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

Diego Aníbal Rodríguez-Serrano, Emilia Roy‐Vallejo, Nelly Daniela Zurita Cruz, Alexandra Martín Ramírez, S. C. Rodriguez-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 Rodríguez-Cortés, Laura Esparcia, Ana Marcos‐Jiménez, Santiago Sánchez‐Alonso, I. Llorente, Joan B. 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, Rosa Méndez Hernández, Mar Orts, Carlos A. Figueroa, Carlos Román, A. Planas Roca, Lourdes Domínguez Arganda, Pablo Martínez Vives, Guillermo Diego Nieto, Alberto Cecconi, Amparo Benedicto, Antonio Rojas González, Jesús Jiménez-Borreguero, Carmen del Arco, Juan Mariano Aguilar Mulet, Natalia Villalba, Mónica Negro, Elvira Contreras, Ana del Rey, Cristina Santiago, Manuel Junquera, Raquel Caminero, Francisco Javier Val, Sonia González, M. Piqueras Cano, Isabel López, Andrés von Wernitz, Iñigo Guerra, Jorge Sorando, Lydia Chao, María José Cárdenas, Verónica Espiga, Alberto Pizarro, Ángela Figuera Álvarez, Beatriz Aguado, Jimena Cannata, Javier Ortíz, Alberto Morell, Esther Ramírez, A Ibáñez Zurriaga, María Pérez Abánades, S Ruíz García, Tomás Gallego Aranda, María Nuria Mane Ruiz, Concepción Nieto, J. M. Serra, Francisco Sánchez‐Madrid, Ildefonso Sánchez‐Cerrillo, Pedro Martínez‐Fleta, Celia López‐Sanz, Ligia Gabrie, Luciana del Campo Guerola, Elena Fernández, Reyes Tejedor, Pablo A. Patiño Haro, Marina Trigueros Genao, Begoña Quicios Dorado, David Jiménez, Macarena Alonso González, Pablo Villamayor, Ignacio de los Santos, Eduardo Sánchez Sánchez, Fernando Moldenhauer, Pedro Casado, José Curbelo, Ángela Gutiérrez, Azucena Bautista, Nuria Ruiz Giménez, A. Alonso Fernández, Lucio García-Fraile

2021Scientific Reports36 citationsDOIOpen Access PDF

Abstract

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 (PaO 2 /FiO 2 ; 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.

Topics & Concepts

ViremiaMedicineProcalcitoninInternal medicineCoronavirus disease 2019 (COVID-19)BiomarkerRetrospective cohort studyViral loadProportional hazards modelSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)GastroenterologyIntraclass correlationImmunologyVirusBiologyDiseaseSepsisPsychometricsBiochemistryClinical psychologyInfectious disease (medical specialty)COVID-19 Clinical Research StudiesSARS-CoV-2 and COVID-19 ResearchSARS-CoV-2 detection and testing