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Patients who survive critical COVID-19 frequently report post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during their ICU stays. The association between ICU predictors and psychosomatic, respiratory, and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression, and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation, and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

ObjectivesTo assess the association between socioeconomic status (SES) and self-reported adherence to preventive measures in Switzerland during the COVID-19 pandemic.Methods4,299 participants from a digital cohort were followed between September 2020 and November 2021. Baseline equivalised disposable income and education were used as SES proxies. Adherence was assessed over time. We investigated the association between SES and adherence using multivariable mixed logistic regression, stratifying by age (below/above 65 years) and two periods (before/after June 2021, to account for changes in vaccine coverage and epidemiological situation).ResultsAdherence was high across all SES strata before June 2021. After, participants with higher equivalised disposable income were less likely to adhere to preventive measures compared to participants in the first (low) quartile [second (Adj.OR, 95% CI) (0.56, 0.37–0.85), third (0.38, 0.23–0.64), fourth (0.60, 0.36–0.98)]. We observed similar results for education.ConclusionNo differences by SES were found during the period with high SARS-CoV-2 incidence rates and stringent measures. Following the broad availability of vaccines, lower incidence, and eased measures, differences by SES started to emerge. Our study highlights the need for contextual interpretation when assessing SES impact on adherence to preventive measures.

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.

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

Abstract Objective We aimed to evaluate the association between post-appendectomy SSI rates and the two most commonly used regimens for perioperative antimicrobial prophylaxis in Swiss children. Methods We conducted a retrospective cohort study, analysing data from the Swiss national SSI surveillance database with a study period from 2014 to 2018. All hospitals undertaking paediatric appendectomies in Switzerland participate in the surveillance. We compared the cumulative incidence and odds of post-appendectomy SSI within 30 days of surgery in children ≤ 16 years of age undergoing appendectomy for uncomplicated appendicitis and receiving perioperative antimicrobial prophylaxis with cefuroxime plus metronidazole or with amoxicillin/clavulanic acid using multivariable adjusted logistic regression and propensity-score matching. Results A total of 6207 cases were recorded in the study time frame. Overall SSI cumulative incidence was 1.9% (n = 119). 4256 children (54.9% male, median (IQR) age 12 [10, 14] years) received either cefuroxime plus metronidazole (n = 2348, 53.8% male) or amoxicillin/clavulanic acid (n = 1491, 57.0% male). SSI cumulative incidence was 1.1% (25/2348) among children receiving cefuroxime plus metronidazole and 2.8% (42/1491, p

Abstract 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.

Objectives: Our study aims to evaluate developments in vaccine uptake and digital proximity tracing app use in a localized context of the SARS-CoV-2 pandemic.Methods: We report findings from two population-based longitudinal cohorts in Switzerland from January to December 2021. Failure time analyses and Cox proportional hazards regression models were conducted to assess vaccine uptake and digital proximity tracing app (SwissCovid) uninstalling outcomes.Results: We observed a dichotomy of individuals who did not use the SwissCovid app and did not get vaccinated, and who used the SwissCovid app and got vaccinated during the study period. Increased vaccine uptake was observed with SwissCovid app use (aHR, 1.51; 95% CI: 1.40–1.62 [CI-DFU]; aHR, 1.79; 95% CI: 1.62–1.99 [CSM]) compared to SwissCovid app non-use. Decreased SwissCovid uninstallation risk was observed for participants who got vaccinated (aHR, 0.55; 95% CI: 0.38–0.81 [CI-DFU]; aHR, 0.45; 95% CI: 0.27–0.78 [CSM]) compared to participants who did not get vaccinated.Conclusion: In evolving epidemic contexts, these findings underscore the need for communication strategies as well as flexible digital proximity tracing app adjustments that accommodate different preventive measures and their anticipated interactions.

