Successful reduction of urinary catheter placement for correct and incorrect indications after introduction of a prevention bundle.

The prospective before-after quality improvement study was to assess bundle effectiveness to reduce urinary catheter days and prevent associated complications. All patients with preexisting or new urinary catheters in a regional hospital in Switzerland were included. We showed a reduction of catheter days, incorrect urinary catheter indications, and most strikingly formally correct indications.

SARS-CoV-2 immunity and reasons for non-vaccination among healthcare workers from eastern and northern Switzerland: results from a nested multicentre cross-sectional study.

AIMS OF THE STUDY: We aimed to assess the extent of SARS-CoV-2 humoral immunity elicited by previous infections and/or vaccination among healthcare workers, and to identify reasons why healthcare workers decided against vaccination. METHODS: This nested cross-sectional study included volunteer healthcare workers from 14 healthcare institutions in German-speaking Switzerland. In January 2021, SARS-CoV-2 vaccines were available for healthcare workers. In May and June 2022, participants answered electronic questionnaires regarding baseline characteristics including SARS-CoV-2 vaccination status (with one or more vaccine doses defined as vaccinated) and previous SARS-CoV-2 infections. Unvaccinated participants indicated their reasons for non-vaccination. Participants underwent testing for SARS-CoV-2 anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibodies. Antibody prevalence was described across age groups. In addition, we performed multivariable logistic regression to identify baseline characteristics independently associated with non-vaccination and described reasons for non-vaccination. RESULTS: Among 22,438 eligible employees, 3,436 (15%) participated; the median age was 43.7 years (range 16-73), 2,794 (81.3%) were female, and 1,407 (47.7%) identified as nurses; 3,414 (99.4%) underwent serology testing, among whom 3,383 (99.0%) had detectable anti-S (3,357, 98.3%) antibodies, anti-N (2,396, 70.1%) antibodies, or both (2,370, 69.4%). A total of 296 (8.6%) healthcare workers were unvaccinated, whereas 3,140 (91.4%) were vaccinated. In multivariable analysis, age (adjusted OR [aOR] 1.02 per year, 95% CI 1.01-1.03), being a physician (aOR 3.22, 95% CI 1.75-5.92) or administrator (aOR 1.88, 95% CI 1.27-2.80), and having higher education (aOR 2.23, 95% CI 1.09-4.57) were positively associated with vaccine uptake, whereas working in non-acute care (aOR 0.58, 95% CI 0.34-0.97), active smoking (aOR 0.68, 95% CI 0.51-0.91), and taking prophylactic home remedies against SARS-CoV-2 (aOR 0.42, 95% CI 0.31-0.56) were negatively associated. Important reasons for non-vaccination were a belief that the vaccine might not have long-lasting immunity (267/291, 92.1%) and a preference for gaining naturally acquired instead of vaccine-induced immunity (241/289, 83.4%). CONCLUSIONS: Almost all healthcare workers in our cohort had specific antibodies against SARS-CoV-2 from natural infection and/or from vaccination. Young healthcare workers and those working in non-acute settings were less likely to be vaccinated, whereas physicians and administrative staff showed higher vaccination uptake. Presumed ineffectiveness of the vaccine is an important reason for non-vaccination.

Impact of shift work and other work-related factors on anti-SARS-CoV-2 spike-protein serum concentrations in healthcare workers after primary mRNA vaccination - a retrospective cohort study.

