ArticleCritical care (London, England)2020
Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.
Article in Critical care (London, England), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 173 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
173 citing papers in PubMed, 2 syntheses or guidelines pooled it, 266 citations in OpenAlex.
- Hospitalised versus outpatient COVID-19 patients' background characteristics and comorbidities: A systematic review and meta-analysis.Reviews in medical virology · 2022Pooled it
- Quantitative assessment of SARS-CoV-2 RNAemia and outcome in patients with coronavirus disease 2019.Journal of medical virology · 2021Pooled it
- SARS-CoV-2 RNA and Nucleocapsid Antigen Are Blood Biomarkers Associated With Severe Disease Outcomes That Improve in Response to Remdesivir.The Journal of infectious diseases · 2024Trial
- Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19.The Journal of infectious diseases · 2024Trial
- Novel subtypes of severe COVID-19 respiratory failure based on biological heterogeneity: a secondary analysis of a randomized controlled trial.Critical care (London, England) · 2024Trial
- Prognostic value of severe acute respiratory syndrome coronavirus-2 viral load and antibodies in patients hospitalized with COVID-19.Clinical and translational science · 2023Trial
- Safety and long-term improvement of mesenchymal stromal cell infusion in critically COVID-19 patients: a randomized clinical trial.Stem cell research & therapy · 2022Trial
- Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial.Frontiers in immunology · 2022Trial
- Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome.Critical care (London, England) · 2021Trial
- Sensitive tracking of circulating viral RNA through all stages of SARS-CoV-2 infection.The Journal of clinical investigation · 2021Trial
- Combined elevated C-reactive protein and detectable plasma RNA has predictive value for hospitalization during an outpatient COVID-19 convalescent plasma clinical trial.Journal of clinical virology plus · 2026Article
- A review of bloodstream infections-pathogens, pathogenesis, diagnostic strategies, treatment methods-challenges and future aspects.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Review
- A decoy virus strategy using plant-produced SARS-CoV-2 virus-like-particles to inhibit infection and lung injury.Journal of translational medicine · 2026Article
- Key factors of the deranged antiviral response in elderly patients with COVID-19: a machine-learning analysis.GeroScience · 2026Article
- Cell-free nucleic acids as a non-invasive biomarker for predicting COVID-19 disease severity and outcome: a retrospective cohort study.BMC infectious diseases · 2026Article
- The role of corticosteroids in severe viral pneumonia: lessons from COVID-19 and influenza.Pneumonia (Nathan Qld.) · 2026Review
- Viral Prognosis Using Proteomics.Advances in experimental medicine and biology · 2026Review
- Viral and Immune Factors Associated With COVID-19 Outcome in the C3PO Trial of Convalescent Plasma.The Journal of infectious diseases · 2025Article
- Droplet Digital PCR or Real-Time PCR as a Method for Quantifying SARS-CoV-2 RNA in Plasma-Is There a Difference?Viruses · 2025Article
- Machine-learning analysis identifies "elite" viral controllers with increased survival and homeostatic responses in critical COVID-19.Clinical and translational medicine · 2025Article
113 more citing papers are in PubMed but not listed here.
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Authors and funding
66 authors at 17 institutions in 3 countries.
Funding
Abstract
backgroundCOVID-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.
methodsA 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.
resultsThe 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).
conclusionsSARS-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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.