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

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

Wellcome Open Research. 2020;5:181
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PICO Summary

Population

COVID-19 patients (28 studies with 212 acute and convalescent COVID-19 serum samples and with 462 convalescent plasma samples).

Intervention

Evaluation of the frequency of viral RNA (vRNA) in blood, and to identify associated clinical characteristics, through a systematic literature review.

Comparison

Outcome

The included studies reported SARS-CoV-2 RNA in 0-76% of blood samples. Among the acute and convalescent COVID-19 serum samples, 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. Across all samples collected ≥28 days post symptom onset, 0/494 (0%) had vRNA detected. Among the convalescent COVID-19 serum PCR-positive samples, cycle threshold 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.
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.
Study details
Study Design : Systematic Review
Language : eng
Credits : Bibliographic data from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine