Post-Acute Sequelae After Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Viral Variant and Vaccination Status: A Multicenter Cross-Sectional Study.

BACKGROUND: Disentangling the effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. METHODS: We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in north-eastern Switzerland. HCWs were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCWs without positive swab and with negative serology served as controls. The sum of 18 self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyze the association of mean symptom number with viral variant and vaccination status. RESULTS: Among 2912 participants (median age: 44 years; 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number: 1.12; P < .001; median time since infection: 18.3 months), after Alpha/Delta infection (0.67 symptoms; P < .001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms; P = .005; 3.1 months) versus uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals versus 0.71 with 1-2 vaccinations (P = .028) and 0.49 with ≥3 prior vaccinations (P = .30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR]: 2.81; 95% confidence interval [CI]: 2.08-3.83) and Alpha/Delta infections (aRR: 1.93; 95% CI: 1.10-3.46) were significantly associated with the outcome. CONCLUSIONS: Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCWs. Vaccination before Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population.

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.

Changes in socioeconomic resources and mental health after the second COVID-19 wave (2020-2021): a longitudinal study in Switzerland.

BACKGROUND: During the 2020/2021 winter, the labour market was under the impact of the COVID-19 pandemic. Changes in socioeconomic resources during this period could have influenced individual mental health. This association may have been mitigated or exacerbated by subjective risk perceptions, such as perceived risk of getting infected with SARS-CoV-2 or perception of the national economic situation. Therefore, we aimed to determine if changes in financial resources and employment situation during and after the second COVID-19 wave were prospectively associated with depression, anxiety and stress, and whether perceptions of the national economic situation and of the risk of getting infected modified this association. METHODS: One thousand seven hundred fifty nine participants from a nation-wide population-based eCohort in Switzerland were followed between November 2020 and September 2021. Financial resources and employment status were assessed twice (Nov2020-Mar2021, May-Jul 2021). Mental health was assessed after the second measurement of financial resources and employment status, using the Depression, Anxiety and Stress Scale (DASS-21). We modelled DASS-21 scores with linear regression, adjusting for demographics, health status, social relationships and changes in workload, and tested interactions with subjective risk perceptions. RESULTS: We observed scores above thresholds for normal levels for 16% (95%CI = 15-18) of participants for depression, 8% (95%CI = 7-10) for anxiety, and 10% (95%CI = 9-12) for stress. Compared to continuously comfortable or sufficient financial resources, continuously precarious or insufficient resources were associated with worse scores for all outcomes. Increased financial resources were associated with higher anxiety. In the working-age group, shifting from full to part-time employment was associated with higher stress and anxiety. Perceiving the Swiss economic situation as worrisome was associated with higher anxiety in participants who lost financial resources or had continuously precarious or insufficient resources. CONCLUSION: This study confirms the association of economic stressors and mental health during the COVID-19 pandemic and highlights the exacerbating role of subjective risk perception on this association.

Is living in a household with children associated with SARS-CoV-2 seropositivity in adults? Results from the Swiss national seroprevalence study Corona Immunitas.

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 <18 years of age (number, age group) and SARS-CoV-2 seropositivity. Further, we assessed the influence of reported non-household contacts, employment status, and gender. RESULTS: Of 2393 working age participants (18-64 years), 413 (17.2%) were seropositive. Our results suggest that living with children and SARS-CoV-2 seropositivity are likely to be associated (unadjusted odds ratio (OR) 1.22, 95% confidence interval [0.98-1.52], adjusted OR 1.25 [0.99-1.58]). A pattern of a positive association was also found for subgroups of children aged 0-11 years (OR 1.21 [0.90-1.60]) and 12-17 years (OR 1.14 [0.78-1.64]). Odds of seropositivity were higher with more children (OR 1.14 per additional child [1.02-1.27]). Men had higher risk of SARS-CoV-2 infection when living with children than women (interaction: OR 1.74 [1.10-2.76]). CONCLUSIONS: In adults from the general population living with children seems associated with SARS-CoV-2 seropositivity. However, child-related infection risk is not the same for every subgroup and depends on factors like gender. Further factors determining child-related infection risk need to be identified and causal links investigated. TRIAL REGISTRATION: https://www.isrctn.com/ISRCTN18181860 .