Abstract At our tertiary children’s hospital, infections with newly detected methicillin-resistant Staphylococcus aureus (MRSA) among children attending primary (age 6–12 years) and secondary school (age 13–16 years) nearly doubled in 2018 compared to previous years. This observation initiated an epidemiological outbreak investigation including phenotypic (susceptibility testing) and genotypic (whole genome sequencing) characterization of the isolates. In addition, a cross-sectional study was conducted to determine source of the outbreak, colonization frequency and to identify risk factors for transmission using a questionnaire. As a result, 49 individuals were detected with 57 corresponding isolates. Based on the case definition combined with whole genome sequencing, a core cluster was identified that shared common genetic features and a similar antimicrobial susceptibility pattern (efflux-mediated macrolide resistance, tetracycline susceptibility along with presence of Panton-Valentine leukocidin). Epidemiologic evaluation identified a distinct school as a common risk factor. However, the source of the clustered infections within that school could not be further specified. No further cases could be detected after decolonization of infected and colonized children.

Summary: Background: Low rates of postnatal retention in HIV care and viral suppression have been reported in women living with HIV (WLWH) despite viral suppression at delivery. At the same time, postpartum follow-up is of crucial importance in light of the increasing support offered in many resource-rich countries including Switzerland to WLWH choosing to breastfeed their infant, if optimal scenario criteria are met. Methods: We longitudinally investigated retention in HIV care, viral suppression, and infant follow-up in a prospective multicentre HIV cohort study of WLWH in the optimal scenario who had a live birth between January 2000 and December 2018. Risk factors for adverse outcomes in the first year postpartum were assessed using logistic and proportional hazard models. Findings: Overall, WLWH were retained in HIV care for at least six months after 94.2% of the deliveries (694/737). Late start of combination antiretroviral therapy (cART) during the third trimester was found to be the main risk factor for failure of retention in HIV care (crude odds ratio [OR] 3.91; 95% confidence interval [CI], 1.50–10.22; p = 0.005). Among mothers on cART until at least one year after delivery, 4.4% (26/591) experienced viral failure, with illicit drugs use being the most important risk factor (hazard ratio [HR], 13.2; 95% CI, 2.35–73.6; p = 0.003). The main risk factors for not following the recommendations regarding infant follow-up was maternal depression (OR, 3.52; 95% CI, 1.18–10.52; p = 0.024). Interpretation: Although the results are reassuring, several modifiable risk factors for adverse postpartum outcome, such as late treatment initiation and depression, were identified. These factors should be addressed in HIV care of all WLWH, especially those opting to breastfeed in resource-rich countries. Funding: This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project 850 and by the SHCS research foundation.

BACKGROUND: Currently available messenger ribonucleic acid (mRNA)-based vaccines against coronavirus disease (COVID-19) have been shown to be effective even in highly immunocompromised hosts, including patients with multiple myeloma. However, vaccination failure can be observed in all patient groups. METHODS: This prospective study longitudinally assessed the humoral and cellular responses to a third booster dose of BNT162b2 mRNA-based vaccine in patients with myeloma (n = 59) and healthy controls (n = 22) by measuring the levels of anti-spike (S) antibodies (electro-chemiluminescence immunoassay) including neutralising antibodies and specific T-cells (enzyme-linked immunospot assay) following booster administration. RESULTS: The third booster dose showed a high immunogenicity on the serological level among the patients with multiple myeloma (median anti-S level = 41 binding antibody units [BAUs]/ml pre-booster vs 3902 BAU/ml post-booster, p

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.

The persistence of the immune response to SARS-CoV-2 after recovery from infection is an indicator for subsequent protection against infection. Here the authors follow recovered patients and measure antibody and T cell responses and find that these two parts of the immune response may have different longevity.

Abstract Background We aimed to determine whether living in a household with children is associated with SARS-CoV-2 seropositivity in adults and investigated interacting factors that may influence this association. Methods SARS-CoV-2 serology testing was performed in randomly selected individuals from the general population between end of October 2020 and February 2021 in 11 cantons in Switzerland. Data on sociodemographic and household characteristics, employment status, and health-related history was collected using questionnaires. Multivariable logistic regression was used to examine the association of living with children

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.

