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



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, Dingle, Kate
et al (show 37 more authors) (2020) SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus.

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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: 23 Sep 2021 13:10
DOI: 10.1101/2020.05.21.20105486
Open Access URL: https://doi.org/10.1101/2020.05.21.20105486
URI: https://livrepository.liverpool.ac.uk/id/eprint/3112073