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 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.

A Differential Signature of Circulating miRNAs and Cytokines Between COVID-19 and Community-Acquired Pneumonia Uncovers Novel Physiopathological Mechanisms of COVID-19

“…These efforts were aimed to improve patient stratification and make a better use of the available resources to optimise health care. After several months of intensive research, some prognostic clinical biomarkers have been identified, including lymphocyte count, D-dimer, C reactive protein (CRP), ferritin, Interleukin (IL)-6 or viremia ( 3 , 4 ). Moreover, dysregulation of other cytokines, including IL-2, IL-10, Interferon (IFN)-γ, monocyte chemoattractant protein (MCP)-1 or C-X-C Motif Chemokine Ligand (CXCL)10 in COVID-19 patients have also been reported ( 5 ).…”

Validation of a novel molecular assay to the diagnostic of COVID-19 based on real time PCR with high resolution melting

“…This could result in a decreased detection of this human gene target in serum samples. Regardless, previous studies already described detection of SARS-CoV-2 in serum [ 19 ], which could be associated with increased mortality risk in hospitalized COVID-19 patients [ 20 ].…”

The Role of Surface in the Pathogenesis and Treatment of COVID-19

“…Although the virus demonstrates tissue tropism for some organs [16], early reports suggested that most hospitalized patients did not have detectable levels of viral materials in their sera [17]. Although a more recent report has demonstrated viral materials in 50-60% of sera of moderate-to-critically ill patients, no association has yet been shown between serum detection and the development of multiorgan dysfunction syndrome, either prior to admission or during the first 24 h of intensive care [18]. Overall, the evidence suggests that viremia is not a requirement for either symptomatology or severe disease.…”