scholarly journals SARS-CoV-2 lineage dynamics in England from January to March 2021 inferred from representative community samples

Author(s):  
Oliver Eales ◽  
Andrew Page ◽  
Sonja N. Tang ◽  
Caroline E. Walters ◽  
Haowei Wang ◽  
...  

Genomic surveillance for SARS-CoV-2 lineages informs our understanding of possible future changes in transmissibility and vaccine efficacy. However, small changes in the frequency of one lineage over another are often difficult to interpret because surveillance samples are obtained from a variety of sources. Here, we describe lineage dynamics and phylogenetic relationships using sequences obtained from a random community sample who provided a throat and nose swab for rt-PCR during the first three months of 2021 as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. Overall, diversity decreased during the first quarter of 2021, with the B.1.1.7 lineage (first identified in Kent) predominant, driven by a 0.3 unit higher reproduction number over the prior wild type. During January, positive samples were more likely B.1.1.7 in younger and middle-aged adults (aged 18 to 54) than in other age groups. Although individuals infected with the B.1.1.7 lineage were no more likely to report one or more classic COVID-19 symptoms compared to those infected with wild type, they were more likely to be antibody positive 6 weeks after infection. Viral load was higher in B.1.1.7 infection as measured by cycle threshold (Ct) values, but did not account for the increased rate of testing positive for antibodies. The presence of infections with non-imported B.1.351 lineage (first identified in South Africa) during January, but not during February or March, suggests initial establishment in the community followed by fade-out. However, this occurred during a period of stringent social distancing and targeted public health interventions and does not immediately imply similar lineages could not become established in the future. Sequence data from representative community surveys such as REACT-1 can augment routine genomic surveillance.

2021 ◽  
Author(s):  
Oliver Eales ◽  
Andrew Page ◽  
Leonardo de Oliveira Martins ◽  
Haowei Wang ◽  
Barbara Bodinier ◽  
...  

Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Here we present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. From 9 to 27 September 2021 (round 14) and 19 October to 5 November 2021 (round 15), all lineages sequenced within REACT-1 were Delta or a Delta sub-lineage with 44 unique lineages identified. The proportion of the original Delta variant (B.1.617.2) was found to be increasing between September and November 2021, which may reflect an increasing number of sub-lineages which have yet to be identified. The proportion of B.1.617.2 was greatest in London, which was further identified as a region with an increased level of genetic diversity. The Delta sub-lineage AY.4.2 was found to be robustly increasing in proportion, with a reproduction number 15% (8%, 23%) greater than its parent and most prevalent lineage, AY.4. Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Though no difference in the viral load based on cycle threshold (Ct) values was identified, a lower proportion of those infected with AY.4.2 had symptoms for which testing is usually recommend (loss or change of sense of taste, loss or change of sense of smell, new persistent cough, fever), compared to AY.4 (p = 0.026). The evolutionary rate of SARS-CoV-2, as measured by the mutation rate, was found to be slowing down during the study period, with AY.4.2 further found to have a reduced mutation rate relative to AY.4. As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.


BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e056636
Author(s):  
Thomas Ward ◽  
Alex Glaser ◽  
Alexander Johnsen ◽  
Feng Xu ◽  
Ian Hall ◽  
...  

