Intravascular catheters are crucial devices in medical practice that increase the risk of healthcare-associated infections (HAIs), and related health-economic adverse outcomes. This scoping review aims to provide a comprehensive overview of published automated algorithms for surveillance of catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). We performed a scoping review based on a systematic search of the literature in PubMed and EMBASE from 1 January 2000 to 31 December 2021. Studies were included if they evaluated predictive performance of automated surveillance algorithms for CLABSI/CRBSI detection and used manually collected surveillance data as reference. We assessed the design of the automated systems, including the definitions used to develop algorithms (CLABSI versus CRBSI), the datasets and denominators used, and the algorithms evaluated in each of the studies. We screened 586 studies based on title and abstract, and 99 were assessed based on full text. Nine studies were included in the scoping review. Most studies were monocentric (n = 5), and they identified CLABSI (n = 7) as an outcome. The majority of the studies used administrative and microbiological data (n = 9) and five studies included the presence of a vascular central line in their automated system. Six studies explained the denominator they selected, five of which chose central line-days. The most common rules and steps used in the algorithms were categorized as hospital-acquired rules, infection rules (infection versus contamination), deduplication, episode grouping, secondary BSI rules (secondary versus primary BSI), and catheter-associated rules. The automated surveillance systems that we identified were heterogeneous in terms of definitions, datasets and denominators used, with a combination of rules in each algorithm. Further guidelines and studies are needed to develop and implement algorithms to detect CLABSI/CRBSI, with standardized definitions, appropriate data sources and suitable denominators.

BACKGROUND:Although sex hormones are recognized to induce immune variations, the effect of hormonal therapy use on immunity is only poorly understood. Here, we quantified how hormonal therapy use affects HIV-1 immune markers in cis women (CW) and trans women and non-binary people (TNBP) with HIV. METHODS:We considered CD4, CD8 and lymphocyte measurements from cis men (CM), CW and TNBP in the Swiss HIV Cohort Study. We modelled HIV-1 markers using linear mixed-effects models with an interaction between 'gender' (CW, TNBP) and 'hormonal therapy use' (yes/no). Models were adjusted on age, ethnicity, education level, time since start of antiretroviral therapy and use of intravenous drugs. We assessed the inflammatory effect of hormonal therapy use in 31 TNBP using serum proteomics measurements of 92 inflammation markers. RESULTS:We included 54 083 measurements from 3092 CW and 83 TNBP, and 147 230 measurements from 8611 CM. Hormonal therapy use increased CD4 count and CD4:CD8 ratio in TNBP more than in CW (pinteraction = 0.02 and 0.007, respectively). TNBP with hormonal therapy use had significantly higher CD4 counts [median = 772 cells/μL, interquartile range (IQR): 520-1006] than without (617 cells/μL, 426-892). This was similar to the effect of CW versus CM on CD4 T cells. Hormonal therapy use did not affect serum protein concentrations in TNBP. CONCLUSION:This study highlights the potential role of hormonal therapy use in modulating the immune system among other biological and social factors, especially in TNBP with HIV.

Background: The association between the COVID-19 pandemic and the incidence of invasive infections caused by multidrug-resistant organisms remains a topic of debate. Aim: To analyse the national incidence rates of bloodstream infections (BSI) caused by Escherichia coli (EC) and Klebsiella pneumoniae (KP) with extended-spectrum cephalosporin resistance (ESCR) in two distinct regions in Switzerland, each exhibiting varying antimicrobial resistance patterns and that were impacted differently by the pandemic. Methods: Data was analysed from positive blood cultures prospectively collected by the nationwide surveillance system (ANRESIS) from January 1 st , 2015, to August 31 st , 2022. To explore the potential relationship between COVID-19 patient occupancy and ESCR incidence rates, an in-depth analysis was conducted over the two-year pandemic period from April 1 st , 2020, to March 30 th , 2022, using Quasi-Poisson and logistic regression analyses. Findings: During the study period, 40,997 EC-BSI and 8537 KP-BSI episodes were collected and reported to ANRESIS by the participating hospitals. ESCR was observed in 11% ( N = 4313) of E. coli and 8% ( N = 664) of K. pneumoniae , respectively. A significant reduction in ESCR-EC BSI incidence occurred during the pandemic in the region with the highest COVID19 incidence. Conversely, ESCR-KP BSI incidence initially fell considerably and then increased during the pandemic in both regions, though this effect was not statistically significant. No association between hospital occupancy from COVID-19 patients and these trends was observed.

