Long-term course of neutralising antibodies against SARS-CoV-2 in vaccinated and unvaccinated staff and residents in a Swiss nursing home: a cohort study 2021–2022

BACKGROUND: Given their high-risk resident population, nursing homes were critical institutions in the COVID-19 pandemic, calling for continued monitoring and vaccine administration to healthcare workers and residents. Here, we studied long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in vaccinated and unvaccinated healthcare workers and residents of a nursing home in Switzerland between February 2021 and June 2022. METHODS: Our study comprised 45 participants, of which 39 were healthcare workers and six were residents. All participants were offered a maximum of three mRNA vaccine doses (Pfizer/BioNTech, BNT162b2) in December 2020, January 2021, and November/December 2021. Thirty-five participants received three vaccinations, seven either one or two, and three remained unvaccinated. We collected four blood samples: one in March 2021 and three during follow-ups in November 2021, February 2022, and June 2022. We performed a multifactorial serological SARS-CoV-2 assay (ABCORA) for immunoglobulin G, A, and M responses to spike (receptor-binding domain, S1, and S2) and nucleocapsid (N) proteins. Furthermore, we assessed predicted neutralisation activity based on signal over cutoff in ABCORA. We collected epidemiological data from participants via a standardised questionnaire. RESULTS: Thirty-two (71%) of the 45 participants showed hybrid immunity from combined vaccination and previous infection; 10 (22%) had only vaccine-induced immunity; and three (7%) had only post-infection immunity. Participants with hybrid immunity showed the highest predicted neutralisation activity at the end of the study period (median Sum S1 = 273), and unvaccinated participants showed the lowest (median Sum S1 = 41). Amongst participants who reported a SARS-CoV-2 infection, median Sum S1 levels increased with the number of vaccinations (p = 0.077). The healthcare worker group showed a significant time-dependent decrease in median Sum S1 after base immunisation (93% decrease, p = 0.0005) and the booster dose (26% decrease, p = 0.010). Predicted neutralisation activity was lower amongst residents (adjusted ratio of means [AM] = 0.7, 95% confidence interval [CI] = 0.3–1.0) and amongst smokers (AM = 0.5, 95% CI 0.3–0.8). Activity increased with the number of vaccinations (booster: AM = 3.6, 95% CI 1.5–8.8; no booster: AM = 2.3, 95% CI 0.9–2.5). Positive SARS-CoV-2 infection status tended to confer higher predicted neutralisation levels (AM = 1.5, 95% CI 0.9–2.5). CONCLUSIONS: Our study of the long-term serological course of SARS-CoV-2 in a nursing home showed that the first SARS-CoV-2 booster vaccine was essential for maintaining antiviral antibody levels. Hybrid immunity sustained SARS-CoV-2 immunity at the highest level. In critical settings such as nursing homes, monitoring the SARS-CoV-2 immune status may guide booster vaccinations

Targeted next-generation sequencing to diagnose drug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND Targeted next-generation sequencing (NGS) can rapidly and simultaneously detect mutations associated with resistance to tuberculosis drugs across multiple gene targets. The use of targeted NGS to diagnose drug-resistant tuberculosis, as described in publicly available data, has not been comprehensively reviewed. We aimed to identify targeted NGS assays that diagnose drug-resistant tuberculosis, determine how widely this technology has been used, and assess the diagnostic accuracy of these assays. METHODS In this systematic review and meta-analysis, we searched MEDLINE, Embase, Cochrane Library, Web of Science Core Collection, Global Index Medicus, Google Scholar, ClinicalTrials.gov, and the WHO International Clinical Trials Registry Platform for published and unpublished reports on targeted NGS for drug-resistant tuberculosis from Jan 1, 2005, to Oct 14, 2022, with updates to our search in Embase and Google Scholar until Feb 13, 2024. Studies eligible for the systematic review described targeted NGS approaches to predict drug resistance in Mycobacterium tuberculosis infections using primary samples, reference strain collections, or cultured isolates from individuals with presumed or confirmed tuberculosis. Our search had no limitations on study type or language, although only reports in English, German, and French were screened for eligibility. For the meta-analysis, we included test accuracy studies that used any reference standard, and we assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The primary outcomes for the meta-analysis were sensitivity and specificity of targeted NGS to diagnose drug-resistant tuberculosis compared to phenotypic and genotypic drug susceptibility testing. We used a Bayesian bivariate model to generate summary receiver operating characteristic plots and diagnostic accuracy measures, overall and stratified by drug and sample type. This study is registered with PROSPERO, CRD42022368707. FINDINGS We identified and screened 2920 reports, of which 124 were eligible for our systematic review, including 37 review articles and 87 reports of studies collecting samples for targeted NGS. Sequencing was mainly done in the USA (14 [16%] of 87), western Europe (ten [11%]), India (ten [11%]), and China (nine [10%]). We included 24 test accuracy studies in the meta-analysis, in which 23 different tuberculosis drugs or drug groups were assessed, covering first-line drugs, injectable drugs, and fluoroquinolones and predominantly comparing targeted NGS with phenotypic drug susceptibility testing. The combined sensitivity of targeted NGS across all drugs was 94·1% (95% credible interval [CrI] 90·9-96·3) and specificity was 98·1% (97·0-98·9). Sensitivity for individual drugs ranged from 76·5% (52·5-92·3) for capreomycin to 99·1% (98·3-99·7) for rifampicin; specificity ranged from 93·1% (88·0-96·3) for ethambutol to 99·4% (98·3-99·8) for amikacin. Diagnostic accuracy was similar for primary clinical samples and culture isolates overall and for rifampicin, isoniazid, ethambutol, streptomycin, and fluoroquinolones, and similar after excluding studies at high risk of bias (overall sensitivity 95·2% [95% CrI 91·7-97·1] and specificity 98·6% [97·4-99·3]). INTERPRETATION Targeted NGS is highly sensitive and specific for detecting drug resistance across panels of tuberculosis drugs and can be performed directly on clinical samples. There is a paucity of data on performance for some currently recommended drugs. The barriers preventing the use of targeted NGS to diagnose drug-resistant tuberculosis in high-burden countries need to be addressed. FUNDING National Institutes of Allergy and Infectious Diseases and Swiss National Science Foundation