BACKGROUND: Knowing whether shift work negatively affects the immune system's response to COVID-19 vaccinations could be valuable for planning future vaccination campaigns for healthcare workers. We aimed to determine the impact of working late or night shifts on serum anti-SARS-CoV-2 spike protein immunoglobulin G (anti-S) antibody levels after primary SARS-CoV-2-mRNA vaccination. METHODS: To obtain detailed information on shift work, we sent a separate online questionnaire to 1475 eligible healthcare workers who participated in a prospective longitudinal study conducted in 15 healthcare institutions in Switzerland. We asked all vaccinated healthcare workers with available anti-S antibody levels after vaccination to complete a brief online survey on their working schedules within one week before and after primary mRNA vaccination. We used multivariate regression to evaluate the association between work shifts around primary vaccination and anti-S antibody levels. We adjusted for confounders already known to influence vaccine efficacy (e.g. age, sex, immunosuppression, and obesity) and for variables significant at the 0.05 alpha level in the univariate analyses. RESULTS: The survey response rate was 43% (n = 638). Ninety-eight responders were excluded due to unknown vaccination dates, different vaccines, or administration of the second dose shortly (within 14 days) after or before serologic follow-up. Of the 540 healthcare workers included in our analysis, 175 (32.4%) had worked at least one late or night shift within seven days before and/or after primary vaccination. In the univariate analyses, working late or night shifts was associated with a nonsignificant -15.1% decrease in serum anti-S antibody levels (p = 0.090). In the multivariate analysis, prior infection (197.2% increase; p <0.001) and immunisation with the mRNA-1273 vaccine (63.7% increase compared to the BNT162b2 vaccine; p <0.001) were the strongest independent factors associated with increased anti-S antibody levels. However, the impact of shift work remained statistically nonsignificant (-13.5%, p = 0.108). CONCLUSION: Working late or night shifts shortly before or after mRNA vaccination against COVID-19 does not appear to significantly impact serum anti-S antibody levels. This result merits consideration since it supports flexible vaccination appointments for healthcare workers, including those working late or night shifts.

S-Gene Target Failure as an Effective Tool for Tracking the Emergence of Dominant SARS-CoV-2 Variants in Switzerland and Liechtenstein, Including Alpha, Delta, and Omicron BA.1, BA.2, and BA.4/BA.5.

During the SARS-CoV-2 pandemic, the Dr. Risch medical group employed the multiplex TaqPathTM COVID-19 CE-IVD RT-PCR Kit for large-scale routine diagnostic testing in Switzerland and the principality of Liechtenstein. The TaqPath Kit is a widely used multiplex assay targeting three genes (i.e., ORF1AB, N, S). With emergence of the B.1.1.7 (Alpha) variant, a diagnostic flaw became apparent as the amplification of the S-gene target was absent in these samples due to a deletion (ΔH69/V70) in the Alpha variant genome. This S-gene target failure (SGTF) was the earliest indication of a new variant emerging and was also observed in subsequent variants such as Omicron BA.1 and BA4/BA.5. The Delta variant and Omicron BA.2 did not present with SGTF. From September 2020 to November 2022, we investigated the applicability of the SGTF as a surrogate marker for emerging variants such as B.1.1.7, B.1.617.2 (Delta), and Omicron BA.1, BA.2, and BA.4/BA.5 in samples with cycle threshold (Ct) values < 30. Next to true SGTF-positive and SGTF-negative samples, there were also samples presenting with delayed-type S-gene amplification (higher Ct value for S-gene than ORF1ab gene). Among these, a difference of 3.8 Ct values between the S- and ORF1ab genes was found to best distinguish between "true" SGTF and the cycle threshold variability of the assay. Samples above the cutoff were subsequently termed partial SGTF (pSGTF). Variant confirmation was performed by whole-genome sequencing (Oxford Nanopore Technology, Oxford, UK) or mutation-specific PCR (TIB MOLBIOL). In total, 17,724 (7.4%) samples among 240,896 positives were variant-confirmed, resulting in an overall sensitivity and specificity of 93.2% [92.7%, 93.7%] and 99.3% [99.2%, 99.5%], respectively. Sensitivity was increased to 98.2% [97.9% to 98.4%] and specificity lowered to 98.9% [98.6% to 99.1%] when samples with pSGTF were included. Furthermore, weekly logistic growth rates (α) and sigmoid's midpoint (t0) were calculated based on SGTF data and did not significantly differ from calculations based on comprehensive data from GISAID. The SGTF therefore allowed for a valid real-time estimate for the introduction of all dominant variants in Switzerland and Liechtenstein.