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.

Background Although sex hormones are recognized to induce immune variations, little is known on the effect of exogenous sex hormone intake on immune responses in cis and trans women. Here, we aimed at quantifying how sex hormone intake affects HIV-1 immune markers in cis women (CW) and trans women (TW) with HIV. Methods We considered measurements of key HIV-1 immune markers (CD4, CD8, lymphocyte counts, and CD4:CD8 ratio) from cis men (CM), CW, and TW enrolled in the Swiss HIV Cohort Study. We modeled immune markers using linear mixed-effects models with an interaction between the variables “group” (CW, TW) and “with sex hormone intake” (yes/no). We conducted serum proteomics measurements of 92 inflammation markers on samples from 31 TW before and after sex hormone intake to assess the inflammation environment. Results We included 54’141 measurements from 3’092 CW and 83 TW sampled between 2015 and 2022, and 147’298 from 8’611 CM. Sex hormone intake was associated with significant distinct effects on CD4 and CD4:CD8 ratio between the different groups of women (p=0.0025 and 0.015). TW with sex hormone intake had significantly higher CD4 counts (median = 772 (1Q-3Q=520-1’006)) than without (median = 617 (1Q-3Q=426-892)). This increase was similar in magnitude to the difference in CD4 counts between CW and CM. None of the serum inflammation proteins showed significant concentration difference before and after sex hormone intake in TW. Conclusion This study highlights the need to consider the potential role of sex hormone intake in modulating the immune system among other biological and social factors, especially in TW in HIV. ### Competing Interest Statement IAA has received honoraria from MSD and Sanofi, a travel grant from Gilead Sciences, and a grant from the Promedica foundation. RDK has received research fundings from Gilead unrelated to this work. AH's institution has received travel grants, congress and advisory fees from MSD, Viiv and Gilead, unrelated to this work. KAP's institution has received travel grants and advisory fees from MSD, Gilead and ViiV healthcare unrelated to this work. HFG has received grants from the SNF; SHCS; Yvonne Jacob Foundation; University of Zurich's Clinical Research Priority Program, viral disease; Zurich Primary HIV Infection; Systems.X; National Institutes of Health; Gilead Sciences; and Roche; and personal fees from Merck, Gilead Sciences, ViiV, GSK, Janssen, Johnson and Johnson and Novartis, for consultancy or DSMB membership and a travel grant from Gilead. ### Funding Statement This work has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #882 and by the SHCS research foundation. The data were gathered by the 5 Swiss university hospitals, 2 cantonal hospitals, 15 affiliated hospitals, and 36 private physicians (listed at ). IAA is supported by a research grant of the Promedica Foundation. CP is supported by a Fellowship from the Collegium Helveticum. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The SHCS was approved by the local ethical committees of the participating centres: Ethikkommission beider Basel ("Die Ethikkommission beider Basel hat die Dokumente zur Studie zustimmend zur Kenntnis genommen und genehmigt."); Kantonale Ethikkommission Bern (21/88); Comite departemental d'ethique des specialites medicales et de medecine communautaire et de premier recours, Hopitaux Universitaires de Geneve (01-142); Commission cantonale d'ethique de la recherche sur l'etre humain, Canton de Vaud (131/01); Comitato etico cantonale, Repubblica e Cantone Ticino (CE 813); Ethikkommission des Kantons St. Gallen (EKSG 12/003); Kantonale Ethikkommission Zurich (KEK-ZH-NR: EK-793), and written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The individual level datasets generated or analyzed during the current study do not fulfill the requirements for open data access: 1) The SHCS informed consent states that sharing data outside the SHCS network is only permitted for specific studies on HIV infection and its complications, and to researchers who have signed an agreement detailing the use of the data and biological samples; and 2) the data is too dense and comprehensive to preserve patient privacy in persons living with HIV. According to the Swiss law, data cannot be shared if data subjects have not agreed or data is too sensitive to share. Investigators with a request for selected data should send a proposal to the respective SHCS address ([www.shcs.ch/contact][1]). The provision of data will be considered by the Scientific Board of the SHCS and the study team and is subject to Swiss legal and ethical regulations, and is outlined in a material and data transfer agreement. [1]: http://www.shcs.ch/contact

