SARS-CoV-2 RNA detected in blood products from patients with COVID-19 is not associated with infectious virus #MMPMID33283055
Andersson MI; Arancibia-Carcamo CV; Auckland K; Baillie JK; Barnes E; Beneke T; Bibi S; Brooks T; Carroll M; Crook D; Dingle K; Dold C; Downs LO; Dunn L; Eyre DW; Gilbert Jaramillo J; Harvala H; Hoosdally S; Ijaz S; James T; James W; Jeffery K; Justice A; Klenerman P; Knight JC; Knight M; Liu X; Lumley SF; Matthews PC; McNaughton AL; Mentzer AJ; Mongkolsapaya J; Oakley S; Oliveira MS; Peto T; Ploeg RJ; Ratcliff J; Robbins MJ; Roberts DJ; Rudkin J; Russell RA; Screaton G; Semple MG; Skelly D; Simmonds P; Stoesser N; Turtle L; Wareing S; Zambon M
Wellcome Open Res 2020[]; 5 (?): 181 PMID33283055show ga
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.
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Wellcome+Open+Res 2020 ; 5 (?): 181