Exposure to avian coronavirus vaccines is associated with increased levels of SARS-CoV-2-cross-reactive antibodies.

BACKGROUND: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. METHODS: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. RESULTS: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared with pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared with pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. CONCLUSION: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings may be useful for further studies on the adaptive immunity against COVID-19.

Hospital outcomes of community-acquired COVID-19 versus influenza: Insights from the Swiss hospital-based surveillance of influenza and COVID-19.

BackgroundSince the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data.AimThis study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland.MethodsThis retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders.ResultsIn 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54-78) than the patients with influenza (median 74 years; IQR: 61-84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22-4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00-3.00, p < 0.001) for ICU admission.ConclusionCommunity-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.

Granulomatous interstitial nephritis in a patient with SARS-CoV-2 infection.

BACKGROUND: Acute kidney injury (AKI) associated with severe coronavirus disease 19 (COVID-19) is common and is a significant predictor of morbidity and mortality, especially when dialysis is required. Case reports and autopsy series have revealed that most patients with COVID-19 - associated acute kidney injury have evidence of acute tubular injury and necrosis - not unexpected in critically ill patients. Others have been found to have collapsing glomerulopathy, thrombotic microangiopathy and diverse underlying kidney diseases. A primary kidney pathology related to COVID-19 has not yet emerged. Thus far direct infection of the kidney, or its impact on clinical disease remains controversial. The management of AKI is currently supportive. CASE PRESENTATION: The patient presented here was positive for SARS-CoV-2, had severe acute respiratory distress syndrome and multi-organ failure. Within days of admission to the intensive care unit he developed oliguric acute kidney failure requiring dialysis. Acute kidney injury developed in the setting of hemodynamic instability, sepsis and a maculopapular rash. Over the ensuing days the patient also developed transfusion-requiring severe hemolysis which was Coombs negative. Schistocytes were present on the peripheral smear. Given the broad differential diagnoses for acute kidney injury, a kidney biopsy was performed and revealed granulomatous tubulo-interstitial nephritis with some acute tubular injury. Based on the biopsy findings, a decision was taken to adjust medications and initiate corticosteroids for presumed medication-induced interstitial nephritis, hemolysis and maculo-papular rash. The kidney function and hemolysis improved over the subsequent days and the patient was discharged to a rehabilitation facility, no-longer required dialysis. CONCLUSIONS: Acute kidney injury in patients with severe COVID-19 may have multiple causes. We present the first case of granulomatous interstitial nephritis in a patient with COVID-19. Drug-reactions may be more frequent than currently recognized in COVID-19 and are potentially reversible. The kidney biopsy findings in this case led to a change in therapy, which was associated with subsequent patient improvement. Kidney biopsy may therefore have significant value in pulling together a clinical diagnosis, and may impact outcome if a treatable cause is identified.

Burden and Timeline of Infectious Diseases in the First Year After Solid Organ Transplantation in the Swiss Transplant Cohort Study.

