Wellcome Open Research (Oct 2020)
SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus [version 2; peer review: 2 approved]
- Monique I. Andersson,
- Carolina V. Arancibia-Carcamo,
- Kathryn Auckland,
- J. Kenneth Baillie,
- Eleanor Barnes,
- Tom Beneke,
- Sagida Bibi,
- Tim Brooks,
- Miles Carroll,
- Derrick Crook,
- Kate Dingle,
- Christina Dold,
- Louise O. Downs,
- Laura Dunn,
- David W. Eyre,
- Javier Gilbert Jaramillo,
- Heli Harvala,
- Sarah Hoosdally,
- Samreen Ijaz,
- Tim James,
- William James,
- Katie Jeffery,
- Anita Justice,
- Paul Klenerman,
- Julian C. Knight,
- Michael Knight,
- Xu Liu,
- Sheila F. Lumley,
- Philippa C. Matthews,
- Anna L. McNaughton,
- Alexander J. Mentzer,
- Juthathip Mongkolsapaya,
- Sarah Oakley,
- Marta S. Oliveira,
- Timothy Peto,
- Rutger J. Ploeg,
- Jeremy Ratcliff,
- Melanie J. Robbins,
- David J. Roberts,
- Justine Rudkin,
- Rebecca A. Russell,
- Gavin Screaton,
- Malcolm G. Semple,
- Donal Skelly,
- Peter Simmonds,
- Nicole Stoesser,
- Lance Turtle,
- Susan Wareing,
- Maria Zambon
Affiliations
- Monique I. Andersson
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Carolina V. Arancibia-Carcamo
- Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Kathryn Auckland
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- J. Kenneth Baillie
- Roslin Institute, The University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK
- Eleanor Barnes
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Tom Beneke
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
- Sagida Bibi
- Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Tim Brooks
- Porton Down, Public Health England, Manor Farm Road, Porton Down, Salisbury, SP4 0JG, UK
- Miles Carroll
- Porton Down, Public Health England, Manor Farm Road, Porton Down, Salisbury, SP4 0JG, UK
- Derrick Crook
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Kate Dingle
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Christina Dold
- Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Louise O. Downs
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Laura Dunn
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- David W. Eyre
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Javier Gilbert Jaramillo
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
- Heli Harvala
- NHS Blood and Transfusion, 26 Margaret St, Marylebone, London, W1W 8NB, UK
- Sarah Hoosdally
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Samreen Ijaz
- Public Health England, 61 Colindale Ave, London, NW9 5EQ, UK
- Tim James
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- William James
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
- Katie Jeffery
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Anita Justice
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Paul Klenerman
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Julian C. Knight
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Michael Knight
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
- Xu Liu
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
- Sheila F. Lumley
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Philippa C. Matthews
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Anna L. McNaughton
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Alexander J. Mentzer
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Juthathip Mongkolsapaya
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Sarah Oakley
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Marta S. Oliveira
- NHS Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Timothy Peto
- NIHR Oxford Biomedical Research Centre (BRC), John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Rutger J. Ploeg
- Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Jeremy Ratcliff
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Melanie J. Robbins
- Component Development Laboratory, NHS Blood and Transplant, Cambridge Donor Centre, Cambridge, CB2 0PT, UK
- David J. Roberts
- NHS Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Justine Rudkin
- Big Data Institute, Roosevelt Drive, Old Road Campus, Headington, Oxford, OX3 7LF, UK
- Rebecca A. Russell
- Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK
- Gavin Screaton
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Malcolm G. Semple
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 3BX, UK
- Donal Skelly
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Peter Simmonds
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Nicole Stoesser
- Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Lance Turtle
- NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 3BX, UK
- Susan Wareing
- Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
- Maria Zambon
- Public Health England, 61 Colindale Ave, London, NW9 5EQ, UK
- DOI
- https://doi.org/10.12688/wellcomeopenres.16002.2
- Journal volume & issue
-
Vol. 5
Abstract
Background: Laboratory diagnosis of SARS-CoV-2 infection (the cause of COVID-19) uses PCR to detect viral RNA (vRNA) in respiratory samples. SARS-CoV-2 RNA has also been detected in other sample types, but there is limited understanding of the clinical or laboratory significance of its detection in blood. Methods: We undertook a systematic literature review to assimilate the evidence for the frequency of vRNA in blood, and to identify associated clinical characteristics. We performed RT-PCR in serum samples from a UK clinical cohort of acute and convalescent COVID-19 cases (n=212), together with convalescent plasma samples collected by NHS Blood and Transplant (NHSBT) (n=462 additional samples). To determine whether PCR-positive blood samples could pose an infection risk, we attempted virus isolation from a subset of RNA-positive samples. Results: We identified 28 relevant studies, reporting SARS-CoV-2 RNA in 0-76% of blood samples; pooled estimate 10% (95%CI 5-18%). Among serum samples from our clinical cohort, 27/212 (12.7%) had SARS-CoV-2 RNA detected by RT-PCR. RNA detection occurred in samples up to day 20 post symptom onset, and was associated with more severe disease (multivariable odds ratio 7.5). Across all samples collected ≥28 days post symptom onset, 0/494 (0%, 95%CI 0-0.7%) had vRNA detected. Among our PCR-positive samples, cycle threshold (ct) values were high (range 33.5-44.8), suggesting low vRNA copy numbers. PCR-positive sera inoculated into cell culture did not produce any cytopathic effect or yield an increase in detectable SARS-CoV-2 RNA. There was a relationship between RT-PCR negativity and the presence of total SARS-CoV-2 antibody (p=0.02). Conclusions: vRNA was detectable at low viral loads in a minority of serum samples collected in acute infection, but was not associated with infectious SARS-CoV-2 (within the limitations of the assays used). This work helps to inform biosafety precautions for handling blood products from patients with current or previous COVID-19.
