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.

Figure 1

Detection of SARS-CoV-2 RNA in serum (viremia) is more frequent in patients requiring intensive care unit (ICU) admission. (A) Roche technique. (B) Thermo Fisher Scientific technique. Statistical significance was determined with the Chi squared test. For one of the patients TFS determination could not be performed due to lack of sample.

Figure 2

Comprehensive analysis of viremia as a prognostic marker of mortality in patients hospitalized for severe COVID-19. ROC curve-analysis for mortality prediction with Ct values in serum of all patients, according to Roche (A) and Thermo Fisher Scientific [TFS] (B) techniques. Proportion of deceased patients according to the presence (positive) of absence (negative) of relevant viremia determined by Roche (C) and TFS (D) techniques. Survival analysis with Kaplan–Meier estimator of patients hospitalized for COVID-19 who presented (dotted lines) and patients who did not present (solid lines) relevant viremia according to Roche (E) and TFS (F) techniques.

Figure 3

Association between viremia and main sociodemographic and clinical characteristics of patients hospitalized with severe COVID-19. Correlation between viremia levels (Ct value) and (A) age (years) and (B) Charlson comorbidity index (score). Distribution of viremia levels according to qSOFA index (C), and CURB65 scale (D) scores. All Ct data shown here were obtained by rRT-PCR in serum with Thermo Fisher Scientific (TFS) technique. In (A) and (B) data are shown as dot plots of the corresponding values and the fitted linear prediction (black line) obtained with the option lfit of the command twoway of Stata. Correlation coefficients and significance levels were estimated with the Pearson’s test. In (C) and (D) data are shown as box-plot representing the interquartile range (p75 upper edge, p25 lower edge, p50 midline in the box), p95 (line above the box), and p5 (line below the box). Significance level was determined with the Kruskal Wallis test.

Figure 4

Viremia correlates with the main laboratory prognosis biomarkers described in patients hospitalized with severe COVID-19. Correlation between viremia levels (Ct value by Thermo Fisher Scientific [TFS] technique) and IL-6 levels (pg/mL) (A), lymphocytes count (cel/mm³) (B), LDH levels (U/L) (C), ferritin levels (ng/mL) (D), d-Dimer levels (mg/mL) (E). Data are shown as dot plots of the corresponding values and the fitted linear prediction (black line) obtained with the option lfit of the command twoway of Stata. Correlation coefficients and significance levels were estimated with the Pearson’s test.