SARS-CoV-2 RNA detected in blood samples from patients with COVID-19 is not associated with infectious virus
cell biology clinical virology
Authors: Andersson et. al 2020
Journal/ Pre-Print: medRxiv
Tags: Cell biology, clinical, statistics, and virology
1. Blood samples isolated from COVID-19 infected patients contain low copy numbers of SARS-CoV-2 RNA after 28 days post symptom onset.
2. Blood samples isolated from COVID-19 infected patients pose limited risk to health workers and laboratory staff.
3. Using serum isolated from COVID-19 or control patients they found some cytopathic effects of SARS-CoV-2 on cells, but low levels of viral replication.
Currently it is unknown whether blood of COVID-19 infected patients contains active SARS-CoV-2 RNA. Andersson et al conducted a systematic literature review and meta-analysis of 22 relevant papers including those from MedRxiv, describing the presence of SARS CoV-2 RNA in human blood. Additionally, they locally sourced blood samples from 424 acutely infected or convalescent patients to assess for SARS CoV-2 RNA. The authors estimate that 10% of blood samples obtained from individuals with COVID-19 within 28 days of symptoms onset contained SARS-CoV-2 RNA at low copy numbers which was below threshold for viral infectivity. Vero E6 cells were cultured with serum isolated from COVID-19 and control patients and cytopathic effects of SARS-CoV-2 on cells, but low levels of viral replication after 3 days depending on diagnostic panel used (CDC NP1, CDC NP2 and HKU ORF1b) were found.
Impact for SARS-CoV2/COVID19 research efforts
The study primarily explores whether SARS CoV-2 RNA from blood of COVID-19 infected patients can be transmitted to healthcare workers and laboratory staff handling the samples. This study informs on safety measures that need to be applied and could certainly make future research easier if biosafety containment 3 level procedures do not need to be used. Analysis of serum samples may be be affected by chemical or temperature-based efforts to neutralise infectious agents, as many biomarkers are destroyed in the process.
· Clinical Cohort study
· In vitro
Strengths and limitations of the paper
Novelty: There appears to be no risk of catching SARS-Cov-2 from blood or blood products, of people who have confirmed COVID19.
Authors performed a meta-analysis of the literature, compared with a local cohort and used in vitro experiments to strengthen their findings.
Standing in the field: This is the latest and most comprehensive systematic review to our knowledge assessing the detectability of SARS-CoV-2 RNA in patient blood samples and it’s infectability.
Appropriate statistics: Yes
Viral model used: SARS-Cov-2 from patient serum samples were used to infect Vero E6 cells.
Translatability: This will be useful for anyone in contact or working with blood or blood products from infected patients. It is also useful for people performing serology-based research on SARS-Cov-2, if future studies confirm that vRNA in blood and blood products is not infectious.
Main limitations: Systematic review contains published reports that do not describe timing of collection samples relative to symptom onset. Additionally, those with milder or unreported symptoms are under-represented in the literature.
CT values from PCR are often unreported and are very high 33.6-44.8. The authors included these in the study but indicate that this could be fragments of viral RNA and not active SARS-CoV-2.
Amplification of viral RNA from blood samples in in vitro work could have been affected small volume used (50ul) and also by freeze-thaw cycles. Further work is needed to understand the origins of SARS-Cov-2 RNA; if it is predictive of disease, or infectious.
The main question of infectivity of SARS-Cov-2 RNA in blood, cannot inform changes in safety policies, where the evidence is just from 20 samples, of which 12 are unique individuals.