Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

In this study, we evaluated the impact of viral variant, in addition to other variables, on within-host viral burden, by analysing cycle threshold (Ct) values derived from nose and throat swabs, collected as part of the UK COVID-19 Infection Survey. Because viral burden distributions determined from community survey data can be biased due to the impact of variant epidemiology on the time-since-infection of samples, we developed a method to explicitly adjust observed Ct value distributions to account for the expected bias. By analysing the adjusted Ct values using partial least squares regression, we found that among unvaccinated individuals with no known prior exposure, viral burden was 44% lower among Alpha variant infections, compared to those with the predecessor strain, B.1.177. Vaccination reduced viral burden by 67%, and among vaccinated individuals, viral burden was 286% higher among Delta variant, compared to Alpha variant, infections. In addition, viral burden increased by 17% for every 10-year age increment of the infected individual. In summary, within-host viral burden increases with age, is reduced by vaccination, and is influenced by the interplay of vaccination status and viral variant.

Correction: Viral burden is associated with age, vaccination, and viral variant in a population-representative study of SARS-CoV-2 that accounts for time-since-infection-related sampling bias.

[This corrects the article DOI: 10.1371/journal.ppat.1011461.].

Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.

Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients. Whether the risk extends postdischarge has been controversial. Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020. We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes. Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged. Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM). Principal safety outcome was major bleeding (MB). Among 4906 patients (53.7% male), mean age was 61.7 years. Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%). Postdischarge thromboprophylaxis was prescribed in 13.2%. VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%. Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17). Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81). Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization. Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk. Postdischarge anticoagulation reduced risk by 46%.

It is the egg, not the chicken; dorsal visual deficits present in dyslexia are not present in illiterate adults.

Some individuals with dyslexia demonstrate deficits in reading, visual attention, and visual processing which can be attributed to a functional failure of the magnocells in the visual system or in the dorsal visual pathway. The study examines the role of magno/dorsal function in dyslexic adults compared with normal, illiterate, and semi-literate readers. Coherent motion and coherent form were used in Experiment 1, and the frequency doubling illusion and static-gratings were used in Experiment 2. If a magno/dorsal deficit is demonstrated for dyslexic readers but not illiterate, semi-literate, and normal reading adults, then the deficit cannot be attributed to reading experience. Illiterate adults performed the same as normal and semi-literate readers in coherent motion and frequency doubling tasks, and all three groups performed better than the dyslexic readers. There was no difference between any of the groups in the coherent form or static grating tasks. Together, these studies show that illiterate and semi-literate adults do not demonstrate a magno/dorsal deficit that is a characteristic of some sufferers of dyslexia. Therefore, magno/dorsal deficits in dyslexia are unlikely to be a consequence of failing to learn to read but rather provides evidence to suggest a causal role for reduced visual magno/dorsal processing.

Experimental and Genomic Evaluation of the Oestrogen Degrading Bacterium Rhodococcus equi ATCC13557.

Rhodococcus equi ATCC13557 was selected as a model organism to study oestrogen degradation based on its previous ability to degrade 17α-ethinylestradiol (EE2). Biodegradation experiments revealed that R. equi ATCC13557 was unable to metabolise EE2. However, it was able to metabolise E2 with the major metabolite being E1 with no further degradation of E1. However, the conversion of E2 into E1 was incomplete, with 11.2 and 50.6% of E2 degraded in mixed (E1-E2-EE2) and E2-only conditions, respectively. Therefore, the metabolic pathway of E2 degradation by R. equi ATCC13557 may have two possible pathways. The genome of R. equi ATCC13557 was sequenced, assembled, and mapped for the first time. The genome analysis allowed the identification of genes possibly responsible for the observed biodegradation characteristics of R. equi ATCC13557. Several genes within R. equi ATCC13557 are similar, but not identical in sequence, to those identified within the genomes of other oestrogen degrading bacteria, including Pseudomonas putida strain SJTE-1 and Sphingomonas strain KC8. Homologous gene sequences coding for enzymes potentially involved in oestrogen degradation, most commonly a cytochrome P450 monooxygenase (oecB), extradiol dioxygenase (oecC), and 17ß-hydroxysteroid dehydrogenase (oecA), were identified within the genome of R. equi ATCC13557. These searches also revealed a gene cluster potentially coding for enzymes involved in steroid/oestrogen degradation; 3-carboxyethylcatechol 2,3-dioxygenase, 2-hydroxymuconic semialdehyde hydrolase, 3-alpha-(or 20-beta)-hydroxysteroid dehydrogenase, 3-(3-hydroxy-phenyl)propionate hydroxylase, cytochrome P450 monooxygenase, and 3-oxosteroid 1-dehydrogenase. Further, the searches revealed steroid hormone metabolism gene clusters from the 9, 10-seco pathway, therefore R. equi ATCC13557 also has the potential to metabolise other steroid hormones such as cholesterol.

