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

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Andersson, Monique, Arancibia-Cárcamo, Carolina, Auckland, Kathryn, Baillie, Kenneth, Barnes, Eleanor ORCID: 0000-0002-0860-0831, Beneke, Tom, Bibi, Sagida ORCID: 0000-0002-0855-2737, Carroll, Miles, Crook, Derrick ORCID: 0000-0002-0590-2850, Dingle, Kate et al (show 37 more authors) , Dold, Christina, Downs, Louise, Dunn, Laura, Eyre, David ORCID: 0000-0001-5095-6367, Jaramillo, Javier Gilbert, Harvala, Heli, Hoosdally, Sarah, Ijaz, Samreen, James, Tim, James, William, Jeffery, Katie, Justice, Anita, Klenerman, Paul ORCID: 0000-0003-4307-9161, Knight, Julian, Knight, Michael, Liu, Xu, Lumley, Sheila, Matthews, Philippa, McNaughton, Anna, Mentzer, Alexander ORCID: 0000-0002-4502-2209, Mongkolsapaya, Juthathip, Oakley, Sarah, Oliveira, Marta, Peto, Timothy, Ploeg, Rutger, Ratcliff, Jeremy, Roberts, David, Rudkin, Justine ORCID: 0000-0002-3044-0459, Russell, Rebecca, Screaton, Gavin ORCID: 0000-0002-3549-4309, Semple, Malcolm ORCID: 0000-0001-9700-0418, Skelly, Donal, Simmonds, Peter, Stoesser, Nicole ORCID: 0000-0002-4508-7969, Turtle, Lance, Wareing, Sue and Zambon, Maria (2020) SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus. MedRxiv.

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Abstract

<h4>ABSTRACT</h4> <h4>Background</h4> 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. <h4>Methods</h4> 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=111 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. <h4>Results</h4> 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, 0/143 (0%, 95%CI 0.0-2.5%) 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. <h4>Conclusions</h4> 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.

Item Type:	Article
Depositing User:	Symplectic Admin
Date Deposited:	08 Jan 2021 15:21
Last Modified:	18 Jan 2023 23:05
DOI:	10.1101/2020.05.21.20105486
Open Access URL:	https://doi.org/10.1101/2020.05.21.20105486
Related URLs:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3112073