scholarly journals Introduction and expansion of the SARS-CoV-2 B.1.1.7 variant and reinfections in Qatar: A nationally representative cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (12) ◽  
pp. e1003879
Author(s):  
Laith J. Abu-Raddad ◽  
Hiam Chemaitelly ◽  
Houssein H. Ayoub ◽  
Peter Coyle ◽  
Joel A. Malek ◽  
...  
Keyword(s):  
Natural Infection ◽  
Natural Immunity ◽  
Wild Type ◽  
National Cohort ◽  
Unknown Status ◽  
Nationally Representative ◽  
Alpha Variant ◽  
Second Wave ◽  
Representative Cohort ◽  
National Comparator

Background The epidemiology of the SARS-CoV-2 B.1.1.7 (or Alpha) variant is insufficiently understood. This study’s objective was to describe the introduction and expansion of this variant in Qatar and to estimate the efficacy of natural infection against reinfection with this variant. Methods and findings Reinfections with the B.1.1.7 variant and variants of unknown status were investigated in a national cohort of 159,003 individuals with prior PCR-confirmed infections and a national cohort of 43,127 antibody-positive individuals. Infections with B.1.1.7 and variants of unknown status were also investigated in a national comparator cohort of 150,106 antibody-negative individuals. B.1.1.7 was first identified in Qatar on 25 December 2020. Sudden, large B.1.1.7 epidemic expansion was observed starting on 18 January 2021, triggering the onset of epidemic’s second wave, 7 months after the first wave. B.1.1.7 was about 60% more infectious than the original (wild-type) circulating variants. Among persons with a prior PCR-confirmed infection, the efficacy of natural infection against reinfection was estimated to be 97.5% (95% CI: 95.7% to 98.6%) for B.1.1.7 and 92.2% (95% CI: 90.6% to 93.5%) for variants of unknown status. Among antibody-positive persons, the efficacy of natural infection against reinfection was estimated to be 97.0% (95% CI: 92.5% to 98.7%) for B.1.1.7 and 94.2% (95% CI: 91.8% to 96.0%) for variants of unknown status. A main limitation of this study is assessment of reinfections based on documented PCR-confirmed reinfections, but other reinfections could have occurred and gone undocumented. Conclusions In this study, we observed that introduction of B.1.1.7 into a naïve population can create a major epidemic wave, but natural immunity in those previously infected was strongly associated with limited incidence of reinfection by B.1.1.7 or other variants.

scholarly journals Relationship satisfaction and concordance in attitudes to maternal employment in British couples with young children

2020 ◽  
Vol 37 (7) ◽  
pp. 2184-2204
Author(s):  
Lauren Bird ◽  
Amanda Sacker ◽  
Anne McMunn
Keyword(s):  
Relationship Satisfaction ◽  
Family Relationships ◽  
Maternal Employment ◽  
Potential Association ◽  
Paid Labor ◽  
Societal Changes ◽  
Nationally Representative ◽  
And Behavior ◽  
Attitudes And Behavior ◽  
Representative Cohort

Changes in paid labor in families have occurred within the wider context of societal changes in gendered attitudes to work. However, changes in behavior and attitudes are not necessarily correlated with each other, and their associations with family relationships are complex. This study uses data from over 12,000 two-parent families in the U.K.’s Millennium Cohort Study, a nationally representative cohort of children born during 2000–2002. The study investigates the potential association between relationship satisfaction and discordance between attitudes to maternal employment and mothers’ actual participation in paid labor, as well as agreement in attitudes within couples. Results show that attitudes in favor of maternal employment and actual maternal employment are generally associated with better relationship satisfaction for both mothers and fathers. In addition, discordance between an individual’s attitudes and behavior in relation to maternal employment, and discordant attitudes within couples, is both associated with significantly lower relationship satisfaction compared with concordant couples.

scholarly journals Modified Monosaccharides Content of Xanthan Gum Impairs Citrus Canker Disease by Affecting the Epiphytic Lifestyle of Xanthomonas citri subsp. citri

2021 ◽  
Vol 9 (6) ◽  
pp. 1176
Author(s):  
Simone Cristina Picchi ◽  
Laís Moreira Granato ◽  
Maria Júlia Festa Franzini ◽  
Maxuel Oliveira Andrade ◽  
Marco Aurélio Takita ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Xanthan Gum ◽  
Wild Type Strain ◽  
Natural Infection ◽  
Citrus Canker ◽  
Wild Type ◽  
Xanthomonas Citri ◽  
Canker Disease ◽  
Key Enzyme ◽  
Citrus Canker Disease