Regional spread of an atypical ESBL-producing Escherichia coli ST131H89 clone among different human and environmental reservoirs in Western Switzerland.

We describe the inter-regional spread of a novel ESBL-producing Escherichia coli subclone (ST131H89) in long-term care facility residents, general population, and environmental water sources in Western Switzerland between 2017 and 2020. The study highlights the importance of molecular surveillance for tracking emerging antibiotic-resistant pathogens in healthcare and community settings.

Healthcare­associated infections in intensive care unit patients with and without COVID-19: a single center prospective surveillance study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic led to a global increase in healthcare-associated infections (HAI) among intensive care unit (ICU) patients. Whether this increase is directly attributable to COVID-19 or whether the pandemic indirectly (via staff shortages or breaches in infection prevention measures) led to this increase, remains unclear. The objectives of this study were to assess HAI incidence and to identify independent risk factors for HAI in COVID-19 and non-COVID-19 ICU patients. METHODS: We established a monocentric prospective HAI surveillance in the medical ICU of our tertiary care center from September 1st 2021 until August 31st 2022, during circulation of the SARS-CoV-2 delta and omicron variants. We consecutively included patients ≥ 18 years of age with an ICU length of stay of > 2 calendar days. HAI were defined according to the European Centre for Disease Prevention and Control definitions. HAI rate was calculated per 1,000 patient-days or device-days; risk ratios (RR) and corresponding 95% confidence intervals (CI) for COVID-19 versus non-COVID-19 patients were calculated. We used multivariable Cox regression to identify independent risk factors for HAI. As a proxy for institutional COVID-19 burden, weekly COVID-19 density (i.e. percentage of COVID-19 patients among all ICU patients) was included in the model as time-dependent co-variable. RESULTS: We included 254 patients, 64 (25.1%) COVID-19 and 190 (74.9%) non-COVID-19 patients; 83 HAI in 72 patients were recorded, thereof 45 ventilator-associated lower respiratory tract infections (VA-LRTI) (54.2%) and 18 blood stream infections (BSI) (21.6%). HAI incidence rate was 49.1/1,000 patient-days in COVID-19 and 22.5/1,000 patient-days in non-COVID-19 patients (RR 2.2, 95%-CI 1.4-3.4). This result was mainly due to different VA-LRTI rates (40.3 vs. 11.7/1,000 ventilator days, p < 0.001), whereas BSI rates were not statistically different (9.4 vs. 5.6/1,000 patient days, p = 0.27). Multivariable analysis identified COVID-19 as main risk factor for HAI development, whereas age, mechanical ventilation and COVID-19 density were not significant. CONCLUSIONS: These data from the fourth and fifth wave of the pandemic show a higher HAI incidence in COVID-19 than in non-COVID-19 ICU patients, mainly due to an increase in pulmonary infections. A diagnosis of COVID-19 was independently associated with HAI development, whereas institutional COVID-19 burden was not.

Autoreactive T cells targeting type II pneumocyte antigens in COVID-19 convalescent patients.