ObjectivesImportations of novel variants of concern (VOC), particularly B.1.617.2, have become the impetus behind recent outbreaks of SARS-CoV-2. Concerns around the impact on vaccine effectiveness, transmissibility and severity are now driving the public health response to these variants. This paper analyses the patterns of growth in hospitalisations and confirmed cases for novel VOCs by age groups, geography and ethnicity in the context of changing behaviour, non-pharmaceutical interventions (NPIs) and the UK vaccination programme. We seek to highlight where strategies have been effective and periods that have facilitated the establishment of new variants.DesignWe have algorithmically linked the most complete testing and hospitalisation data in England to create a data set of confirmed infections and hospitalisations by SARS-CoV-2 genomic variant. We have used these linked data sets to analyse temporal, geographic and demographic distinctions.Setting and participantsThe setting is England from October 2020 to July 2021. Participants included all COVID-19 tests that included RT-PCR CT gene target data or underwent sequencing and hospitalisations that could be linked to these tests.MethodsTo calculate the instantaneous growth rate for VOCs we have developed a generalised additive model fit to multiple splines and varying day of the week effects. We have further modelled the instantaneous reproduction number Rt for the B.1.1.7 and B.1.617.2 variants and included a doubly interval censored model to temporally adjust the confirmed variant cases.ResultsWe observed a clear replacement of the predominant B.1.1.7 by the B.1.617.2 variant without observing sustained exponential growth in other novel variants. Modelled exponential growth of RT PCR gene target triple-positive cases was initially detected in the youngest age groups, although we now observe across all ages a very small doubling time of 10.7 (95% CI 9.1 to 13.2) days and 8 (95% CI 6.9 to 9.1) days for cases and hospitalisations, respectively. We observe that growth in RT PCR gene target triple-positive cases was first detected in the Indian ethnicity group in late February, with a peak of 0.06 (95% CI 0.07 to 0.05) in the instantaneous growth rate, but is now maintained by the white ethnicity groups, observing a doubling time of 6.8 (95% CI 4.9 to 11) days. Rt analysis indicates a reproduction number advantage of 0.45 for B.1.617.2 relative to B.1.1.7, with the Rt value peaking at 1.85 for B.1.617.2.ConclusionsOur results illustrate a clear transmission advantage for the B.1.617.2 variant and the growth in hospitalisations illustrates that this variant is able to maintain exponential growth within age groups that are largely doubly vaccinated. There are concerning signs of intermittent growth in the B.1.351 variant, reaching a 28-day doubling time peak in March 2021, although this variant is presently not showing any evidence of a transmission advantage over B.1.617.2. Step 1b of the UK national lockdown easing was sufficient to precipitate exponential growth in B.1.617.2 cases for most regions and younger adult age groups. The final stages of NPI easing appeared to have a negligible impact on the growth of B.1.617.2 with every region experiencing sustained exponential growth from step 2. Nonetheless, early targeted local NPIs appeared to markedly reduced growth of B.1.617.2. Later localised interventions, at a time of higher prevalence and greater geographic dispersion of this variant, appeared to have a negligible impact on growth.


2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Maya Louvardi ◽  
Panagiotis Pelekasis ◽  
Flora Bacopoulou ◽  
Dimitrios Vlachakis ◽  
George Chrousos ◽  
...  

A growing part of the literature has focused on depression, anxiety, distress and somatization. Identifying their prevalence and recording high-risk populations is essential in order to form relevant interventional programs addressing these symptoms. The aim of this study was to examine the prevalence and associated factors of distress, depression, anxiety and somatization in a community adult sample in Greece. Participants were recruited from two Greek cities; Giannitsa in the northern area and Athens in the southern area of the country and  completed sociodemographic assessments, as well as the 4-Dimensional Symptom Questionnaire (4-DSQ), a self-reported instrument assessing depression, anxiety, distress and somatization.A total of 2,425 adults, females (60.1%) and males (39.9%), 18 to 84 years of age (mean age 46.98 ± SD) participated in the study. Mental health symptoms were reported by 10.8% for depression, 12% for anxiety, 13% for distress and 5.3% for somatization of the participants. Females scored higher than males in anxiety, distress, and somatization (p=0.000 in all cases), while there were no significant sex differences in depression (p=0.593). Statistically significant associations were found between age and depression, anxiety and distress (p=0.000 in all cases), since those between 18-34 years of age had higher scores than the older age groups in all variables. Higher scores of depression, anxiety and distress were reported by students and unemployed participants (p=0.000 in all cases) than participants with other occupations. This study mapped several sociodemographic groups with worse mental health. Studies in representative population samples are needed to guide public health interventions to improve the mental and physical well-being of high-risk populations.


Author(s):  
Mahmoud Ahmed Ebada ◽  
Ahmed Wadaa Allah ◽  
Eshak Bahbah ◽  
Ahmed Negida

: Coronavirus Disease (COVID-19) pandemic has affected more than seven million individuals in 213 countries worldwide with a basic reproduction number ranging from 1.5 to 3.5 and an estimated case fatality rate ranging from 2% to 7%. A substantial proportion of COVID-19 patients are asymptomatic; however, symptomatic cases might present with fever, cough, and dyspnoea or severe symptoms up to acute respiratory distress syndrome. Currently, RNA RT-PCR is the screening tool, while bilateral chest CT is the confirmatory clinical diagnostic test. Several drugs have been repurposed to treat COVID-19, including chloroquine or hydroxychloroquine with or without azithromycin, lopinavir/ritonavir combination, remdesivir, favipiravir, tocilizumab, and EIDD-1931. Recently, Remdesivir gained FDA emergency approval based on promising early findings from the interim analysis of 1063 patients. The recently developed serology testing for SARSCoV-2 antibodies opened the door to evaluate the actual burden of the disease and to determine the rate of the population who have been previously infected (or developed immunity). This review article summarizes current data on the COVID-19 pandemic starting from the early outbreak, viral structure and origin, pathogenesis, diagnosis, treatment, discharge criteria, and future research.