Xanthomonas citri subsp. citri (X. citri) is a plant pathogenic bacterium causing citrus canker disease. The xanA gene encodes a phosphoglucomutase/phosphomannomutase protein that is a key enzyme required for the synthesis of lipopolysaccharides and exopolysaccharides in Xanthomonads. In this work, firstly we isolated a xanA transposon mutant (xanA::Tn5) and analyzed its phenotypes as biofilm formation, xanthan gum production, and pathogenesis on the sweet orange host. Moreover, to confirm the xanA role in the impaired phenotypes we further produced a non-polar deletion mutant (ΔxanA) and performed the complementation of both xanA mutants. In addition, we analyzed the percentages of the xanthan gum monosaccharides produced by X. citri wild-type and xanA mutant. The mutant strain had higher ratios of mannose, galactose, and xylose and lower ratios of rhamnose, glucuronic acid, and glucose than the wild-type strain. Such changes in the saccharide composition led to the reduction of xanthan yield in the xanA deficient strain, affecting also other important features in X. citri, such as biofilm formation and sliding motility. Moreover, we showed that xanA::Tn5 caused no symptoms on host leaves after spraying, a method that mimetics the natural infection condition. These results suggest that xanA plays an important role in the epiphytical stage on the leaves that is essential for the successful interaction with the host, including adaptive advantage for bacterial X. citri survival and host invasion, which culminates in pathogenicity.

scholarly journals Vaccine-induced, but not natural immunity, against the Streptococcal inhibitor of complement protects against invasive disease

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Lionel K. K. Tan ◽  
Mark Reglinski ◽  
Daryl Teo ◽  
Nada Reza ◽  
Lucy E. M. Lamb ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Natural Infection ◽  
Invasive Disease ◽  
Full Length ◽  
Natural Immunity ◽  
Rich Region ◽  
Antibody Recognition ◽  
Naturally Occurring ◽  
Protective Antibodies ◽  
Proline Rich Region

AbstractHighly pathogenic emm1 Streptococcus pyogenes strains secrete the multidomain Streptococcal inhibitor of complement (SIC) that binds and inactivates components of the innate immune response. We aimed to determine if naturally occurring or vaccine-induced antibodies to SIC are protective against invasive S. pyogenes infection. Immunisation with full-length SIC protected mice against systemic bacterial dissemination following intranasal or intramuscular infection with emm1 S. pyogenes. Vaccine-induced rabbit anti-SIC antibodies, but not naturally occurring human anti-SIC antibodies, enhanced bacterial clearance in an ex vivo whole-blood assay. SIC vaccination of both mice and rabbits resulted in antibody recognition of all domains of SIC, whereas naturally occurring human anti-SIC antibodies recognised the proline-rich region of SIC only. We, therefore, propose a model whereby natural infection with S. pyogenes generates non-protective antibodies against the proline-rich region of SIC, while vaccination with full-length SIC permits the development of protective antibodies against all SIC domains.

scholarly journals Effect of Delta variant on viral burden and vaccine effectiveness against new SARS-CoV-2 infections in the UK

2021 ◽  
Author(s):  
Koen B. Pouwels ◽  
Emma Pritchard ◽  
Philippa C. Matthews ◽  
Nicole Stoesser ◽  
David W. Eyre ◽  
...  
Keyword(s):  
Natural Infection ◽  
Absolute Difference ◽  
Community Based ◽  
Symptomatic Infection ◽  
The United Kingdom ◽  
Viral Burden ◽  
Alpha Variant ◽  
The Uk ◽  
Prior Infection ◽  
Similar Peak