BACKGROUND: The role of autoreactive T cells on the course of Coronavirus disease-19 (COVID-19) remains elusive. Type II pneumocytes represent the main target cells of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Autoimmune responses against antigens highly expressed in type II pneumocytes may influence the severity of COVID-19 disease. OBJECTIVE: The aim of this study was to investigate autoreactive T cell responses against self-antigens highly expressed in type II pneumocytes in the blood of COVID-19 patients with severe and non-severe disease. METHODS: We collected blood samples of COVID-19 patients with varying degrees of disease severity and of pre-pandemic controls. T cell stimulation assays with peptide pools of type II pneumocyte antigens were performed in two independent cohorts to analyze the autoimmune T cell responses in patients with non-severe and severe COVID-19 disease. Target cell lysis assays were performed with lung cancer cell lines to determine the extent of cell killing by type II PAA-specific T cells. RESULTS: We identified autoreactive T cell responses against four recently described self-antigens highly expressed in type II pneumocytes, known as surfactant protein A, surfactant protein B, surfactant protein C and napsin A, in the blood of COVID-19 patients. These antigens were termed type II pneumocyte-associated antigens (type II PAAs). We found that patients with non-severe COVID-19 disease showed a significantly higher frequency of type II PAA-specific autoreactive T cells in the blood when compared to severely ill patients. The presence of high frequencies of type II PAA-specific T cells in the blood of non-severe COVID-19 patients was independent of their age. We also found that napsin A-specific T cells from convalescent COVID-19 patients could kill lung cancer cells, demonstrating the functional and cytotoxic role of these T cells. CONCLUSIONS: Our data suggest that autoreactive type II PAA-specific T cells have a protective role in SARS-CoV-2 infections and the presence of high frequencies of these autoreactive T cells indicates effective viral control in COVID-19 patients. Type II-PAA-specific T cells may therefore promote the killing of infected type II pneumocytes and viral clearance.

Effective infection prevention and control measures in long-term care facilities in non-outbreak and outbreak settings: a systematic literature review.

BACKGROUND: Healthcare-associated infections in long-term care are associated with substantial morbidity and mortality. While infection prevention and control (IPC) guidelines are well-defined in the acute care setting, evidence of effectiveness for long-term care facilities (LTCF) is missing. We therefore performed a systematic literature review to examine the effect of IPC measures in the long-term care setting. METHODS: We systematically searched PubMed and Cochrane libraries for articles evaluating the effect of IPC measures in the LTCF setting since 2017, as earlier reviews on this topic covered the timeframe up to this date. Cross-referenced studies from identified articles and from mentioned earlier reviews were also evaluated. We included randomized-controlled trials, quasi-experimental, observational studies, and outbreak reports. The included studies were analyzed regarding study design, type of intervention, description of intervention, outcomes and quality. We distinguished between non-outbreak and outbreak settings. RESULTS: We included 74 studies, 34 (46%) in the non-outbreak setting and 40 (54%) in the outbreak setting. The most commonly studied interventions in the non-outbreak setting included the effect of hand hygiene (N = 10), oral hygiene (N = 6), antimicrobial stewardship (N = 4), vaccination of residents (N = 3), education (N = 2) as well as IPC bundles (N = 7). All but one study assessing hand hygiene interventions reported a reduction of infection rates. Further successful interventions were oral hygiene (N = 6) and vaccination of residents (N = 3). In outbreak settings, studies mostly focused on the effects of IPC bundles (N = 24) or mass testing (N = 11). In most of the studies evaluating an IPC bundle, containment of the outbreak was reported. Overall, only four articles (5.4%) were rated as high quality. CONCLUSION: In the non-outbreak setting in LTCF, especially hand hygiene and oral hygiene have a beneficial effect on infection rates. In contrast, IPC bundles, as well as mass testing seem to be promising in an outbreak setting.

Resistance development in Escherichia coli to delafloxacin at pHs 6.0 and 7.3 compared to ciprofloxacin.

