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

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Matthews, PC, Andersson, MI ORCID: 0000-0003-0619-1074, Arancibia-Carcamo, CV, Auckland, K, Baillie, JK, Barnes, E, Beneke, T ORCID: 0000-0001-9117-2649, Bibi, S, Brooks, T, Carroll, M et al (show 39 more authors) , Crook, D, Dingle, K ORCID: 0000-0002-2303-5957, Dold, C, Downs, LO ORCID: 0000-0002-6088-4704, Dunn, L, Eyre, DW, Gilbert Jaramillo, J ORCID: 0000-0003-1268-2304, Harvala, H, Hoosdally, S, Ijaz, S, James, T, James, W ORCID: 0000-0002-2506-1198, Jeffery, K ORCID: 0000-0002-6506-2689, Justice, A, Klenerman, P, Knight, JC, Knight, M ORCID: 0000-0002-8780-1630, Liu, X ORCID: 0000-0003-1254-7970, Lumley, SF, McNaughton, AL ORCID: 0000-0002-7436-8727, Mentzer, AJ, Mongkolsapaya, J, Oakley, S, Oliveira, MS, Peto, T, Ploeg, RJ ORCID: 0000-0001-7801-665X, Ratcliff, J ORCID: 0000-0001-6522-138X, Robbins, MJ, Roberts, DJ, Rudkin, J, Russell, RA, Screaton, G, Semple, MG ORCID: 0000-0001-9700-0418, Skelly, D, Simmonds, P, Stoesser, N, Turtle, L ORCID: 0000-0002-0778-1693, Wareing, S and Zambon, M ORCID: 0000-0002-8897-7881 (2020) SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus Wellcome Open Research, 5. p. 181. ISSN 2398-502X

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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.

Item Type:	Article
Depositing User:	Symplectic Admin
Date Deposited:	28 Oct 2020 10:00
Last Modified:	22 Jan 2026 02:37
DOI:	10.12688/wellcomeopenres.16002.2
Open Access URL:	https://doi.org/10.12688/wellcomeopenres.16002.2
Related Websites:	Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3105284
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