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      Misuse of SARS-CoV-2 testing in symptomatic health-care staff in the UK – Authors' reply

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          Abstract

          We thank Bernard Freudenthal for his response to our previous Correspondence. 1 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. 2 Crucially, viable virus has been isolated up to 6 days before symptom onset. 3 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. 4 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. 5 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 6 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, 1 while rapid point-of-care antigen tests facilitate early intervention to limit transmission. 6 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. © 2020 Bloomberg/Getty Images 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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          Most cited references6

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          Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

          The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
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            Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility

            Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can spread rapidly within skilled nursing facilities. After identification of a case of Covid-19 in a skilled nursing facility, we assessed transmission and evaluated the adequacy of symptom-based screening to identify infections in residents. Methods We conducted two serial point-prevalence surveys, 1 week apart, in which assenting residents of the facility underwent nasopharyngeal and oropharyngeal testing for SARS-CoV-2, including real-time reverse-transcriptase polymerase chain reaction (rRT-PCR), viral culture, and sequencing. Symptoms that had been present during the preceding 14 days were recorded. Asymptomatic residents who tested positive were reassessed 7 days later. Residents with SARS-CoV-2 infection were categorized as symptomatic with typical symptoms (fever, cough, or shortness of breath), symptomatic with only atypical symptoms, presymptomatic, or asymptomatic. Results Twenty-three days after the first positive test result in a resident at this skilled nursing facility, 57 of 89 residents (64%) tested positive for SARS-CoV-2. Among 76 residents who participated in point-prevalence surveys, 48 (63%) tested positive. Of these 48 residents, 27 (56%) were asymptomatic at the time of testing; 24 subsequently developed symptoms (median time to onset, 4 days). Samples from these 24 presymptomatic residents had a median rRT-PCR cycle threshold value of 23.1, and viable virus was recovered from 17 residents. As of April 3, of the 57 residents with SARS-CoV-2 infection, 11 had been hospitalized (3 in the intensive care unit) and 15 had died (mortality, 26%). Of the 34 residents whose specimens were sequenced, 27 (79%) had sequences that fit into two clusters with a difference of one nucleotide. Conclusions Rapid and widespread transmission of SARS-CoV-2 was demonstrated in this skilled nursing facility. More than half of residents with positive test results were asymptomatic at the time of testing and most likely contributed to transmission. Infection-control strategies focused solely on symptomatic residents were not sufficient to prevent transmission after SARS-CoV-2 introduction into this facility.
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              COVID-19: the case for health-care worker screening to prevent hospital transmission