Understanding the resistance mechanisms of antibiotics in the micro-environment of the infection is important to assess their clinical applicability and potentially prevent resistance development. We compared the laboratory resistance evolution of Escherichia coli to delafloxacin (DLX) compared to ciprofloxacin (CIP), the co-resistance evolution, and underlying resistance mechanisms at different pHs. Three clones from each of the eight clinical E. coli isolates were subjected to subinhibitory concentrations of DLX or CIP in parallel at either pH 7.3 or 6.0. Minimum inhibitory concentrations (MICs) were regularly tested (at respective pHs), and the antibiotic concentration was adjusted accordingly. After 30 passages, MICs were determined in the presence of the efflux pump inhibitor phenylalanine-arginine-ß-naphthylamide. Whole genome sequencing of the parental isolates and their resistant derivatives (n = 54) was performed. Complementation assays were carried out for selected mutations. Quantitative PCR and efflux experiments were carried out for selected derivatives. For DLX-challenged strains, resistance to DLX evolved much slower in acidic than in neutral pH, whereas for CIP-challenged strains, the opposite was the case. Mutations in the quinolone resistance-determining region were mainly seen in CIP-challenged E. coli, whereas a multifactorial mechanism including mutations in efflux-related genes played a role in DLX resistance evolution (predominantly at pH 6.0). This work provides novel insights into the resistance mechanisms of E. coli to delafloxacin and highlights the importance of understanding micro-environmental conditions at the infection site that might affect the true clinical efficacy of antibiotics and challenges our current antibiotic susceptibility-testing paradigm.

Changes in Healthcare Utilization During the COVID-19 Pandemic and Potential Causes-A Cohort Study From Switzerland.

Objectives: To describe the frequency of and reasons for changes in healthcare utilization in those requiring ongoing treatment, and to assess characteristics associated with change, during the second wave of the pandemic. Methods: Corona Immunitas e-cohort study (age ≥20 years) participants completed monthly questionnaires. We compared participants reporting a change in healthcare utilization with those who did not using descriptive and bivariate statistics. We explored characteristics associated with the number of changes using negative binomial regression. Results: The study included 3,190 participants from nine research sites. One-fifth reported requiring regular treatment. Among these, 14% reported a change in healthcare utilization, defined as events in which participants reported that they changed their ongoing treatment, irrespective of the reason. Reasons for change were medication changes and side-effects, specifically for hypertension, or pulmonary embolism treatment. Females were more likely to report changes [Incidence Rate Ratio (IRR) = 2.15, p = 0.002]. Those with hypertension were least likely to report changes [IRR = 0.35, p = 0.019]. Conclusion: Few of those requiring regular treatment reported changes in healthcare utilization. Continuity of care for females and chronic diseases besides hypertension must be emphasized.

SARS-CoV-2 risk in household contacts of healthcare workers: a prospective cohort study.

BACKGROUND: Few studies have assessed whether the increased SARS-CoV-2 risk of healthcare workers (HCW) is carried on to their household contacts. Within a prospective HCW cohort, we assessed the SARS-CoV-2 risk of household contacts of HCW depending on the HCWs cumulative exposure to COVID-19 patients and identified factors influencing this association. METHODS: HCW aged ≥ 16 years from nine Swiss healthcare networks participated. HCW without any household contacts were excluded. For HCW, cumulative patient exposure (number of COVID-19 patient contacts times average contact duration during a 12-month follow-up) was calculated. During follow-up, HCW reported SARS-CoV-2 nasopharyngeal swab results and positive swab results of their household contacts. We used multivariable logistic regression to identify variables associated with SARS-CoV-2 household positivity. RESULTS: Of 2406 HCW, 466 (19%) reported ≥ 1 SARS-CoV-2 positive household. In multivariable analysis, patient exposure of HCW (adjusted OR [aOR] 1.08 per category, 95% CI 1.04-1.12), household size (aOR 1.53 per household member, 95% CI 1.35-1.73) and having children (aOR 0.70, 95% CI 0.53-0.94) remained associated with household positivity. Vaccinated HCW had a lower risk (aOR 0.54, 95% CI 0.38-0.77) of reporting a positive contact, as were those using respirator masks in contact with COVID-19 patients (aOR 0.65, 95% CI 0.49-0.86). Among vaccinated HCW, delayed first vaccination was associated with increased household SARS-CoV-2 positivity (aOR 1.14 per month, 95% CI 1.08-1.21). CONCLUSIONS: SARS-CoV-2 positivity in household contacts of HCW increases with higher cumulative COVID-19 patient exposure of HCWs. Measures reducing the SARS-CoV-2 risk in HCW might indirectly reduce the infection risk of their households.

Structural complexity biases vegetation greenness measures.

