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      SARS-CoV-2: too infectious to handle?

      brief-report
      ,
      Nature Reviews. Immunology
      Nature Publishing Group UK
      SARS-CoV-2

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          Abstract

          In this preprint, Andersson et al. assessed whether blood samples obtained from patients with COVID-19 carry active infectious SARS-CoV-2 RNA. A systematic review of 22 recently published preprints combined with the authors’ own patient data (424 individuals) showed that 10% of blood samples taken within 28 days of symptom onset contain SARS-CoV-2 RNA at low copy number, but no sample exceeded the threshold for viral infectivity. Incubation of VeroE6 cells with SARS-CoV-2-RNA-positive serum samples from patients did not reveal any cytopathic effects or lead to viral replication. Further studies will be required to determine the safety of blood samples to inform changes to biosafety policies.

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

          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=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. 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, 0/143 (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. 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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            Author and article information

            Contributors
            covid19lit@medsci.ox.ac.uk
            covid19lit@medsci.ox.ac.uk
            Journal
            Nat Rev Immunol
            Nat. Rev. Immunol
            Nature Reviews. Immunology
            Nature Publishing Group UK (London )
            1474-1733
            1474-1741
            26 June 2020
            : 1
            Affiliations
            ISNI 0000 0004 1936 8948, GRID grid.4991.5, OxImmuno Literature Initiative, , University of Oxford, ; Oxford, UK
            Article
            383
            10.1038/s41577-020-0383-5
            7317894
            be468692-e2e2-48be-b4a1-57ae86ada476
            © Springer Nature Limited 2020

            This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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            sars-cov-2

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