gil, M, Resino, S, Martín-Fernández, M, Ryan Murua, P, Pérez-García, F, Tamayo, L, Lopez-Izquierdo, R, Bustamante, E, Aldecoa, C, Gómez, JM, Rico-Feijoo, J, Orduña, A, Méndez, R, Fernández Natal, I, Megías, G, González-Estecha, M, Carriedo, D, Doncel, C, Jorge, N, Ortega, A, de la Fuente, A, del Campo, F, Fernández-Ratero, JA, Trapiello, W, González-Jiménez, P, Ruiz, G, Kelvin, AA, Ostadgavahi, AT, Oneizat, R, Ruiz, LM, Miguéns, I, Gargallo, E, Muñoz, I, Pelegrin, S, Martín, S, García Olivares, P, Cedeño, JA, Ruiz Albi, T, Puertas, C, Berezo, JÁ, Renedo, G, Herrán, R, Bustamante-Munguira, J, Enríquez, P, Cicuendez, R, Blanco, J, Abadia, J, Gómez Barquero, J, Mamolar, N, Blanca-López, N, Valdivia, LJ, Fernández Caso, B, Mantecón, MÁ, Motos, A, Fernandez-Barat, L, Ferrer, R, Barbé, F, Torres, A, Menéndez, R, Eiros, JM & Kelvin, DJ 2020, 'Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19', Critical Care, vol. 24, no. 1, 691. https://doi.org/10.1186/s13054-020-03398-0

@article{f9ef4f60201443c5bcada2f433822509,

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

abstract = "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.[Figure not available: see fulltext.]",

author = "Bermejo-Martin, {Jes{\'u}s F.} and Milagros Gonz{\'a}lez-Rivera and Raquel Almansa and Dariela Micheloud and Tedim, {Ana P.} and Marta Dom{\'i}nguez-Gil and Salvador Resino and Marta Mart{\'i}n-Fern{\'a}ndez and {Ryan Murua}, Pablo and Felipe P{\'e}rez-Garc{\'i}a and Luis Tamayo and Ra{\'u}l Lopez-Izquierdo and Elena Bustamante and C{\'e}sar Aldecoa and G{\'o}mez, {Jos{\'e} Manuel} and Jes{\'u}s Rico-Feijoo and Antonio Ordu{\~n}a and Ra{\'u}l M{\'e}ndez and {Fern{\'a}ndez Natal}, Isabel and Gregoria Meg{\'i}as and Montserrat Gonz{\'a}lez-Estecha and Demetrio Carriedo and Cristina Doncel and Noelia Jorge and Alicia Ortega and {de la Fuente}, Amanda and {del Campo}, F{\'e}lix and Fern{\'a}ndez-Ratero, {Jos{\'e} Antonio} and Wysali Trapiello and Paula Gonz{\'a}lez-Jim{\'e}nez and Guadalupe Ruiz and Kelvin, {Alyson A.} and Ostadgavahi, {Ali Toloue} and Ruth Oneizat and Ruiz, {Luz Mar{\'i}a} and Iria Migu{\'e}ns and Esther Gargallo and Ioana Mu{\~n}oz and Sara Pelegrin and Silvia Mart{\'i}n and {Garc{\'i}a Olivares}, Pablo and Cede{\~n}o, {Jamil Antonio} and {Ruiz Albi}, Tom{\'a}s and Carolina Puertas and Berezo, {Jose {\'A}ngel} and Gloria Renedo and Rub{\'e}n Herr{\'a}n and Juan Bustamante-Munguira and Pedro Enr{\'i}quez and Ram{\'o}n Cicuendez and Jes{\'u}s Blanco and Jesica Abadia and {G{\'o}mez Barquero}, Julia and Nuria Mamolar and Natalia Blanca-L{\'o}pez and Valdivia, {Luis Jorge} and {Fern{\'a}ndez Caso}, Bel{\'e}n and Mantec{\'o}n, {Mar{\'i}a {\'A}ngeles} and Anna Motos and Laia Fernandez-Barat and Ricard Ferrer and Ferr{\'a}n Barb{\'e} and Antoni Torres and Rosario Men{\'e}ndez and Eiros, {Jos{\'e} Mar{\'i}a} and Kelvin, {David J.}",