BACKGROUND: The burden and timeline of posttransplant infections are not comprehensively documented in the current era of immunosuppression and prophylaxis. METHODS: In this prospective study nested within the Swiss Transplant Cohort Study (STCS), all clinically relevant infections were identified by transplant-infectious diseases physicians in persons receiving solid organ transplant (SOT) between May 2008 and December 2014 with ≥12 months of follow-up. RESULTS: Among 3541 SOT recipients, 2761 (1612 kidney, 577 liver, 286 lung, 213 heart, and 73 kidney-pancreas) had ≥12 months of follow-up; 1520 patients (55%) suffered 3520 infections during the first year posttransplantation. Burden and timelines of clinically relevant infections differed between transplantations. Bacteria were responsible for 2202 infections (63%) prevailing throughout the year, with a predominance of Enterobacteriaceae (54%) as urinary pathogens in heart, lung, and kidney transplant recipients, and as digestive tract pathogens in liver transplant recipients. Enterococcus spp (20%) occurred as urinary tract pathogens in kidney transplant recipients and as digestive tract pathogens in liver transplant recipients, and Pseudomonas aeruginosa (9%) in lung transplant recipients. Among 1039 viral infections, herpesviruses predominated (51%) in kidney, liver, and heart transplant recipients. Among 263 fungal infections, Candida spp (60%) prevailed as digestive tract pathogens in liver transplant recipients. Opportunistic pathogens, including Aspergillus fumigatus (1.4%) and cytomegalovirus (6%), were rare, scattering over 12 months across all SOT recipients. CONCLUSIONS: In the current era of immunosuppression and prophylaxis, SOT recipients experience a high burden of infections throughout the first year posttransplantation, with rare opportunistic pathogens and a predominance of bacteria.

Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort.

BACKGROUND: Descriptive data on Pneumocystis jirovecii pneumonia (PJP) in solid organ transplant recipients (SOTr) in the era of routine Pneumocystis-prophylaxis are lacking. METHODS: All adult SOTr between 2008 and 2016 were included. PJP was diagnosed based on consensus guidelines. Early-onset PJP was defined as PJP within the first-year-post-transplant. RESULTS: 41/2842 SOTr (1.4%) developed PJP (incidence rate: 0.01/1000 person-days) at a mean of 493-days post-transplant: 21 (51.2%) early vs 20 (48.8%) late-onset PJP. 2465 (86.7%) SOTr received Pneumocystis-prophylaxis for a mean 316 days. PJP incidence was 0.001% and 0.003% (log-rank < 0.001) in SOTr with and without Pneumocystis-prophylaxis, respectively. PJP was an early event in 10/12 (83.3%) SOTr who did not receive Pneumocystis-prophylaxis and developed PJP, compared to those patients who received prophylaxis (11/29, 37.9%; P-value: 0.008). Among late-onset PJP patients, most cases (13/20, 65%) were observed during the 2nd year post-transplant. Age ≥65 years (OR: 2.4, P-value: 0.03) and CMV infection during the first 6 months post-SOT (OR: 2.5, P-value: 0.006) were significant PJP predictors, while Pneumocystis-prophylaxis was protective for PJP (OR: 0.3, P-value: 0.006) in the overall population. Most patients (35, 85.4%) were treated with trimethoprim-sulfamethoxazole for a mean 20.6 days. 1-year mortality was 14.6%. CONCLUSIONS: In the Pneumocystis-prophylaxis-era, PJP remains a rare post-transplant complication. Most cases occurred post-PJP-prophylaxis-discontinuation, particularly during the second-year-post-transplant. Additional research may help identify indications for Pneumocystis-prophylaxis prolongation.

Ventricular assist devices as bridge to heart transplantation: impact on post-transplant infections.

BACKGROUND: Ventricular assist devices (VAD) are valuable options for patients with heart failure awaiting cardiac transplantation. We assessed the impact of pre-transplant VAD implantation on the incidence of post-transplant infections in a nationwide cohort of heart transplant recipients. METHODS: Heart transplant recipients included in the Swiss Transplant Cohort Study between May 2008 and December 2012 were analyzed. Cumulative incidence curves were used to calculate the incidence of bacterial or Candida infections (primary endpoint) and of other infections (secondary endpoint) after transplant. Cox regression models treating death as a competing risk were used to identify risk factors for the development of infection after transplant. RESULTS: Overall, 119 patients were included in the study, 35 with a VAD and 84 without VAD. Cumulative incidences of post-transplant bacterial or Candida infections were 37.7 % in VAD patients and 40.4 % in non-VAD patients. In multivariate analysis, the use of cotrimoxazole prophylaxis was the only variable associated with bacterial/Candida infections after transplant (HR 0.29 [95 % CI 0.15-0.57], p < 0.001), but presence of a VAD was not (HR 0.94, [95 % CI 0.38-2.32], p = 0.89, for continuous-flow devices, and HR 0.45 [0.15 - 1.34], p = 0.15, for other devices). Risk for post-transplant viral and all fungal infections was not increased in patients with VAD. One-year survival was 82.9 % (29/35) in the VAD group and 82.1 % (69/84) in the non-VAD group. All 6 patients in the VAD group that died after transplant had a history of pre-transplant VAD infection. CONCLUSION: In this nationwide cohort of heart transplant recipients, the presence of VAD at the time of transplant had no influence on the development of post-transplant infections.