Abstract Background There is insufficient evidence regarding the role of respirators in the prevention of SARS-CoV-2 infection. We analysed the impact of filtering facepiece class 2 (FFP2) versus surgical masks on the risk of SARS-CoV-2 acquisition among Swiss healthcare workers (HCW). Methods Our prospective multicentre cohort enrolled HCW from June to August 2020. Participants were asked about COVID-19 risk exposures/behaviours, including preferentially worn mask type when caring for COVID-19 patients outside of aerosol-generating procedures. The impact of FFP2 on (1) self-reported SARS-CoV-2-positive nasopharyngeal PCR/rapid antigen tests captured during weekly surveys, and (2) SARS-CoV-2 seroconversion between baseline and January/February 2021 was assessed. Results We enrolled 3259 participants from nine healthcare institutions, whereof 716 (22%) preferentially used FFP2. Among these, 81/716 (11%) reported a SARS-CoV-2-positive swab, compared to 352/2543 (14%) surgical mask users; seroconversion was documented in 85/656 (13%) FFP2 and 426/2255 (19%) surgical mask users. Adjusted for baseline characteristics, COVID-19 exposure, and risk behaviour, FFP2 use was non-significantly associated with decreased risk for SARS-CoV-2-positive swab (adjusted hazard ratio [aHR] 0.8, 95% CI 0.6–1.0) and seroconversion (adjusted odds ratio [aOR] 0.7, 95% CI 0.5–1.0); household exposure was the strongest risk factor (aHR 10.1, 95% CI 7.5–13.5; aOR 5.0, 95% CI 3.9–6.5). In subgroup analysis, FFP2 use was clearly protective among those with frequent (> 20 patients) COVID-19 exposure (aHR 0.7 for positive swab, 95% CI 0.5–0.8; aOR 0.6 for seroconversion, 95% CI 0.4–1.0). Conclusions Respirators compared to surgical masks may convey additional protection from SARS-CoV-2 for HCW with frequent exposure to COVID-19 patients.

AIMS OF THE STUDY: Globally, since the introduction of conjugate-vaccines against encapsulated bacteria, respiratory viruses have caused most hospitalisations for community-acquired pneumonia. The aim of this study was to describe pathogens detected and their association with clinical findings in Switzerland. METHODS: Baseline data were analysed for all trial participants enrolled between September 2018 and September 2020 into the KIDS-STEP Trial, a randomised controlled superiority trial on the effect of betamethasone on clinical stabilisation of children admitted with community-acquired pneumonia. Data included clinical presentation, antibiotic use and results of pathogen detection. In addition to routine sampling, nasopharyngeal specimens were analysed for respiratory pathogens using a panel polymerase chain reaction test covering 18 viral and 4 bacterial pathogens. RESULTS: 138 children with a median age of 3 years were enrolled at the eight trial sites. Fever (obligatory for enrolment) had been present for median 5 days before admission. Most common symptoms were reduced activity (129, 93.5%) and reduced oral intake (108, 78.3%). Oxygen saturation

Abstract Certain immunizations including vaccination against tick-borne encephalitis virus (TBEV) have been suggested to confer cross-protection against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Within a prospective healthcare worker (HCW) cohort, we assessed the potentially protective role of anti-TBEV antibodies against SARS-CoV-2 infection. Among 3352 HCW, those with ≥ 1 previous TBEV vaccination (n = 2018, 60%) showed a reduced risk of SARS-CoV-2 seroconversion (adjusted odds ratio: 0.8, 95% CI: 0.7–1.0, P = 0.02). However, laboratory testing of a subgroup of 26 baseline and follow-up samples did not demonstrate any neutralizing effect of anti-TBEV antibodies against SARS-CoV-2 in live-virus neutralization assay. However, we observed significantly higher anti-TBEV antibody titers in follow-up samples of participants with previous TBEV vaccination compared to baseline, both TBEV neutralizing (p = 0.001) and total IgG (P

