ProteomicsDB: toward a FAIR open-source resource for life-science research.

ProteomicsDB (https://www.ProteomicsDB.org) is a multi-omics and multi-organism resource for life science research. In this update, we present our efforts to continuously develop and expand ProteomicsDB. The major focus over the last two years was improving the findability, accessibility, interoperability and reusability (FAIR) of the data as well as its implementation. For this purpose, we release a new application programming interface (API) that provides systematic access to essentially all data in ProteomicsDB. Second, we release a new open-source user interface (UI) and show the advantages the scientific community gains from such software. With the new interface, two new visualizations of protein primary, secondary and tertiary structure as well an updated spectrum viewer were added. Furthermore, we integrated ProteomicsDB with our deep-neural-network Prosit that can predict the fragmentation characteristics and retention time of peptides. The result is an automatic processing pipeline that can be used to reevaluate database search engine results stored in ProteomicsDB. In addition, we extended the data content with experiments investigating different human biology as well as a newly supported organism.

SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event.

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26th until March 23rd. We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2nd, although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T ('Basel cluster'), including 157 identical sequences at the root of the 'Basel cluster', some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions. Trial Registration: ClinicalTrials.gov NCT04351503.

Delirium: Prevalence and outcome in the very old in 27 medical departments during a one-year prospective study.

OBJECTIVE: The prevalence and effects of delirium in very old individuals aged ≥80 years have not yet been systematically evaluated. Therefore, this large single-center study of the one-year prevalence of delirium in 3,076 patients in 27 medical departments of the University Hospital of Zurich was conducted. METHODS: Patient scores on the Delirium Observation Screening scale, Intensive Care Delirium Screening Checklist, Diagnostic and Statistical Manual, 5th edition, and electronic Patient Assessment-Acute Care (nursing tool) resulted in the inclusion of 3,076 individuals in 27 departments. The prevalence rates were determined by simple logistic regressions, odds ratios (ORs), and confidence intervals. RESULTS: Of the 3,076 patients, 1,285 (41.8%) developed delirium. The prevalence rates in the 27 departments ranged from 15% in rheumatology (OR = 0.30) to 73% in intensive care (OR = 5.25). Delirious patients were more likely to have been admitted from long-term care facilities (OR = 2.26) or because of emergencies (OR = 2.24). The length of their hospital stay was twice as long as that for other patients. Some died before discharge (OR = 24.88), and others were discharged to nursing homes (OR = 2.96) or assisted living facilities (OR = 2.2). CONCLUSION: This is the largest study to date regarding the prevalence of delirium in patients aged ≥80 years and the medical characteristics of these patients. Almost two out of five patients developed delirium, with a high risk of loss of independence and mortality.

Calcium affects CHP1 and CHP2 conformation and their interaction with sodium/proton exchanger 1.

Calcineurin B homologous proteins (CHPs) belong to the EF-hand Ca2+ -binding protein (EFCaBP) family. They have multiple important functions including the regulation of the Na+ /H+ exchanger 1 (NHE1). The human isoforms CHP1 and CHP2 share high sequence similarity, but have distinct expression profiles with CHP2 levels for instance increased in malignant cells. These CHPs bind Ca2+ with high affinity. Biochemical data indicated that Ca2+ can regulate their functions. Experimental evidence for Ca2+ -modulated structural changes was lacking. With a newly established fluorescent probe hydrophobicity (FPH) assay, we detected Ca2+ -induced conformational changes in both CHPs. These changes are in line with an opening of their hydrophobic pocket that binds the CHP-binding region (CBD) of NHE1. Whereas the pocket is closed in the absence of Ca2+ in CHP2, it is still accessible for the dye in CHP1. Both CHPs interacted with CBD in the presence and absence of Ca2+ . Isothermal titration calorimetry (ITC) analysis revealed high binding affinity for both CHPs to CBD with equilibrium dissociation constants (KD s) in the nanomolar range. The KD for CHP1:CBD was not affected by Ca2+ , whereas Ca2+ -depletion increased the KD 7-fold for CHP2:CBD showing a decreased affinity. The data indicate an isoform specific regulatory interaction of CHP1 and CHP2 with NHE1.

Predisposing and Precipitating Factors for Delirium in the Very Old (≥80 Years): A Prospective Cohort Study of 3,076 Patients.

