REGULAR MASS SCREENING FOR SARS-CoV-2 INFECTION IN CARE HOMES ALREADY AFFECTED BY COVID-19 OUTBREAKS: implications of false positive test results

Abstract

Dear Editor, We recently reported in the Journal of Infection high rates of symptomatic and asymptomatic SARS-CoV-2 infections associated with high fatality in residents across four London care homes experiencing a COVID-19 outbreak during the peak of the COVID-19 pandemic in England. 1 Similar findings were reported in other London care homes. 2 By 11 May 2020, 44% of all London care homes had experienced a COVID-19 outbreak, 3 leading to the national implementation of widespread screening of care home staff every week and of residents every 28 days to identify and isolate infected individuals and limit the spread of SARS-CoV-2 in care homes. 4 In July 2020, Public Health England (PHE) was informed of two asymptomatic staff and one asymptomatic resident in the same care home who tested positive for SARS-CoV-2 through national screening (Table 1 ). This care home had been part of the initial outbreak investigation in April 2020 and all three individuals were known to have SARS-CoV-2 antibodies. 5 We, therefore, undertook additional investigations to assess whether these were re-infections or false positive results and discuss the implications of our findings for residents, staff and care homes in general. Table 1 . Tests performed in two staff members and a resident who tested positive in the national SARS-CoV-2 infection screening programme for care homes in England. Table 1 Staff or resident Floor in care home Previous illness Confirmed COVID-19? SARS-CoV-2 Swab Results SARS-CoV-2 IgG antibody Results New outbreak: date swab taken Date results available New outbreak: date swab result Repeat SARS-CoV-2 antibody test Staff 1st floor Yes (March 2020) No Negative: 04 June Positive 2.91 (04 June) Positive (18 July) 22 July Negative (24 July) Positive 1.3 (24 July) Positive 1.1 (24 August) Resident Ground Yes (April 2020l) Yes Positive (16 April)Positive (13 May)Negative (28 May)Negative (05 June) Positive (25 June) Positive (21 July) 23 July Negative (24 July) Positive (24 July) Staff office Yes (March 2020) No Negative (15 May)Negative (22 May)Negative (01 June)Negative (05 June) Positive 5.93 (05 June) Positive (22 July) 25 July Negative (25 July) Positive 5.35 (25 July) Positive 5.40 (24 August) *subsequent investigations identified that only one of three RT-PCR targets was positive at the limit of detection of the assay (Ct 34) at the national testing centre Following our initial COVID-19 outbreak investigations in April 2020, 3 the four London care homes implemented strict lockdown procedures, with closure to new admissions and cessation of family visits. To prevent re-introduction of SARS-CoV-2 into the care homes, we implemented a local intervention to collect weekly nasal swabs from all residents and staff for four consecutive weeks in mid-May. No new infections were identified. SARS-CoV-2 antibody testing after the 4-week swabbing using the Abbott SARS-CoV-2 IgG assay 6 found two-thirds of residents and staff to be seropositive, 5 consistent with other care home investigations in London. 7 Since July 2020, the four London care homes have been participating in national screening for SARS-CoV-2, whereby swabs for residents and staff are ordered online and sent to one of several national testing centres. 4 Only qualitative results with no RT-PCR cycle threshold (Ct) values or other parameters are reported back to the care home. Between 22-25 July 2020, three asymptomatic individuals – a care worker, a resident and an office staff member – in one of the care homes under investigation tested positive for SARS-CoV-2 RNA as part of national screening. These tests were performed in two different national testing centres and on different days. The three individuals all had a history of COVID-19 like symptoms during March-April 2020, had subsequently repeatedly tested negative for SARS-CoV-2 during the weekly local nasal swab screening during May-June 2020 and were seropositive for SARS-CoV-2 antibodies in mid-June 2020 (Table 1). The care home immediately re-instituted lockdown procedures. Following the new positive SARS-CoV-2 RT-PCR result, all three individuals were re-tested at PHE national reference laboratory within 24 hours and were RT-PCR negative with detectable SARS-CoV-2 antibodies. Additionally, all residents and staff – including the three individuals – were re-tested for SARS-CoV-2 RNA as part of the outbreak management and were negative. Four weeks later, repeat testing in the two staff showed no rise in SARS-CoV-2 antibodies. The resident was also antibody positive 4 weeks later but the test was performed in a different laboratory which did not report quantitative results. The protective role of SARS-CoV-2 antibodies against re-infection and disease remains to be established, but there is increasing evidence showing that those with neutralising antibodies are unlikely to be infected with live virus, 8 which in turn reduces their risk of infecting others. Despite the large numbers of ongoing COVID-19 outbreaks in England, 9 these four London care homes did not have any additional cases prior to the national screening programme. The reporting of three positive results in a single care home was, therefore, unexpected and prompted additional investigations, which included repeat swabs, which were all negative, and blood sampling which confirmed their seropositivity at the time of re-testing. The lack of an antibody rise four weeks later confirms that these detections were not new infections and, therefore, false positive screening tests. Further work needs to be undertaken to assess the value of repeated mass swab testing in care homes during periods of low community prevalence, 10 particularly if SARS-CoV-2 positivity rates fall below 1%, when the likelihood of false positive results increases exponentially even with RT-PCR assays that have very high specificity rates (Figure 1 ). This can have a significant impact on care homes, in terms of unnecessary isolation of vulnerable residents and loss of workforce leading to suboptimal care provision. 11 Declaration of an outbreak places additional constraints on the care home, including closures to external visitors and new residents. 4 Repeated unnecessary interventions are also likely to be detrimental to the long-term mitigation strategy in care homes, have significant resource implications and impact on the wellbeing of residents and staff. In addition, there is the danger of behavioural fatigue so that, when strict infection control measures are required in a genuine outbreak, recommended measures may not be adhered to. Figure 1 Positive predictive value (PPV) of testing based on population prevalence and specificity of the test. PPV falls rapidly when prevalence falls below 1% even with the most specific test assay. Figure 1 This problem of false positivity has recently been recognised, with new national guidance published on how to interpret low level RT-PCR positive samples, including a recommendation to retest all samples testing positive at the level of detection of the assay before undertaking wider public health action. 12 It is hoped that this recommendation will reduce the number of similar closures of care homes or other institutions exposed to mass testing as a result of non-reproducible positive SARS-CoV-2 RT-PCR results. In conclusion, in care homes that have already experienced a COVID-19 outbreak, up to two-thirds of staff and surviving residents develop neutralising antibodies which is likely to reduce the risk of new infections and, particularly, further outbreaks. Whilst community SARS-CoV-2 prevalence is low, rather than repeated mass swabbing, there is an opportunity to assess a role for wider testing for SARS-CoV-2 antibodies to assess past exposure accompanied with early and rapid testing for SARS-CoV-2 RNA as needed. Any positive result could then initiate wider testing for SARS-CoV-2 RNA in the care home, include retesting the index case, and a more nuanced risk assessment of the likelihood of a true outbreak. Ethics: PHE has legal permission, provided by Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to process patient confidential information for national surveillance of communicable diseases and as such, individual patient consent is not required. Conflicts of interest: none None