Abstract Background In a prospective healthcare worker (HCW) cohort, we assessed the risk of SARS-CoV-2 infection according to baseline serostatus. Methods Baseline serologies were performed among HCW from 23 Swiss healthcare institutions between June and September 2020, before the second COVID-19 wave. Participants answered weekly electronic questionnaires covering information about nasopharyngeal swabs (PCR/rapid antigen tests) and symptoms compatible with coronavirus disease 2019 (COVID-19). Screening of symptomatic staff by nasopharyngeal swabs was routinely performed in participating facilities. We compared numbers of positive nasopharyngeal tests and occurrence of COVID-19 symptoms between HCW with and without anti-nucleocapsid antibodies. Results A total of 4812 HCW participated, wherein 144 (3%) were seropositive at baseline. We analyzed 107,807 questionnaires with a median follow-up of 7.9 months. Median number of answered questionnaires was similar (24 vs. 23 per person, P = 0.83) between those with and without positive baseline serology. Among 2712 HCW with ≥ 1 SARS-CoV-2 test during follow-up, 3/67 (4.5%) seropositive individuals reported a positive result (one of whom asymptomatic), compared to 547/2645 (20.7%) seronegative participants, 12 of whom asymptomatic (risk ratio [RR] 0.22; 95% confidence interval [CI] 0.07 to 0.66). Seropositive HCWs less frequently reported impaired olfaction/taste (6/144, 4.2% vs. 588/4674, 12.6%, RR 0.33, 95% CI 0.15–0.73), chills (19/144, 13.2% vs. 1040/4674, 22.3%, RR 0.59, 95% CI 0.39–0.90), and limb/muscle pain (28/144, 19.4% vs. 1335/4674, 28.6%, RR 0.68 95% CI 0.49–0.95). Impaired olfaction/taste and limb/muscle pain also discriminated best between positive and negative SARS-CoV-2 results. Conclusions Having SARS-CoV-2 anti-nucleocapsid antibodies provides almost 80% protection against SARS-CoV-2 re-infection for a period of at least 8 months.

Abstract Background and purpose Continuous improvement of health and healthcare system is hampered by inefficient processes of generating new evidence, particularly in the case of rare diseases and paediatrics. Currently, most evidence is generated through specific research projects, which typically require extra encounters with patients, are costly and entail long delays between the recognition of specific needs in healthcare and the generation of necessary evidence to address those needs. The Swiss Personalised Health Network (SPHN) aims to improve the use of data obtained during routine healthcare encounters by harmonizing data across Switzerland and facilitating accessibility for research. The project “Harmonising the collection of health-related data and biospecimens in paediatric hospitals throughout Switzerland (SwissPedData)” was an infrastructure development project funded by the SPHN, which aimed to identify and describe available data on child health in Switzerland and to agree on a standardised core dataset for electronic health records across all paediatric teaching hospitals. Here, we describe the results of a two-day symposium that aimed to summarise what had been achieved in the SwissPedData project, to put it in an international context, and to discuss the next steps for a sustainable future. The target audience included clinicians and researchers who produce and use health-related data on children in Switzerland. Key highlights The symposium consisted of state-of-the-art lectures from national and international keynote speakers, workshops and plenary discussions. This manuscript summarises the talks and discussions in four sections: (I) a description of the Swiss Personalized Health Network and the results of the SwissPedData project; (II) examples of similar initiatives from other countries; (III) an overview of existing health-related datasets and projects in Switzerland; and (IV) a summary of the lessons learned and future prospective from workshops and plenary discussions. Implications Streamlined processes linking initial collection of information during routine healthcare encounters, standardised recording of this information in electronic health records and fast accessibility for research are essential to accelerate research in child health and make it affordable. Ongoing projects prove that this is feasible in Switzerland and elsewhere. International collaboration is vital to success. The next steps include the implementation of the SwissPedData core dataset in the clinical information systems of Swiss hospitals, the use of this data to address priority research questions, and the acquisition of sustainable funding to support a slim central infrastructure and local support in each hospital. This will lay the foundation for a national paediatric learning health system in Switzerland.

Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland.

Objectives: To describe changes in adherence to recommendations for physical activity (PA), screen time (ST), and sleep duration over the first two waves of the pandemic in Switzerland, and to assess the associations of these lifestyle behaviours with life satisfaction and overall health as well-being indicators.Methods: In this observational study, we included 2,534 participants (5–16 years) from four Swiss cantons. Participants, or their parents, completed repeated questionnaires and reported on their (child’s) lifestyle and well-being, between June 2020 and April 2021. We used linear and logistic regression models to assess the associations between lifestyle and well-being.Results: The percentage of children meeting the recommendations for PA and ST decreased from the pre-pandemic period to the first wave, with a slight recovery during the second wave. Participants meeting all three recommendations during the second wave were more likely to report excellent health (OR: 1.65 [95% CI: 1.00–2.76]) and higher life satisfaction (β: 0.46 [0.16–0.77]) in early 2021 than participants not meeting any recommendation.Conclusion: We showed a substantial impact of the COVID-19 pandemic on children’s and adolescents’ lifestyle, and a positive association between meeting lifestyle recommendations and well-being.