Background: Previous studies reported higher incidence of surgical site infection (SSI) after procedures performed in summer or with high temperatures. However, no study used detailed climate data to assess this risk after hip and knee arthroplasty, and no study specifically investigated the role of heatwaves. Aim: To assess the impact of higher environmental temperatures and heatwaves on SSI rates after hip and knee arthroplasty. Methods: Data on hip and knee arthroplasty procedures performed between January 2013 and September 2019 in hospitals participating in the Swiss SSI surveillance were linked to climate data extracted from weather stations located in their vicinity. The association between temperature, heatwaves and SSI was studied using mixed effects logistic regression models fitted at the patient level. Poisson mixed models were fitted for both calendar year and month of the year to investigate the SSI incidence trajectory over time. Results: We included 116,981 procedures performed in 122 hospitals. Significantly higher SSI rates were observed for procedures performed in the summertime (incidence rate ratio 1.39, 95% CI (1.20-1.60), P<0.001; reference: autumn) or in calendar months in which the mean temperature was above 20 degrees C (reference 5-10 degrees C; odds ratio 1.59, 95% CI (1.27, 1.98), P<0.001). We observed a slight but non-significant increase in the rate of SSI during heatwaves (1.44% versus 1.01%, P=0.2). Conclusion: SSI rates after hip and knee replacement appear to increase with higher environ-mental temperature. To establish whether, and to what extent, heatwaves increase the risk of SSI, studies involving geographical areas with larger variability in temperature are needed. (c) 2023 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

AIMS OF THE STUDY:Remdesivir has shown benefits against COVID-19. However, it remains unclear whether, to what extent, and among whom remdesivir can reduce COVID-19-related mortality. We explored whether the treatment response to remdesivir differed by patient characteristics.METHODS:We analysed data collected from a hospital surveillance study conducted in 21 referral hospitals in Switzerland between 2020 and 2022. We applied model-based recursive partitioning to group patients by the association between treatment levels and mortality. We included either treatment (levels: none, remdesivir within 7 days of symptom onset, remdesivir after 7 days, or another treatment), age and sex, or treatment only as regression variables. Candidate partitioning variables included a range of risk factors and comorbidities (and age and sex unless included in regression). We repeated the analyses using local centring to correct the results for the propensity to receive treatment.RESULTS:Overall (n = 21,790 patients), remdesivir within 7 days was associated with increased mortality (adjusted hazard ratios 1.28-1.54 versus no treatment). The CURB-65 score caused the most instability in the regression parameters of the model. When adjusted for age and sex, patients receiving remdesivir within 7 days of onset had higher mortality than those not treated in all identified eight patient groups. When age and sex were included as partitioning variables instead, the number of groups increased to 19-20; in five to six of those branches, mortality was lower among patients who received early remdesivir. Factors determining the groups where remdesivir was potentially beneficial included the presence of oncological comorbidities, male sex, and high age.CONCLUSIONS:Some subgroups of patients, such as individuals with oncological comorbidities or elderly males, may benefit from remdesivir.

Background: Since 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. Aim: This study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland. Methods: This 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. Results: In 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. Conclusion: Community-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.

