Background The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10•6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. Methods In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1-RR. Findings During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2•20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2•11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0•65% [95% CI 0•51-0•82]) tested positive again during the second surge compared with 16 819 (3•27% [3•22-3•32]) of 514 271 who tested negative during the first surge (adjusted RR 0•195 [95% CI 0•155-0•246]). Protection against repeat infection was 80•5% (95% CI 75•4-84•5). The alternative cohort analysis gave similar estimates (adjusted RR 0•212 [0•179-0•251], estimated protection 78•8% [74•9-82•1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47•1% (95% CI 24•7-62•8). We found no difference in estimated protection against repeat infection by sex (male 78•4% [72•1-83•2] vs female 79•1% [73•9-83•3]) or evidence of waning protection over time (3-6 months of follow-up 79•3% [74•4-83•3] vs ≥7 months of follow-up 77•7% [70•9-82•9]). Interpretation Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on.
Our investigations identified sprouts as the most likely outbreak vehicle, underlining the need to take into account food items that may be overlooked during subjects' recall of consumption.
Shiga toxin 2 (Stx2) from Shiga toxin-producing Escherichia coli (STEC) was subtyped by a method involving partial sequencing of the stxAB 2 operon. Of 255 strains from the Danish STEC cohort, all 20 cases of hemolytic-uremic syndrome were associated with subtype Stx2 (11 cases), subtype Stx2c (1 case), or the two combined (8 cases).
We present an analysis of strain and patient factors associated with the development of bloody diarrhea and hemolytic uremic syndrome (HUS) among Shiga toxin-producing Escherichia coli (STEC) patients registered in Denmark in a 6-year period. Of 343 STEC patients, bloody diarrhea developed in 36.4% and HUS in 6.1%. In a multivariate logistic regression model, risk factors for bloody diarrhea were the eae and stx2 genes, O groups O157 and O103, and increasing age. Risk factors for HUS were presence of the stx2 (odds ratio [OR] 18.9) and eae (OR undefined) genes, being a child, and having bloody diarrhea. O group O157, although associated with HUS in a univariate analysis (OR 4.0), was not associated in the multivariate analysis (OR 1.1). This finding indicates that, rather than O group, the combined presence of the eae and stx2 genes is an important predictor of HUS.
Elongator is a histone acetyltransferase complex that associates with the elongating form of RNA polymerase II. We purified Elongator to virtual homogeneity via a rapid three-step procedure based largely on affinity chromatography. The purified factor, holo-Elongator, is a labile six-subunit factor composed of two discrete subcomplexes: one comprised of the previously identified Elp1, Elp2, and Elp3 proteins and another comprised of three novel polypeptides, termed Elp4, Elp5, and Elp6. Disruption of the yeast genes encoding the new Elongator proteins confers phenotypes indistinguishable from those previously described for the other elp mutants, and concomitant disruption of genes encoding proteins in either subcomplex does not confer new phenotypes. Taken together, our results indicate that holo-Elongator is a functional entity in vitro as well as in vivo. Metazoan homologues of Elp1 and Elp3 have previously been reported. We cloned the human homologue of yeast ELP4 and show that this gene is ubiquitously expressed in human tissues.The form of RNA polymerase II (RNAPII) 1 responsible for transcript elongation is fundamentally different from the form that enters a promoter to form a preinitiation complex (1, 2). During initiation, RNAPII is hypo-phosphorylated and associated with the functionally conserved Mediator complex, a multisubunit factor required for regulation of transcription (3, 4). The association of RNAPII with Mediator and the general transcription factors is severed during promoter clearance, triggered by TFIIH-mediated hyperphosphorylation of the carboxyl-terminal repeat domain (CTD) of the largest RNAPII subunit (5-7). During elongation, hyperphosphorylated yeast RNAPII is associated with the Elongator complex. Elongator binds directly to RNAPII, at least partly via the CTD, and the interaction is stabilized by CTD hyperphosphorylation (8).
Discussions from the expert group supported joint working across countries to better monitor the epidemiology and possible changes in risk of virus acquisition at a European level. There was agreement to share surveillance strategies and algorithms but also importantly the collation of HEV data from human and animal populations. These data collected at a European level would serve the 'One Health' approach to better informing on human exposure to HEV.
Extraintestinal pathogenic Escherichia coli (ExPEC) is the main cause of urinary tract infections and septicemia. Significant attention has been given to the ExPEC sequence type ST131, which has been categorized as a “high-risk” clone. High-risk clones are globally distributed clones associated with various antimicrobial resistance determinants, ease of transmission, persistence in hosts, and effective transmission between hosts. The high-risk clones have enhanced pathogenicity and cause severe and/or recurrent infections. We show that clones of the E. coli ST410 lineage persist and/or cause recurrent infections in humans, including bloodstream infections. We found evidence of ST410 being a highly resistant globally distributed lineage, capable of patient-to-patient transmission causing hospital outbreaks. Our analysis suggests that the ST410 lineage should be classified with the potential to cause new high-risk clones. Thus, with the clonal expansion over the past decades and increased antimicrobial resistance to last-resort treatment options, ST410 needs to be monitored prospectively.
The incidence of multidrug-resistant (MDR) Salmonella Typhimurium infections in humans, and in particular MDR definitive phage type 104 (DT104), has increased substantially in many countries in the last 2 decades, often associated with increased illness. To examine the magnitude of this problem, a survey was conducted among countries with available antimicrobial resistance or phage typing surveillance data. A total of 29, primarily industrialized, countries participated in the survey, which covered the years 1992–2001. Overall, the incidence of MDR S. Typhimurium and DT104 increased continuously during this period, although the problem affected primarily Europe and North America. The increase appeared to have peaked in the United Kingdom but not in other countries. Also, the incidence of quinolone-resistant S. Typhimurium was increasing. This survey implies that MDR S. Typhimurium constitutes an increasing public health problem in large parts of the world and emphasizes the importance of surveillance and control programs.
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