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Aims: The objective was to compare anxiety, depression, and quality of life (QoL) in individuals living with type 1 (T1D) and type 2 (T2D) diabetes with matched controls during the second wave of the COVID-19 pandemic. Methods: Via randomization, individuals living with diabetes T1D (n = 203) and T2D (n = 413), were identified during February-July 2021 through health-care registers. Population controls (n = 282) were matched for age, gender, and residential area. Questionnaires included self-assessment of anxiety, depression, QoL, and demographics in relation to SARS-CoV-2 exposure. Blood was collected through home-capillary sampling, and SARS-CoV-2 Nucleocapsid (NCP) and Spike antibodies (SC2_S1) were determined by multiplex Antibody Detection by Agglutination-PCR (ADAP) assays. Results: Younger age and health issues were related to anxiety, depression, and QoL, with no differences between the study groups. Female gender was associated with anxiety, while obesity was associated with lower QoL. The SARS-CoV-2 NCP seroprevalence was higher in T1D (8.9 %) compared to T2D (3.9 %) and controls (4.0 %), while the SARS-CoV-2 SC2_S1 seroprevalence was higher for controls (25.5 %) compared to T1D (16.8 %) and T2D (14.0 %). Conclusions: A higher SARS-CoV-2 infection rate in T1D may be explained by younger age and higher employment rate, and the associated increased risk for viral exposure., This work was supported by NIH SBIR 2R44DK110005-02, Strategic Research Area Exodiab Dnr 2009-1039, and the Swedish Foundation for Strategic Research Dnr IRC15-0067.

I detta dokument beskrivs rekommenderade metoder för blododling inkluderat fungemi(svampinfektion i blod) samt metodik för diagnostik av endokardit och misstanke om infektion relaterad till kärlkatetrar. Rekommendationerna är baserade på internationella riktlinjer och relevant vetenskaplig litteratur. Där det finns icke tillräcklig vetenskapligt stöd har arbetsgruppen antingen avstått från en rekommendation eller givit en rekommendation baserad på de ingående medlemmarnas erfarenhet och kunnande.

Objective: Investigate the performance of real-time 16S PCR and third-generation 16S sequencing in the diagnosis of external ventricular drain related infections (EVDRI). Methods: Subjects with suspected EVDRI were prospectively included at Uppsala University Hospital. Subjects were included into three groups: subjects with negative CSF culture with and without antibiotic treatment and subjects with positive CSF culture, respectively. CSF was analysed with real-time 16S PCR and third-generation 16S sequencing. Real-time 16S PCR positivity/negativity and number of 16S sequence reads were compared between groups. For culture positive subjects, species identification in third-generation sequencing and routine culture was compared. Results: 84 subjects were included. There were 18, 44 and 22 subjects in the three groups. Real-time PCR was positive in 17 of 22 subjects in the culture positive group and negative in 61 of the 62 subjects in the two culture negative groups. The sensitivity and specificity for real-time 16S PCR compared to culture was estimated to 77% and 98%, respectively. Species identification in 16S sequencing and culture was concordant in 20 of 22 subjects. The number of 16S sequence reads were significantly higher in the culture positive group than in both culture negative groups (p < 0.001). There was no significant difference in number of 16S sequences between the two culture negative groups. Conclusions: Real-time 16S PCR predict culture results with sufficient reliability. Third-generation 16S sequencing could enhance sensitivity and species identification in diagnostics of EVD-related infections. False negative culture results appear to be uncommon in patients with suspected EVDRI., W received financing for his work with this study by grants from the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (grant number 2019-ST0044).GW received funding from the Regional Research Council Mid Sweden (Sjukvårdsregionalaforskningsrådet Mellansverige) for his work with this study (grant number RFR-560661 and RFR-981134).JM received funding from the family Olinder-Nielsen’s foundation (Stiftelsen Familjen Olinder-Nielsens fond f€or infektionsmedicinsk-forskning) for his work with this study.