Background: Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies and the performance in clinical practice is essentially unclear. Objectives: We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease-2019 (COVID-19) and (b) prediction of neutralizing antibodies against SARS-CoV-2 in real-life clinical settings. Methods: We prospectively included 2’573 consecutive health-care workers and 1’085 inpatients with suspected or possible previous COVID-19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme-linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; lateral-flow immunoassay, LFI), epitopes of SARS-CoV-2 (nucleocapsid, N; receptor-binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan-Ig) were conducted. A positive real-time PCR test from a nasopharyngeal swab was defined as previous COVID-19. Neutralization assays with live SARS-CoV-2 were performed in a subgroup of patients to assess neutralization activity (n=201). Results: The sensitivity to detect patients with previous COVID-19 was ≥85% in anti-N ECLIA (86.8%) and anti-S1 ELISA (86.2%). Sensitivity was 84.7% in anti-S1/S2 CLIA, 84.0% in anti-RBD+ LFI, 81.0% in anti-N CLIA, 79.2% in anti-RBD ELISA, and 65.6% in anti-N ELISA. The specificity was 98.4% in anti-N ECLIA, 98.3% in anti-N CLIA, 98.2% in anti-S1 ELISA, 97.7% in anti-N ELISA, 97.6% in anti-S1/S2 CLIA, 97.2% in anti-RBD ELISA, and 96.1% in anti-RBD+ LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti-S1 ELISA (92.7%), anti-N ECLIA (91.7%), anti-S1/S2 CLIA (90.3%), anti-RBD+ LFI (87.9%), and anti-RBD ELISA (85.8%). Sensitivity was 84.1% in anti-N CLIA, and 66.2% in anti-N ELISA. The specificity was ≥97% in anti-N CLIA (100%), anti-S1/S2 CLIA (97.7%), and anti-RBD+ LFI (97.9%). Specificity was 95.9% in anti-RBD ELISA, 93.0% in anti-N ECLIA, 92% in anti-S1 ELISA, and 65.3% in anti-N ELISA. Diagnostic accuracy measures were consistent among subgroups. Conclusions: The diagnostic accuracy of serological tests for SARS-CoV-2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID-19 deviated substantially from the manufacturer’s specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re-infection.

The reason why most individuals with COVID-19 have relatively limited symptoms while other develop respiratory distress with life-threatening complications remains unknown. Increasing evidence suggests that COVID-19 associated adverse outcomes mainly rely on dysregulated immunity. Here, we compared transcriptomic profiles of blood cells from 103 patients with different severity levels of COVID-19 with that of 27 healthy and 22 influenza-infected individuals. Data provided a complete overview of SARS-CoV-2-induced immune signature, including a dramatic defect in IFN responses, a reduction of toxicity-related molecules in NK cells, an increased degranulation of neutrophils, a dysregulation of T cells, a dramatic increase in B cell function and immunoglobulin production, as well as an important over-expression of genes involved in metabolism and cell cycle in patients infected with SARS-CoV-2 compared to those infected with influenza viruses. These features also differed according to COVID-19 severity. Overall and specific gene expression patterns across groups can be visualized on an interactive website ( https://bix.unil.ch/covid/ ). Collectively, these transcriptomic host responses to SARS-CoV-2 infection are discussed in the context of current studies, thereby improving our understanding of COVID-19 pathogenesis and shaping the severity level of COVID-19.

Changing microorganism distributions and decreasing antibiotic susceptibility over the duration of hospitalization have been described for the colonization or infection of selected organ systems. Few data are available on bacteremias in the intensive care unit (ICU) setting. We conducted a nationwide study on bloodstream infection (BSI) using data from the Swiss Centre for Antibiotic Resistance (ANRESIS). We analyzed data on BSI detected in the ICU from hospitals that sent information on a regular basis during the entire study period (2008–2017). We described specific trends of pathogen distribution and resistance during hospitalization duration. We included 6505 ICU- BSI isolates from 35 Swiss hospitals. We observed 2587 possible skin contaminants, 3788 bacteremias and 130 fungemias. The most common microorganism was Escherichia coli (23.2%, 910), followed by Staphylococcus aureus (18.7%, 734) and enterococci (13.1%, 515). Enterococcus spp (p < 0.0001) and Candida spp (p < 0.0001) increased in proportion, whereas E. coli (p < 0.0001) and S. aureus (p < 0.0001) proportions decreased during hospitalization. Resistances against first- and second-line antibiotics increased linearly during hospitalization. Pathogen distribution and antimicrobial resistance in ICU-BSI depends on the duration of the hospitalization. The proportion of enterococcal BSI, candidemia and resistant microorganisms against first- and second-line antibiotics increased during hospitalization.