BACKGROUND: Predisposing and precipitating factors for delirium for the elderly, over the age of 65 years, are known, but not for the very old, over 80 years. As the society is getting older and evermore patients will reach >80 years, more evidence of the factors and their contribution to delirium is required in this patient group. METHODS: In the course of 1 year, 3,076 patients above 80 years were screened prospectively for delirium based on a Delirium Observation Screening (DOS) scale, Intensive Care Delirium Screening Checklist (ICDSC), and a DSM (Diagnostic and Statistical Manual)-5 nursing instrument (ePA-AC) construct. Relevant predisposing and precipitating factors for delirium were assessed with a multiple regression analysis. RESULTS: Of 3,076 patients above 80 years, 1,285 (41.8%) developed a delirium, which led to twice prolonged hospitalization (p < 0.001), requirement for subsequent assisted living (OR 2.2, CI: 1.73-2.8, p < 0.001), and increased mortality (OR 24.88, CI: 13.75-45.03, p < 0.001). Relevant predisposing factors were dementia (OR 15.6, CI: 10.17-23.91, p < 0.001), pressure sores (OR 4.61, CI: 2.74-7.76, p < 0.001), and epilepsy (OR 3.65, CI: 2.12-6.28, p < 0.0001). Relevant precipitating factors were acute renal failure (4.96, CI: 2.38-10.3, p < 0.001), intracranial hemorrhage (OR 8.7, CI: 4.27-17.7, p < 0.001), and pleural effusions (OR 3.25, CI: 1.77-17.8, p < 0.001). CONCLUSION: Compared to the general delirium rate of approximately 20%, the prevalence of delirium doubled above the age of 80 years (41.8%) due to predisposing factors uncommon in younger patients.

Delirium at the end of life.

BACKGROUND: The general in-hospital mortality and interrelationship with delirium are vastly understudied. Therefore, this study aimed to assess the rates of in-hospital mortality and terminal delirium. METHOD: In this prospective cohort study of 28,860 patients from 37 services including 718 in-hospital deaths, mortality rates and prevalence of terminal delirium were determined with simple logistic regressions and their respective odds ratios (ORs). RESULTS: Although overall in-hospital mortality was low (2.5%), substantial variance between services became apparent: Across intensive care services the rate was 10.8% with a 5.8-fold increased risk, across medical services rates were 4.4% and 2.4-fold, whereas at the opposite end, across surgical services rates were 0.7% and 87% reduction, respectively. The highest in-hospital mortality rate occurred on the palliative care services (27.3%, OR 19.45). The general prevalence of terminal delirium was 90.7% and ranged from 83.2% to 100%. Only across intensive care services (98.1%, OR 7.48), specifically medical intensive care (98.1%, OR 7.48) and regular medical services (95.8%, OR 4.12) rates of terminal delirium were increased. In contrast, across medical services (86.4%, OR 0.32) and in particular oncology (73.9%, OR 0.25), pulmonology (72%, OR 0.31) and cardiology (63.2%, OR 0.4) rates were decreased. For the remaining services, rates of terminal delirium were the same. SIGNIFICANCE OF RESULTS: Although in-hospital mortality was low, the interrelationship with delirium was vast: most patients were delirious at the end of life. The implications of terminal delirium merit further studies.

Assessing delirium with nursing care instruments: Evaluation of the cognitive and associated domains.

OBJECTIVE: Nursing instruments have the potential for daily screening of delirium; however, they have not yet been evaluated. Therefore, after assessing the functional domains of the electronic Patient Assessment - Acute Care (ePA-AC), this study evaluates the cognitive and associated domains. METHODS: In this prospective cohort study in the intensive care unit, 277 patients were assessed and 118 patients were delirious. The impacts of delirium on the cognitive domains, consciousness and cognition, communication and interaction, in addition to respiration, pain, and wounds were determined with simple logistic regressions and their respective odds ratios (ORs). RESULTS: Delirium was associated with substantial impairment throughout the evaluated domains. Delirious patients were somnolent (OR 6), their orientation (OR 8.2-10.6) and ability to acquire knowledge (OR 5.5-11.6) were substantially impaired, they lost the competence to manage daily routines (OR 8.2-22.4), and their attention was compromised (OR 12.8). In addition, these patients received psychotropics (OR 3.8), were visually impaired (OR 1.8), unable to communicate their needs (OR 5.6-7.6), displayed reduced self-initiated activities (OR 6.5-6.9) and challenging behaviors (OR 6.2), as well as sleep-wake disturbances (OR 2.2-5), Furthermore, delirium was associated with mechanical ventilation, abdominal/thoracic injuries or operations (OR 4.2-4.4), and sensory perception impairment (OR 3.9-5.8). SIGNIFICANCE OF RESULTS: Delirium caused substantial impairment in cognitive and associated domains. In addition to the previously described functional impairments, these findings will aid the implementation of nursing instruments in delirium screening.