Influence of IFNL3/4 polymorphisms on the incidence of cytomegalovirus infection after solid-organ transplantation.

BACKGROUND: Polymorphisms in IFNL3 and IFNL4, the genes encoding interferon λ3 and interferon λ4, respectively, have been associated with reduced hepatitis C virus clearance. We explored the role of such polymorphisms on the incidence of cytomegalovirus (CMV) infection in solid-organ transplant recipients. METHODS: White patients participating in the Swiss Transplant Cohort Study in 2008-2011 were included. A novel functional TT/-G polymorphism (rs368234815) in the CpG region upstream of IFNL3 was investigated. RESULTS: A total of 840 solid-organ transplant recipients at risk for CMV infection were included, among whom 373 (44%) received antiviral prophylaxis. The 12-month cumulative incidence of CMV replication and disease were 0.44 and 0.08 cases, respectively. Patient homozygous for the minor rs368234815 allele (-G/-G) tended to have a higher cumulative incidence of CMV replication (subdistribution hazard ratio [SHR], 1.30 [95% confidence interval {CI}, .97-1.74]; P = .07), compared with other patients (TT/TT or TT/-G). The association was significant among patients followed by a preemptive approach (SHR, 1.46 [95% CI, 1.01-2.12]; P = .047), especially in patients receiving an organ from a seropositive donor (SHR, 1.92 [95% CI, 1.30-2.85]; P = .001), but not among those who received antiviral prophylaxis (SHR, 1.13 [95% CI, .70-1.83]; P = .6). These associations remained significant in multivariate competing risk regression models. CONCLUSIONS: Polymorphisms in the IFNL3/4 region influence susceptibility to CMV replication in solid-organ transplant recipients, particularly in patients not receiving antiviral prophylaxis.

IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS: Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS: Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1ß (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and ß-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1ß and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS: Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.

PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant.

Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infections among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patients' risk stratification.

Increased mortality after a first myocardial infarction in human immunodeficiency virus-infected patients; a nested cohort study.

AIMS: HIV infection may be associated with an increased recurrence rate of myocardial infarction. Our aim was to determine whether HIV infection is a risk factor for worse outcomes in patients with coronaray artery disease. METHODS: We compared data aggregated from two ongoing cohorts: (i) the Acute Myocardial Infarction in Switzerland (AMIS) registry, which includes patients with acute myocardial infarction (AMI), and (ii) the Swiss HIV Cohort Study (SHCS), a prospective registry of HIV-positive (HIV+) patients. We included all patients who survived an incident AMI occurring on or after 1st January 2005. Our primary outcome measure was all-cause mortality at one year; secondary outcomes included AMI recurrence and cardiovascular-related hospitalisations. Comparisons used Cox and logistic regression analyses, respectively. RESULTS: There were 133 HIV+, (SHCS) and 5,328 HIV-negative [HIV-] (AMIS) individuals with incident AMI. In the SHCS and AMIS registries, patients were predominantly male (72% and 85% male, respectively), with a median age of 51 years (interquartile range [IQR] 46-57) and 64 years (IQR 55-74), respectively. Nearly all (90%) of HIV+ individuals were on successful antiretroviral therapy. During the first year of follow-up, 5 (3.6%) HIV+ and 135 (2.5%) HIV- individuals died. At one year, HIV+ status after adjustment for age, sex, calendar year of AMI, smoking status, hypertension and diabetes was associated with a higher risk of death (HR 4.42, 95% CI 1.73-11.27). There were no significant differences in recurrent AMIs (4 [3.0%] HIV+ and 146 [3.0%] HIV- individuals, OR 1.16, 95% CI 0.41-3.27) or in hospitalization rates (OR 0.68 [95% CI 0.42-1.11]). CONCLUSIONS: HIV infection was associated with a significantly increased risk of all-cause mortality one year after incident AMI.

