Severe Acute Respiratory Syndrome Coronavirus 2 RNA in Plasma Is Associated With Intensive Care Unit Admission and Mortality in Patients Hospitalized With Coronavirus Disease 2019

Prebensen, Christian; Myhre, Peder L.; Jonassen, Christine Monceyron; Rangberg, Anbjørg; Blomfeldt, Anita; Svensson, My; Omland, Torbjørn; Berdal, Jan-Erik

doi:10.1093/cid/ciaa1338

Cited by 68 publications

(82 citation statements)

References 10 publications

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“…Nasopharyngeal viral shedding peaks shortly before the onset of symptoms and declines thereafter, making the timing of sampling relative to symptom onset an important determinant of test performance [ 3 , 162 ]. Viral load in the lungs or plasma may be more reflective of disease progression [ 163 ]; the detection of viral RNA in plasma (“RNAemia”) correlates with more severe illness [ 164–168 ]. Some studies have correlated nasopharyngeal viral load at the time of presentation with clinical outcomes and the ability to isolate SARS-CoV-2 in culture [ 157 , 169–173 ].…”

Section: Diagnosismentioning

confidence: 99%

COVID-19—Lessons Learned and Questions Remaining

Fang

Benson

Rı́o

et al. 2020

Clinical Infectious Diseases

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Section: Diagnosismentioning

confidence: 99%

COVID-19—Lessons Learned and Questions Remaining

Fang

Benson

Rı́o

et al. 2020

Clinical Infectious Diseases

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“…In this context, circulating SARS-CoV-2 RNA (RNAemia) has been highlighted as a promising prognostic biomarker in hospitalized COVID-19 patients, as it is associated with disease severity 7 and mortality [8][9][10] , with an estimated prevalence of 10% (95% CI 5-18%, random effects model) 7 . Further, we hypothesized that the acute and profound alterations in the innate and adaptive immune system in COVID-19 patients 3,[11][12][13] , especially in RNAemic patients [14][15][16][17][18] , will be accompanied by marked changes in the circulating proteome and interactome and that the proteome in COVID-19 patients will highlight mechanistically relevant signatures and trajectories, when compared to non-COVID-19 sepsis and healthy controls.…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

Mayr

Gutmann

Takov

et al. 2020

Preprint

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Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia was associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). In longitudinal comparisons, COVID-19 ICU patients had a distinct proteomic trajectory associated with RNAemia and mortality. Among COVID-19-enriched proteins, galectin-3 binding protein (LGALS3BP) and proteins of the complement system were identified as interaction partners of SARS-CoV-2 spike glycoprotein. Finally, machine learning identified ‘Age, RNAemia’ and ‘Age, pentraxin-3 (PTX3)’ as the best binary signatures associated with 28-day ICU mortality.

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“…Aside from a possible role in disease pathogenesis, blood–borne viral RNA could also be an important indicator of lung tissue breakdown leading to release of intact virions, viral proteins and nucleic acids, or infected cells into the bloodstream. Along these lines, a few groups have found that the detection of SARS-CoV-2 RNA in plasma (SARS-CoV-2 RNAemia) is associated with severe disease [ 45 ▪ , 46 ▪ , 47 , 48 ▪ – 50 ▪ ], although to inconsistent degrees. The inconsistency in proportion of patients with plasma RNA and the amount of plasma RNA is likely due to differences in definitions of disease severity and in the RT-PCR methods used.…”

Section: Sensitive Methods For Measuring Viral Rnamentioning

confidence: 99%

Adaptation of advanced clinical virology assays from HIV-1 to SARS-CoV-2

McCormick

Mellors

Jacobs

2020

Current Opinion in HIV and AIDS

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Purpose of review In response to the HIV–AIDS pandemic, great strides have been made in developing molecular methods that accurately quantify nucleic acid products of HIV-1 at different stages of viral replication and to assess HIV-1 sequence diversity and its effect on susceptibility to small molecule inhibitors and neutralizing antibodies. Here, we review how knowledge gained from these approaches, including viral RNA quantification and sequence analyses, have been rapidly applied to study SARS-CoV-2 and the COVID-19 pandemic. Recent findings Recent studies have shown detection of SARS-CoV-2 RNA in blood of infected individuals by reverse transcriptase PCR (RT-PCR); and, as in HIV-1 infection, there is growing evidence that the level of viral RNA in plasma may be related to COVID disease severity. Unlike HIV-1, SARS-CoV-2 sequences are highly conserved limiting SARS-CoV-2 sequencing applications to investigating interpatient genetic diversity for phylogenetic analysis. Sensitive sequencing technologies, originally developed for HIV-1, will be needed to investigate intrapatient SARS-CoV-2 genetic variation in response to antiviral therapeutics and vaccines. Summary Methods used for HIV-1 have been rapidly applied to SARS-CoV-2/COVID-19 to understand pathogenesis and prognosis. Further application of such methods should improve precision of therapy and outcome.

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Severe Acute Respiratory Syndrome Coronavirus 2 RNA in Plasma Is Associated With Intensive Care Unit Admission and Mortality in Patients Hospitalized With Coronavirus Disease 2019

Cited by 68 publications

References 10 publications

COVID-19—Lessons Learned and Questions Remaining

COVID-19—Lessons Learned and Questions Remaining

SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

Adaptation of advanced clinical virology assays from HIV-1 to SARS-CoV-2

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