AbstractThe effectiveness of the BNT162b2 and ChAdOx1 vaccines against new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections requires continuous re-evaluation, given the increasingly dominant B.1.617.2 (Delta) variant. In this study, we investigated the effectiveness of these vaccines in a large, community-based survey of randomly selected households across the United Kingdom. We found that the effectiveness of BNT162b2 and ChAdOx1 against infections (new polymerase chain reaction (PCR)-positive cases) with symptoms or high viral burden is reduced with the B.1.617.2 variant (absolute difference of 10–13% for BNT162b2 and 16% for ChAdOx1) compared to the B.1.1.7 (Alpha) variant. The effectiveness of two doses remains at least as great as protection afforded by prior natural infection. The dynamics of immunity after second doses differed significantly between BNT162b2 and ChAdOx1, with greater initial effectiveness against new PCR-positive cases but faster declines in protection against high viral burden and symptomatic infection with BNT162b2. There was no evidence that effectiveness varied by dosing interval, but protection was higher in vaccinated individuals after a prior infection and in younger adults. With B.1.617.2, infections occurring after two vaccinations had similar peak viral burden as those in unvaccinated individuals. SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with B.1.617.2.

scholarly journals Associations between social and intellectual activities with cognitive trajectories in Chinese middle-aged and older adults: a nationally representative cohort study

2020 ◽  
Author(s):  
Haibin Li ◽  
Changwei Li ◽  
Anxin Wang ◽  
Yanling Qi ◽  
Wei Feng ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Aging ◽  
Trajectory Analysis ◽  
Multinomial Logistic Regression ◽  
Middle Aged ◽  
Cognitive Assessments ◽  
Visuospatial Skills ◽  
Nationally Representative ◽  
Intellectual Activities ◽  
Representative Cohort

Abstract Background: Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study.Methods: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 year from 2011 to 2016. Cognitive trajectories over the study period were analyzed using group-based trajectory model, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odd ratios (OR) and 95% confidence intervals (CI) were reported.Results: Among 8204 participants aged 50-75 years, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: “persistently low trajectory” (n = 1550, 18.9%); “persistently moderate trajectory” (n = 3194, 38.9%); and “persistently high trajectory” (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms and health conditions, more frequent intellectual activities (OR: 0.54, 95% CI: 0.38-0.77) and social activities (OR: 0.79, 95% CI: 0.65-0.95) were both associated with a lower likelihood of being in the “persistently low trajectory” for global cognitive function.Conclusions: These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.

scholarly journals An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

2021 ◽  
Author(s):  
Sheila F Lumley ◽  
Gillian Rodger ◽  
Bede Constantinides ◽  
Nicholas Sanderson ◽  
Kevin K Chau ◽  
...  
Keyword(s):  
Cohort Study ◽  
Single Dose ◽  
Positive Result ◽  
Healthcare Workers ◽  
Natural Infection ◽  
Natural Immunity ◽  
Symptomatic Infection ◽  
Gene Target ◽  
Adjusted Incidence Rate ◽  
Induced Immunity

AbstractBackgroundNatural and vaccine-induced immunity will play a key role in controlling the SARS-CoV-2 pandemic. SARS-CoV-2 variants have the potential to evade natural and vaccine-induced immunity.MethodsIn a longitudinal cohort study of healthcare workers (HCWs) in Oxfordshire, UK, we investigated the protection from symptomatic and asymptomatic PCR-confirmed SARS-CoV-2 infection conferred by vaccination (Pfizer-BioNTech BNT162b2, Oxford-AstraZeneca ChAdOx1 nCOV-19) and prior infection (determined using anti-spike antibody status), using Poisson regression adjusted for age, sex, temporal changes in incidence and role. We estimated protection conferred after one versus two vaccinations and from infections with the B.1.1.7 variant identified using whole genome sequencing.Results13,109 HCWs participated; 8285 received the Pfizer-BioNTech vaccine (1407 two doses) and 2738 the Oxford-AstraZeneca vaccine (49 two doses). Compared to unvaccinated seronegative HCWs, natural immunity and two vaccination doses provided similar protection against symptomatic infection: no HCW vaccinated twice had symptomatic infection, and incidence was 98% lower in seropositive HCWs (adjusted incidence rate ratio 0.02 [95%CI <0.01-0.18]). Two vaccine doses or seropositivity reduced the incidence of any PCR-positive result with or without symptoms by 90% (0.10 [0.02-0.38]) and 85% (0.15 [0.08-0.26]) respectively. Single-dose vaccination reduced the incidence of symptomatic infection by 67% (0.33 [0.21-0.52]) and any PCR-positive result by 64% (0.36 [0.26-0.50]). There was no evidence of differences in immunity induced by natural infection and vaccination for infections with S-gene target failure and B.1.1.7.ConclusionNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provide robust protection against SARS-CoV-2 infection, including against the B.1.1.7 variant.SummaryNatural infection resulting in detectable anti-spike antibodies and two vaccine doses both provided ≥ 85% protection against symptomatic and asymptomatic SARS-CoV-2 infection in healthcare workers, including against the B.1.1.7 variant. Single dose vaccination reduced symptomatic infection by 67%.