Monoclonal antibodies (mAbs) are an important treatment option for COVID-19 caused by SARS-CoV-2, especially in immunosuppressed patients. However, this treatment option can become ineffective due to mutations in the SARS-CoV-2 genome, mainly in the receptor binding domain (RBD) of the spike (S) protein. In the present study, 7950 SARS-CoV-2 positive samples from the Uppsala and Örebro regions of central Sweden, collected between March 2022 and May 2023, were whole-genome sequenced using amplicon-based sequencing methods on Oxford Nanopore GridION, Illumina MiSeq, Illumina HiSeq, or MGI DNBSEQ-G400 instruments. Pango lineages were determined and all single nucleotide polymorphism (SNP) mutations that occurred in these samples were identified. We found that the dominant sublineages changed over time, and mutations conferring resistance to currently available mAbs became common. Notable ones are R346T and K444T mutations in the RBD that confer significant resistance against tixagevimab and cilgavimab mAbs. Further, mutations conferring a high-fold resistance to bebtelovimab, such as the K444T and V445P mutations, were also observed in the samples. This study highlights that resistance mutations have over time rendered currently available mAbs ineffective against SARS-CoV-2 in most patients. Therefore, there is a need for continued surveillance of resistance mutations and the development of new mAbs that target more conserved regions of the RBD.

Myocardial infarction (MI) with obstructive coronary artery disease (MI-CAD) and MI in the absence of obstructive coronary artery disease (MINOCA) affect different populations and may have separate pathophysiological mechanisms, with greater inflammatory activity in MINOCA compared to MI-CAD. Helicobacter pylori (Hp) can cause systemic inflammation and has been associated with cardiovascular disease (CVD). We aimed to investigate whether Hp infection is associated with concentrations of protein biomarkers of inflammation and CVD. In a case-control study, patients with MINOCA (n = 99) in Sweden were included, complemented by matched subjects with MI-CAD (n = 99) and controls (n = 100). Protein biomarkers were measured with a proximity extension assay in plasma samples collected 3 months after MI. The seroprevalence of Hp and cytotoxin-associated gene A (CagA) was determined using ELISA. The associations between protein levels and Hp status were studied with linear regression. The prevalence of Hp was 20.2%, 19.2%, and 16.0% for MINOCA, MI-CAD, and controls, respectively (p = 0.73). Seven proteins were associated with Hp in an adjusted model: tissue plasminogen activator (tPA), interleukin-6 (IL-6), myeloperoxidase (MPO), TNF-related activation-induced cytokine (TRANCE), pappalysin-1 (PAPPA), soluble urokinase plasminogen activator receptor (suPAR), and P-selectin glycoprotein ligand 1 (PSGL-1). Hp infection was present in one in five patients with MI, irrespective of the presence of obstructive CAD. Inflammatory proteins were elevated in Hp-positive subjects, thus not ruling out that Hp may promote an inflammatory response and potentially contribute to the development of CVD.

Background Rapidly instituted antimicrobial therapy is important in severe infections, and reduced time to the antimicrobial susceptibility testing (AST) report is thus of importance. Disc diffusion (DD) is a cheap, rapidly adaptable, flexible and comprehensive method for phenotypic AST. Previous studies have shown that early reading of inhibition zones for non-fastidious species is possible.Objectives To evaluate zone reading after short incubation of DD in Haemophilus influenzae (n = 73) and Streptococcus pneumoniae (n = 112).Methods The readability was evaluated and susceptibility interpretation (SIR) was performed, using the EUCAST 18 & PLUSMN; 2 h incubation breakpoint table (version 12.0), after 6 and 8 h of incubation. Categorical agreement (CA) and error rates were calculated using standard DD and broth microdilution as reference.Results The proportion of readable zones in H. influenzae was 19% (6 h) and 89% (8 h). The CA was 98% after 8 h. The corresponding readability in S. pneumoniae was 63%/98% and CA was 95%/97% after 6 and 8 h, respectively. Early reading of the screening discs (benzylpenicillin 1 unit in H. influenzae and oxacillin 1 & mu;g in S. pneumoniae) correctly identified 18/22 of the H. influenzae isolates and all the readable S. pneumoniae isolates with reduced & beta;-lactam susceptibility. For non-& beta;-lactam agents, very major errors were most common for quinolones in S. pneumoniae. Introduction of areas of technical uncertainty (ATUs) reduced the error rate to & LE;1.1%.Conclusions We conclude that shortened incubation is feasible for H. influenzae and S. pneumoniae. To reduce the risk of false categorization a buffer zone (i.e. ATU) near the breakpoints must be used., Funding Agencies|Part of the results from this study have been presented at the Thirtieth NSCMID, Aarhus; Denmark 2013 (Abstract and poster: Susceptibility testing of Haemophilus influenzae with DD interpreted after 8 h of incubation using EUCAST methodology and Twenty-Fo

