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

Abstract

BackgroundCOVID-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.Methods and FindingsRetrospective observational study including 193 patients admitted for COVID-19. Detection of SARS-CoV-2 RNA in serum (CoVemia) was performed with samples collected at 48-72 hours 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.CoVemia 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 CoVemia 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 CoVemia” when detection Ct was < 34 with Roche and < 31 for TFS. These thresholds had 95% sensitivity and 35 % specificity. Relevant CoVemia 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 CoVemia (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.ConclusionsCoVemia assessment at admission is the most useful biomarker for predicting mortality in COVID-19 patients. CoVemia 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.AUTHOR SUMMARYCOVID-19 shows a very heterogeneous clinical picture. In addition, it has overloaded national health services worldwide. Therefore, early identification of patients with poor prognosis is critical to improve the use of limited health resources. In this work, we evaluated whether baseline SARS-CoV2 RNA detection in blood (CoVemia) is associated with worse outcomes. We studied almost 200 patients admitted to our hospital and about 50-60% of them showed positive CoVemia. Patients with positive CoVemia were older and had more severe disease; CoVemia was also more frequent in patients requiring admission to the ICU. Moreover, we defined “relevant CoVemia”, as the amount of viral load that better predicted mortality obtaining 95% sensitivity and 35% specificity. In addition, relevant CoVemia was a better predictor than other biomarkers such as LDH, lymphocyte count, interleukin-6, and indexes used in ICU such as qSOFA and CURB65.In summary, detection of CoVemia is the best biomarker to predict death in COVID-19 patients. Furthermore, it is easy to be implemented and is reproducible with two techniques (Roche and Thermo Fisher Scientific) that are currently used for diagnosis in nasopharyngeal swabs samples.

Validation of a Novel Molecular Assay to the Diagnostic of COVID-19 Based on Real Time PCR with High Resolution Melting

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

Usefulness of real-time RT-PCR to understand the kinetics of SARS-CoV-2 in blood: a prospective study

“…Our previous results suggested that the Ct value is a good approximation for the stratification of severely ill patients (13). However, the variation due to the sample type and handling, the All rights reserved.…”

“…Recently, detection of SARS-CoV-2 RNA in blood samples (viremia) has been considered as a potential predictor of poor prognosis, due to its association with rapid deterioration and death (9)(10)(11)(12)(13). Nevertheless, there is a lack of reports analysing viral load quantification over time in sequential samples, which could allow understanding viremia kinetics and its relationship with the patient clinical outcome.…”

Novel easy-to-use approach to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA-carrying extracellular vesicles in plasma

“…On the other hand, lower respiratory tract specimens are more difficult to obtain on an outpatient basis, but appear critical for proper diagnosis of severely ill patients especially (2). In addition, detection of viral RNA in plasma begins to be considered in COVID-19 diagnosis and patient monitoring (5), especially that SARS-CoV-2 RNAemia seems to correlate strongly with disease severity and clinical outcome (6,7). However, some studies showed the very low positive rate of blood samples (4).…”