scholarly journals Bayesian inference across multiple models suggests a strong increase in lethality of COVID-19 in late 2020 in the UK

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0258968
Author(s):  
Patrick Pietzonka ◽  
Erik Brorson ◽  
William Bankes ◽  
Michael E. Cates ◽  
Robert L. Jack ◽  
...  
Keyword(s):  
Bayesian Inference ◽  
Time Window ◽  
Fold Increase ◽  
Strong Increase ◽  
Mortality Data ◽  
New Variant ◽  
Model Evidence ◽  
Age Structured ◽  
The Uk ◽  
Inference Methods

We apply Bayesian inference methods to a suite of distinct compartmental models of generalised SEIR type, in which diagnosis and quarantine are included via extra compartments. We investigate the evidence for a change in lethality of COVID-19 in late autumn 2020 in the UK, using age-structured, weekly national aggregate data for cases and mortalities. Models that allow a (step-like or graded) change in infection fatality rate (IFR) have consistently higher model evidence than those without. Moreover, they all infer a close to two-fold increase in IFR. This value lies well above most previously available estimates. However, the same models consistently infer that, most probably, the increase in IFR preceded the time window during which variant B.1.1.7 (alpha) became the dominant strain in the UK. Therefore, according to our models, the caseload and mortality data do not offer unequivocal evidence for higher lethality of a new variant. We compare these results for the UK with similar models for Germany and France, which also show increases in inferred IFR during the same period, despite the even later arrival of new variants in those countries. We argue that while the new variant(s) may be one contributing cause of a large increase in IFR in the UK in autumn 2020, other factors, such as seasonality, or pressure on health services, are likely to also have contributed.

scholarly journals Efficient Bayesian inference of fully stochastic epidemiological models with applications to COVID-19

2021 ◽  
Vol 8 (8) ◽  
pp. 211065
Author(s):  
Yuting I. Li ◽  
Günther Turk ◽  
Paul B. Rohrbach ◽  
Patrick Pietzonka ◽  
Julian Kappler ◽  
...  
Keyword(s):  
Bayesian Inference ◽  
Information Matrix ◽  
Monte Carlo Sampling ◽  
Epidemiological Models ◽  
Large Populations ◽  
Model Evidence ◽  
Age Structured ◽  
The Uk ◽  
Functional Central Limit

Epidemiological forecasts are beset by uncertainties about the underlying epidemiological processes, and the surveillance process through which data are acquired. We present a Bayesian inference methodology that quantifies these uncertainties, for epidemics that are modelled by (possibly) non-stationary, continuous-time, Markov population processes. The efficiency of the method derives from a functional central limit theorem approximation of the likelihood, valid for large populations. We demonstrate the methodology by analysing the early stages of the COVID-19 pandemic in the UK, based on age-structured data for the number of deaths. This includes maximum a posteriori estimates, Markov chain Monte Carlo sampling of the posterior, computation of the model evidence, and the determination of parameter sensitivities via the Fisher information matrix. Our methodology is implemented in PyRoss, an open-source platform for analysis of epidemiological compartment models.

scholarly journals The course of the UK COVID 19 pandemic; no measurable impact of new variants

2021 ◽  
Author(s):  
D Ellis ◽  
D Papadopoulos ◽  
S Mukherjee ◽  
U Ukwu ◽  
N Chari ◽  
...  
Keyword(s):  
Pearson Correlation ◽  
Time Lag ◽  
Reproductive Rate ◽  
Viral Transmission ◽  
Mortality Data ◽  
Daily Mortality ◽  
Pearson Coefficient ◽  
New Variant ◽  
Temperature And Humidity ◽  
The Uk