The utility of nursing instruments for daily screening for delirium: Delirium causes substantial functional impairment.

OBJECTIVE: Nursing assessments have been recommended for the daily screening for delirium; however, the utility of individual items have not yet been tested. In a first step in establishing the potential of the electronic Patient Assessment-Acute Care (ePA-AC) as such, the impact of delirium on the functional domains was assessed. METHOD: In this prospective observational cohort study, 277 patients were assessed and 118 patients were delirious. The impact of delirium on functional domains of the ePA-AC related to self-initiated activity, nutrition, and elimination was determined with simple logistic regressions. RESULTS: Patients with delirium were older, sicker, were more commonly sedated during the assessment, stayed longer in the intensive care unit (ICU) and floors, and less commonly discharged home. A general pattern was the loss of abilities and full functioning equivalent to global impairment. For self-initiated mobility, in and out of the bed sizable limitations were noted and substantial inability to transfer caused friction and shearing. Similarly, any exhaustion and fatigue were associated with delirium. For self-initiated grooming and dressing, the impairment was greater in the upper body. Within the nutritional domain, delirium affected self-initiated eating and drinking, the amount of food and fluids, energy and nutrient, as well as parenteral nutrition requirement. In delirious patients, the fluid demand was rather increased than decreased, tube feeding more often required and dysphagia occurred. For the elimination domain, urination was not affected - of note, most patients were catheterized, whereas abilities to initiate or control defecation were affected. SIGNIFICANCE OF RESULTS: Delirium was associated with sizable impairment in the level of functioning. These impairments could guide supportive interventions for delirious patients and perspectively implement nursing instruments for delirium screening.

Air-conditioner cooling towers as complex reservoirs and continuous source of Legionella pneumophila infection evidenced by a genomic analysis study in 2017, Switzerland.

IntroductionWater supply and air-conditioner cooling towers (ACCT) are potential sources of Legionella pneumophila infection in people. During outbreaks, traditional typing methods cannot sufficiently segregate L. pneumophila strains to reliably trace back transmissions to these artificial water systems. Moreover, because multiple L. pneumophila strains may be present within these systems, methods to adequately distinguish strains are needed. Whole genome sequencing (WGS) and core genome multilocus sequence typing (cgMLST), with their higher resolution are helpful in this respect. In summer 2017, the health administration of the city of Basel detected an increase of L. pneumophila infections compared with previous months, signalling an outbreak.AimWe aimed to identify L. pneumophila strains populating suspected environmental sources of the outbreak, and to assess the relations between these strains and clinical outbreak strains.MethodsAn epidemiological and WGS-based microbiological investigation was performed, involving isolates from the local water supply and two ACCTs (n = 60), clinical outbreak and non-outbreak related isolates from 2017 (n = 8) and historic isolates from 2003-2016 (n = 26).ResultsIn both ACCTs, multiple strains were found. Phylogenetic analysis of the ACCT isolates showed a diversity of a few hundred allelic differences in cgMLST. Furthermore, two isolates from one ACCT showed no allelic differences to three clinical isolates from 2017. Five clinical isolates collected in the Basel area in the last decade were also identical in cgMLST to recent isolates from the two ACCTs.ConclusionCurrent outbreak-related and historic isolates were linked to ACCTs, which form a complex environmental habitat where strains are conserved over years.

Association between the number of symptomatic mpox cases and the detection of mpox virus DNA in wastewater in Switzerland: an observational surveillance study.