note = "Funding Information: We thank SEIMC-GESIDA Foundation for the scientific sponsoring of this project. We thank also the “Biobanco del Centro de Hemoterapia y Hemodonaci{\'o}n de Castilla y Le{\'o}n”, which provided the plasma simples used in the healthy control group. Funding Information: This 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 concesi{\'o}n directa para proyectos y programas de investigaci{\'o}n del virus SARS‐CoV2, causante del COVID‐19”, FONDO–COVID19, Instituto de Salud Carlos III (COV20/00110, CIBERES, 06/06/0028), (AT) and finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y Le{\'o}n, para la financiaci{\'o}n de proyectos de investigaci{\'o}n en enfermedad COVID-19” (GRS COVID 53/A/20) (CA). DJK is a recipient of the Canada Research Chair in Translational Vaccinology and Inflammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-financed 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. Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

doi = "10.1186/s13054-020-03398-0",

language = "English",

volume = "24",

journal = "Critical Care",

issn = "1364-8535",

publisher = "Springer Science + Business Media",

number = "1",

}

TY - JOUR

T1 - Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19

AU - Bermejo-Martin, Jesús F.

AU - González-Rivera, Milagros

AU - Almansa, Raquel

AU - Micheloud, Dariela

AU - Tedim, Ana P.

AU - Domínguez-Gil, Marta

AU - Resino, Salvador

AU - Martín-Fernández, Marta

AU - Ryan Murua, Pablo

AU - Pérez-García, Felipe

AU - Tamayo, Luis

AU - Lopez-Izquierdo, Raúl

AU - Bustamante, Elena

AU - Aldecoa, César

AU - Gómez, José Manuel

AU - Rico-Feijoo, Jesús

AU - Orduña, Antonio

AU - Méndez, Raúl

AU - Fernández Natal, Isabel

AU - Megías, Gregoria

AU - González-Estecha, Montserrat

AU - Carriedo, Demetrio

AU - Doncel, Cristina

AU - Jorge, Noelia

AU - Ortega, Alicia

AU - de la Fuente, Amanda

AU - del Campo, Félix

AU - Fernández-Ratero, José Antonio

AU - Trapiello, Wysali

AU - González-Jiménez, Paula

AU - Ruiz, Guadalupe

AU - Kelvin, Alyson A.

AU - Ostadgavahi, Ali Toloue

AU - Oneizat, Ruth

AU - Ruiz, Luz María

AU - Miguéns, Iria

AU - Gargallo, Esther

AU - Muñoz, Ioana

AU - Pelegrin, Sara

AU - Martín, Silvia

AU - García Olivares, Pablo

AU - Cedeño, Jamil Antonio

AU - Ruiz Albi, Tomás

AU - Puertas, Carolina

AU - Berezo, Jose Ángel

AU - Renedo, Gloria

AU - Herrán, Rubén

AU - Bustamante-Munguira, Juan

AU - Enríquez, Pedro

AU - Cicuendez, Ramón

AU - Blanco, Jesús

AU - Abadia, Jesica

AU - Gómez Barquero, Julia

AU - Mamolar, Nuria

AU - Blanca-López, Natalia

AU - Valdivia, Luis Jorge

AU - Fernández Caso, Belén

AU - Mantecón, María Ángeles

AU - Motos, Anna

AU - Fernandez-Barat, Laia

AU - Ferrer, Ricard

AU - Barbé, Ferrán

AU - Torres, Antoni

AU - Menéndez, Rosario

AU - Eiros, José María

AU - Kelvin, David J.

N1 - Funding Information: We thank SEIMC-GESIDA Foundation for the scientific sponsoring of this project. We thank also the “Biobanco del Centro de Hemoterapia y Hemodonación de Castilla y León”, which provided the plasma simples used in the healthy control group. Funding Information: This 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 finally by the “Convocatoria extraordinaria y urgente de la Gerencia Regional de Salud de Castilla y León, para la financiación 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 Inflammation. APT was funded by the Sara Borrell Research Grant CD018/0123 funded by Instituto de Salud Carlos III and co-financed 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. Publisher Copyright: © 2020, The Author(s).

PY - 2020/12

Y1 - 2020/12

N2 - 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.[Figure not available: see fulltext.]

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.[Figure not available: see fulltext.]

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UR - http://www.scopus.com/inward/citedby.url?scp=85098475738&partnerID=8YFLogxK

U2 - 10.1186/s13054-020-03398-0

DO - 10.1186/s13054-020-03398-0

M3 - Article

C2 - 33317616

AN - SCOPUS:85098475738

SN - 1364-8535

VL - 24

JO - Critical Care

JF - Critical Care

IS - 1

M1 - 691

ER -

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

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