Objectives: During the COVID-19 pandemic, few scientific congresses have been held on-site. We prospectively evaluated the safety concept of the congress of the Swiss Societies of Infectious Diseases and Hospital Hygiene.Methods: The congress was held in Geneva (Switzerland) while local COVID-19 incidence (with SARS-CoV-2 wild type circulating) was 65/100,000 population (September 2020). A rigorous safety concept was implemented. Congress attendees filled out a questionnaire to assess risk perception, exposures, symptoms and diagnoses of SARS-CoV-2 before, during and after the congress. Dried blood spots were taken on-site and 4 weeks later to detect SARS-CoV-2 seroconversions.Results: Of 365 congress attendees, 196 (54%) either answered the questionnaire (N = 150) or provided baseline and follow-up blood samples (N = 168). None of the participants reported a positive PCR in the 2 weeks after the congress. Five of 168 (3%) participants were seropositive at follow-up, all of which had already been positive at baseline.Conclusion: Findings indicate that congresses with a rigorous safety concept may take place, even in areas with moderately-high COVID-19 activity. Whether this holds true in vaccinated populations and with more transmissible viral variants circulating remains unclear.

Myalgic encephalomyelitis (ME) or Chronic Fatigue Syndrome (CFS) is a neglected, debilitating multi-systemic disease without diagnostic marker or therapy. Despite evidence for neurological, immunological, infectious, muscular and endocrine pathophysiological abnormalities, the etiology and a clear pathophysiology remains unclear. The gut microbiome gained much attention in the last decade with manifold implications in health and disease. Here we review the current state of knowledge on the interplay between ME/CFS and the microbiome, to identify potential diagnostic or interventional approaches, and propose areas where further research is needed. We iteratively selected and elaborated on key theories about a correlation between microbiome state and ME/CFS pathology, developing further hypotheses. Based on the literature we hypothesize that antibiotic use throughout life favours an intestinal microbiota composition which might be a risk factor for ME/CFS. Main proposed pathomechanisms include gut dysbiosis, altered gut-brain axis activity, increased gut permeability with concomitant bacterial translocation and reduced levels of short-chain-fatty acids, D-lactic acidosis, an abnormal tryptophan metabolism and low activity of the kynurenine pathway. We review options for microbiome manipulation in ME/CFS patients including probiotic and dietary interventions as well as fecal microbiota transplantations. Beyond increasing gut permeability and bacterial translocation, specific dysbiosis may modify fermentation products, affecting peripheral mitochondria. Considering the gut-brain axis we strongly suspect that the microbiome may contribute to neurocognitive impairments of ME/CFS patients. Further larger studies are needed, above all to clarify whether D-lactic acidosis and early-life antibiotic use may be part of ME/CFS etiology and what role changes in the tryptophan metabolism might play. An association between the gut microbiome and the disease ME/CFS is plausible. As causality remains unclear, we recommend longitudinal studies. Activity levels, bedridden hours and disease progression should be compared to antibiotic exposure, drug intakes and alterations in the composition of the microbiota. The therapeutic potential of fecal microbiota transfer and of targeted dietary interventions should be systematically evaluated.

BACKGROUND: Improvement of paediatric healthcare is hampered by inefficient processes for generating new evidence. Clinical research often requires extra encounters with patients, is costly, takes place in an artificial situation with a biased selection of patients, and entails long delays until new evidence is implemented into health care. Electronic health records (EHR) contain detailed information on real patients and cover the entirety of patients. However, the use of EHR for research is limited because they are not standardised between hospitals. This leads to disproportionate amounts of work for extracting data of interest and frequently data are incomplete and of poor quality. AIMS: SwissPedData aims to lay the foundation for a paediatric learning health system in Switzerland by facilitating EHR-based research. In this project, we aimed to assess the way routine clinical data are currently recorded in large paediatric clinics in Switzerland and to develop a national EHR-based set of common data elements (CDEs) that covers all processes of routine paediatric care in hospitals. METHODS: A taskforce of paediatricians from large Swiss children’s hospitals reviewed the current status of routine data documentation in paediatric clinical care and the extent of digitalisation. We then used a modified Delphi method to reach a broad consensus on a national EHR-based set of CDEs. RESULTS: All Swiss children’s hospitals use EHR to document some or all aspects of care. One hundred and nineteen paediatricians, representing eight hospitals and all paediatric subspecialties, participated in an extended Delphi process to create SwissPedData. The group agreed on a national set of CDEs that comprises a main module with general paediatric data and sub-modules relevant to paediatric subspecialties. The data dictionary includes 336 CDEs: 76 in the main module on general paediatrics and between 11 and 59 CDEs per subspecialty module. Among these, 266 were classified as mandatory, 52 as recommended and 18 as optional. CONCLUSION: SwissPedData is a set of CDEs for information to be collected in EHR of Swiss children’s hospitals. It covers all care processes including clinical and paraclinical assessment, diagnosis, treatment, disposition and care site. All participating hospitals agreed to implement SwissPedData in their clinical routine and clinic information systems. This will pave the way for a national paediatric learning health system in Switzerland that enables fast and efficient answers to urgent clinical questions by facilitating high-quality nationwide retrospective and prospective observational studies and recruitment of patients for nested prospective studies and clinical trials.

