Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients

Abstract COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patien...

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Main Authors: Diego A. Rodríguez-Serrano, Emilia Roy-Vallejo, Nelly D. Zurita Cruz, Alexandra Martín Ramírez, Sebastián C. Rodríguez-García, Nuria Arevalillo-Fernández, José María Galván-Román, Leticia Fontán García-Rodrigo, Lorena Vega-Piris, Marta Chicot Llano, David Arribas Méndez, Begoña González de Marcos, Julia Hernando Santos, Ana Sánchez Azofra, Elena Ávalos Pérez-Urria, Pablo Rodriguez-Cortes, Laura Esparcia, Ana Marcos-Jimenez, Santiago Sánchez-Alonso, Irene Llorente, Joan Soriano, Carmen Suárez Fernández, Rosario García-Vicuña, Julio Ancochea, Jesús Sanz, Cecilia Muñoz-Calleja, Rafael de la Cámara, Alfonso Canabal Berlanga, Isidoro González-Álvaro, Laura Cardeñoso, the REINMUN-COVID Group
Format: Article
Language:English
Published: Nature Publishing Group 2021-06-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-92497-1
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author Diego A. Rodríguez-Serrano
Emilia Roy-Vallejo
Nelly D. Zurita Cruz
Alexandra Martín Ramírez
Sebastián C. Rodríguez-García
Nuria Arevalillo-Fernández
José María Galván-Román
Leticia Fontán García-Rodrigo
Lorena Vega-Piris
Marta Chicot Llano
David Arribas Méndez
Begoña González de Marcos
Julia Hernando Santos
Ana Sánchez Azofra
Elena Ávalos Pérez-Urria
Pablo Rodriguez-Cortes
Laura Esparcia
Ana Marcos-Jimenez
Santiago Sánchez-Alonso
Irene Llorente
Joan Soriano
Carmen Suárez Fernández
Rosario García-Vicuña
Julio Ancochea
Jesús Sanz
Cecilia Muñoz-Calleja
Rafael de la Cámara
Alfonso Canabal Berlanga
Isidoro González-Álvaro
Laura Cardeñoso
the REINMUN-COVID Group
spellingShingle Diego A. Rodríguez-Serrano
Emilia Roy-Vallejo
Nelly D. Zurita Cruz
Alexandra Martín Ramírez
Sebastián C. Rodríguez-García
Nuria Arevalillo-Fernández
José María Galván-Román
Leticia Fontán García-Rodrigo
Lorena Vega-Piris
Marta Chicot Llano
David Arribas Méndez
Begoña González de Marcos
Julia Hernando Santos
Ana Sánchez Azofra
Elena Ávalos Pérez-Urria
Pablo Rodriguez-Cortes
Laura Esparcia
Ana Marcos-Jimenez
Santiago Sánchez-Alonso
Irene Llorente
Joan Soriano
Carmen Suárez Fernández
Rosario García-Vicuña
Julio Ancochea
Jesús Sanz
Cecilia Muñoz-Calleja
Rafael de la Cámara
Alfonso Canabal Berlanga
Isidoro González-Álvaro
Laura Cardeñoso
the REINMUN-COVID Group
Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
Scientific Reports
author_facet Diego A. Rodríguez-Serrano
Emilia Roy-Vallejo
Nelly D. Zurita Cruz
Alexandra Martín Ramírez
Sebastián C. Rodríguez-García
Nuria Arevalillo-Fernández
José María Galván-Román
Leticia Fontán García-Rodrigo
Lorena Vega-Piris
Marta Chicot Llano
David Arribas Méndez
Begoña González de Marcos
Julia Hernando Santos
Ana Sánchez Azofra
Elena Ávalos Pérez-Urria
Pablo Rodriguez-Cortes
Laura Esparcia
Ana Marcos-Jimenez
Santiago Sánchez-Alonso
Irene Llorente
Joan Soriano
Carmen Suárez Fernández
Rosario García-Vicuña
Julio Ancochea
Jesús Sanz
Cecilia Muñoz-Calleja
Rafael de la Cámara
Alfonso Canabal Berlanga
Isidoro González-Álvaro
Laura Cardeñoso
the REINMUN-COVID Group
author_sort Diego A. Rodríguez-Serrano
title Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
title_short Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
title_full Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
title_fullStr Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
title_full_unstemmed Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
title_sort detection of sars-cov-2 rna in serum is associated with increased mortality risk in hospitalized covid-19 patients
publisher Nature Publishing Group
series Scientific Reports
issn 2045-2322
publishDate 2021-06-01
description Abstract COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8–22.6] for Roche, OR 10.3 [3.6–29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13–23.57] for TFS viremia and HR = 7.09 [3.3–14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.
