Detection of SARS-Cov-2 RNA in serum is associated with increased mortality risk in hospitalized COVID-19 patients
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Abstract
Background
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.
Methods and Findings
Retrospective 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.
Conclusions
CoVemia 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 SUMMARY
COVID-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.
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SciScore for 10.1101/2021.01.14.21249372: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Model 3 and 4 were developed as model 2 but substituting low lymphocyte count by high IL-6 and high LDH, respectively. Ethics: This study was approved by the local Research Ethics Committee (register number 4070) and it was carried out following the ethical principles established in the Declaration of Helsinki.
Consent: All included patients (or their representatives) were informed about the study and gave an oral informed consent (registered in the electronic clinical chart) as proposed by AEMPS (Agencia Española de Medicamentos y Productos Sanitarios, The Spanish Agency for Medicines and Medical Devices) due to the COVID-19 emergency [26].Randomization not… SciScore for 10.1101/2021.01.14.21249372: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IRB: Model 3 and 4 were developed as model 2 but substituting low lymphocyte count by high IL-6 and high LDH, respectively. Ethics: This study was approved by the local Research Ethics Committee (register number 4070) and it was carried out following the ethical principles established in the Declaration of Helsinki.
Consent: All included patients (or their representatives) were informed about the study and gave an oral informed consent (registered in the electronic clinical chart) as proposed by AEMPS (Agencia Española de Medicamentos y Productos Sanitarios, The Spanish Agency for Medicines and Medical Devices) due to the COVID-19 emergency [26].Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:However, this study has some limitations. Firstly, a single-center and retrospective design and, therefore, variability on the day of sample extraction. Nevertheless, the average time from beginning of symptoms to sample extraction (median of two days) was equal in patients with positive and negative CoVemia. Secondly, the moderate specificity of relevant CoVemia at admission to predict mortality. This finding could be associated to the variability over time of SARS-CoV-2 RNA detection in serum in COVID-19 patients [22]. Because of this variability, CoVemia detection at a specific time point may not properly reflect the state of viral infection, thereby influencing the assessment of severity outcomes. This could explain why previous descriptions of SARS-CoV-2 RNA detection in blood provided heterogeneous information on its value as severity biomarker [13,14,17]. Therefore, sequential assessment of CoVemia may be needed to improve its specificity to predict mortality. Last but not least, our findings are restricted to the so-called “first wave”, when an overloaded health system could not cover all the needs to provide critical care in some severity ill patients. Although the results are solid, studies in new waves experienced elsewhere are needed to validate their utility throughout the pandemic. In summary, the study presented here has established the usefulness of SARS-CoV-2 RNA detection in blood in the initial assessment of patients admitted for COVID-19 due to its capabil...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
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