Background: Echocardiography is routinely used to evaluate patients with known or suspected myocardial infarction (MI). Cardiovascular magnetic resonance imaging (CMR) provides the ability to quantify myocardial infarction size (IS), and to establish an underlying diagnosis in MI cases with nonobstructive coronary arteries (MINOCA). While echocardiography provides valuable information regarding cardiac function, the relationships between how pathology is manifested on CMR, and the information gleaned from echocardiography are not fully explored. The focus of this thesis was 1) to assess diastolic function and mechanics in MI, and 2) to assess the ability of echocardiography to identify patients needing further evaluation by CMR in MINOCA. Methods and results: In Study I, a software application was developed for the purpose of facilitating the analysis of diastolic function using the parameterized diastolic filling (PDF) method. Inter- and intraobserver variability was studied using patients from Study III and Study IV. The software was successfully developed and made publicly available at www.echoewaves.org, and inter- and intraobserver reliability was good or excellent for most PDF measures (intraclass correlation coefficient 0.80-0.99). In Study II, an available clinical database of patients undergoing resting and stress echocardiography was used to identify a cohort of patients with normal echocardiographic findings. PDF analysis was performed in 138 patients for the establishment of normal reference values for the method, and presented as sex-specific 95% reference intervals. In Study III, a pre-planned substudy of the RECOND trial, the association between myocardial infarction size (IS) and parameters of diastolic function, and whether the peri-infarction edema of the myocardium at risk (MaR) influenced these relationships was investigated. Weak associations were found between IS and deceleration time (R² = 0.24, p < 0.001), left atrial volume index (R² = 0.13

The severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) pandemic has led to extensive virological monitoring by whole genome sequencing (WGS). Investigating the advantages and limitations of different protocols is key when conducting population-level WGS. SARS-CoV-2 positive samples with Ct values of 14-30 were run using three different protocols: the Twist Bioscience SARS‑CoV‑2 protocol with bait hybridization enrichment sequenced with Illumina, and two tiled amplicon enrichment protocols, ARTIC V3 and Midnight, sequenced with Illumina and Oxford Nanopore Technologies, respectively. Twist resulted in better coverage uniformity and coverage of the entire genome, but has several drawbacks: high human contamination, laborious workflow, high cost, and variation between batches. The ARTIC and Midnight protocol produced an even coverage across samples, and almost all reads were mapped to the SARS-CoV-2 reference. ARTIC and Midnight represent robust, cost-effective, and highly scalable methods that are appropriate in a clinical environment. Lineage designations were uniform across methods, representing the dominant lineages in Sweden during the period of collection. This study provides insights into methodological differences in SARS‑CoV‑2 sequencing and guidance in selecting suitable methods for various purposes.

The rapid administration of optimal antimicrobial treatment is paramount for the treatment of bloodstream infections (BSIs), and rapid antimicrobial susceptibility testing (AST) results are essential. Q-linea has developed the ASTar system, a rapid phenotypic AST device. Here, we report the performance of the ASTar BC G- (Gram-negative) kit when assessed according to the ISO 20776-2:2007 standard for performance evaluation of in vitro diagnostic AST devices. The evaluated ASTar BC G- kit uses a broad panel of 23 antimicrobials for the treatment of BSIs caused by Gram-negative fastidious and nonfastidious bacteria across a range of 6 to 14 2-fold dilutions, including cefoxitin as a screening agent for AmpC-producing Enterobacterales. The ASTar system processes blood culture samples to generate data on MICs and susceptible, intermediate, or resistant (SIR) category. The automated protocol includes concentration determination and concentration adjustment to enable a controlled inoculum, followed by broth microdilution (BMD) and microscopy performed continuously to generate MIC values within approximately 6 h once the test is run on the ASTar system. The performance of the ASTar system was assessed against the ISO 20776-2:2007 standard BMD reference method. Testing was performed across three sites, with results from 412 contrived blood cultures and 74 fresh clinical blood cultures. The ASTar system was also tested for reproducibility, with triplicate testing of 11 strains. The accuracy study comprised 8,650 data points of bacterium-antimicrobial tests. The ASTar system demonstrated an overall essential agreement (EA) of 95.8% (8,283/8,650) and a categorical agreement (CA) of 97.6% (8,433/8,639) compared to the reference BMD method. The overall rate of major discrepancies (MDs) was 0.9% (62/6,845), and that of very major discrepancies (VMDs) was 2.4% (30/1,239). This study shows that the ASTar system delivers reproducible results with overall EA and CA of >95%.

