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.
【저자키워드】 COVID-19, SARS-CoV-2, Biomarker, RNA, Viral load, Blood, Viraemia, Laboratory safety, 【초록키워드】 convalescent plasma, Clinical characteristics, SARS-COV-2 infection, RT-PCR, Laboratory, biosafety, Cohort, PCR, SARS-CoV-2 antibody, Transplant, virus isolation, cycle threshold, acute infection, sera, Cell culture, Patient, SARS-CoV-2 RNA, Viral RNA, laboratory diagnosis, infection risk, convalescent, Respiratory samples, Precaution, Evidence, Cytopathic effect, Frequency, Odds ratio, severe disease, literature review, symptom onset, NHS, 95%CI, COVID-19 case, PCR-positive, blood sample, help, vRNA, limitation, handling, negativity, serum sample, blood product, NHSBT, multivariable, identify, performed, detect, collected, occurred, inoculated, detectable, determine, increase in, subset, did not produce, 【제목키워드】 SARS-CoV-2 RNA, Infectious virus, blood product, patients with COVID-19,