              The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has placed unprecedented strain on health-care services worldwide, leading to more than 100 000 deaths worldwide, as of April 15, 2020. 1 Most testing for SARS-CoV-2 aims to identify current infection by molecular detection of the SARS-CoV-2 antigen; this involves a RT-PCR of viral RNA in fluid, typically obtained from the nasopharynx or oropharynx. 2 The global approach to SARS-CoV-2 testing has been non-uniform. In South Korea, testing has been extensive, with emphasis on identifying individuals with respiratory illness, and tracing and testing any contacts. Other countries (eg, Spain) initially limited testing to individuals with severe symptoms or those at high risk of developing them. Here we outline the case for mass testing of both symptomatic and asymptomatic health-care workers (HCWs) to: (1) mitigate workforce depletion by unnecessary quarantine; (2) reduce spread in atypical, mild, or asymptomatic cases; and (3) protect the health-care workforce. Staff shortages in health care are significant amidst the global effort against coronavirus disease 2019 (COVID-19). In the UK, guidance for staffing of intensive care units has changed drastically, permitting specialist critical care nurse-to-patient ratios of 1:6 when supported by non-specialists (normally 1:1) and one critical care consultant per 30 patients (formerly 1:8–1:15). 3 Fears of the impact of this shortage have led to other measures that would, in normal circumstances, be considered extreme: junior doctors’ rotations have been temporarily halted during the outbreak; annual leave for staff has been delayed; and doctors undertaking research activities have been redeployed. Workforce depletion will not only affect health care; the Independent Care Group, representing care homes in the UK, has suggested that social care is already “at full stretch”, 4 with providers calling for compulsory testing of social and health workers to maintain staffing. In spite of this, a lack of effective testing has meant that a large number of HCWs are self-isolating (125 000 HCWs, according to one report 5 ). In one small sample, only one in seven self-isolating HCWs were found to have the virus. 6 A letter to National Health Service (NHS) Trust executives on April 12, 2020, outlined that priority is being given to staff in critical care, emergency departments, and ambulance services to prevent the impact of absenteeism in those areas. 7 Increased testing capacity will enable all staff who are self-isolating unnecessarily to bolster a depleted workforce. Asymptomatic HCWs are an underappreciated potential source of infection and worthy of testing. The number of asymptomatic cases of COVID-19 is significant. In a study of COVID-19 symptomatic and asymptomatic infection on the Diamond Princess cruise ship, 328 of the 634 positive cases (51·7%) were asymptomatic at the time of testing. 8 Estimated asymptomatic carriage was 17·9%. 8 Among 215 obstetric cases in New York City, 29 (87·9%) of 33 positive cases were asymptomatic, 9 whereas China's National Health Commission 10 recorded on April 1, 2020, that 130 (78%) of 166 positive cases were asymptomatic. Moreover, transmission before the onset of symptoms has been reported11, 12, 13, 14 and might have contributed to spread among residents of a nursing facility in Washington, USA. 15 Furthermore, evidence from modelled COVID-19 infectiousness profiles suggests that 44% of secondary cases were infected during the presymptomatic phase of illnesses from index cases, 16 whereas a study of COVID-19 cases in a homeless shelter in Boston, MA, USA, implies that individual COVID-19 symptoms might be uncommon and proposed universal testing irrespective of symptomatic burden. 17 Substantial asymptomatic transmission might also mean that current estimates of the basic reproduction number, R0, for COVID-19 are inaccurate. 18 HCW testing could reduce in-hospital transmission. In a retrospective, single-centre study in Wuhan, 41% of 138 patients were thought to have acquired infection in hospital. 19 At the Royal Gwent Hospital in Newport, Wales, approximately half of the emergency room workforce have tested positive. 20 Blanket testing near Venice, Italy, helped to identify asymptomatic cases and might have helped eliminate SARS-CoV-2 in a village. 21 Moreover, asymptomatic and presymptomatic HCWs continue to commute to places of work where personal protective equipment (PPE) might be suboptimal. This disease spread could, in turn, propagate out of hospitals: during a period of lockdown asymptomatic COVID-19 carriage among hospital staff could conceivably act as a potent source of ongoing transmission. Protecting the health of HCWs is paramount when staffing is limited. As well as by the provision of adequate PPE, the wellbeing of HCWs can be promoted by ensuring that infected colleagues are promptly tested and isolated. The scale of this problem is not yet fully understood, nor is the full potential for asymptomatic and presymptomatic HCWs to transmit infection to patients who do not have COVID-19, other HCWs, or the public. However, given that asymptomatic transmission has been documented, utmost caution is urged.11, 12, 13, 14 Our own NHS Trust at University College London Hospitals, London, UK, will soon be testing asymptomatic HCWs. In partnership with the Francis Crick Institute in London, UK, where COVID-19 testing will be performed, this initiative is an attempt to further limit nosocomial transmission. It could also alleviate a critical source of anxiety for HCWs. 22 A healthy, COVID-19-free workforce that is not burned out will be an asset to the prolonged response to the COVID-19 crisis. As testing facilities increase in number and throughput in the coming weeks, testing should aim to accommodate weekly or fortnightly screening of HCWs working in high-risk areas. There is a powerful case in support of mass testing of both symptomatic and asymptomatic HCWs to reduce the risk of nosocomial transmission. At the time of writing, the UK is capable of performing 18 000 tests per day, 23 with the Health Secretary targeting a capacity of 100 000 tests per day by the end of April, 2020. Initially, the focus of testing was patients, with NHS England stating only 15% of available testing would be used to test NHS staff. 24 Although this cap has been lifted, symptomatic HCWs, rather than asymptomatic HCWs, are currently prioritised in testing. This approach could mean that presymptomatic HCWs who are capable of transmitting the virus are not being tested; if they were tested and found to be COVID-19 positive, they could be advised to isolate and await the onset of symptoms or, if no symptoms develop, undergo repeat testing. As countries seek to flatten the growth phase of COVID-19, we see a significant opportunity in expanding testing among HCWs; this will be critical when pursuing an exit strategy from strict lockdown measures that curb spread of the virus.
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                Author and article information

                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier Ltd.
                0140-6736
                1474-547X
                22 October 2020
                24-30 October 2020
                22 October 2020
                : 396
                : 10259
                : 1329-1330
                Affiliations
                [a ]Cancer Genome Evolution Research Group, University College London Cancer Institute, University College London, London, UK
                [b ]Cancer Research UK Lung Cancer Centre of Excellence, University College London Cancer Institute, University College London, London, UK
                [c ]Cancer Evolution and Genome Instability Laboratory, Francis Crick Institute, London NW1 1AT, UK
                [d ]Francis Crick Institute, London, UK
                [e ]University College London Hospitals NHS Trust, London, UK
                Article
                S0140-6736(20)32145-0
                10.1016/S0140-6736(20)32145-0
                7581353
                c1093791-5e9b-4841-813d-c37f19b5acb3
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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