Vegetation 'greenness' characterized by spectral vegetation indices (VIs) is an integrative measure of vegetation leaf abundance, biochemical properties and pigment composition. Surprisingly, satellite observations reveal that several major VIs over the US Corn Belt are higher than those over the Amazon rainforest, despite the forests having a greater leaf area. This contradicting pattern underscores the pressing need to understand the underlying drivers and their impacts to prevent misinterpretations. Here we show that macroscale shadows cast by complex forest structures result in lower greenness measures compared with those cast by structurally simple and homogeneous crops. The shadow-induced contradictory pattern of VIs is inevitable because most Earth-observing satellites do not view the Earth in the solar direction and thus view shadows due to the sun-sensor geometry. The shadow impacts have important implications for the interpretation of VIs and solar-induced chlorophyll fluorescence as measures of global vegetation changes. For instance, a land-conversion process from forests to crops over the Amazon shows notable increases in VIs despite a decrease in leaf area. Our findings highlight the importance of considering shadow impacts to accurately interpret remotely sensed VIs and solar-induced chlorophyll fluorescence for assessing global vegetation and its changes.

Elucidating climatic drivers of photosynthesis by tropical forests.

Tropical forests play a pivotal role in regulating the global carbon cycle. However, the response of these forests to changes in absorbed solar energy and water supply under the changing climate is highly uncertain. Three-year (2018-2021) spaceborne high-resolution measurements of solar-induced chlorophyll fluorescence (SIF) from the TROPOspheric Monitoring Instrument (TROPOMI) provide a new opportunity to study the response of gross primary production (GPP) and more broadly tropical forest carbon dynamics to differences in climate. SIF has been shown to be a good proxy for GPP on monthly and regional scales. Combining tropical climate reanalysis records and other contemporary satellite products, we find that on the seasonal timescale, the dependence of GPP on climate variables is highly heterogeneous. Following the principal component analyses and correlation comparisons, two regimes are identified: water limited and energy limited. GPP variations over tropical Africa are more correlated with water-related factors such as vapor pressure deficit (VPD) and soil moisture, while in tropical Southeast Asia, GPP is more correlated with energy-related factors such as photosynthetically active radiation (PAR) and surface temperature. Amazonia is itself heterogeneous: with an energy-limited regime in the north and water-limited regime in the south. The correlations of GPP with climate variables are supported by other observation-based products, such as Orbiting Carbon Observatory-2 (OCO2) SIF and FluxSat GPP. In each tropical continent, the coupling between SIF and VPD increases with the mean VPD. Even on the interannual timescale, the correlation of GPP with VPD is still discernable, but the sensitivity is smaller than the intra-annual correlation. By and large, the dynamic global vegetation models in the TRENDY v8 project do not capture the high GPP seasonal sensitivity to VPD in dry tropics. The complex interactions between carbon and water cycles in the tropics illustrated in this study and the poor representation of this coupling in the current suite of vegetation models suggest that projections of future changes in carbon dynamics based on these models may not be robust.

Factors Associated With COVID-19 Non-Vaccination in Switzerland: A Nationwide Study.

Objectives: We compared socio-demographic characteristics, health-related variables, vaccination-related beliefs and attitudes, vaccination acceptance, and personality traits of individuals who vaccinated against COVID-19 and who did not vaccinate by December 2021. Methods: This cross-sectional study used data of 10,642 adult participants from the Corona Immunitas eCohort, an age-stratified random sample of the population of several cantons in Switzerland. We used multivariable logistic regression models to explore associations of vaccination status with socio-demographic, health, and behavioral factors. Results: Non-vaccinated individuals represented 12.4% of the sample. Compared to vaccinated individuals, non-vaccinated individuals were more likely to be younger, healthier, employed, have lower income, not worried about their health, have previously tested positive for SARS-CoV-2 infection, express lower vaccination acceptance, and/or report higher conscientiousness. Among non-vaccinated individuals, 19.9% and 21.3% had low confidence in the safety and effectiveness of SARS-CoV-2 vaccine, respectively. However, 29.1% and 26.7% of individuals with concerns about vaccine effectiveness and side effects at baseline, respectively vaccinated during the study period. Conclusion: In addition to known socio-demographic and health-related factors, non-vaccination was associated with concerns regarding vaccine safety and effectiveness.