Cystic fibrosis patients frequently suffer from recurring respiratory infections caused by colonizing pathogenic and commensal bacteria. Although modern therapies can sometimes alleviate respiratory symptoms by ameliorating residual function of the protein responsible for the disorder, management of chronic respiratory infections remains an issue.

Background: Since its discovery, the respiratory microbiome has been implicated in the pathogenesis of multiple pulmonary diseases. Even though corticosteroid treatments are widely prescribed for pulmonary diseases, their effects on the respiratory microbiome are still poorly understood. This systematic review summarizes the current understanding of the effects of corticosteroids on the microbiome of the airways.Research Question: How does treatment with corticosteroids impact the respiratory microbiome?Study Design and Methods: According to the PRISMA guidelines, Embase, Medline, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were systematically searched for all observational or randomized-controlled studies comparing the microbiome parameters of patients receiving corticosteroids to those of controls. The primary outcomes of interest were changes in the diversity, composition and total burden of the respiratory microbiome as assessed by culture-independent molecular methods.Results: Out of 1,943 identified reports, five studies could be included: two on patients with asthma, two on patients with chronic obstructive pulmonary disease and one on patients with chronic rhinosinusitis. The studies were highly heterogeneous with regards to the methods used and the populations investigated. Microbiome diversity increased with corticosteroids at least transiently in three studies and decreased in one study. The effects of corticosteroids on the composition of the respiratory microbiome were significant but without a clear shared direction. A significant increase in microbial burden after corticosteroids was seen in one study.Interpretation: Data on the effect of corticosteroids on the respiratory microbiome are still limited, with considerable heterogeneity between studies. However, available data suggest that corticosteroid treatment may have significant effects on the composition and possibly the diversity of the respiratory microbiome. Further research is needed to better understand the influence of corticosteroids on the respiratory microbiome and thus better target its widespread therapeutic use.

Abstract Background We evaluated data from isolates of nursing home (NH) patients sent to the Swiss centre for antibiotic resistance (ANRESIS). We focussed on carbapenem-resistance (CR) among Gram-negative pathogens, extended-spectrum cephalosporin-resistant (ESC-R) Escherichia coli/Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and glycopeptide-resistant enterococci (GRE). Methods NH patient isolates from 01/2007 to 10/2017 were extracted. Temporal trends in resistance were described and risk factors associated with ESC-R and MRSA were assessed. For every administrative subdivision in Switzerland (i.e. canton), we calculated a coverage rate, defined as number of beds of governmentally-supported nursing homes, which sent ≥1 isolate in each 2014, 2015, and 2016, divided by the total number of supported beds. Results We identified 16′804 samples from 9′940 patients. A majority of samples (12′040; 71.6%) originated from the French/Italian speaking part of Switzerland. ESC-R E. coli increased from 5% (16/299) in 2007 to 22% (191/884) in 2017 (P

