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Funder: Kennedy Trust Rheumatology Research Prize Studentship, Funder: DFG Cluster of Excellence ���Precision Medicine in Chronic In-flammation��� (PMI; ID: EXC2167), Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: ���Ideas��� Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): 715772, Funder: NWO-VIDI grant 016.178.056, the Netherlands Heart Foundation CVON grant 2018-27, and NWO Gravitation grant ExposomeNL, Funder: Li Ka Shing Foundation (Li Ka Shing Foundation Limited); doi: https://doi.org/10.13039/100007421, Irritable bowel syndrome (IBS) results from disordered brain���gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain���gut interactions underlying IBS.

Background During the coronavirus disease 2019 (COVID-19) pandemic, many countries experienced infection in health care workers (HCW) due to overburdened health care systems. Whether infected HCW acquire protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Methods In a Norwegian prospective cohort study, we enrolled 607 HCW before and after the first COVID-19 wave. Exposure history, COVID-19–like symptoms, and serum samples were collected. SARS-CoV-2–specific antibodies were characterized by spike-protein IgG/IgM/IgA enzyme-linked immunosorbent and live-virus neutralization assays. Results Spike-specific IgG/IgM/IgA antibodies increased after the first wave in HCW with, but not in HCW without, COVID-19 patient exposure. Thirty-two HCW (5.3%) had spike-specific antibodies (11 seroconverted with ≥4-fold increase, 21 were seropositive at baseline). Neutralizing antibodies were found in 11 HCW that seroconverted, of whom 4 (36.4%) were asymptomatic. Ninety-seven HCW were tested by reverse transcriptase polymerase chain reaction (RT-PCR) during follow-up; 8 were positive (7 seroconverted, 1 had undetectable antibodies). Conclusions We found increases in SARS-CoV-2 neutralizing antibodies in infected HCW, especially after COVID-19 patient exposure. Our data show a low number of SARS-CoV-2–seropositive HCW in a low-prevalence setting; however, the proportion of seropositivity was higher than RT-PCR positivity, highlighting the importance of antibody testing., Low numbers of SARS-CoV-2–seropositive HCW were found in Norway and 1.8% of HCW seroconverted with neutralizing antibodies. Seropositivity was higher than RT-PCR positivity in HCW with 36% asymptomatic, representing a risk of infection within the health care setting.

Introduction: Carbapenem-resistant Enterobacteriaceae are emerging as a global public-health threat and cause substantial challenges in clinical practice. \ud Gap Statement: There is a need for increased and continued genomic surveillance of antimicrobial resistance genes globally in order to detect outbreaks and dissemination of clinically important resistance genes and their associated mobile genetic elements in human pathogens.\ud Aim: To describe the resistance mechanisms of carbapenem-resistant Escherichia coli. \ud Methods: Rectal swabs from neonates and newly diagnosed human immunodeficiency virus (HIV) infected adults were collected between April 2017 and May 2018 and screened for fecal carriage of carbapenamases and OXA-48 producing Enterobacteriaceae. Bacterial isolates were identified using matrix assisted laser desorption ionization time of flight mass spectrometry. Antimicrobial susceptibility testing was performed by E-test. Whole genomes of carbapenem resistant E. coli were investigated using a hybrid assembly of Illumina and Oxford Nanopore Technologies sequencing reads. \ud Results: Three carbapenem-resistant E. coli were detected, two from neonates and one from an HIV infected adult. All three isolates carried blaNDM-5. Two E. coli from neonates belong to ST167 and blaNDM-5 co-existed with blaCTX-M-15 and blaOXA-01, and all were carried on IncFIA type plasmids. The E. coli from the HIV infected adult belongs to ST2083, and carried blaNDM-5 on an IncX3 type plasmid and blaCMY-42 on an IncI type plasmid. All blaNDM-5 carrying plasmids contained conjugation related genes. In addition, E. coli from the HIV infected adult carried three more plasmid types; IncFIA, IncFIB and Col(BS512). One E. coli from a neonate also carried one extra plasmid Col(BS512). All three E. coli harbored resistance genes to fluoroquinolone, aminoglycosides, sulfamethoxazole, trimethoprim, macrolides and tetracycline, carried on the IncFIA type plasmid. Furthermore, E. coli from the neonates carried a chloramphenicol resistance gene (catB3) also on the IncFIA plasmid. All three isolates were susceptible to colistin.\ud Conclusion: This is the first report from Tanzania detecting blaNDM-5 producing E. coli. The carbapenemase gene was carried on an IncFIA and IncX3 type plasmids. Our findings highlight the urgent need for a robust antimicrobial resistance (AMR) surveillance system to monitor and rapidly report on the incidence and spread of emerging resistant bacteria in Tanzania.