SARS-CoV-2 Vaccination is Not Associated With Involuntary Childlessness in Female Healthcare Workers: A Multicenter Cohort Study.

BACKGROUND: There is debate about the causes of the recent birth rate decline in high-income countries worldwide. During the pandemic, concern about the effects on reproductive health has caused vaccine hesitancy. We investigated the association of SARS-CoV-2 vaccination and infection with involuntary childlessness. METHODS: Females in fertility age within a prospective multicenter cohort of healthcare workers (HCW) were followed since August 2020. Data on baseline health, SARS-CoV-2-infection, and vaccination were obtained and regularly updated, in which serum samples were collected repetitively and screened for anti-nucleocapsid and anti-spike antibodies. In October 2023, participants indicated the presence of involuntary childlessness with onset during the pandemic, whereas those indicating an onset before the pandemic were excluded. The association of involuntary childlessness and SARS-CoV-2-vaccination and infection was investigated using univariable and multivariable analysis. Sensitivity analysis was performed to compare those reporting involuntary childlessness with those birthing a child since 2020. RESULTS: Of 798 participants, 26 (3.2%) reported involuntary childlessness starting since the pandemic. Of the involuntary childless women, 73.1% (19/26) were vaccinated compared to 86.0% (664/772) without involuntary childlessness (p = 0.73). SARS-CoV-2 infection was reported by 76.9% (20/26) compared to 72.4% (559/772) of controls (p = 0.64). Neither SARS-CoV-2 vaccination (aOR 0.91 per dose, 95%CI 0.67-1.26) nor infection (aOR per infection 1.05, 95%CI 0.62-1.71) was associated with involuntary childlessness. Sensitivity analysis confirmed these results. CONCLUSIONS: Among female HCW of fertility age, 3.2% indicated involuntary childlessness, which is comparable to pre-pandemic data. No association between involuntary childlessness and SARS-CoV-2 vaccination or infection was found.

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.

Association of institutional masking policies with healthcare-associated SARS-CoV-2 infections in Swiss acute care hospitals during the BA.4/5 wave (CH-SUR study): a retrospective observational study.

BACKGROUND: In the initial phase of the SARS-CoV-2 pandemic, masking has been widely accepted in healthcare institutions to mitigate the risk of healthcare-associated infection. Evidence, however, is still scant and the role of masks in preventing healthcare-associated SARS-CoV-2 acquisition remains unclear.We investigated the association of variation in institutional mask policies with healthcare-associated SARS-CoV-2 infections in acute care hospitals in Switzerland during the BA.4/5 2022 wave. METHODS: SARS-CoV-2 infections in hospitalized patients between June 1 and September 5, 2022, were obtained from the "Hospital-based surveillance of COVID-19 in Switzerland"-database and classified as healthcare- or community-associated based on time of disease onset. Institutions provided information regarding institutional masking policies for healthcare workers and other prevention policies. The percentage of healthcare-associated SARS-CoV-2 infections was calculated per institution and per type of mask policy. The association of healthcare-associated SARS-CoV-2 infections with mask policies was tested using a negative binominal mixed-effect model. RESULTS: We included 2'980 SARS-CoV-2 infections from 13 institutions, 444 (15%) were classified as healthcare-associated. Between June 20 and June 30, 2022, six (46%) institutions switched to a more stringent mask policy. The percentage of healthcare-associated infections subsequently declined in institutions with policy switch but not in the others. In particular, the switch from situative masking (standard precautions) to general masking of HCW in contact with patients was followed by a strong reduction of healthcare-associated infections (rate ratio 0.39, 95% CI 0.30-0.49). In contrast, when compared across hospitals, the percentage of health-care associated infections was not related to mask policies. CONCLUSIONS: Our findings suggest switching to a more stringent mask policy may be beneficial during increases of healthcare-associated SARS-CoV-2 infections at an institutional level.

