Personal Decisions, Public Consequences: On Distinguishing between the Vaccinated and the Non-Vaccinated in Coronavirus Management (preprint)

We here sketch – in brief, and with no pretense of completeness – a moral and legal framework for analyzing distinctions between the vaccinated and the non-vaccinated, as a part of the efforts to reopen businesses and public institutions in Israel. We discuss the relevant constraints on personal liberty and what could justify them, what incentives may justifiably be used and in what circumstances, and who should bear the costs of the decision by some not to be vaccinated. While some of the particular applications are particular to Israeli circumstances, the general considerations may be helpful in other countries.We argue that the collective attributes of the pandemic affect the measures required to cope with it, as well as their morality and legality. We discuss four ends that may justify distinctions between the vaccinated and the non-vaccinated: reducing the numbers of infections and controlling pandemic-related harms and derivative, general, health harms; gradually returning to economic and social normalcy; imposing the costs of the decision not to be vaccinated on those making it; and incentivizing inoculation. Multiple measures could be designed to achieve these ends and not all means are justifiable. Given the considerable variation in the design and implementation of inoculation-based distinctions, we settle for suggesting general guidelines for analyzing the proportionality and morality of possible measures. In general, we argue that measures that preserve access of the non-vaccinated to essential activities and maintain their ability to participate in other activities either remotely (as with remote teaching or studying) or by providing a ‘proof of safety’ (e.g., a recent negative COVID test) are likely to be proportional. In addition, we reject the claim that distinguishing between the vaccinated and the non-vaccinated constitutes impermissible discrimination. A crucial assumption here is that vaccination is available to all residents, namely there are no residents who want to get vaccinated but cannot (other than for medical reasons, see below). Under this assumption, in the context of lifting COVID-related restrictions, the vaccinated and the non-vaccinated are relevantly different groups. Opening up activities while conditioning access upon vaccination (or a recent negative test) does not significantly harm the non-vaccinated compared to the COVID-restrictions (implemented in Israel during the past year) – rather, it benefits the vaccinated. And the non-vaccinated are always free to change their decision and come to enjoy the benefits – health-related and others – of the publicly available vaccines. Of course, any acceptable model will have to include arrangements for those who cannot (rather than will not) be vaccinated (i.e., for medical reasons), and should also include a discretionary mechanism providing specific arrangements for exceptional, hard-to-predict-cases.

Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia (preprint)

Background The diagnosis of infectious diseases has been hampered by reliance on microbial culture. Cultures take several days to return a result and organisms frequently fail to grow. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and mitigates against stewardship. Methods Single ICU observational cohort study with contemporaneous comparator group. We developed and implemented a TaqMan array card (TAC) covering 52 respiratory pathogens in ventilated patients undergoing bronchoscopic investigation for suspected pneumonia. The time to result was compared against conventional culture, and sensitivity compared to conventional microbiology and metagenomic sequencing. We observed the clinician decisions in response to array results, comparing antibiotic free days (AFD) between the study cohort and comparator group. Findings 95 patients were enrolled with 71 forming the comparator group. TAC returned results 61 hours (IQR 42-90) faster than culture. The test had an overall sensitivity of 93% (95% CI 88-97%) compared to a combined standard of conventional culture and metagenomic sequencing, with 100% sensitivity for most individual organisms. In 54% of cases the TAC results altered clinical management, with 62% of changes leading to de-escalation, 30% to an increase in spectrum, and investigations for alternative diagnoses in 9%. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). Interpretation Implementation of a customised syndromic diagnostic for pneumonia led to faster results, with high sensitivity and measurable impact on clinical decision making. Funding Addenbrookes Charitable Trust, Wellcome Trust and Cambridge NIHR BRC

Rapid point of care nucleic acid testing for SARS-CoV-2 in hospitalised patients: a clinical trial and implementation study (preprint)

BackgroundThere is urgent need for safe and efficient triage protocols for hospitalized COVID-19 suspects to appropriate isolation wards. A major barrier to timely discharge of patients from the emergency room and hospital is the turnaround time for many SARS-CoV-2 nucleic acid tests. We validated a point of care nucleic acid amplification based platform SAMBA II for diagnosis of COVID-19 and performed an implementation study to assess its impact on patient disposition at a major academic hospital. MethodsWe prospectively recruited COVID-19 suspects admitted to hospital (NCT04326387). In an initial pilot phase, individuals were tested using a nasal/throat swab with the SAMBA II SARS-CoV-2 rapid diagnostic platform in parallel with a combined nasal/throat swab for standard central laboratory RT-PCR testing. In the second implementation phase, we examined the utility of adding the SAMBA platform to routine care. In the pilot phase, we measured concordance and assay validity using the central laboratory as the reference standard and assessed assay turnaround time. In the implementation phase, we assessed 1) time to definitive bed placement from admission, 2) time spent on COVID-19 holding wards, 3) proportion of patients in isolation versus COVID negative areas following a test, comparing the implementation phase with the 10 days prior to implementation. ResultsIn phase I, 149 participants were included in the pilot. By central laboratory RT-PCR testing, 32 (21.5%) tested positive and 117 (78.5%). Sensitivity and specificity of the SAMBA assay compared to RT-PCR lab test were 96.9% (95% CI 0.838-0.999) and 99.1% (0.953-0.999), respectively. Median time to result was 2.6 hours (IQR 2.3 to 4.8) for SAMBA II SARS-CoV-2 test and 26.4 hours (IQR 21.4 to 31.4) for the standard lab RT-PCR test (p<0.001). In the first 10 days of the SAMBA implementation phase, we conducted 992 tests, with the majority (59.8%) used for hospital admission, and the remainder for pre-operative screening (11.3%), discharge planning (10%), in-hospital screening of new symptoms (9.7%). Comparing the pre-implementation (n=599) with the implementation phase, median time to definitive bed placement from admission was reduced from 23.4 hours (8.6-41.9) to 17.1 hours (9.0-28.8), P=0.02 in Cox analysis, adjusted for age, sex, comorbidities and clinical severity at presentation. Mean length of stay on a COVID-19 holding ward decreased from 58.5 hours to 29.9 hours (P<0.001). Use of single occupancy rooms amongst those tested fell from 30.8% before to 21.2% (P=0.03) and 11 hospital bay closures (on average 6 beds each) were avoided after implementation of the POC assay. ConclusionsThe SAMBA II SARS-CoV-2 rapid assay performed well compared to a centralized laboratory RT-PCR platform and demonstrated shorter time to result both in trial and real-world settings. It was also associated with faster time to definitive bed placement from the emergency room, greater availability of isolation rooms, avoidance of hospital bay closures, and greater movement of patients to COVID negative open "green" category wards. Rapid testing in hospitals has the potential to transform ability to deal with the COVID-19 epidemic.