BACKGROUND SARS-CoV-2/COVID-19, which emerged in China in late 2019, rapidly spread across the world with several million victims in 213 countries. Switzerland was severely hit by the virus, with 43,000 confirmed cases as of 1 September 2020. AIM In cooperation with the Federal Office of Public Health, we set up a surveillance database in February 2020 to monitor hospitalised patients with COVID-19, in addition to their mandatory reporting system. METHODS Patients hospitalised for more than 24 hours with a positive polymerase chain-reaction test, from 20 Swiss hospitals, are included. Data were collected in a customised case report form based on World Health Organisation recommendations and adapted to local needs. Nosocomial infections were defined as infections for which the onset of symptoms was more than 5 days after the patient’s admission date. RESULTS As of 1 September 2020, 3645 patients were included. Most patients were male (2168, 59.5%), and aged between 50 and 89 years (2778, 76.2%), with a median age of 68 (interquartile range 54–79). Community infections dominated with 3249 (89.0%) reports. Comorbidities were frequently reported, with hypertension (1481, 61.7%), cardiovascular diseases (948, 39.5%) and diabetes (660, 27.5%) being the most frequent in adults; respiratory diseases and asthma (4, 21.1%), haematological and oncological diseases (3, 15.8%) were the most frequent in children. Complications occurred in 2679 (73.4%) episodes, mostly respiratory diseases (2470, 93.2% in adults; 16, 55.2% in children), and renal (681, 25.7%) and cardiac (631, 23.8%) complications for adults. The second and third most frequent complications in children affected the digestive system and the liver (7, 24.1%). A targeted treatment was given in 1299 (35.6%) episodes, mostly with hydroxychloroquine (989, 76.1%). Intensive care units stays were reported in 578 (15.8%) episodes. A total of 527 (14.5%) deaths were registered, all among adults. CONCLUSION The surveillance system has been successfully initiated and provides a robust set of data for Switzerland by including about 80% (compared with official statistics) of SARS-CoV-2/COVID-19 hospitalised patients, with similar age and comorbidity distributions. It adds detailed information on the epidemiology, risk factors and clinical course of these cases and, therefore, is a valuable addition to the existing mandatory reporting.

There is limited and conflicting information on the prevalence of contamination of haematopoietic stem and progenitor cell products (HPCPs), and their optimal management remains unclear. The authors reviewed the microbial surveillance data of HPCPs collected between January 2002 and December 2019 for autologous transplantation at the study institution to determine the prevalence of microbial contamination and the potential infectious complications among recipients. Among 3935 HPCPs, 25 (0.6%) were contaminated. Ultimately, 22 patients received contaminated grafts, with pre-emptive antimicrobial therapy initiated in six of these patients. No patients developed subsequent infectious complications. These data suggest that microbial contamination of autologous HPCPs and associated adverse outcomes are rare.