Background The burden and duration of persistent symptoms after nonsevere coronavirus disease 2019 (COVID-19) remains uncertain. This study aimed to assess postinfection symptom trajectories in home-isolated COVID-19 cases compared with age- and time- matched seronegative controls, and investigate immunological correlates of long COVID. Methods A prospective case-control study included home-isolated COVID-19 cases between February 28 and April 4, 2020, and followed for 12 (n = 233) to 18 (n = 149) months, and 189 age-matched severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive controls. We collected clinical data at baseline, 6, 12, and 18 months postinfection, and blood samples at 2, 4, 6, and 12 months for analysis of SARS-CoV-2-specific humoral and cellular responses. Results Overall, 46% (108/233) had persisting symptoms 12 months after COVID-19. Compared with controls, adult cases had a high risk of fatigue (27% excess risk, sex, and comorbidity adjusted odds ratio [aOR] 5.86; 95% confidence interval [CI], 3.27–10.5), memory problems (21% excess risk; aOR 7.42; CI, 3.51–15.67), concentration problems (20% excess risk; aOR 8.88; 95% CI, 3.88–20.35), and dyspnea (10% excess risk; aOR 2.66; 95% CI, 1.22–5.79). The prevalence of memory problems increased overall from 6 to 18 months (excess risk 11.5%; 95% CI, 1.5–21.5; P = .024) and among women (excess risk 18.7%; 95% CI, 4.4–32.9; P = .010). Longitudinal spike immunoglobulin G was significantly associated with dyspnea at 12 months. The spike-specific clonal CD4+ T-cell receptor β depth was significantly associated with both dyspnea and number of symptoms at 12 months. Conclusions This study documents a high burden of persisting symptoms after mild COVID-19 and suggests that infection induced SARS-CoV-2-specific immune responses may influence long-term symptoms. publishedVersion

Background Immune dysregulation is a major factor in the development of severe coronavirus disease 2019 (COVID-19). The homeostatic chemokines CCL19 and CCL21 have been implicated as mediators of tissue inflammation, but data on their regulation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is limited. We thus investigated the levels of these chemokines in COVID-19 patients. Methods Serial blood samples were obtained from patients hospitalized with COVID-19 (n = 414). Circulating CCL19 and CCL21 levels during hospitalization and 3-month follow-up were analyzed. In vitro assays and analysis of RNAseq data from public repositories were performed to further explore possible regulatory mechanisms. Results A consistent increase in circulating levels of CCL19 and CCL21 was observed, with high levels correlating with disease severity measures, including respiratory failure, need for intensive care, and 60-day all-cause mortality. High levels of CCL21 at admission were associated with persisting impairment of pulmonary function at the 3-month follow-up. Conclusions Our findings highlight CCL19 and CCL21 as markers of immune dysregulation in COVID-19. This may reflect aberrant regulation triggered by tissue inflammation, as observed in other chronic inflammatory and autoimmune conditions. Determination of the source and regulation of these chemokines and their effects on lung tissue is warranted to further clarify their role in COVID-19. Clinical Trials Registration NCT04321616 and NCT04381819.