AIMS OF THE STUDY Combination antiretroviral therapy (cART) has reduced mother-to-child transmissions (MTCT) and improved the prognosis of HIV-infected newborns. However, drug resistance mutations (DRM) in HIV-infected children, either transmitted by MTCT (HIV-tDRM) or selected by suboptimal adherence and drug levels (HIV-sDRM), remain a concern. We sought to determine the rate of HIV-tDRM and HIV-sDRM in MTCT pairs in Switzerland. METHODS We performed a retrospective analysis of prospectively collected clinical data and available stored samples from MTCT pairs participating in the Swiss Mother-Child HIV (MoCHIV) cohort. RESULTS We identified 22 HIV-infected mother-child pairs with delivery between 1989 and 2009 who had 15 years of follow-up (33% white ethnicity). Twenty-one women (96%) were treatment-naïve before pregnancy, 8 (36%) had an unknown HIV status and delivered vaginally, 2 were diagnosed but not treated, and 11 (50%) received antiretrovirals during pregnancy or at delivery, of whom only 6 cases (27%) had cART. HIV subtypes were concordant in all mother-child pairs (subtype B 13/22 [59%]). Using stored plasma (n = 66) and mononuclear cell (n = 43) samples from the children, HIV-tDRM (M184V) was identified in 1 of 22 (4.5%) mothers (1/11 treated, 9%) and was followed by HIV-sDRM at 10 months of age. HIV-sDRM (M184V 23%; K103N 4.5%; D67N 13.6%) occurred in 16/22 (73%) after 4 years, half of whom were treatment naïve. HIV-sDRM were associated with a lower CD4 T-cell nadir (p

AIMS OF THE STUDY Nevirapine has an exceptional record for long-term tolerability with few side effects in human immunodeficiency virus (HIV) combined antiretroviral therapy (cART). Owing to relatively frequent hypersensitivity reactions (HSR) (15–25%) in the first 3 months after treatment initiation (especially in patients with a high CD4 count (>250/µl in women, >400/µl in men)), it is being used less and less. However, the rate of adverse events is lower when patients are already under suppressive cART. We present the results of a single centre strategy to offer the switch to a nevirapine-containing regimen and evaluate the potential role nevirapine could play in current antiretroviral treatment. METHODS All adult HIV-positive patients starting nevirapine at our centre since 2010 were evaluated in this retrospective analysis. We examined the proportion of patients on cART containing nevirapine, as well as the number of starts and stops every 6 months. Nevirapine discontinuation rates were analysed by sex, age, hepatitis C virus (HCV) status, time on nevirapine, ethnicity, CD4 nadir as well as CD4 count, HIV-RNA and ART backbone at nevirapine start. RESULTS Since 2014, more than a third of our treated HIV patients have been on nevirapine-containing therapy, with a stable percentage in the following years; 277 patients starting nevirapine for the first time were analysed. Thirty-three percent (92/277) of these first nevirapine therapies were discontinued, with 16 cases (17%) resuming nevirapine later during follow-up. Of the patients who continued nevirapine for more than 90 days (n = 221), 80% maintained nevirapine until their last follow-up. The nevirapine stop rate after the first 90 days was 15-fold lower (5.4 per 100 patient years, 95% confidence interval [CI] 4.0–7.2) than in the first 90 days. Overall, nevirapine was used for a median of 2.9 years (interquartile range [IQR] 0.5–5.6). In HCV co-infected patients, the treatment stop rate was 4-fold higher than in HIV mono-infected patients, but this difference was mainly due to treatment interruptions caused by drug-drug interactions with intermittent HCV therapy. Six out of seven Asian patients experienced HSR (hepatotoxicity / skin rash). In a population with 74% 3TC/ABC backbone, 81% fully suppressed, median CD4 nadir 240/µl (IQR 120–360) and median CD4 count at nevirapine start 590/µl (IQR 400–840), both high CD4 nadir and high CD4 count at nevirapine start were associated with lower rather than higher discontinuation rates. In fully suppressed patients with high CD4 count at nevirapine start, high CD4 nadir was not a risk factor for HSR. Major reasons for the discontinuation of nevirapine were HSR (liver, skin rash) in 38 cases (41% of all discontinuations) followed by other adverse drug reactions (n = 17) and non-adherence (n = 14). In patients who stopped nevirapine after more than 90 days, the major cause was non-adherence or other adverse drug reaction (both n = 12). CONCLUSIONS In this study, two thirds of the patients continued nevirapine with favourable long-term tolerability and efficacy. Thus, this low-cost “old drug” may still represent a valid treatment switch option for maintenance therapy in selected patients with a fully suppressed viral load. However, further evaluation is needed.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