url https://doi.org/10.1038/s41598-021-92497-1
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spelling doaj-97c9df8d7dbb43738740dce63bc7937c2021-06-27T11:32:46ZengNature Publishing GroupScientific Reports2045-23222021-06-0111111110.1038/s41598-021-92497-1Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patientsDiego A. Rodríguez-Serrano0Emilia Roy-Vallejo1Nelly D. Zurita Cruz2Alexandra Martín Ramírez3Sebastián C. Rodríguez-García4Nuria Arevalillo-Fernández5José María Galván-Román6Leticia Fontán García-Rodrigo7Lorena Vega-Piris8Marta Chicot Llano9David Arribas Méndez10Begoña González de Marcos11Julia Hernando Santos12Ana Sánchez Azofra13Elena Ávalos Pérez-Urria14Pablo Rodriguez-Cortes15Laura Esparcia16Ana Marcos-Jimenez17Santiago Sánchez-Alonso18Irene Llorente19Joan Soriano20Carmen Suárez Fernández21Rosario García-Vicuña22Julio Ancochea23Jesús Sanz24Cecilia Muñoz-Calleja25Rafael de la Cámara26Alfonso Canabal Berlanga27Isidoro González-Álvaro28Laura Cardeñoso29the REINMUN-COVID GroupIntensive Care Unit, Hospital Universitario La PrincesaInternal Medicine Department, Hospital Universitario La Princesa, IIS-IPMicrobiology Department, Hospital Universitario La Princesa, IIS-IPMicrobiology Department, Hospital Universitario La Princesa, IIS-IPRheumatology Department, Hospital Universitario La Princesa, IIS-IPIntensive Care Unit, Hospital Universitario La PrincesaInternal Medicine Department, Hospital Universitario La Princesa, IIS-IPMicrobiology Department, Hospital Universitario La Princesa, IIS-IPMethodology Unit, Biomedical Research Institute, Hospital Universitario La Princesa, IIS-IPIntensive Care Unit, Hospital Universitario La PrincesaAnaesthesiology Department, Hospital Universitario La Princesa, IIS-IPIntensive Care Unit, Hospital Universitario La PrincesaAnaesthesiology Department, Hospital Universitario La Princesa, IIS-IPPneumology Department, Hospital Universitario La Princesa, IIS-IPPneumology Department, Hospital Universitario La Princesa, IIS-IPInternal Medicine Department, Hospital Universitario La Princesa, IIS-IPImmunology Department, Hospital Universitario La Princesa, IIS-IPImmunology Department, Hospital Universitario La Princesa, IIS-IPImmunology Department, Hospital Universitario La Princesa, IIS-IPRheumatology Department, Hospital Universitario La Princesa, IIS-IPPneumology Department, Hospital Universitario La Princesa, IIS-IPInternal Medicine Department, Hospital Universitario La Princesa, IIS-IPRheumatology Department, Hospital Universitario La Princesa, IIS-IPPneumology Department, Hospital Universitario La Princesa, IIS-IPInternal Medicine Department, Hospital Universitario La Princesa, IIS-IPImmunology Department, Hospital Universitario La Princesa, IIS-IPHematology Department, Hospital Universitario La Princesa, IIS-IPIntensive Care Unit, Hospital Universitario La PrincesaRheumatology Department, Hospital Universitario La Princesa, IIS-IPMicrobiology Department, Hospital Universitario La Princesa, IIS-IPAbstract COVID-19 has overloaded national health services worldwide. Thus, early identification of patients at risk of poor outcomes is critical. Our objective was to analyse SARS-CoV-2 RNA detection in serum as a severity biomarker in COVID-19. Retrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (viremia) was performed with samples collected at 48–72 h of admission by two techniques from Roche and Thermo Fischer Scientific (TFS). Main outcome variables were mortality and need for ICU admission during hospitalization for COVID-19. Viremia was detected in 50–60% of patients depending on technique. The correlation of Ct in serum between both techniques was good (intraclass correlation coefficient: 0.612; p < 0.001). Patients with viremia were older (p = 0.006), had poorer baseline oxygenation (PaO2/FiO2; p < 0.001), more severe lymphopenia (p < 0.001) and higher LDH (p < 0.001), IL-6 (p = 0.021), C-reactive protein (CRP; p = 0.022) and procalcitonin (p = 0.002) serum levels. We defined "relevant viremia" when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35% specificity. Relevant viremia predicted death during hospitalization (OR 9.2 [3.8–22.6] for Roche, OR 10.3 [3.6–29.3] for TFS; p < 0.001). Cox regression models, adjusted by age, sex and Charlson index, identified increased LDH serum levels and relevant viremia (HR = 9.87 [4.13–23.57] for TFS viremia and HR = 7.09 [3.3–14.82] for Roche viremia) as the best markers to predict mortality. Viremia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. Viremia is highly reproducible with two different techniques (TFS and Roche), has a good consistency with other severity biomarkers for COVID-19 and better predictive accuracy.https://doi.org/10.1038/s41598-021-92497-1