Genetics ◽  
2000 ◽  
Vol 155 (3) ◽  
pp. 1105-1117 ◽  
Author(s):  
W John Haynes ◽  
Kit-Yin Ling ◽  
Robin R Preston ◽  
Yoshiro Saimi ◽  
Ching Kung

Abstract Pawn mutants of Paramecium tetraurelia lack a depolarization-activated Ca2+ current and do not swim backward. Using the method of microinjection and sorting a genomic library, we have cloned a DNA fragment that complements pawn-B (pwB/pwB). The minimal complementing fragment is a 798-bp open reading frame (ORF) that restores the Ca2+ current and the backward swimming when expressed. This ORF contains a 29-bp intron and is transcribed and translated. The translated product has two putative transmembrane domains but no clear matches in current databases. Mutations in the available pwB alleles were found within this ORF. The d4-95 and d4-96 alleles are single base substitutions, while d4-662 (previously pawn-D) harbors a 44-bp insertion that matches an internal eliminated sequence (IES) found in the wild-type germline DNA except for a single C-to-T transition. Northern hybridizations and RT-PCR indicate that d4-662 transcripts are rapidly degraded or not produced. A second 155-bp IES in the wild-type germline ORF excises at two alternative sites spanning three asparagine codons. The pwB ORF appears to be separated from a 5′ neighboring ORF by only 36 bp. The close proximity of the two ORFs and the location of the pwB protein as indicated by GFP-fusion constructs are discussed.


2020 ◽  
Author(s):  
Jens Schittenhelm ◽  
Lukas Ziegler ◽  
Jan Sperveslage ◽  
Michel Mittelbronn ◽  
David Capper ◽  
...  

Abstract Background Fibroblast growth factor receptor (FGFR) inhibitors are currently used in clinical development. A subset of glioblastomas carries gene fusion of FGFR3 and transforming acidic coiled-coil protein 3. The prevalence of other FGFR3 alterations in glioma is currently unclear. Methods We performed RT-PCR in 101 glioblastoma samples to detect FGFR3-TACC3 fusions (“RT-PCR cohort”) and correlated results with FGFR3 immunohistochemistry (IHC). Further, we applied FGFR3 IHC in 552 tissue microarray glioma samples (“TMA cohort”) and validated these results in two external cohorts with 319 patients. Gene panel sequencing was carried out in 88 samples (“NGS cohort”) to identify other possible FGFR3 alterations. Molecular modeling was performed on newly detected mutations. Results In the “RT-PCR cohort,” we identified FGFR3-TACC3 fusions in 2/101 glioblastomas. Positive IHC staining was observed in 73/1024 tumor samples of which 10 were strongly positive. In the “NGS cohort,” we identified FGFR3 fusions in 9/88 cases, FGFR3 amplification in 2/88 cases, and FGFR3 gene mutations in 7/88 cases in targeted sequencing. All FGFR3 fusions and amplifications and a novel FGFR3 K649R missense mutation were associated with FGFR3 overexpression (sensitivity and specificity of 93% and 95%, respectively, at cutoff IHC score > 7). Modeling of these data indicated that Tyr647, a residue phosphorylated as a part of FGFR3 activation, is affected by the K649R mutation. Conclusions FGFR3 IHC is a useful screening tool for the detection of FGFR3 alterations and could be included in the workflow for isocitrate dehydrogenase (IDH) wild-type glioma diagnostics. Samples with positive FGFR3 staining could then be selected for NGS-based diagnostic tools.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fatima Khadadah ◽  
Abdullah A. Al-Shammari ◽  
Ahmad Alhashemi ◽  
Dari Alhuwail ◽  
Bader Al-Saif ◽  
...  

Abstract Background Aggressive non-pharmaceutical interventions (NPIs) may reduce transmission of SARS-CoV-2. The extent to which these interventions are successful in stopping the spread have not been characterized in countries with distinct socioeconomic groups. We compared the effects of a partial lockdown on disease transmission among Kuwaitis (P1) and non-Kuwaitis (P2) living in Kuwait. Methods We fit a modified metapopulation SEIR transmission model to reported cases stratified by two groups to estimate the impact of a partial lockdown on the effective reproduction number ($$ {\mathcal{R}}_e $$ R e ). We estimated the basic reproduction number ($$ {\mathcal{R}}_0 $$ R 0 ) for the transmission in each group and simulated the potential trajectories of an outbreak from the first recorded case of community transmission until 12 days after the partial lockdown. We estimated $$ {\mathcal{R}}_e $$ R e values of both groups before and after the partial curfew, simulated the effect of these values on the epidemic curves and explored a range of cross-transmission scenarios. Results We estimate $$ {\mathcal{R}}_e $$ R e at 1·08 (95% CI: 1·00–1·26) for P1 and 2·36 (2·03–2·71) for P2. On March 22nd, $$ {\mathcal{R}}_e $$ R e for P1 and P2 are estimated at 1·19 (1·04–1·34) and 1·75 (1·26–2·11) respectively. After the partial curfew had taken effect, $$ {\mathcal{R}}_e $$ R e for P1 dropped modestly to 1·05 (0·82–1·26) but almost doubled for P2 to 2·89 (2·30–3·70). Our simulated epidemic trajectories show that the partial curfew measure greatly reduced and delayed the height of the peak in P1, yet significantly elevated and hastened the peak in P2. Modest cross-transmission between P1 and P2 greatly elevated the height of the peak in P1 and brought it forward in time closer to the peak of P2. Conclusion Our results indicate and quantify how the same lockdown intervention can accentuate disease transmission in some subpopulations while potentially controlling it in others. Any such control may further become compromised in the presence of cross-transmission between subpopulations. Future interventions and policies need to be sensitive to socioeconomic and health disparities.


Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 619
Author(s):  
Lirong Cao ◽  
Shi Zhao ◽  
Jingzhi Lou ◽  
Hong Zheng ◽  
Renee W. Y. Chan ◽  
...  

Assessment of influenza vaccine effectiveness (VE) and identification of relevant influencing factors are the current priorities for optimizing vaccines to reduce the impacts of influenza. To date, how the difference between epidemic strains and vaccine strains at genetic scale affects age-specific vaccine performance remains ambiguous. This study investigated the association between genetic mismatch on hemagglutinin and neuraminidase genes and A(H1N1)pdm09 VE in different age groups with a novel computational approach. We found significant linear relationships between VE and genetic mismatch in children, young adults, and middle-aged adults. In the children’s group, each 3-key amino acid mutation was associated with an average of 10% decrease in vaccine effectiveness in a given epidemic season, and genetic mismatch exerted no influence on VE for the elderly group. We demonstrated that present vaccines were most effective for children, while protection for the elderly was reduced and indifferent to vaccine component updates. Modeling such relationships is practical to inform timely evaluation of VE in different groups of populations during mass vaccination and may inform age-specific vaccination regimens.


Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1100
Author(s):  
Ignacio Parrón ◽  
Elsa Plasencia ◽  
Thais Cornejo-Sánchez ◽  
Mireia Jané ◽  
Cristina Pérez ◽  
...  

We investigated an outbreak of acute gastroenteritis due to human astrovirus in a daycare center, describing the transmission mechanism, the most affected age groups, conditioning factors and the extent of the outbreak among household contacts of the daycare center attenders. Data were collected from persons exposed at the daycare center and their home contacts. Fecal samples from affected and non-affected daycare center attenders were analyzed for viruses causing acute gastroenteritis by RT-PCR. The percentage of households affected and the attack rates (AR) were calculated. The attack rates were compared using the rate ratio (RR) with 95% confidence intervals. Information was obtained from 245 people (76 attenders and 169 contacts) of whom 49 were clinical cases. Five HAstV-4, two HAstV-8 and three non-typable HAstV cases were identified (six from clinical cases and four from asymptomatic infected people). The global AR was 20% (41.2% in children aged < 2 years). Data were obtained from 67 households: 20 households of affected attenders and 47 of non-affected attendees. Household contacts of affected attenders had a higher AR (74.3%) than that of non-affected attendees (2.4%). We found asymptomatic infections amongst daycare attendees. The transmission of HAstV during the outbreak was not limited to the daycare center but extended to household contacts of both affected and non-affected attenders.


2013 ◽  
Vol 61 (4) ◽  
pp. 517-528 ◽  
Author(s):  
Zoran Lipej ◽  
Dinko Novosel ◽  
Lea Vojta ◽  
Besi Roić ◽  
Miljenko Šimpraga ◽  
...  

Hepatitis E is a viral zoonotic disease infecting swine worldwide. Since pigs represent a likely animal reservoir for the hepatitis E virus, the epidemiology of naturally occurring hepatitis E was investigated in Croatian swine herds. Nearly all tested animals were seropositive for antibodies against the hepatitis E virus (55/60, 91.7%). Active infection was detected in all age groups by RT-PCR of viral RNA in serum (8/60, 13.3%) and bile samples (3/37, 8.1%), which was further confirmed by histopathological findings of characteristic lesions in the livers of the infected animals. Three new strains of hepatitis E virus were isolated from Croatian pig herds. Phylogenetic analysis using median-joining networks clustered those Croatian strains with isolates from various parts of the world, indicating their likely origin in international trade. Similarity to human isolates implies a zoonotic potential of Croatian strains, which raises a public health concern, especially in the light of the high prevalence of hepatitis E in the herds studied.


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