AIM OF THE STUDY: The COVID-19 pandemic has drawn attention to the benefit of wastewater-based epidemiology, particularly when case numbers are underreported. Underreporting may be an issue with mpox, where biological reasons and stigma may prevent patients from getting tested. Therefore, we aimed to assess the validity of wastewater surveillance for monitoring mpox virus DNA in wastewater of a Central European city and its association with official case numbers. METHODS: Wastewater samples were collected between 1 July and 28 August 2022 in the catchment area of Basel, Switzerland, and the number of mpox virus genome copies they contained was determined by real-time quantitative PCR. Logistic regression analyses were used to determine the odds of detectability of mpox virus DNA in wastewater, categorised as detectable or undetectable. Mann-Whitney U tests were used to determine associations between samples that tested positive for the mpox virus and officially reported cases and patients' recorded symptomatic phases. RESULTS: Mpox virus DNA was detected in 15 of 39 wastewater samples. The number of positive wastewater samples was associated with the number of symptomatic cases (odds ratio [OR] = 2.18, 95% confidence interval (CI) = 1.38-3.43, p = 0.001). The number of symptomatic cases differed significantly between days with positive versus negative wastewater results (median = 11 and 8, respectively, p = 0.0024). CONCLUSION: Mpox virus DNA was detectable in wastewater, even when officially reported case numbers were low (0-3 newly reported mpox cases corresponding to 6-12 symptomatic patients). Detectability in wastewater was significantly associated with the number of symptomatic patients within the catchment area. These findings illustrate the value of wastewater-based surveillance systems when assessing the prevalence of emerging and circulating infectious diseases.

Influenza transmission dynamics quantified from RNA in wastewater in Switzerland.

INTRODUCTION: Influenza infections are challenging to monitor at the population level due to many mild and asymptomatic cases and similar symptoms to other common circulating respiratory diseases, including COVID-19. Methods for tracking cases outside of typical reporting infrastructure could improve monitoring of influenza transmission dynamics. Influenza shedding into wastewater represents a promising source of information where quantification is unbiased by testing or treatment-seeking behaviours. METHODS: We quantified influenza A and B virus loads from influent at Switzerland's three largest wastewater treatment plants, serving about 14% of the Swiss population (1.2 million individuals). We estimated trends in infection incidence and the effective reproductive number (Re) in these catchments during a 2021/22 epidemic and compared our estimates to typical influenza surveillance data. RESULTS: Wastewater data captured the same overall trends in infection incidence as laboratory-confirmed case data at the catchment level. However, the wastewater data were more sensitive in capturing a transient peak in incidence in December 2021 than the case data. The Re estimated from the wastewater data was roughly at or below the epidemic threshold of 1 during work-from-home measures in December 2021 but increased to at or above the epidemic threshold in two of the three catchments after the relaxation of these measures. The third catchment yielded qualitatively the same results but with wider confidence intervals. The confirmed case data at the catchment level yielded comparatively less precise R_e estimates before and during the work-from-home period, with confidence intervals that included one before and during the work-from-home period. DISCUSSION: Overall, we show that influenza RNA in wastewater can help monitor nationwide influenza transmission dynamics. Based on this research, we developed an online dashboard for ongoing wastewater-based influenza surveillance in Switzerland.

Overcoming the matrix effect in the element analysis of steel: Laser ablation-spark discharge-optical emission spectroscopy (LA-SD-OES) and Laser-induced breakdown spectroscopy (LIBS).

The optical emission of plasma on industrial steel samples induced by Laser Ablation-Spark Discharge-Optical Emission Spectroscopy (LA-SD-OES) and by Laser-Induced Breakdown Spectroscopy (LIBS) is investigated and correlated to the volume of ablated steel material. The 36 steel samples investigated have an iron content C(Fe) above 94 wt%. The excitation energy in LIBS (laser pulse of 55 mJ) and in LA-SD-OES (laser pulse of 5 mJ and spark discharge of 50 mJ) is the same. In LA-SD-OES, the optical emission of plasma and the size of ablation craters are very similar for all samples and a linear calibration curve for Mn is measured (R2 = 0.99). In LIBS, however, a pronounced dependence of the plasma emission and of the crater volume on the steel matrix is observed and calibration curves show a strong cross-sensitivity to other elements such as Si (matrix effect). The hardness, grain size, and phase of steel samples are analyzed to correlate the matrix effect in LIBS measurements to a physical property of the specimen. The different behavior for LA-SD-OES and LIBS is probably due to different processes of sampling and plasma excitation. From our results we conclude that LA-SD-OES enables for the element analysis of industrial steel largely independent of composition and structure of samples while in LIBS the matrix effect has to be taken into account.