While lateral flow test formats can be utilized with whole blood and low sample volumes, their diagnostic characteristics are inferior to immunoassays based on chemiluminescence immunoassay (CLIA) or enzyme-linked immunosorbent assay (ELISA) technology. CLIAs and ELISAs can be automated to a high degree but commonly require larger serum or plasma volumes for sample processing. We addressed the suitability of EDTA-anticoagulated whole blood as an alternative sample material for antibody testing against SARS-CoV-2 by electro-CLIA (ECLIA; Roche, Rotkreuz, Switzerland) and ELISA (IgG and IgA; Euroimmun, Germany). Simultaneously drawn venous serum and EDTA-anticoagulated whole blood samples from 223 individuals were included. Correction of the whole blood results for hematocrit led to a good agreement with the serum results for weakly to moderately positive antibody signals. In receiver-operating characteristic curve analysis, all three assays displayed comparable diagnostic accuracy (area under the curve (AUC)) using corrected whole blood and serum (AUCs: 0.97 for ECLIA and IgG ELISA; 0.84 for IgA ELISA). In conclusion, our results suggest that the investigated assays can reliably detect antibodies against SARS-CoV-2 in hemolyzed whole blood anticoagulated with EDTA. Correction of these results for hematocrit is suggested. This study demonstrates that the automated processing of whole blood for identification of SARS-CoV-2 antibodies with common ECLIA and ELISA methods is accurate and feasible.

Background: Blood cultures are essential for the diagnosis and further appropriate treatment in children with suspected sepsis. In most hospitals, children will be empirically treated or closely monitored for at least 48 h awaiting results of blood cultures. Several studies have challenged the optimal duration of empiric treatment in the era of continuously monitored blood culture systems. The aim of our study was to investigate time-to-positivity (TTP) of blood cultures in children with proven sepsis.Methods: The Swiss Pediatric Sepsis Study prospectively enrolled children 0–16 years of age with blood culture positive sepsis between September 2011 and October 2015. TTP was prospectively assessed in six participating academic pediatric hospitals by fully automated blood culture systems.Results: In 521 (93%) of 562 bacteremia episodes (493 children, median age 103 days, range 0 days−16.9 years) a valid TTP was available. Median TTP was 12 h (IQR 8–17 h, range 0–109 h). By 24, 36, and 48 h, 460 (88%), 498 (96%), and 510 (98%) blood cultures, respectively, were positive. TTP was independent of age, sex, presence of comorbidities, site of infection and severity of infection. Median TTP in all age groups combined was shortest for group B streptococcus (8.7 h) and longest for coagulase-negative staphylococci (16.2 h).Conclusion: Growth of bacteria in blood cultures is detectable within 24 h in 9 of 10 children with blood culture-proven sepsis. Therefore, a strict rule to observe or treat all children with suspected sepsis for at least 48 h is not justified.

Combined antiretroviral treatment (cART) has reduced mother-to-child transmission (MTCT) of the human immunodeficiency virus (HIV) to virtually zero in industrialised countries, where strictly bottle feeding is recommended for HIV-infected mothers, and to as low as 0.7% after 12 months in low-resource settings, where breastfeeding is strongly encouraged. Given the theoretically very low risk of transmission by breastfeeding with cART, and the advantages and benefits of breastfeeding, also in industrialised countries, the strong recommendation to HIV-infected mothers to refrain from breastfeeding in this setting may no longer be justified. We have evaluated risks of breastfeeding for HIV MTCT in the light of accessible cART, the general benefits of breastfeeding, and the women's autonomy to consent to any intervention. As we found no evidence in the literature of HIV MTCT via breastfeeding whilst on effective cART, we identified a situation of clinical equipoise. We propose how to proceed in Switzerland when HIV-infected women consider breastfeeding. We advocate a shared decision-making process and suggest a list of topics on which to provide unbiased information for the HIV-infected mother to enable her comprehensive understanding of one or the other decision. Although breastfeeding still should not be actively recommended in Switzerland, any HIV-infected mother, regardless of her geographical and cultural background, who decides to breastfeed should be supported by the best strategy to achieve optimal medical care for both herself and her child. This includes continuous support of cART adherence and regular maternal HIV plasma viral load monitoring.