Novel recombinant SARS-CoV-2 lineage detected through genomic surveillance in Wales, UK

Recombination, the process whereby a segment of genetic material from one genome is inserted into another, producing a new chimeric genome, is an important evolutionary mechanism frequently observed in coronaviruses. The risks posed by recombination include the shuffling of advantageous mutations that may increase transmissibility, severity or vaccine escape. We present a genomic and epidemiological description of a new recombinant lineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), XR, first identified in Wales. The Pathogen Genomics Unit (Public Health Wales, UK) sequences positive SARS-CoV-2 PCR tests using the ARTIC SARS-CoV-2 sequencing protocol. Recombinants were detected using an in-house pipeline and the epidemiological data analysed in R. Nosocomial cases were defined as those with samples taken after >7 days in hospital. Between February and March 2022, we identified 78 samples with highly similar genomes, comprising a BA.1-like 5' end, a BA.2-like 3' end and a BA.2-like spike protein. This signature is consistent with recombination and was defined as XR by Pangolin (PANGO v1.8). A total of 50 % of cases had a sample collected whilst in hospital and the first three cases were immunocompromised patients. The patient median age was 58 years (range: 4–95 years) and most of the patients were fully vaccinated against SARS-CoV-2 (74 % third dose/booster). Three patients died within 28 days of their sample collection date, one of whom had COVID-19 listed amongst ICD10 (International Classification of Diseases 10) coded causes of death. Our integrated system enabled real-time monitoring of recombinant SARS-CoV-2 for early detection, in order to rapidly risk assess and respond. This work highlights the importance of setting-based surveillance of recombinant SARS-CoV-2, as well as the need to monitor immunocompromised populations through repeat testing and sequencing

Epidemiological analysis of the first 1000 cases of SARS-CoV-2 lineage BA.1 (B.1.1.529, Omicron) compared with co-circulating Delta in Wales, UK

Background The Omicron (lineage B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wales, UK, on 3 December 2021. The aim of the study was to describe the first 1000 cases of the Omicron variant by demographic, vaccination status, travel and severe outcome status and compare this to contemporaneous cases of the Delta variant. Methods Testing, typing and contact tracing data were collected by Public Health Wales and analysis undertaken by the Communicable Disease Surveillance Centre (CDSC). Risk ratios for demographic factors and symptoms were calculated comparing Omicron cases to Delta cases identified over the same time period. Results By 14 December 2021, 1000 cases of the Omicron variant had been identified in Wales. Of the first 1000, just 3% of cases had a prior history of travel revealing rapid community transmission. A higher proportion of Omicron cases were identified in individuals aged 20–39, and most cases were double vaccinated (65.9%) or boosted (15.7%). Age-adjusted analysis also revealed that Omicron cases were less likely to be hospitalised (0.4%) or report symptoms (60.8%). Specifically a significant reduction was observed in the proportion of Omicron cases reporting anosmia (8.9%). Conclusion Key findings include a lower risk of anosmia and a reduced risk of hospitalisation in the first 1000 Omicron cases compared with co-circulating Delta cases. We also identify that existing measures for travel restrictions to control importations of new variants identified outside the United Kingdom did not prevent the rapid ingress of Omicron within Wales

Intestinal Tumorigenesis Is Not Affected by Progesterone Signaling in Rodent Models

Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR) is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO) to the ApcMin/+ mouse, a model for spontaneous intestinal polyposis. PRKO-ApcMin/+mice exhibited no change in polyp number, size or localization compared to ApcMin/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis

VARIETIES OF MODAL LATTICES

0. Introduction. A modal operator on a lattice (L,v, ^ ) is a function f: L-} L such that, for all x,y C L, (1) x •< f(x) (2) f(x) = f(f(x)) (3) f(x ^ y) = f(x) ^ fly)