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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.

To better understand the development of SARS-CoV-2-specific immunity over time, a detailed evaluation of humoral and cellular responses is required. Here, we characterize anti-Spike (S) IgA and IgG in a representative population-based cohort of 431 SARS-CoV-2-infected individuals up to 217 days after diagnosis, demonstrating that 85% develop and maintain anti-S responses. In a subsample of 64 participants, we further assess anti-Nucleocapsid (N) IgG, neutralizing antibody activity, and T cell responses to Membrane (M), N, and S proteins. In contrast to S-specific antibody responses, anti-N IgG levels decline substantially over time and neutralizing activity toward Delta and Omicron variants is low to non-existent within just weeks of Wildtype SARS-CoV-2 infection. Virus-specific T cells are detectable in most participants, albeit more variable than antibody responses. Cluster analyses of the co-evolution of antibody and T cell responses within individuals identify five distinct trajectories characterized by specific immune patterns and clinical factors. These findings demonstrate the relevant heterogeneity in humoral and cellular immunity to SARS-CoV-2 while also identifying consistent patterns where antibody and T cell responses may work in a compensatory manner to provide protection. 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.

Increased blood leukocytes are associated with all-cause mortality and death from coronary disease and cancer in the general population. Limited information is available in people with HIV. We analyzed blood leukocytes in 1850 participants of the Swiss HIV Cohort Study who died (2000-2023) and 1850 matched controls (median age at death 52 years, 77% male, 77% with suppressed HIV RNA on antiretroviral therapy). We assessed uni-/multivariable odds ratios (OR) for all-cause mortality, considering major clinical and HIV-related mortality risk factors, leukocytes measured >1 year before death (primary analysis) and in the latest available blood sample, and potential confounders for leukocytes. Leukocytes showed a U-shaped association with mortality. At a median of 433 (interquartile range [IQR], 396-495) days before death, multivariable-adjusted OR for death in the highest (leukocytes ≥7730/μL) vs. middle quintile (leukocytes 5290-6260/μL) was 1.56 (95% confidence interval, 1.20-2.02). Multivariable-adjusted OR in the lowest (leukocytes ≤4250/μL) vs. middle leukocyte quintile was 1.51 (1.14-2.01). For comparison, death-OR for hypertension, diabetes and current smoking were 1.27 (1.06-1.53), 1.91 (1.41-2.57), and 2.72 (2.14-3.45), respectively. Leukocytosis was uncommon (cases, 4.4% vs. controls, 2.3%; p = 0.004). The effect size of the highest leukocyte quintile increased in the latest blood sample (median 86 [IQR], 43-152 days before death; OR=1.99 [1.44-2.76]). High leukocytes were associated with death from non-AIDS/non-hepatic cancer, cardiovascular, and respiratory causes. Low leukocytes were associated with liver-related death. High leukocytes, measured >1 year before death and mostly within the normal range, are independently associated with mortality in people with HIV in Switzerland.

Polygenic risk scores (PRS) are likely to enter routine clinical care for individual disease risk prediction in the next 10 years. We recently showed that the bone mineral density-associated gSOS-PRS is independently associated with a > 4-fold increased risk of osteoporosis in the Swiss HIV Cohort Study (SHCS). Here we investigate whether this PRS is also associated with low trauma fractures (LTF) in people with HIV in the SHCS. Applying a case-control design, cases had a first LTF (1994-2022) and LTF-free controls were matched on age, sex and observation time. We obtained univariable odds ratios (OR) for LTF in SHCS participants of European descent, based on a genome-wide PRS built from 9413 LTF-associated single nucleotide polymorphisms (SNPs). In multivariable analysis, LTF odds ratios of the PRS were adjusted for non-genetic (traditional and HIV-related) LTF risk factor profile including potentially adverse antiretroviral exposures. We included 277 SHCS participants with a first LTF (cases) and 796 LTF-free controls (median age 55 years; 68% male; 91% with suppressed HIV RNA). Participants with the most unfavorable genetic background (top quintile of the gSOS-PRS) had univariable and multivariable LTF-OR of 2.30 (95% confidence interval, 1.49-3.56) and 2.30 (1.43-3.72), respectively, compared to participants with the most favorable genetic background (bottom gSOS-PRS quintile). Participants with the most unfavorable non-genetic risk factor profile (top quintile) had an adjusted gSOS-OR of 7.42 (95% confidence interval [CI], 4.3-12.82), compared with participants in the bottom quintile. In people with HIV in Switzerland, an unfavorable PRS was independently associated with LTF risk after adjustment for traditional and HIV-related LTF risk factors.

Background This study examines the longitudinal effects of COVID-19 pandemic regulations on health-related quality of life (HrQoL), glycaemic control and lifestyle characteristics and describes the epidemiology of COVID-19 in children with type 1 diabetes (T1D). Methods This monocentric, prospective study included, from May to November 2020, pediatric outpatients up to 18 years with T1D. During the first 16 weeks, COVID-19–associated symptoms were assessed weekly, while HrQoL, COVID-19 affectedness and appraisal, screen time, and physical activity were assessed monthly. Body-mass-index standard deviation scores (BMI-SDS), HbA1c, and glycaemic monitoring data were collected at clinical visits three monthly. All parameters were reassessed at final visit after 10 months and assigned to the pandemic restriction phases. Estimates of correlation (est) were tested by a linear mixed-effects model. Results 55 children with T1D were included, with a median age of 11 years and 56.4% male. HrQoL remained normal and stable throughout the pandemic, but showed significant associations with physical activity (est 3.63, p  < 0.01), screen time (est − 1.66, p  < 0.01) and financial situation (est − 9.15, p  < 0.05). During the pandemic, BMI-SDS increased ( p  < 0.01), but mean HbA1c remained at about 7.5% and glucose time in range improved ( p  < 0.01). During the lockdown phases, screen time tended to be highest ( p  < 0.1), while physical activity was lowest ( p  < 0.01). At baseline, one of 55 patients (1.8%) was COVID-19 seropositive from infection. At the study’s end 20.5% were positive from infection, and 4.9% from vaccination. Conclusions In children with T1D, HrQoL and metabolic control remained stable under pandemic regulations, but BMI-SDS and physical activity worsened. Continuation of outpatient care and opening of schools may have contributed to a healthy lifestyle and resilience. Trial registration Not applicable.