scholarly journals SARS CoV-2 Variants and Spike Mutations Involved in Second Wave of COVID-19 Pandemic in India

2021 ◽  
Author(s):  
Muttineni Radhakrishna ◽  
Binitha R ◽  
Kalyani Putty ◽  
Kavitha Marpakala ◽  
Panyam Jaslin ◽  
...  
Keyword(s):  
Biological Significance ◽  
Transmembrane Region ◽  
Genome Sequences ◽  
Neutralising Antibodies ◽  
S Protein ◽  
Terminal Domain ◽  
Alpha Variant ◽  
National Trends ◽  
Second Wave ◽  
Peptide Region

Against the backdrop of the second wave of COVID-19 pandemic in India that started in March 2021, we have monitored the spike (S) protein mutations in all the reported (GISAID portal) whole genome sequences of SARS CoV-2 circulating in India from 1 January 2021 to 31 August 2021. In the 43,102 SARS-CoV-2 genomic sequences analysed, we have identified 24, 260 mutations in the S protein, based on which 265 pango lineages could be categorised. The dominant lineage in most of the 28 states of India and its 8 union territories was B.1.617.2 (the delta variant). However, the states Madhya Pradesh, Jammu & Kashmir, and Punjab had B.1.1.7 (alpha variant) as the major lineage, while the Himachal Pradesh state reported B.1.36 as the dominating lineage. A detailed analysis of various domains of S protein was carried out for detecting mutations having a prevalence of >1%; 70, 18, 7, 3, 9, 4, and 1 (N=112) such mutations were observed in the N -terminal domain, receptor binding domain, C -terminal domain, fusion peptide region, heptapeptide repeat (HR)-1 domains, signal peptide domain, and transmembrane region, respectively. However, no mutations were recorded in the HR-2, and cytoplasmic domains of the S protein. Interestingly, 13.39% (N=15) of these mutations were reported to increase the infectivity and pathogenicity of the virus; 2%(N=3) were known to be vaccine breakthrough mutations; and 0.89%(N=1) were known to escape neutralising antibodies. Biological significance of 82% (N=92) of the reported mutations is yet unknown. As SARS-CoV-2 variants are emerging rapidly, it is critical to continuously monitor local viral mutations to understand national trends of virus circulation. This can tremendously help in designing better preventive regimens in the country, and avoid vaccine breakthrough infections.

scholarly journals Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

2021 ◽  
Author(s):  
Michael Stumpp
Keyword(s):  
Single Agent ◽  
Standard Of Care ◽  
Cooperative Binding ◽  
Wild Type ◽  
Inhibitory Potency ◽  
Alpha Variant ◽  
The Individual ◽  
Very High ◽  
Comprehensive Study

Abstract SARS-CoV-2 has infected millions of people globally and continues to undergo evolution. Emerging variants can be partially resistant to vaccine induced and therapeutic antibodies, emphasizing the urgent need for accessible, broad-spectrum therapeutics. Here, we report a comprehensive study of ensovibep, the first trispecific clinical DARPin candidate, that can simultaneously engage all three units of the spike protein trimer to potently inhibit ACE2 interaction, as revealed by structural analyses. The cooperative binding of the individual modules enables ensovibep to retain inhibitory potency against all frequent SARS-CoV-2 variants, including Omicron, as of December 2021. Moreover, viral passaging experiments show that ensovibep, when used as a single agent, can prevent development of escape mutations comparably to a cocktail of monoclonal antibodies (mAb). Finally, we demonstrate that the very high in vitro antiviral potency also translates into significant therapeutic protection and reduction of pathogenesis in Roborovski dwarf hamsters infected with either the SARS-CoV-2 wild-type or the Alpha variant. In this model, ensovibep prevents fatality and provides substantial protection equivalent to the standard of care mAb cocktail. These results support further clinical evaluation and indicate that ensovibep could be a valuable alternative to mAb cocktails and other treatments for COVID-19.

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