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 language | English |
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Article number | 181 |
Journal | Wellcome Open Research |
Volume | 5 |
Early online date | 29 Jul 2020 |
DOIs | |
Publication status | Published - 12 Oct 2020 |
Bibliographical note
Funding Information:This work uses data provided by patients and collected by the NHS. We are grateful to the frontline NHS clinical and research staff and volunteer medical students, who contributed in challenging circumstances, and the generosity of the participants and their families for their individual contributions in difficult times. We thank the BRC Oxford GI Biobank which is funded by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). Laboratory work for this study was also funded by the generous support of philanthropic donors to the University of Oxford's COVID-19 Research Response Fund. We also acknowledge the IBD Cohort Investigators for support in the Oxford GI Biobank, and thank Marco Kaiser (GenExpress, Germany) for providing RNA standards and advice for qRT-PCR experiments. Thank you to Carla Wright and Rosie McMahon for administrative help. Competing interests: DWE has received personal fees from Gilead, outside the submitted work. Grant information: This work was supported by the Wellcome Trust through an Investigators award to JK [204969], a DFID-Wellcome Epidemic Preparedness Grant [215091], and Fellowship Grants to PCM and LT [110110 and 205228]. A full list of all funding supporting
the current study is provided below: ● National Institute for Health Research [CO-CIN-01], ● Medical Research Council [MC_PC_19059], ● National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine and the
University of Oxford [NIHR award 200907], ● The Bill and Melinda Gates Foundation [OPP1209135], ● Liverpool Experimental Cancer Medicine Centre (infrastructure support) [ref: C18616/A25153]. ● TB, CVA-C, PCM, PK and DC received funding from NIHR Oxford Biomedical Research Centre. ● DWE is a Robertson Foundation Fellow. ● EB is an NIHR Senior Investigator. The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Open Access: This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher Copyright:© 2020 Andersson MI et al.
Citation: Andersson MI, Arancibia-Carcamo CV, Auckland K et al. 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] Wellcome Open Research 2020, 5:181
DOI: https://doi.org/10.12688/wellcomeopenres.16002.2
Keywords
- Biomarker
- Blood
- COVID-19
- Laboratory safety
- RNA
- SARS-CoV-2
- Viraemia
- Viral load