SARS-CoV-2 Viremia is Associated with COVID-19 Severity and Predicts Clinical Outcomes.

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Jacobs, Jana L

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Bain, William

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Naqvi, Asma

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Staines, Brittany

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Castanha, Priscila MS

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Yang, Haopu

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Boltz, Valerie F

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Barratt-Boyes, Simon

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Marques, Ernesto TA

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Mitchell, Stephanie L

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Methé, Barbara

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Olonisakin, Tolani F

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Haidar, Ghady

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Burke, Thomas W

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Petzold, Elizabeth

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Denny, Thomas

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Woods, Chris W

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McVerry, Bryan J

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Lee, Janet S

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Watkins, Simon C

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St Croix, Claudette M

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Morris, Alison

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Kearney, Mary F

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Ladinsky, Mark S

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Bjorkman, Pamela J

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Kitsios, Georgios D

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Mellors, John W

dc.date.accessioned

2022-05-03T18:51:35Z

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2022-05-03T18:51:35Z

dc.date.issued

2021-08-10

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2022-05-03T18:51:33Z

dc.description.abstract

Background

SARS-CoV-2 viral RNA (vRNA) is detected in the bloodstream of some patients with COVID-19 ("RNAemia") but it is not clear whether this RNAemia reflects viremia (i.e., virus particles) and how RNAemia/viremia is related to host immune responses and outcomes.

Methods

SARS-CoV-2 vRNA was quantified by ultra-sensitive RT-PCR in plasma samples (0.5-1.0 ml) from observational cohorts of 51 COVID-19 patients including 9 outpatients, 19 hospitalized (non-ICU), and 23 ICU patients, and vRNA levels compared with cross-sectional indices of COVID-19 severity and prospective clinical outcomes. We used multiple imaging methods to visualize virions in pelleted plasma.

Results

SARS-CoV-2 vRNA was detected in plasma of 100%, 52.6% and 11.1% of ICU, non-ICU, and outpatients respectively. Virions were detected in plasma pellets by electron tomography and immunostaining. Plasma vRNA levels were significantly higher in ICU > non-ICU > outpatients (p<0.0001); and for inpatient, plasma vRNA levels were strongly associated with higher WHO score at admission (p=0.01), maximum WHO score (p=0.002) and discharge disposition (p=0.004). A plasma vRNA level >6,000 copies/ml was strongly associated with mortality (HR: 10.7). Levels of vRNA were significantly associated with several inflammatory biomarkers (p<0.01) but not with plasma neutralizing antibody titers (p=0.8).

Conclusions

Visualization of virus particles in plasma indicates that SARS-CoV-2 RNAemia is due, at least in part, to viremia. The levels of SARS-CoV-2 RNAemia quantified by ultrasensitive RT-PCR correlate strongly with disease severity, patient outcome and specific inflammatory biomarkers but not neutralizing antibody titers.
dc.identifier

6347519

dc.identifier.issn

1058-4838

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1537-6591

dc.identifier.uri

https://hdl.handle.net/10161/25002

dc.language

eng

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Oxford University Press (OUP)

dc.relation.ispartof

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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10.1093/cid/ciab686

dc.subject

COVID-19 outcome

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SARS-CoV-2 RNAemia

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SARS-CoV-2 viremia

dc.title

SARS-CoV-2 Viremia is Associated with COVID-19 Severity and Predicts Clinical Outcomes.

dc.type

Journal article

duke.contributor.orcid

Woods, Chris W|0000-0001-7240-2453

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Duke

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School of Medicine

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Staff

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Clinical Science Departments

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Institutes and Centers

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Medicine

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Medicine, Duke Human Vaccine Institute

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Duke Human Vaccine Institute

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Institutes and Provost's Academic Units

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University Institutes and Centers

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Duke Global Health Institute

pubs.publication-status

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