The bacterium Neisseria meningitidis causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine N. meningitidis carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period. Meningococcal isolates were characterised using whole-genome sequencing. The carriage rate among the students was 9.1% (319/3488; 95% CI 8.2-10.1). Factors associated with higher carriage rate were age ≤22 years, previous tonsillectomy, cigarette smoking, drinking alcohol and attending parties, pubs and clubs. Female gender and sharing a household with children aged 0-9 years were associated with lower carriage. The most frequent genogroups were capsule null locus (cnl), group B and group Y and the most commonly identified clonal complexes (cc) were cc198 and cc23. Persistent carriage with the same meningococcal strain for 12 months was observed in two students. Follow-up times exceeding 12 months are recommended for future studies investigating long-term carriage of N. meningitidis.

The COVID-19 pandemic has challenged the societies and health care systems globally, and resulted in many social and physical distancing restrictions to limit the spread of SARS-CoV-2. These restrictions have also likely affected the frequency of intimate contacts and the spread of sexually transmitted infections (STIs). Compared to most other countries, Sweden especially in Spring-Autumn 2020 pursued mainly milder voluntary, i.e. not mandatory enforced by laws, recommended restrictions and the impacts of these on society and spread of STIs remain largely unknown. We describe the potential impact of the COVID-19 pandemic on the national and regional incidence, epidemiology and diagnostic testing of chlamydia and gonorrhoea in Sweden in 2020. Compared to 2019, we found a significant decrease in incidence of chlamydia (-4.5%) and gonorrhoea (-17.5%), and in diagnostic testing (-10.5% for chlamydia, -9.4% for gonorrhoea) in 2020. However, the decrease in chlamydia incidence, which has mainly been decreasing last 10 years, was not significant when compared with the average incidence in 2017-2019. The largest decrease in national incidence of both infections was observed among young and heterosexual patients, however some Swedish regions showed an increased incidence, particularly of chlamydia. Increased "internet-based self-sampling" testing approach partly compensated for a decreased attendance at STI clinics. Studies, including sexual behavior, prevention, reasons for attending STI health care, STIs in different anatomical sites, and management of STIs, are required to elucidate the impact of COVID-19-associated social and physical distancing restrictions on sexual activity and the incidence and epidemiology of chlamydia and gonorrhoea in Sweden., Funding agencies:Örebro County Council Research CommitteeFoundation for Medical Research at Örebro University Hospital, Örebro, Sweden

Whole genome sequencing (WGS) of methicillin-resistant Staphylococcus aureus (MRSA) provides high-resolution typing, facilitating surveillance and outbreak investigations. The aim of this study was to evaluate the genomic variation rate in MRSA, by comparing commonly used core genome multilocus sequencing (cgMLST) against single nucleotide polymorphism (SNP) analyses. WGS was performed on 95 MRSA isolates, collected from 20 carriers during years 2003-2019. To assess variation and methodological-related differences, two different cgMLST schemes were obtained using Ridom SeqSphere+ and the cloud-based 1928 platform. In addition, two SNP methods, 1928 platform and Northern Arizona SNP Pipeline (NASP) were used. The cgMLST using Ridom SeqSphere+ and 1928 showed a median of 5.0 and 2.0 allele variants/year, respectively. In the SNP analysis, performed with two reference genomes COL and Newman, 1928 showed a median of 13 and 24 SNPs (including presumed recombination) and 3.8 respectively 4.0 SNPs (without recombination) per individual/year. Accordantly, NASP showed a median of 5.5 and 5.8 SNPs per individual/year. In conclusion, an estimated genomic variation rate of 2.0-5.8 genetic events per year (without recombination), is suggested as a general guideline to be used at clinical laboratories for surveillance and outbreak investigations independently of analysis approach used., Funding agencies:Swedish governmentReseach committee at Örebro University hospital

BACKGROUND: COVID-19 has a most variable prognosis. Several risk factors for an unfavourable outcome have been identified including extensive lung involvement on chest CT and high viral load estimated by RT-PCR cycle threshold (Ct) values. We investigated Ct value for outcome prediction, relation between Ct value and extent of lung involvement on chest CT and the combination of Ct value and chest CT lung involvement to predict outcome in COVID-19. METHODS: Population-based retrospective study on all patients (n = 286) hospitalised for COVID-19 in Örebro Region, Sweden, between 1 March and 31 August 2020. Nasopharyngeal samples and chest CT at hospital admission were evaluated in relation to outcome of COVID-19. RESULTS: Both Ct value and chest CT lung involvement were independently associated with risk for ICU admission or death. Lung involvement was superior as a single parameter, but addition of Ct value increased the prediction performance. Ct value was especially useful to identify patients with high risk for severe disease despite limited lung involvement. CONCLUSIONS: The addition of RT-PCR Ct value to the assessment of lung involvement on chest CT adds valuable prognostic information in COVID-19. We believe that this information can be used to support clinical decision-making when managing COVID-19 patients.