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

Andersson, Monique I; Arancibia-Carcamo, Carolina V; Auckland, Kathryn; Baillie, J Kenneth; Barnes, Eleanor; Beneke, Tom; Bibi, Sagida; Brooks, Tim; Carroll, Miles; Crook, Derrick; Dingle, Kate; Dold, Christina; Downs, Louise O; Dunn, Laura; Eyre, David W; Gilbert Jaramillo, Javier; Harvala, Heli; Hoosdally, Sarah; Ijaz, Samreen; James, Tim; James, William; Jeffery, Katie; Justice, Anita; Klenerman, Paul; Knight, Julian C; Knight, Michael; Liu, Xu; Lumley, Sheila F; Matthews, Philippa C; McNaughton, Anna L; Mentzer, Alexander J; Mongkolsapaya, Juthathip; Oakley, Sarah; Oliveira, Marta S; Peto, Timothy; Ploeg, Rutger J; Ratcliff, Jeremy; Robbins, Melanie J; Roberts, David J; Rudkin, Justine; Russell, Rebecca A; Screaton, Gavin; Semple, Malcolm G; Skelly, Donal; Simmonds, Peter; Stoesser, Nicole; Turtle, Lance; Wareing, Susan; Zambon, Maria

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. 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.