Abstract Purpose Clinical signs and symptoms related to invasive fungal disease are nonspecific and need to be followed up by appropriate diagnostic procedures. The goal of this study was to analyze CT imaging patterns in invasive fungal infections and their correlation with the immune status and clinical outcome. Materials and Methods We performed a retrospective multicenter study including 85 consecutive patients with invasive pulmonary fungal infection (2011–2014). Lung patterns on computed tomography (CT) scans were classified according to the Fleischner Society glossary. The patients were grouped according to immune status (neutropenia, steroid therapy, organ transplant recipient, and other cause) and outcome (positive outcome, progressive disease, and death). The Chi square test or Fisher exact test was used. Bonferroni correction was applied. Results The total number of patients with invasive Aspergillus and non-Aspergillus infection (IANA), Pneumocystis jirovecii pneumonia (PCP), and Cryptococcus (CRY) was 60, 22, and 3, respectively. Patients with IANA demonstrated significantly more nodules (93 % vs. 59 %, p = 0.001), significantly fewer ground glass opacities (58 % vs. 96 %, p = 0.005), and significantly fewer positive lymph nodes (5 % vs. 41 %, p < 0.001) than patients with PCP. All patients with PCP and CRY had a favorable outcome. Patients with IANA and an adverse outcome demonstrated significantly more nodules with halo sign than patients with IANA and a favorable outcome (42.5 % vs. 15.9 %, p < 0.0001). Interestingly, patients with IANA and a favorable outcome had a higher prevalence of pulmonary infarction than patients with an adverse outcome (8 % vs. 1 %, p = 0.047). Patients with neutropenia showed significantly more consolidations (66 %) than organ transplant recipients (27 %, p = 0.045). Conclusion Patients with IANA showed a higher prevalence of nodules and a lower prevalence of ground glass opacities than patients with PCP. In patients with IANA, nodules with halo sign were associated with an adverse outcome. Patients with neutropenia showed generally more consolidations, but the consolidations were not associated with an adverse outcome. Key Points:  Nodules, ground glass opacities, and consolidations are common CT findings in all invasive pulmonary fungal infections. There is no pattern that is unique for one specific pathogen, although nodules are more predominant in IANA and Cryptococcus, and ground glass opacities are more predominant in PCP patients. Immune status had an impact on CT findings in fungal pneumonia with less consolidation in patients after organ transplantation compared to patients with neutropenia. Nodules with a halo sign are associated with a worse outcome. Citation Format Obmann VC, Bickel F, Hosek N et al. Radiological CT Patterns and Distribution of Invasive Pulmonary Aspergillus, Non-Aspergillus, Cryptococcus and Pneumocystis Jirovecii Mold Infections – A Multicenter Study. Fortschr Röntgenstr 2021; 193: 1304 – 1314

BACKGROUND:The epidemiology of candidemia is evolving with raising concern about the emergence of intrinsically resistant non-albicans Candida species and acquisition of antifungal resistance. In addition to microbiological surveys, epidemiological studies including clinical data are needed to assess the impact of candidemia on morbidity and mortality. OBJECTIVES:To assess the clinical and microbiological trends of candidemia in a Swiss university hospital. PATIENTS/METHODS:This single-centre retrospective study compared the incidence of candidemia, Candida species distribution, antifungal resistance profiles, clinical characteristics and outcomes between two periods separated by one decade. RESULTS:A total of 170 candidemic episodes were included (68 from period 1, 2004-2006, and 102 from period 2, 2014-2017). Incidence of candidemia (0.85 to 0.97 episode/10,000 patient-days), species distribution (55%-57% C albicans) and antifungal susceptibilities remained unchanged. During period 2, candidemia was more frequently observed in intensive care units (ICU, 38% vs 19% in period 1, P = .01) and amongst older patients (median age 68 vs 59 years old, P < .01) with more immunosuppressive conditions (24% vs 9%, P = .01). Candidemia in period 2 was more frequently followed by septic shock (23% vs 7% in period 1, P = .01) and ICU admission (42% vs 12%, P < .01) and was associated with higher mortality (34% vs 18%, P = .03). Overall, factors associated with mortality in multivariate analyses included cirrhosis, solid malignancies and ICU stay at the time of candidemia. CONCLUSIONS:Despite stable incidence, species distribution and antifungal resistance of candidemia, an epidemiological shift of the disease towards older and more critically ill patients was observed, with higher mortality rates.

AbstractBackgroundCoronavirus disease 19 (COVID-19) has frequently been colloquially compared to the seasonal influenza, but comparisons based on empirical data are scarce.AimsTo compare in-hospital outcomes for patients admitted with community-acquired COVID-19 to patients with community-acquired influenza in Switzerland.MethodsPatients >18 years, who were admitted with PCR proven COVID-19 or influenza A/B infection to 14 participating Swiss hospitals were included in a prospective surveillance. Primary and secondary outcomes were the in-hospital mortality and intensive care unit (ICU) admission between influenza and COVID-19 patients. We used Cox regression (cause-specific models, and Fine & Gray subdistribution) to account for time-dependency and competing events with inverse probability weighting to account for confounders.ResultsIn 2020, 2843 patients with COVID-19 were included from 14 centers and in years 2018 to 2020, 1361 patients with influenza were recruited in 7 centers. Patients with COVID-19 were predominantly male (n=1722, 61% vs. 666 influenza patients, 48%, p<0.001) and were younger than influenza patients (median 67 years IQR 54-78 vs. median 74 years IQR 61-84, p<0.001). 363 patients (12.8%) died in-hospital with COVID-19 versus 61 (4.4%) patients with influenza (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 to influenza, and 2.44 (95% CI, 2.00-3.00, p<0.001) for ICU admission.ConclusionEven in a national healthcare system with sufficient human and financial resources, community-acquired COVID-19 was associated with worse outcomes compared to community-acquired influenza, as the hazards of in-hospital death and ICU admission were ∼3-fold higher.

