Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19
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Abstract
Background
COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response.
Methods
A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients.
Results
The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) ( p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p ): RNAemia (3.92 [1.183–12.968], 0.025), viral RNA load (N1) (1.962 [1.244–3.096], 0.004); viral RNA load (N2) (2.229 [1.382–3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia).
Conclusions
SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.
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SciScore for 10.1101/2020.08.25.20154252: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable from 20 blood donors (10 men and 10 women) Table 2: Resources
Software and Algorithms Sentences Resources IgG specific for the Nucleocapsid Protein of SARSCoV-2 was detected in 150 l of plasma using the Abbott Architect SARS-CoV-2 IgG Assay (Illinois, U.S.A) Abbott Architectsuggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)Statistical analysis was performed with IBM SPSS version 20 (IBM, Armonk SPSSsuggested: (SPSS, RRID:SCR_002865)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to …
SciScore for 10.1101/2020.08.25.20154252: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable from 20 blood donors (10 men and 10 women) Table 2: Resources
Software and Algorithms Sentences Resources IgG specific for the Nucleocapsid Protein of SARSCoV-2 was detected in 150 l of plasma using the Abbott Architect SARS-CoV-2 IgG Assay (Illinois, U.S.A) Abbott Architectsuggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)Statistical analysis was performed with IBM SPSS version 20 (IBM, Armonk SPSSsuggested: (SPSS, RRID:SCR_002865)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:A limitation of our work is its observational nature, which precludes to infer causality. Nonetheless, the observed associations could serve as hypothesis generators, leading to the development of animal models to confirm the potential link between SARS-CoV-2 replication and the dysregulated host responses observed in severe COVID-19.
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04457505 Recruiting One Year Follow-ups of Patients Admitted to Spanish Intensiv… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
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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