Conformational regulation and target-myristoyl switch of calcineurin B homologous protein 3.

Calcineurin B homologous protein 3 (CHP3) is an EF-hand Ca2+-binding protein involved in regulation of cancerogenesis, cardiac hypertrophy, and neuronal development through interactions with sodium/proton exchangers (NHEs) and signalling proteins. While the importance of Ca2+ binding and myristoylation for CHP3 function has been recognized, the underlying molecular mechanism remained elusive. In this study, we demonstrate that Ca2+ binding and myristoylation independently affect the conformation and functions of human CHP3. Ca2+ binding increased local flexibility and hydrophobicity of CHP3 indicative of an open conformation. The Ca2+-bound CHP3 exhibited a higher affinity for NHE1 and associated stronger with lipid membranes compared to the Mg2+-bound CHP3, which adopted a closed conformation. Myristoylation enhanced the local flexibility of CHP3 and decreased its affinity to NHE1 independently of the bound ion, but did not affect its binding to lipid membranes. The data exclude the proposed Ca2+-myristoyl switch for CHP3. Instead, a Ca2+-independent exposure of the myristoyl moiety is induced by binding of the target peptide to CHP3 enhancing its association to lipid membranes. We name this novel regulatory mechanism 'target-myristoyl switch'. Collectively, the interplay of Ca2+ binding, myristoylation, and target binding allows for a context-specific regulation of CHP3 functions.

Estimating multimodal brain variability in schizophrenia spectrum disorders: A worldwide ENIGMA study.

Objective: Schizophrenia is a multifaceted disorder associated with structural brain heterogeneity. Despite its relevance for identifying illness subtypes and informative biomarkers, structural brain heterogeneity in schizophrenia remains incompletely understood. Therefore, the objective of this study was to provide a comprehensive insight into the structural brain heterogeneity associated with schizophrenia. Methods: This meta- and mega-analysis investigated the variability of multimodal structural brain measures of white and gray matter in individuals with schizophrenia versus healthy controls. Using the ENIGMA dataset of MRI-based brain measures from 22 international sites with up to 6139 individuals for a given brain measure, we examined variability in cortical thickness, surface area, folding index, subcortical volume and fractional anisotropy. Results: We found that individuals with schizophrenia are distinguished by higher heterogeneity in the frontotemporal network with regard to multimodal structural measures. Moreover, individuals with schizophrenia showed higher homogeneity of the folding index, especially in the left parahippocampal region. Conclusions: Higher multimodal heterogeneity in frontotemporal regions potentially implies different subtypes of schizophrenia that converge on impaired frontotemporal interaction as a core feature of the disorder. Conversely, more homogeneous folding patterns in the left parahippocampal region might signify a consistent characteristic of schizophrenia shared across subtypes. These findings underscore the importance of structural brain variability in advancing our neurobiological understanding of schizophrenia, and aid in identifying illness subtypes as well as informative biomarkers.

Corrigendum: Risk Factors for Delirium Are Different in the Very Old: A Comparative One-Year Prospective Cohort Study of 5,831 Patients.

[This corrects the article DOI: 10.3389/fpsyt.2021.655087.].

Delirium in trauma patients: a 1-year prospective cohort study of 2026 patients.