AbstractIntroductionIn November 2020, a new SARS-COV-2 variant or the ‘Kent variant’ emerged in the UK, and became the dominant UK SARS-COV-2 variant, demonstrating faster transmission than the original variant, which rapidly died out. However, it is unknown if this altered the overall course of the pandemic as genomic analysis was not common place at the outset and other factors such as the climate could alter the viral transmission rate over time. We aimed to test the hypothesis that the overall observed viral transmission was not altered by the emergence of the new variant, by testing a model generated earlier in the pandemic based on lockdown stringency, temperature and humidity.MethodsFrom 1/1/20 to 4/2/21, the daily incidence of SARS-COV-2 deaths and the overall stringency of National Lockdown policy on each day was extracted from the Oxford University Government response tracker. The daily average temperature and humidity for London was extracted from Wunderground.com.The viral reproductive rate was calculated on a daily basis from the daily mortality data for each day. The correlation between log10 of viral reproductive rate and lockdown stringency and weather parameters were compared by Pearson correlation to determine the time lag associated with the greatest correlation.A multivariate model for the log10 of viral reproductive rate was constructed using lockdown stringency, temperature and humidity for the period 1/1/20 to 30/9/20. This model was extrapolated forward from 1/10/20 to 4/2/21 and the predicted viral reproductive rate, daily mortality and cumulative mortality were compared with official data.ResultsOn multivariate linear regression, the optimal model had and R2 0f 0.833 for prediction of log10 viral reproductive rate 13 days later in the model construction period, with (coefficient, probability) lockdown stringency (−0.0109, p=0.0000), humidity (0.0038, p=0.0041) and temperature (−0.0035, p=0.0008). When extrapolated to the validation period (1/10/20 to 4/2/21), the model was highly correlated with daily (Pearson coefficient 0.88, p=0.0000) and cumulated SARS-COV-2 mortality (Pearson coefficient 0.99, p=0.0000).ConclusionThe course of the SARS-COV-2 pandemic in the UK seems highly predicted by an earlier model based on the lockdown stringency, humidity and temperature and unaltered by the emergence of a newer viral genotype.

scholarly journals Isolation and characterization of the new SARS-CoV-2 variant in travellers from the United Kingdom to India: VUI-202012/01 of the B.1.1.7 lineage

2021 ◽  
Vol 28 (2) ◽  
Author(s):  
Pragya D Yadav ◽  
Dimpal A Nyayanit ◽  
Rima R Sahay ◽  
Prasad Sarkale ◽  
Jayshri Pethani ◽  
...  
Keyword(s):  
United Kingdom ◽  
Severe Acute Respiratory Syndrome ◽  
Surveillance System ◽  
The United Kingdom ◽  
Isolation And Characterization ◽  
New Variant ◽  
The Uk ◽  
Local Transmission

We have isolated the new severe acute respiratory syndrome coronavirus-2 variant of concern 202 012/01 from the positive coronavirus disease 2019 cases that travelled from the UK to India in the month of December 2020. This emphasizes the need for the strengthened surveillance system to limit the local transmission of this new variant.

scholarly journals Impact of Relaxing Covid-19 Social Distancing Measures on Rural North Wales: A Simulation Analysis

2020 ◽  
Vol 8 ◽  
Author(s):  
Rhodri P. Hughes ◽  
Dyfrig A. Hughes
Keyword(s):  
Simulation Analysis ◽  
Model Averaging ◽  
Incidence Rates ◽  
Mortality Data ◽  
Rural Regions ◽  
Social Distancing ◽  
North Wales ◽  
The Uk ◽  
Sigmoidal Growth ◽  
Related Mortality

Background: Social distancing policies aimed to limit Covid-19 across the UK were gradually relaxed between May and August 2020, as peak incidences passed. Population density is an important driver of national incidence rates; however peak incidences in rural regions may lag national figures by several weeks. We aimed to forecast the timing of peak Covid-19 mortality rate in rural North Wales.Methods: Covid-19 related mortality data up to 7/5/2020 were obtained from Public Health Wales and the UK Government. Sigmoidal growth functions were fitted by non-linear least squares and model averaging used to extrapolate mortality to 24/8/2020. The dates of peak mortality incidences for North Wales, Wales and the UK; and the percentage of predicted mortality at 24/8/2020 were calculated.Results: The peak daily death rates in Wales and the UK were estimated to have occurred on the 14/04/2020 and 15/04/2020, respectively. For North Wales, this occurred on the 07/05/2020, corresponding to the date of analysis. The number of deaths reported in North Wales on 07/05/2020 represents 33% of the number predicted to occur by 24/08/2020, compared with 74 and 62% for Wales and the UK, respectively.Conclusion: Policies governing the movement of people in the gradual release from lockdown are likely to impact significantly on areas–principally rural in nature–where cases of Covid-19, deaths and immunity are likely to be much lower than in populated areas. This is particularly difficult to manage across jurisdictions, such as between England and Wales, and in popular holiday destinations.