Microbial communities in the respiratory tract of patients with interstitial lung disease.

BACKGROUND: Molecular methods based on phylogenetic differences in the 16S rRNA gene are able to characterise the microbiota of the respiratory tract in health and disease. OBJECTIVES: Our goals were (1) to characterise bacterial communities in lower and upper airways of patients with interstitial lung disease (ILD) and (2) to compare the results with the microbiota of patients with Pneumocystis pneumonia (PCP) and normal controls. METHODS: We examined the upper and lower respiratory tract of 18 patients with ILD of whom 5, 6, and 7 had idiopathic interstitial pneumonia (IIP), non-IIP and sarcoidosis, respectively. In addition, six immune-compromised patients with PCP and nine healthy subjects were included as controls. Exclusion criteria were recent bacterial/viral respiratory tract infection, HIV-positivity and subjects receiving antibiotic therapy. Bronchoalveolar lavage fluid and oropharyngeal swabs were simultaneously collected, and microbiota was characterised by ultra-deep 16S rRNA gene sequencing. RESULTS: The microbiota in lower airways of the majority of patients (30; 90%) primarily consisted of Prevotellaceae, Streptococcaceae and Acidaminococcaceae. α and ß diversity measurements revealed no significant differences in airway microbiota composition between the five different groups of patients. Comparison of bacterial populations in upper and lower respiratory tract showed significant topographical discontinuities for 7 (23%) individuals. CONCLUSIONS: IIP, non-IIP and sarcoidosis are not associated with disordered airway microbiota and a pathogenic role of commensals in the disease process is therefore unlikely. Nevertheless, molecular analysis of the topographical microbiota continuity along the respiratory tract may provide additional information to assist management of individual patients.

[Surgery, Antibiotic Treatment or Both?]

INTRODUCTION: The 90-year-old female patient with underlying rheumatoid arthritis and spinal canal stenosis was admitted to hospital for pain control. The clinical exam of the lower abdomen was impressively painful and the inflammatory parameters were significantly increased. For further diagnosis a computer tomography was performed, showing a covered perforated appendicitis with a perityphlitic abscess. The conservative therapy with abscess drainage and antibiotics was successful.

Relevance of cohort studies for the study of transplant infectious diseases.

PURPOSE OF REVIEW: The debate on the merits of observational studies as compared with randomized trials is ongoing. We will briefly touch on this subject, and demonstrate the role of cohort studies for the description of infectious disease patterns after transplantation. The potential benefits of cohort studies for the clinical management of patients outside of the expected gain in epidemiological knowledge are reviewed. The newly established Swiss Transplantation Cohort Study and in particular the part focusing on infectious diseases will serve as an illustration. RECENT FINDINGS: A neglected area of research is the indirect value of large, multicenter cohort studies. These benefits can range from a deepened collaboration to the development of common definitions and guidelines. Unfortunately, very few data exist on the role of such indirect effects on improving quality of patient management. SUMMARY: This review postulates an important role for cohort studies, which should not be viewed as inferior but complementary to established research tools, in particular randomized trials. Randomized trials remain the least bias-prone method to establish knowledge regarding the significance of diagnostic or therapeutic measures. Cohort studies have the power to reflect a real-world situation and to pinpoint areas of knowledge as well as of uncertainty. Prerequisite is a prospective design requiring a set of inclusive data coupled with the meticulous insistence on data retrieval and quality.