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First Author: Jesús F Bermejo-Martin et al.  

Journal/preprint name: medRxiv 

Tags: immunity, sepsis, cytokines, viremia 


In this study Jesus Bermejo-Martin and colleagues look at how Sars-Cov2 RNA levels in patient plasma associate with disease severity and other immunological signatures. Subject were divided in outpatients (50), hospitalised (100) and ICU patients (100). The study shows how SARS-CoV2 RNA viremia correlates with higher levels of cytokines (CXCL10, IL-10, IL-15…), higher levels of ferritin and LDH as well as lymphopenia. Patients admitted in ICU were more likely than others to have detectable plasma SARS-CoV2 RNA. The author points out how all these immunological response is compatible with sepsis, calling it “viral sepsis. 

Research Highlights 

  1. SARS-CoV2 RNA positivity in patient plasma is independently associated with some plasma cytokines (G-CSF, IL-10, CXCL10, IL1-ra, CCL-2, IL-15) 

  1. SARS-CoV2 RNA positivity in patient plasma is independently associated with ferritin and LDH 

  1. SARS-CoV2 RNA positivity in patient plasma is independently associated with lymphopenia 

  1. SARS-CoV2 RNA in patient plasma is independently associated with critical illness 

  1. Severe COVID-19 patients display a sepsis-like phenotype 

Impact for COVID-19 research:  

  • Most of the data in this article were already known. It has been established that severe COVID-19 patients have elevated pro-inflammatory cytokines, LDH and ferritin as well as lymphopenia 

  • The study suggests IL-15 level as possible clinical signature for critical illness 


  • Study Typepatient cohort 

  • Important cell lines/viral models used: N/A 

  • Key Techniques: cytokine measurement, viral RNA detection, IgG detection SARS-CoV2 


  • the main limitation of the study is its failure to address viral levels anywhere but in the plasma. The study suggests that plasma viral RNA could be somewhat deleterious for COVID-19 outcome, but it could simply reflect overall viral load. All the phenotypic characteristics that they correlate with plasma SARS-Cov-2 RNA are already known to be associated with severe COVIS-19 

  • As they point out presence of live virus in peripheral blood is not confirmed  

  • The study suggests that worst COVID-19 outcome is driven by TLR stimulation by viral RNA in the periphery, but there are no direct experiments to prove that.