Clinical symptoms of SARS-CoV-2 breakthrough infection during the Omicron period in relation to baseline immune status and booster vaccination-A prospective multicentre cohort of health professionals (SURPRISE study).

The effects of different types of pre-existing immunity on the frequency of clinical symptoms caused by the SARS-CoV-2 breakthrough infection were prospectively assessed in healthcare workers during the Omicron period. Among 518 participants, hybrid immunity was associated with symptom reduction for dizziness, muscle or limb pain and headache as compared to vaccination only. Moreover, the frequencies of dizziness, cough and muscle or limb pain were lower in participants who had received a booster vaccine dose. Thus, hybrid immunity appeared to be superior in preventing specific symptoms during breakthrough infection compared to vaccination alone. A booster vaccine dose conferred additional symptom reduction.

Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults-A randomized blinded controlled trial.

Background: Echinacea purpurea has clinical antiviral activity against respiratory viruses and modulates immune functions. In this study, we compared higher doses of new Echinacea formulations with conventional formulations at lower, preventive doses for therapy of respiratory tract infections (RTIs). Methods: In this randomized, blinded, controlled trial, healthy adults (n = 409) were randomized between November 2018 and January 2019 to one of four Echinacea formulations, which were taken in case of an RTI for up to 10 days. New formulations A (lozenges) and B (spray) delivered an increased dose of 16,800 mg/d Echinacea extract during days 1-3 and 2,240-3,360 mg/d afterward; as controls, conventional formulations C (tablets) and D (drops) delivered a lower daily dose of 2,400 mg, usually taken for prevention. The primary endpoint was time to clinical remission of first RTI episodes based on the Kaplan-Meier analysis of patient-reported, investigator-confirmed, respiratory symptoms assessed for up to 10 days. In a sensitivity analysis, the mean time to remission beyond day 10 was calculated by extrapolating the treatment effects observed on days 7 to 10. Results: A total of 246 participants (median age 32 years, 78% female participants) were treated for at least one RTI. Recovery by day 10 (complete absence of symptoms) was achieved in 56 and 44% of patients with the new and conventional formulations, respectively, showing a median time to recovery of 10 and 11 days, respectively (p = 0.10 in intention-to-treat analysis, p = 0.07 in per-protocol analysis). In the extrapolated sensitivity analysis, new formulations resulted in a significantly shorter mean time to remission (9.6 vs. 11.0 days, p < 0.001). Among those with an identified respiratory virus, viral clearance until day 10 based on real-time PCR from nasopharyngeal swabs was more frequent with new formulations (70 vs. 53%, p = 0.046). Tolerability and safety (adverse events: 12 vs. 6%, p = 0.19) were good and similar between formulations. There was one severe adverse event with a potential hypersensitivity reaction in a recipient of the novel spray formulation. Conclusion: In adults with acute RTI, new Echinacea formulations with higher doses resulted in faster viral clearance than conventional formulations in prophylactic dosages. The trend for faster clinical recovery was not significant by day 10 but became so upon extrapolation. A dose increase during acute respiratory symptoms might improve the clinical benefits of orally administered Echinacea formulations. Trial registration: The study was registered in the Swiss National Clinical Trials Portal (SNCTP000003069) and on ClinicalTrials.gov (NTC03812900; URL https://clinicaltrials.gov/ct2/show/NCT03812900?cond=echinacea&draw=3&rank=14).

COVID-19 burden and influencing factors in Swiss long-term-care facilities: a cross-sectional analysis of a multicentre observational cohort.

