Detection of SARS-CoV-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
Authors: Rodríguez-Serrano Diego A. , Roy-Vallejo Emilia , Zurita Cruz Nelly D. , Martín Ramírez Alexandra , Rodríguez-García Sebastián C. , Arevalillo-Fernández Nuria , Galván-Román José María , Fontán García-Rodrigo Leticia , Vega-Piris Lorena , Chicot Llano Marta , Arribas Méndez David , González de Marcos Begoña , Hernando Santos Julia , Sánchez Azofra Ana , Ávalos Pérez-Urria Elena , Rodriguez-Cortes Pablo , Esparcia Laura , Marcos-Jimenez Ana , Sánchez-Alonso Santiago , Llorente Irene , Soriano Joan , Suárez Fernández Carmen , García-Vicuña Rosario , Ancochea Julio , Sanz Jesús , Muñoz-Calleja Cecilia , de la Cámara Rafael , Canabal Berlanga Alfonso , González-Álvaro Isidoro , Cardeñoso Laura ,   the REINMUN-COVID Group, Hernández Rosa Méndez , Orts Mar , Figueroa Carlos , Román Carlos , Planas Antonio , Domínguez Arganda Lourdes , Martínez Vives Pablo , Diego Nieto Guillermo , Cecconi Alberto , Benedicto Amparo , Rojas González Antonio , Jiménez-Borreguero Jesús , del Arco Carmen , Aguilar Juan Mariano , Villalba Natalia , Negro Mónica , Contreras Elvira , del Rey Ana , Santiago Cristina , Junquera Manuel , Caminero Raquel , Val Francisco Javier , González Sonia , Caño Marta , López Isabel , von Wernitz Andrés , Guerra Iñigo , Sorando Jorge , Chao Lydia , Cárdenas María José , Espiga Verónica , Pizarro Alberto , Figuera Álvarez Ángela , Aguado Beatriz , Cannata Jimena , Ortiz Javier , Morell Alberto , Ramírez Esther , Ibáñez Zurriaga Amparo , Abanades María Pérez , García Silvia Ruiz , Gallego Aranda Tomás , Ruiz María , Martínez Nieto Concepción , Serra José María , Sánchez-Madrid Francisco , Sánchez-Cerrillo Ildefonso , Martínez-Fleta Pedro , López-Sanz Celia , Gabrie Ligia , del Campo Guerola Luciana , Fernández Elena , Tejedor Reyes , Patiño Haro Pablo A. , Trigueros Genao Marina , Quicios Dorado Begoña , Jiménez Jiménez David , Alonso González Macarena , Villamayor Pablo , de los Santos Ignacio , Sánchez Eduardo , Moldenhauer Fernando , Casado Pedro , Curbelo Jose , Gutiérrez Angela , Bautista Azucena , Giménez Nuria Ruiz , Fernández Angelica , García Fraile Lucio , Parra Pedro , Moyano Berta , Barrios Ana , Gil Paloma , García Polo Iluminada , Real de Asúa Diego , Sánchez Beatriz , Sáez Carmen , Ciudad Marianela , Fernández Rico Marta , Arévalo Román Cristina , Morillo Rodríguez Esperanza , Navas Desiré , Cuevas Torresano María del Carmen , Domingo García Diego , Alarcón Cavero Teresa , García Blanco Alicia , Semiglia Chong María Auxiliadora , Gutiérrez Cobos Ainhoa , Fraile Torres Arturo Manuel , Alonso Tamara , Landete Pedro , Soriano Joan , Cisneros Carolina , Castillo Elena García , Valenzuela Claudia , García Pérez Francisco Javier , Girón Rosa María , Aspa Javier , Marcos Celeste , Zamora Enrique , Iturricastillo Gorane , Barrio Mayo Mar , Rubia Garrido Encarna , Castañeda Santos , Fernández-Díaz Carlos , Tomero Eva G. , García Castañeda Noelia , Ortiz Ana Ma , Valero Cristina , Uriarte Miren , Montes Nuria , García Sanz Iñigo , Viamontes Francisco Eduardo , Delgado Valdueza Jesús 
Published: June 2021

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.