Background: Serological immunoassays that are able to identify protective immunity against SARS-CoV-2 are urgently required to adapt quarantine measures, assess vaccination responses and evaluate donor plasma. To date, however the utility of such immunoassays remains unclear. In a mixed-design evaluation study, we compared the performance of serological immunoassays that are based on various SARS-CoV-2 proteins and assessed the neutralizing activity of COVID-19 patient sera. Methods: Patients admitted with confirmed SARS-CoV-2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in-house enzyme-linked immunosorbent assay utilizing recombinant receptor binding domain (RBD) of the SARS-CoV-2 spike protein was developed and compared to three commercially available enzyme-linked immunosorbent assays (ELISAs) targeting the nucleocapsid (N), the S1 domain of the spike protein (S1) and a lateral flow immunoassay (LFI) based on full-length spike protein. Neutralisation assays with live SARS-CoV-2 were performed to determine immunity. Findings: With a prevalence of 19.9%, we find 106 COVID-19 positive results among the 534 tested individuals. Time to IgG seroconversion occurred between day 0 and day 21 after the start of symptoms or positive RT-PCR. While the ELISAs showed sensitivities of 84.9% for RBD, 85.9% for S1 and 68.9% for Nprotein, the measured specificity amounted to 94.6% for the RBD, 97.7% for the S1 and 96.3% for the N protein. The LFI performed inferior with 71.4% sensitivity and 95.8% specificity. Out of 54 COVID-19 positive individuals 96.3% showed full neutralisation of live SARS-CoV-2 at serum dilutions ≥1:16, while none of the 6 COVID-19 negative sera revealed neutralizing activity. Interpretation: Our data suggest that ELISAs based on RBD and S1 protein of SARS-CoV-2 are adequate diagnostic predictors of protective immunity. Funding Statement: Development of SARS-CoV-2 reagents was partially supported by the NIAID Centers of Excellence for Influenza Research and Surveillance (CEIRS) contract HHSN272201400008C. MN is supported by a research grant of the Swiss National Science Foundation (#179334). AE received grant support from the Research Fund of the Swiss Lung Association, Bern and the Uniscientia foundation. Declaration of Interests: All authors declare that there is no conflict of interests. Ethics Approval Statement: The study protocol was approved by the appropriate ethics committee and the authorities of the University Hospital and conducted in accordance with the Declaration of Helsinki.

BACKGROUND:Candidemia is an opportunistic infection associated with high morbidity and mortality in patients hospitalized both inside and outside intensive care units (ICUs). Identification of patients at risk is crucial to ensure prompt antifungal therapy. We sought to assess risk factors for candidemia and death, both outside and inside ICUs.METHODS:This prospective multicenter matched case-control study involved six teaching hospitals in Switzerland and France. Cases were defined by positive blood cultures for Candida sp. Controls were matched to cases using the following criteria: age, hospitalization ward, hospitalization duration, and, when applicable, type of surgery. One to three controls were enrolled by case. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia.RESULTS:One hundred ninety-two candidemic patients and 411 matched controls were included. Forty-four percent of included patients were hospitalized in ICUs, and 56% were hospitalized outside ICUs. Independent risk factors for candidemia in the ICU population included total parenteral nutrition, acute kidney injury, heart disease, prior septic shock, and exposure to aminoglycoside antibiotics. Independent risk factors for candidemia in the non-ICU population included central venous catheter, total parenteral nutrition, and exposure to glycopeptides and nitroimidazoles. The accuracy of the scores based on these risk factors is better in the ICU than in the non-ICU population. Independent risk factors for death in candidemic patients included septic shock, acute kidney injury, and the number of antibiotics to which patients were exposed before candidemia.DISCUSSION:While this study shows a role for known and novel risk factors for candidemia, it specifically highlights important differences in their distribution according to the hospital setting (ICU versus non-ICU).CONCLUSION:This study provides novel risk scores for candidemia accounting for the hospital setting and recent progress in patients' management strategies and fungal epidemiology.