Knowledge about protection conferred by previous Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or vaccination against emerging viral variants allows clinicians, epidemiologists, and health authorities to predict and reduce the future Coronavirus Disease 2019 (COVID-19) burden. We investigated the risk and symptoms of SARS-CoV-2 (re)infection and vaccine breakthrough infection during the Delta and Omicron waves, depending on baseline immune status and subsequent vaccinations. In this prospective, multicentre cohort performed between August 2020 and March 2022, we recruited hospital employees from ten acute/nonacute healthcare networks in Eastern/Northern Switzerland. We determined immune status in September 2021 based on serology and previous SARS-CoV-2 infections/vaccinations: Group N (no immunity); Group V (twice vaccinated, uninfected); Group I (infected, unvaccinated); Group H (hybrid: infected and ≥1 vaccination). Date and symptoms of (re)infections and subsequent (booster) vaccinations were recorded until March 2022. We compared the time to positive SARS-CoV-2 swab and number of symptoms according to immune status, viral variant (i.e., Delta-dominant before December 27, 2021; Omicron-dominant on/after this date), and subsequent vaccinations, adjusting for exposure/behavior variables. Among 2,595 participants (median follow-up 171 days), we observed 764 (29%) (re)infections, thereof 591 during the Omicron period. Compared to group N, the hazard ratio (HR) for (re)infection was 0.33 (95% confidence interval [CI] 0.22 to 0.50, p < 0.001) for V, 0.25 (95% CI 0.11 to 0.57, p = 0.001) for I, and 0.04 (95% CI 0.02 to 0.10, p < 0.001) for H in the Delta period. HRs substantially increased during the Omicron period for all groups; in multivariable analyses, only belonging to group H was associated with protection (adjusted HR [aHR] 0.52, 95% CI 0.35 to 0.77, p = 0.001); booster vaccination was associated with reduction of breakthrough infection risk in groups V (aHR 0.68, 95% CI 0.54 to 0.85, p = 0.001) and H (aHR 0.67, 95% CI 0.45 to 1.00, p = 0.048), largely observed in the early Omicron period. Group H (versus N, risk ratio (RR) 0.80, 95% CI 0.66 to 0.97, p = 0.021) and participants with booster vaccination (versus nonboosted, RR 0.79, 95% CI 0.71 to 0.88, p < 0.001) reported less symptoms during infection. Important limitations are that SARS-CoV-2 swab results were self-reported and that results on viral variants were inferred from the predominating strain circulating in the community at that time, rather than sequencing. Our data suggest that hybrid immunity and booster vaccination are associated with a reduced risk and reduced symptom number of SARS-CoV-2 infection during Delta- and Omicron-dominant periods. For previously noninfected individuals, booster vaccination might reduce the risk of symptomatic Omicron infection, although this benefit seems to wane over time.

Abstract Background Population-based studies assessing the impact of pneumococcal conjugate vaccines (PCV) on burden of pneumococcal sepsis in children are lacking. We aimed to assess this burden following introduction of PCV-13 in a nationwide cohort study. Methods The Swiss Pediatric Sepsis Study (September 2011 to December 2015) prospectively recruited children <17 years of age with blood culture-proven sepsis due to Streptococcus pneumoniae, meeting criteria for systemic inflammatory response syndrome. Infection with vaccine serotype in children up to date with PCV immunization was defined as vaccine failure. Main outcomes were admission to pediatric intensive care unit (PICU) and length of hospital stay (LOS). Results Children with pneumococcal sepsis (n = 117) accounted for a crude incidence of 2.0 per 100 000 children (95% confidence interval [CI] 1.7–2.4) and 25% of community-acquired sepsis episodes. Case fatality rate was 8%. Forty-two (36%) patients required PICU admission. Children with meningitis (29; 25%) were more often infected by serotypes not included in PCV (69% vs 31%; P < .001). Sixteen (26%) of 62 children up to date with PCV immunization presented with vaccine failure, including 11 infected with serotype 3. In multivariable analyses, children with meningitis (odds ratio [OR] 6.8; 95% CI 2.4–19.3; P < .001) or infected with serotype 3 (OR 2.8; 95% CI 1.1–7.3; P = .04) were more often admitted to PICU. Children infected with serotype 3 had longer LOS (β coefficient 0.2, 95% CI .1–1.1; P = .01). Conclusions The incidence of pneumococcal sepsis in children shortly after introduction of PCV-13 remained substantial. Meningitis mostly due to non-vaccine serotypes and disease caused by serotype 3 represented significant predictors of severity. Shortly following introduction of PCV-13 in Switzerland, blood culture-proven pneumococcal sepsis accounted for 25% of community-acquired sepsis in children, with an 8% case fatality rate. Presence of meningitis and infection by serotype 3 were associated with severe disease.

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.

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.

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.