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

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

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.