BACKGROUND: Delirium in trauma surgery is common, especially post-operatively, but medical characteristics, risk factors and residence post-discharge have not comprehensively been investigated in all trauma patients. METHODS: Over 1 year, 2026 trauma patients were prospectively screened for delirium with the following tools: Delirium Observation screening scale (DOS), Intensive Care Delirium Screening Checklist (ICDSC) and a DSM (Diagnostic and Statistical Manual)-5, nursing tool (ePA-AC) construct. Risk factors-predisposing und precipitating-for delirium were assessed via multiple regression analysis. RESULTS: Of 2026 trauma patients, 440 (21.7%) developed delirium, which was associated with an increased risk of assisted living (OR 6.42, CI 3.92-10.49), transfer to nursing home (OR 4.66, CI 3.29-6.6), rehabilitation (OR 3.96, CI 3.1-5.1), or death (OR 70.72, CI 22-227.64). Intensive care management (OR 18.62, CI 14.04-24.68), requirement of ventilation (OR 32.21, CI 21.27-48.78), or its duration (OR 67.22, CI 33.8-133.71) all increased the risk for developing delirium. Relevant predisposing risk factors were dementia (OR 50.92, CI 15.12-171.45), cardiac insufficiency (OR 11.76, CI 3.6-38.36), and polypharmacy (OR 5.9, CI 4.01-8.68).Relevant precipitating risk factors were brain edema (OR 40.53, CI 4.81-341.31), pneumonia (OR 39.66, CI 8.89-176.93) and cerebral inflammation (OR 21.74, CI 2.34-202.07). CONCLUSION: Delirium in trauma patients is associated with poor outcome as well as with intensive care management and various predisposing and/or precipitating factors. Three quarters of patients who had undergone delirium were not able to live independently at home any more.

Delirium screening in an acute care setting with a machine learning classifier based on routinely collected nursing data: A model development study.

Delirium screening in acute care settings is a resource intensive process with frequent deviations from screening protocols. A predictive model relying only on daily collected nursing data for delirium screening could expand the populations covered by such screening programs. Here, we present the results of the development and validation of a series of machine-learning based delirium prediction models. For this purpose, we used data of all patients 18 years or older which were hospitalized for more than a day between January 1, 2014, and December 31, 2018, at a single tertiary teaching hospital in Zurich, Switzerland. A total of 48,840 patients met inclusion criteria. 18,873 (38.6%) were excluded due to missing data. Mean age (SD) of the included 29,967 patients was 71.1 (12.2) years and 12,231 (40.8%) were women. Delirium was assessed with the Delirium Observation Scale (DOS) with a total score of 3 or greater indicating that a patient is at risk for delirium. Additional measures included structured data collected for nursing process planning and demographic characteristics. The performance of the machine learning models was assessed using the area under the receiver operating characteristic curve (AUC). The training set consisted of 21,147 patients (mean age 71.1 (12.1) years; 8,630 (40.8%) women|) including 233,024 observations with 16,167 (6.9%) positive DOS screens. The test set comprised 8,820 patients (median age 71.1 (12.4) years; 3,601 (40.8%) women) with 91,026 observations with 5,445 (6.0%) positive DOS screens. Overall, the gradient boosting machine model performed best with an AUC of 0.933 (95% CI, 0.929 - 0.936). In conclusion, machine learning models based only on structured nursing data can reliably predict patients at risk for delirium in an acute care setting. Prediction models, using existing data collection processes, could reduce the resources required for delirium screening procedures in clinical practice.

Wastewater monitoring of SARS-CoV-2 shows high correlation with COVID-19 case numbers and allowed early detection of the first confirmed B.1.1.529 infection in Switzerland: results of an observational surveillance study.

AIMS OF THE STUDY: Wastewater-based epidemiology has contributed significantly to the comprehension of the dynamics of the current COVID-19 pandemic. Its additional value in monitoring SARS-CoV-2 circulation in the population and identifying newly arising variants independently of diagnostic testing is now undisputed. As a proof of concept, we report here correlations between SARS-CoV-2 detection in wastewater and the officially recorded COVID-19 case numbers, as well as the validity of such surveillance to detect emerging variants, exemplified by the detection of the B.1.1.529 variant Omicron in Basel, Switzerland. METHODS: From July 1 to December 31, 2021, wastewater samples were collected six times a week from the inflow of the local wastewater treatment plant that receives wastewater from the catchment area of the city of Basel, Switzerland, comprising 273,075 inhabitants. The number of SARS-CoV-2 RNA copies was determined by reverse transcriptase-quantitative PCR. Spearman's rank correlation coefficients were calculated to determine correlations with the median seven-day incidence of genome copies per litre of wastewater and official case data. To explore delayed correlation effects between the seven-day median number of genome copies/litre wastewater and the median seven-day incidence of SARS-CoV-2 cases, time-lagged Spearman's rank correlation coefficients were calculated for up to 14 days. RNA extracts from daily wastewater samples were used to genotype circulating SARS-CoV-2 variants by next-generation sequencing. RESULTS: The number of daily cases and the median seven-day incidence of SARS-CoV-2 infections in the catchment area showed a high correlation with SARS-CoV-2 measurements in wastewater samples. All correlations between the seven-day median number of genome copies/litre wastewater and the time-lagged median seven-day incidence of SARS-CoV-2 cases were significant (p<0.001) for the investigated lag of up to 14 days. Correlation coefficients declined constantly from the maximum of 0.9395 on day 1 to the minimum of 0.8016 on day 14. The B.1.1.529 variant Omicron was detected in wastewater samples collected on November 21, 2021, before its official acknowledgement in a clinical sample by health authorities. CONCLUSIONS: In this proof-of-concept study, wastewater-based epidemiology proved a reliable and sensitive surveillance approach, complementing routine clinical testing for mapping COVID-19 pandemic dynamics and observing newly circulating SARS-CoV-2 variants.

