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 JamesWilliam 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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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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.

Original languageEnglish
Article number181
Number of pages21
JournalWellcome Open Research
Volume5
DOIs
Publication statusPublished - 12 Oct 2020

Structured keywords

  • Covid19

Keywords

  • COVID-19
  • SARS-CoV-2
  • viral load
  • viraemia
  • RNA
  • blood
  • biomarker
  • laboratory safety

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