SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus

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

doi:10.12688/wellcomeopenres.16002.2

SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus

Wellcome Open Res. 2020 Oct 12:5:181. doi: 10.12688/wellcomeopenres.16002.2. eCollection 2020.

Authors

Monique I Andersson¹, Carolina V Arancibia-Carcamo^{2

3

4}, Kathryn Auckland³, J Kenneth Baillie⁵, Eleanor Barnes^{1

2

4}, Tom Beneke⁶, Sagida Bibi⁷, Tim Brooks⁸, Miles Carroll⁸, Derrick Crook^{1

3

4}, Kate Dingle³, Christina Dold⁷, Louise O Downs¹, Laura Dunn¹, David W Eyre^{1

3

4

9}, Javier Gilbert Jaramillo⁶, Heli Harvala^{10

11}, Sarah Hoosdally³, Samreen Ijaz¹², Tim James¹, William James⁶, Katie Jeffery¹, Anita Justice¹, Paul Klenerman^{1

2

3}, Julian C Knight^{1

3}, Michael Knight⁶, Xu Liu⁶, Sheila F Lumley^{1

3}, Philippa C Matthews^{1

3

4}, Anna L McNaughton³, Alexander J Mentzer^{1

3}, Juthathip Mongkolsapaya³, Sarah Oakley¹, Marta S Oliveira^{13

14}, Timothy Peto^{1

3

4}, Rutger J Ploeg¹⁴, Jeremy Ratcliff³, Melanie J Robbins¹⁵, David J Roberts¹³, Justine Rudkin^{9

16}, Rebecca A Russell⁶, Gavin Screaton³, Malcolm G Semple¹⁷, Donal Skelly^{1

3}, Peter Simmonds^{1

3}, Nicole Stoesser^{1

3}, Lance Turtle¹⁷, Susan Wareing¹, Maria Zambon¹²

Affiliations

¹ Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
² Translational Gastroenterology Unit, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
³ Nuffield Department of Medicine, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
⁴ NIHR Oxford Biomedical Research Centre (BRC), John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
⁵ Roslin Institute, The University of Edinburgh, Easter Bush Campus, Midlothian, EH25 9RG, UK.
⁶ Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
⁷ Department of Paediatrics, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
⁸ Porton Down, Public Health England, Manor Farm Road, Porton Down, Salisbury, SP4 0JG, UK.
⁹ Big Data Institute, Roosevelt Drive, Old Road Campus, Headington, Oxford, OX3 7LF, UK.
¹⁰ NHS Blood and Transfusion, 26 Margaret St, Marylebone, London, W1W 8NB, UK.
¹¹ University College London, Gower St, Bloomsbury, London, WC1E 6BT, UK.
¹² Public Health England, 61 Colindale Ave, London, NW9 5EQ, UK.
¹³ NHS Blood and Transplant, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
¹⁴ Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
¹⁵ Component Development Laboratory, NHS Blood and Transplant, Cambridge Donor Centre, Cambridge, CB2 0PT, UK.
¹⁶ Nuffield Department of Population Health, University Oxford Richard Doll Building, Old Road Campus, Headington, Oxford, OX3 7LF, UK.
¹⁷ NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, L69 3BX, UK.

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.

Keywords: COVID-19; RNA; SARS-CoV-2; biomarker; blood; laboratory safety; viraemia; viral load.

Associated data

figshare/10.6084/m9.figshare.12278249.v8

Abstract

Associated data

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