OBJECTIVES: To describe the burden of COVID-19 in Swiss long-term care facilities in 2020, to identify its influencing factors, and to assess vaccination rates among residents and healthcare workers at the end of the vaccine campaign in Switzerland in May 2021. DESIGN: Cross-sectional survey. SETTING AND PARTICIPANTS: Long-term care facilities from two Swiss cantons (St. Gallen / Eastern Switzerland and Vaud / Western Switzerland). METHODS: We collected numbers of COVID-19 cases and related deaths and all-cause mortality for 2020, potential risk factors at the institutional level (e.g. size, infection prevention and control measures, and resident characteristics), and vaccination rates among residents and healthcare workers. Univariate and multivariate analyses were used to identify factors associated with resident mortality in 2020. RESULTS: We enrolled 59 long-term care facilities with a median of 46 (interquartile range [IQR]: 33-69) occupied beds. In 2020, the median COVID-19 incidence was 40.2 (IQR: 0-108.6) per 100 occupied beds, with higher rates in VD (49.9%) than in SG (32.5%; p = 0.037). Overall, 22.7% of COVID-19 cases died, of which 24.8% were COVID-19-related deaths. In the univariate analysis, higher resident mortality was associated with COVID-19 rates among residents (p < 0.001) and healthcare workers (p = 0.002) and age (p = 0.013). Lower resident mortality was associated with the proportion of single rooms (p = 0.012), isolation of residents with COVID-19 in single rooms (p = 0.003), symptom screening of healthcare workers (p = 0.031), limiting the number of visits per day (p = 0.004), and pre-scheduling visits (p = 0.037). In the multivariate analysis, higher resident mortality was only associated with age (p = 0.03) and the COVID-19 rate among residents (p = 0.013). Among 2936 residents, 2042 (69.9%) received ≥1 dose of the COVID-19 vaccine before 31 May 2021. Vaccine uptake among healthcare workers was 33.8%. CONCLUSION AND IMPLICATIONS: COVID-19 burden was high but also highly variable in Swiss long-term care facilities. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers was a modifiable factor associated with increased resident mortality. Symptom screening of healthcare workers appeared to be an effective preventive strategy and should be included in routine infection prevention and control measures. Promoting COVID-19 vaccine uptake among healthcare workers should be a priority in Swiss long-term care facilities.

Seroprevalence trends of anti-SARS-CoV-2 antibodies and associated risk factors: a population-based study.

PURPOSE: We aimed to assess the seroprevalence trends of SARS-CoV-2 antibodies in several Swiss cantons between May 2020 and September 2021 and investigate risk factors for seropositivity and their changes over time. METHODS: We conducted repeated population-based serological studies in different Swiss regions using a common methodology. We defined three study periods: May-October 2020 (period 1, prior to vaccination), November 2020-mid-May 2021 (period 2, first months of the vaccination campaign), and mid-May-September 2021 (period 3, a large share of the population vaccinated). We measured anti-spike IgG. Participants provided information on sociodemographic and socioeconomic characteristics, health status, and adherence to preventive measures. We estimated seroprevalence with a Bayesian logistic regression model and the association between risk factors and seropositivity with Poisson models. RESULTS: We included 13,291 participants aged 20 and older from 11 Swiss cantons. Seroprevalence was 3.7% (95% CI 2.1-4.9) in period 1, 16.2% (95% CI 14.4-17.5) in period 2, and 72.0% (95% CI 70.3-73.8) in period 3, with regional variations. In period 1, younger age (20-64) was the only factor associated with higher seropositivity. In period 3, being aged ≥ 65 years, with a high income, retired, overweight or obese or with other comorbidities, was associated with higher seropositivity. These associations disappeared after adjusting for vaccination status. Seropositivity was lower in participants with lower adherence to preventive measures, due to a lower vaccination uptake. CONCLUSIONS: Seroprevalence sharply increased over time, also thanks to vaccination, with some regional variations. After the vaccination campaign, no differences between subgroups were observed.