Comparison of citrated native and kaolin-activated samples for thrombelastographic analysis in healthy dogs.

BACKGROUND: Thrombelastographic (TEG) analysis is a test of global hemostasis in veterinary medicine; however, there have been limited comparisons of analysis of citrated native and kaolin-activated samples. OBJECTIVES: The purpose of this study was to determine the variation in TEG variables between citrated native and kaolin-activated whole blood samples and to establish reference intervals for both sample types. METHODS: Citrated whole blood samples were obtained from 40 healthy dogs. Thirty minutes after collection, TEG analysis was performed simultaneously on samples with and without kaolin-activation. Reaction time (R), clotting time (K), angle (α), maximum amplitude (MA), global clot strength (G), and clot lysis at 30 minutes (LY30) were recorded, and the concordance correlation coefficient (ρ(c)) was calculated for each sample type. RESULTS: Significant differences between results obtained for kaolin-activated and native samples were obtained for R (mean difference -1.3 minute, P = .0009), K (-0.7 minute, P = .0003), α (+5.1º, P = .002), MA (+2.4 mm, P = .002), and G (+568 dyn/cm(2), P = .0009). LY30 was not different between methods. There was substantial agreement between methods for G (ρ(c) = .69) and MA (ρ(c) = .65), moderate agreement for R (ρ(c) = .45) and α (ρ(c) = .44), fair agreement for K (ρ(c) = .29), and slight agreement for LY30 (ρ(c) = .04). CONCLUSIONS: The TEG variables were significantly altered by kaolin activation; however, some agreement between sample types suggests a consistent bias. In citrated whole blood activated with kaolin, clot formation time is shortened and the amplitude of the tracing is increased, resulting in a TEG tracing that appears to indicate relative hypercoagulability compared with that obtained using native citrated whole blood samples.

Independent and combined effects of prednisone and acetylsalicylic acid on thromboelastography variables in healthy dogs.

OBJECTIVE: To describe the effects of prednisone and acetylsalicylic acid (ASA) on results of thromboelastography in healthy dogs. ANIMALS: 16 male mixed-breed dogs. PROCEDURES: Dogs were randomly assigned to 3 treatment groups (4 dogs/group) that received prednisone (median dose, 2.07 mg/kg), ASA (median dose, 0.51 mg/kg), or both drugs, PO, every 24 hours from days 0 through 6. Another group received no treatment (control dogs; n = 4). Thromboelastography variables (reaction time, clotting time, α-angle, maximum amplitude [MA], global clot strength, coagulation index, and percentage of clot lysis at 60 minutes [CL(60)]) were evaluated in blood samples collected (prior to drug administration in treated dogs) on days 0 (baseline), 2, 4, and 6. RESULTS: Administration of ASA alone did not alter TEG variables. For treatment effect, mean global clot strength was increased in the prednisone and drug combination groups, compared with values for control dogs; MA was also increased in the prednisone and drug combination groups, compared with that of controls. For treatment-by-time effect, median CL(60) was increased in the prednisone group on day 6, compared with baseline value in the same dogs and with median CL(60) of the control group on day 6. Median CL(60) was also increased in the drug combination group on day 6, compared with the baseline value and with that of the control group on day 6. CONCLUSIONS AND CLINICAL RELEVANCE: Prednisone administered at approximately 2 mg/kg/d, PO, for 7 days with or without concurrently administered ASA increased clot strength and decreased clot lysis in healthy dogs.