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

Wellcome Open Res. 2020 Oct 12;5:181. doi: 10.12688/wellcomeopenres.16002.2. eCollection 2020.

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.

Keywords: COVID-19; RNA; SARS-CoV-2; biomarker; blood; laboratory safety; viraemia; viral load.

Associated data

  • figshare/10.6084/m9.figshare.12278249.v8

Grant support

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.