SARS-CoV-2 Vaccine Alpha and Delta Variant Breakthrough Infections Are Rare and Mild but Can Happen Relatively Early after Vaccination.

(1) Background: Some COVID-19 vaccine recipients show breakthrough infection. It remains unknown, which factors contribute to risks and severe outcomes. Our aim was to identify risk factors for SCoV2 breakthrough infections in fully vaccinated individuals. (2) Methods: We conducted a retrospective case-control study from 28 December 2020 to 25 October 2021. Data of all patients with breakthrough infection was compared to data of all vaccine recipients in the Canton of Basel-City, Switzerland. Further, breakthrough infections by Alpha- and Delta-variants were compared. (3) Results: Only 0.39% (488/126,586) of all vaccine recipients suffered from a breakthrough infection during the observational period, whereof most cases were asymptomatic or mild (97.2%). Breakthrough infections after full vaccination occurred in the median after 78 days (IQR 47-123.5). Factors with lower odds for breakthrough infection were age (OR 0.987) and previous COVID-19 infection prior to vaccination (OR 0.296). Factors with higher odds for breakthrough infection included vaccination with Pfizer/BioNTech instead of Moderna (OR 1.459), chronic disease (OR 2.109), and healthcare workers (OR 1.404). (4) Conclusions: Breakthrough infections are rare and mild but can occur early after vaccination. This implies that booster vaccination might be initiated earlier, especially for risk groups. Due to new variants emerging repeatedly, continuous monitoring of breakthrough infections is crucial.

Determinants of SARS-CoV-2 transmission to guide vaccination strategy in an urban area.

Transmission chains within small urban areas (accommodating ∼30 per cent of the European population) greatly contribute to case burden and economic impact during the ongoing coronavirus pandemic and should be a focus for preventive measures to achieve containment. Here, at very high spatio-temporal resolution, we analysed determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in a European urban area, Basel-City (Switzerland). We combined detailed epidemiological, intra-city mobility and socio-economic data sets with whole-genome sequencing during the first SARS-CoV-2 wave. For this, we succeeded in sequencing 44 per cent of all reported cases from Basel-City and performed phylogenetic clustering and compartmental modelling based on the dominating viral variant (B.1-C15324T; 60 per cent of cases) to identify drivers and patterns of transmission. Based on these results we simulated vaccination scenarios and corresponding healthcare system burden (intensive care unit (ICU) occupancy). Transmissions were driven by socio-economically weaker and highly mobile population groups with mostly cryptic transmissions which lacked genetic and identifiable epidemiological links. Amongst more senior population transmission was clustered. Simulated vaccination scenarios assuming 60-90 per cent transmission reduction and 70-90 per cent reduction of severe cases showed that prioritising mobile, socio-economically weaker populations for vaccination would effectively reduce case numbers. However, long-term ICU occupation would also be effectively reduced if senior population groups were prioritised, provided there were no changes in testing and prevention strategies. Reducing SARS-CoV-2 transmission through vaccination strongly depends on the efficacy of the deployed vaccine. A combined strategy of protecting risk groups by extensive testing coupled with vaccination of the drivers of transmission (i.e. highly mobile groups) would be most effective at reducing the spread of SARS-CoV-2 within an urban area.