scholarly journals Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 808
Author(s):  
Laura Pérez-Lago ◽  
Teresa Aldámiz-Echevarría ◽  
Rita García-Martínez ◽  
Leire Pérez-Latorre ◽  
Marta Herranz ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Evolutionary Dynamics ◽  
Viral Evolution ◽  
Special Focus ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
New Variant ◽  
History Of ◽  
Evolution Dynamics ◽  
The Uk

A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases.

Necrotising (malignant) otitis externa in the UK: a growing problem. Review of five cases and analysis of national Hospital Episode Statistics trends

2015 ◽  
Vol 129 (6) ◽  
pp. 600-603 ◽  
Author(s):  
G Chawdhary ◽  
N Liow ◽  
J Democratis ◽  
O Whiteside
Keyword(s):  
Otitis Externa ◽  
Severe Infection ◽  
Fold Increase ◽  
Antibiotic Resistant ◽  
Catchment Population ◽  
Malignant Otitis Externa ◽  
The Mean ◽  
The Uk ◽  
High Index Of Suspicion ◽  
Park Hospital

AbstractBackground:Necrotising (malignant) otitis externa is a severe infection causing temporal bone osteomyelitis. Although rare, our experience (reported herein) shows local doubling of cases in 2013. Hospital Episodes Statistics data for England over 14 years also indicate increased incidence nationally. Specific learning points in management are also discussed.Methods:A retrospective review was conducted of patients admitted in 2013 to Wexham Park Hospital, Slough, UK (catchment population, 450 000). In addition, the UK Government Hospital Episodes Statistics data were interrogated.Results:There were five cases of necrotising (malignant) otitis externa in 2013, representing a local doubling on previous years. The mean age of patients was 82 years. All cultures grew Pseudomonas aeruginosa; no isolates were antibiotic resistant. All patients responded to systemic anti-pseudomonals on clinical, biochemical and radiological parameters. Hospital Episodes Statistics data showed a six-fold increase in the number of cases from 1999 (n = 67) to 2013 (n = 421).Conclusion:Our experience suggests increasing necrotising (malignant) otitis externa incidence, and retrospective analysis of Hospital Episodes Statistics data supports this observation. Necrotising (malignant) otitis externa poses challenges in management, as exemplified in our cases, requiring a high index of suspicion and early aggressive treatment to achieve cure.

scholarly journals The emergence of rabbit haemorrhagic disease virus: will a non-pathogenic strain protect the UK?

2001 ◽  
Vol 356 (1411) ◽  
pp. 1087-1095 ◽  
Author(s):  
P.J. White ◽  
R.A. Norman ◽  
R.C. Trout ◽  
E.A. Gould ◽  
P.J. Hudson
Keyword(s):  
Disease Virus ◽  
Pathogenic Strain ◽  
Rabbit Haemorrhagic Disease Virus ◽  
Rabbit Haemorrhagic Disease ◽  
Seroprevalence Data ◽  
Age Structured ◽  
Reproductive Rates ◽  
The Uk ◽  
Haemorrhagic Disease ◽  
Age Structured Model

Rabbit haemorrhagic disease virus emerged in China in 1984, and has killed hundreds of millions of wild rabbits in Australia and Europe. In the UK there appears to be an endemic non–pathogenic strain, with high levels of seroprevalence being recorded, in the absence of associated mortality. Using a seasonal, age–structured model we examine the hypothesis that differences in rabbit population demography differentially affect the basic reproductive rates ( R 0 ) of the pathogenic and non–pathogenic strains, leading to each dominating in some populations and not others. The strain with the higher R 0 excluded the other, with the dynamics depending upon the ratio of the two R 0 values. When the non–pathogenic strain dominated, the pathogenic strain caused only transient mortality, although this could be significant when the two R 0 values were similar. When the pathogenic strain dominated, repeated epidemics led to host eradication. Seroprevalence data suggest that the non–pathogenic strain may be protecting some, but not all UK populations, with half being ‘at risk’ from invasion by the pathogenic strain and a fifth prone to significant transient mortality. We identify key questions for empirical research to test this prediction.

