James R M Black1, Chris Bailey2, Joanna Przewrocka2, Krijn K Dijkstra2, Sonia Gandhi3, Steve Gamblin3, Sam Barrell3, Charles Swanton4. 1. Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK. 2. Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK. 3. Francis Crick Institute, London, UK. 4. Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK; Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK; University College London Hospitals NHS Trust, London, UK. Electronic address: charles.swanton@crick.ac.uk.
We thank Bernard Freudenthal for his response to our previous Correspondence. We agree that use of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing among health-care workers (HCWs) solely to reduce absenteeism is inappropriate. Freudenthal correctly outlines the risks, posed by false-negative results, of advising potentially infectious HCWs to return to work. Moreover, staffing levels are currently far less problematic within UK health-care settings than during the peak of the pandemic.HCW testing should aim to identify infectious cases and reduce nosocomial transmission of SARS-CoV-2: testing only self-reported symptomatic cases risks missing many infectious cases. For instance, HCWs might unwittingly attend work with mild or non-specific symptoms. Furthermore, although the relationship between RT-PCR cycle threshold (Ct) values and infectivity requires further elucidation, evidence suggests that Ct values among asymptomatic and symptomatic cases are similar. Crucially, viable virus has been isolated up to 6 days before symptom onset.Robust epidemiological studies help detail asymptomatic spread. Results have been heterogeneous; assumptions vary between studies which might be subject to recall bias, definitions of symptoms are inconsistent, and some studies do not account for the critical pre-symptomatic phase of infection. Nonetheless, most such studies find evidence of asymptomatic SARS-CoV-2 transmission.False-positive results can also limit HCW screening utility. They can be biological, with dead virus detected in non-infectious cases, and technical, where a test is positive in the absence of viral RNA. Regular screening risks identification of biological false positives; however, more research is required to understand the biology of persistent viral RNA shedding. Technical false positives might be reduced to manageable levels by testing in duplicate.We believe a symptom-agnostic testing approach for SARS-CoV-2 among HCWs is an effective measure of reducing viral transmission. This approach is advocated on a population level and might be particularly beneficial among HCWs given reports of hospitals acting as hotbeds of COVID-19.Arguments against mass testing approaches previously have suggested a lack of resources might make this ineffective. However, UK daily testing capacity has increased tenfold since the publication of our Correspondence, while rapid point-of-care antigen tests facilitate early intervention to limit transmission.Screening for SARS-CoV-2 in asymptomatic HCWs could be a vital weapon in the fight against COVID-19 now and over the winter months. This will help the National Health Service to maintain the capacity to treat other diseases in the face of a second wave. We must act to prevent further virus spread, economic disruption, and unnecessary death.
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