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 ORCID: 0000-0002-0590-2850, 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. MedRxiv. 2020.05.21.20105486-.

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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
Uncontrolled Keywords: 32 Biomedical and Clinical Sciences, 3202 Clinical Sciences, Coronaviruses Diagnostics and Prognostics, Emerging Infectious Diseases, Genetics, Clinical Research, Infectious Diseases, Coronaviruses, 4.1 Discovery and preclinical testing of markers and technologies, 2.2 Factors relating to the physical environment, Infection, 3 Good Health and Well Being
Depositing User: Symplectic Admin
Date Deposited: 08 Jan 2021 15:21
Last Modified: 24 Oct 2024 18:45
DOI: 10.1101/2020.05.21.20105486
Open Access URL: https://doi.org/10.1101/2020.05.21.20105486
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3112073