Validation of a locally derived serum calcium adjustment equation: relationship with total 25(OH) vitamin D and PTH levels

2016 ◽  
Vol 70 (1) ◽  
pp. 69-74 ◽  
Author(s):  
Jonathan Joseph Scargill ◽  
John Mark Guy
Keyword(s):  
Vitamin D ◽  
Fold Increase ◽  
Reference Interval ◽  
Albumin Concentration ◽  
Vitamin D Levels ◽  
Significant Difference ◽  
25 Oh Vitamin D ◽  
New Equation ◽  
The Uk ◽  
Adjustment Equation

AimsMany clinical laboratories in the UK use a standard equation to adjust total calcium for albumin concentration. To assess the validity of this practice, we assessed the effect of the use of a traditional and locally derived calcium adjustment equation on parathyroid hormone (PTH) and 25(OH, hydroxy) vitamin D levels.MethodsSamples requested for calcium and albumin measurement over a 6 month period that met inclusion criteria were used to derive a calcium adjustment equation (n=60 941). The traditional and locally derived calcium adjustment equations were then applied to a second cohort of adult patients that underwent calcium measurement over a 1 year period (n=275 456). Patients were classified as hypocalcaemic, normocalcaemic or hypercalcaemic using a UK Pathology Harmony adjusted calcium reference interval (2.2–2.6 mmol/L).ResultsThe local calcium adjustment equation provided a 7.1-fold reduction in the prevalence of hypocalcaemia. Patients classified as hypocalcaemic using the locally derived equation had statistically significantly lower 25(OH) vitamin D and higher PTH levels. A 2.4-fold increase in the prevalence of hypercalcaemia was also observed using the new equation, but with no significant difference in 25(OH) vitamin D or PTH levels.ConclusionsA locally derived calcium adjustment equation reclassified the calcium status of 61 278 (22%) patients. Patients classified as hypocalcaemic by the locally derived equation had significantly lower 25(OH) vitamin D and significantly higher PTH values, providing evidence that use of this adjustment equation generates adjusted calcium results of greater clinical relevance. This study provides further and novel evidence that individual laboratories should determine local equations for adjusted calcium where possible.

Xylodon bambusinus and X. xinpingensis spp. nov. (Hymenochaetales) from southern China

Phytotaxa ◽  
2021 ◽  
Vol 511 (3) ◽  
Author(s):  
XIANG MA ◽  
CHANG-LIN ZHAO
Keyword(s):  
New Species ◽  
Bayesian Inference ◽  
Maximum Likelihood ◽  
Growth Habit ◽  
Southern China ◽  
Phylogenetic Analyses ◽  
Molecular Data ◽  
Two New Species ◽  
Thin Walled ◽  
Inference Methods

Two new species, Xylodon bambusinus and X. xinpingensis, are proposed based on morphological and molecular evidences. Both species share the annual growth habit, resupinate basidiomata and monomitic hyphal system with clamped, colorless generative hyphae, smooth, thin-walled basidiospores, but X. bambusinus is characterized by the smooth to tuberculate hymenial surface, presence of capitate and fusiform cystidia, broad ellipsoid basidiospores, while X. xinpingensis by the reticulate hymenophore with cream hymenial surface, and subglobose basidiospores (4.5–6 × 3.5–5 µm). Sequences of ITS and LSU nrRNA gene regions of the studied samples were generated, and phylogenetic analyses were performed with maximum likelihood, maximum parsimony and Bayesian inference methods. The phylogenetic analyses based on molecular data of ITS and ITS+nLSU sequences showed that X. bambusinus was sister to X. subclavatus, while X. xinpingensis grouped with X. astrocystidiatus and X. paradoxus. The nLSU dataset revealed that X. bambusinus grouped with X. asperus and X. brevisetus with lower supports, and that X. xinpingensis grouped with X. astrocystidiatus and X. paradoxus and then with X. rimosissimus without supports. Both morphological and molecular evidences confirmed the placement of two new species in Xylodon. Description and figures from the new species and a key to the known species of Xylodon from China are presented.

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