Long-term course of neutralising antibodies against SARS-CoV-2 in vaccinated and unvaccinated staff and residents in a Swiss nursing home: a cohort study 2021–2022

BACKGROUND: Given their high-risk resident population, nursing homes were critical institutions in the COVID-19 pandemic, calling for continued monitoring and vaccine administration to healthcare workers and residents. Here, we studied long-term severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity in vaccinated and unvaccinated healthcare workers and residents of a nursing home in Switzerland between February 2021 and June 2022. METHODS: Our study comprised 45 participants, of which 39 were healthcare workers and six were residents. All participants were offered a maximum of three mRNA vaccine doses (Pfizer/BioNTech, BNT162b2) in December 2020, January 2021, and November/December 2021. Thirty-five participants received three vaccinations, seven either one or two, and three remained unvaccinated. We collected four blood samples: one in March 2021 and three during follow-ups in November 2021, February 2022, and June 2022. We performed a multifactorial serological SARS-CoV-2 assay (ABCORA) for immunoglobulin G, A, and M responses to spike (receptor-binding domain, S1, and S2) and nucleocapsid (N) proteins. Furthermore, we assessed predicted neutralisation activity based on signal over cutoff in ABCORA. We collected epidemiological data from participants via a standardised questionnaire. RESULTS: Thirty-two (71%) of the 45 participants showed hybrid immunity from combined vaccination and previous infection; 10 (22%) had only vaccine-induced immunity; and three (7%) had only post-infection immunity. Participants with hybrid immunity showed the highest predicted neutralisation activity at the end of the study period (median Sum S1 = 273), and unvaccinated participants showed the lowest (median Sum S1 = 41). Amongst participants who reported a SARS-CoV-2 infection, median Sum S1 levels increased with the number of vaccinations (p = 0.077). The healthcare worker group showed a significant time-dependent decrease in median Sum S1 after base immunisation (93% decrease, p = 0.0005) and the booster dose (26% decrease, p = 0.010). Predicted neutralisation activity was lower amongst residents (adjusted ratio of means [AM] = 0.7, 95% confidence interval [CI] = 0.3–1.0) and amongst smokers (AM = 0.5, 95% CI 0.3–0.8). Activity increased with the number of vaccinations (booster: AM = 3.6, 95% CI 1.5–8.8; no booster: AM = 2.3, 95% CI 0.9–2.5). Positive SARS-CoV-2 infection status tended to confer higher predicted neutralisation levels (AM = 1.5, 95% CI 0.9–2.5). CONCLUSIONS: Our study of the long-term serological course of SARS-CoV-2 in a nursing home showed that the first SARS-CoV-2 booster vaccine was essential for maintaining antiviral antibody levels. Hybrid immunity sustained SARS-CoV-2 immunity at the highest level. In critical settings such as nursing homes, monitoring the SARS-CoV-2 immune status may guide booster vaccinations

Association of part-time clinical work with well-being and mental health in General Internal Medicine: A survey among Swiss hospitalists.

IntroductionBurnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear.Materials and methodsWe conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of ResultsOf 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07-0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction.ConclusionsFull-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms

Adjusted association between part-time vs. full-time work and outcomes based on propensity score models.

Adjusted association between part-time vs. full-time work and outcomes based on propensity score models.</p

Sensitivity analysis considering full-time and part-time employment overall, adjusted for quintiles of the propensity scores.

Abbreviations: CI: confidence interval; ePWBI, extended Physician Well-Being Index; IQR, interquartile range; OR, odds ratio; SF-8: Short-form Health Survey. Results were adjusted for the propensity of working part-time, as well as age, sex, parenthood, relationship status, academic ambition, reduced work capacity due to health reasons, time since transition to hospitalist, and number of patients to care for * the ePWBI consists of 9 questions and ranges from -2 to 9, with lower scores denoting better well-being. A score of ≥3 points was defined as poor wellbeing. § measured by a positive answer to at least one of the two first questions of the Epwbi. ♦ rated on a 5-point Likert scale. † measured by a linear analogue scale with a response range from 0 (as bad as can be) to 10 (as good as it can be). ‡ measured by question 9 of the ePWBI. + 8 items with 5- and 6-point Likert-type scales. Each item generates a norm-based T-score ranging from 0 to 100 with higher scores indicating better health, calibrated to a mean score of 50 in the general U.S. population. The Physical and Mental Component Summary is calculated as the weighted sum of the 8 sub-scale scores and normalised to the U.S. general population. ¶ assessed using the 7-item Stanford Sleepiness Scale, 1 being fully alert and 7 imminent sleep onset. # measured using the 2 first items of the 9-item Patient Health Questionnaire (PHQ-2). (DOCX)</p

Well-being and job satisfaction among full-time and part-time hospitalists.

Well-being and job satisfaction among full-time and part-time hospitalists.</p

Characteristics of participating hospitalists.

IntroductionBurnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear.Materials and methodsWe conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of ResultsOf 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07–0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction.ConclusionsFull-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms.</div

Flowchart: Hospitalists of General Internal Medicine departments included in this study.

Flowchart: Hospitalists of General Internal Medicine departments included in this study.</p