BACKGROUND:Serological immunoassays that can identify protective immunity against SARS-CoV-2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed-design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS-CoV-2 proteins and assessed the neutralizing activity of antibodies in patient sera.METHODS:Consecutive patients admitted with confirmed SARS-CoV-2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in-house enzyme-linked immunosorbent assay utilizing recombinant receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was developed and compared to three commercially available enzyme-linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1), and a lateral flow immunoassay (LFI) based on full-length spike protein. Neutralization assays with live SARS-CoV-2 were performed.RESULTS:One thousand four hundred and seventy-seven individuals were included comprising 112 SARS-CoV-2 positives (defined as a positive real-time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS-CoV-2 positive individuals, 96.3% showed full neutralization of live SARS-CoV-2 at serum dilutions ≥ 1:16, while none of the 6 SARS-CoV-2-negative sera revealed neutralizing activity.CONCLUSIONS:ELISAs targeting RBD and S1 protein of SARS-CoV-2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS-CoV-2.

Background: Significant hope and expectation has been placed on serological immunoassays to test for previous COVID-19 infection, to determine immunity against SARS-CoV2 and to assess the response to vaccination. To date, however the diagnostic utility of such immunoassays remains unclear. In a mixed-design evaluation study, we compared the performance of four serological immunoassays targeting various proteins of the SARS-CoV-2 virus: (a) the receptor binding domain (RBD; ELISA, IgG, IgM), (b) the nucleocapsid (N; ELISA, IgG, IgM), (c) the S1 domain of the spike protein (S1; ELISA, IgG) and (d) the spike protein (S; lateral flow immunoassay, IgG, IgM). Methods: Patients admitted between March and April 2020 to Inselspital University Hospital with confirmed COVID-19 infection were prospectively followed alongside medical staff in a cross-sectional design. Biobank samples from the previous winter period 2018/2019 were additionally tested. An in-house enzyme-linked immunosorbent assay utilising recombinant RBD from the SARS-CoV-2 spike protein was developed and compared to three commercially available serological assays. The primary reference standard was defined as a positive RT-PCR (nasopharyngeal swab). Findings: One-hundred and fifty-nine individuals were included, comprising 25 patients (with 187 data points), 102 medical staff, and 32 biobank samples. Prevalence was 30.8% (n=49). Time to IgG seroconversion occurred between day 2 and day 21 after the start of symptoms and between day 0 and 21 after a positive RT-PCR. Regarding IgG, the area under the receiver operating characteristic curve was 0.97 for RBD (95% confidence interval 0.94 to 1.00), 0.97 for S1 (0.95, 1.00), and 0.94 for N ELISA (0.88, 0.99). Corresponding sensitivity was 79.6% (RBD; 66.4, 88.5), 87.8% (S1; 75.8, 94.3), 67.4% (95% CI 52.5, 80.1), and 71.4% (S LFI; 58.7, 82.1). Specificity was 98.2% (RBD; 93.6, 99.7), 99.1 (S1; 95.0, 100.0), 95.5% (N ELISA 89.7, 98.5), and 95.8% (S LFI). Interpretation: Diagnostic performance of serological immunoassays targeting RBD, S1, N and S appears be adequate for identification of patients with previous COVID-19 infection. This observation should be confirmed by full diagnostic accuracy studies to also derive the precise time-point of seroconversion and presence and duration of immunity. Funding Statement: No specific funding was obtained for the purpose of this study.Declaration of Interests: All authors declare that there is no conflict of interests.Ethics Approval Statement: The study protocol was approved by the appropriate ethics committee and the authorities of the University Hospital and conducted in accordance with the Declaration of Helsinki.