Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS‐CoV‐2 variants

alexandrossfakianakis shared this article with you from Inoreader Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS‐CoV‐2 variants via Journal of Medical Virology Abstract Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from human to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, in order to evaluate the impact of S mutations, we constructed 20 Hela cell lines stably expressing ACE2 orthologs from different animals, and prepared 27 pseudotyped SARS-CoV-2 carrying different spike mutants, among which 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (B.1.429) and Mu (B.1.621). Using pseudoviral reporter assa y, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammals ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to the spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations. This article is protected by copyright. All rights reserved. View on Web

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Estimating Waning of Vaccine Effectiveness: a Simulation Study

alexandrossfakianakis shared this article with you from Inoreader Estimating Waning of Vaccine Effectiveness: a Simulation Study via Clinical Infectious Diseases Advance Access Abstract Background Developing accurate and reliable methods to estimate vaccine protection is a key goal in immunology and public health. While several statistical methods have been proposed, their potential inaccuracy in capturing fast intra-seasonal waning of vaccine-induced protection needs to be rigorously investigated. Methods To compare statistical methods for vaccine effectiveness (VE) estimation, we generated simulated data using a multiscale agent-base d model of an epidemic with an acute viral infection and differing extents of VE waning. We apply a previously proposed framework for VE measures based on the observational data richness to assess changes of vaccine-induced protection over time. Results While VE measures based on hard-to-collect information (e.g. the exact timing of exposures) were accurate, usually VE studies rely on time-to-infection data and the Cox proportional hazard model. We found that its extension utilizing scaled Schoenfeld residuals, previously proposed for capturing VE waning, was unreliable in capturing both the degree of waning and its functional form and identified the mathematical factors contributing to this unreliability. We showed that partitioning time and including a time-vaccine interaction term in the Cox model significantly improved estimation of VE waning, even in the case of dramatic, rapid waning. We also proposed how to optimize the partitioning scheme. Conclusions While appropriate for rejecting the null hypothesis of no waning, scaled Schoenfeld residuals are unreliable for estimating the degree of waning. We propose a Cox-model-based method with a time-vaccine interaction term and further optimization of partitioning time. These findings may guide future analysis of VE waning data. View on Web

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COVID‐19 immunopathology: From acute diseases to chronic sequelae

alexandrossfakianakis shared this article with you from Inoreader COVID‐19 immunopathology: From acute diseases to chronic sequelae via Journal of Medical Virology ABSTRACT The clinical manifestation of COVID-19 mainly targets the lung as a primary affected organ, which is also a critical site of immune cells activation by SARS-CoV-2. However, recent reports also suggest the involvement of extrapulmonary tissues in COVID-19 pathology. The interplay of both innate and adaptive immune responses is key to COVID-19 management. As a result, a robust innate immune response provides the first line of defense, concomitantly, adaptive immunity neutralizes the infection and builds memory for long-term protection. However, dysregulated immunity, both innate and adaptive, can skew towards immunopathology both in acute and chronic cases. Here we have summarized some of the recent findings that provide critical insight into the immunopathology caused by SARS-CoV-2, in acute and post-acute cases. Finally, we further discuss some of the immunomodulatory drugs in preclinical and clinical trials for dampening the immunopathology caused by COVID- 19. This article is protected by copyright. All rights reserved. View on Web

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WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS

alexandrossfakianakis shared this article with you from Inoreader WHOLE GENOME SEQUENCING OF SARS‐CoV‐2: COMPARISON OF TARGET CAPTURE AND AMPLICON SINGLE MOLECULAR REAL TIME SEQUENCING PROTOCOLS via Journal of Medical Virology ABSTRACT Fast, accurate sequencing methods are needed to identify new variants and genetic mutations of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome. Single Molecular Real Time (SMRT) Pacific Biosciences (PacBio) provides long, highly accurate sequences by circular consensus reads. This study compares the performance of a target capture SMRT Pacbio protocol for whole genome sequencing (WGS) of SARS-CoV-2 to that of an amplicon Pacbio SMRT sequencing protocol. The median genome coverage was higher (p<0.05) with the target capture protocol (99.3% [IQR: 96.3-99.5]) than with the amplicon protocol (99.3% [IQR :69.9-99.3]). The clades of 65 samples determined with both protocols were 100% concordant. After adjusting for Ct values, S gene coverage was higher with the target capture protocol than with the amplicon protocol. After stratification on Ct values, higher S gene coverage with the target capture protocol was observed only for samples w ith Ct>17 (p<0.01). Pacbio SMRT sequencing protocols appears to be suitable for WGS, genotyping and detecting mutations of SARS-CoV-2. This article is protected by copyright. All rights reserved. View on Web

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Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling

alexandrossfakianakis shared this article with you from Inoreader Translucency, color stability, and biaxial flexural strength of advanced lithium disilicate ceramic after coffee thermocycling via Journal of Esthetic and Restorative Dentistry Abstract Objective To compare the color stability, translucency, and biaxial flexural strength (BFS) of differently glazed advanced lithium disilicate (ALDS) with those of lithium disilicate (LDS) and zirconia-reinforced lithium silicate (ZLS) after coffee thermocycling. Materials and methods Forty disk-shaped specimens were prepared from three lithium silicate based materials (CEREC Tessera, ALDS; IPS e.max CAD, LDS; Vita Suprinity, ZLS). ALDS specimens were divided into two subgroups according to glazing procedures (reduced glaze duration, ALDS-S and normal glaze duration, ALDS-N), while LDS and ZLS specimens were crystallized and glazed. Color coordinate measurements were performed before and after coffee thermocycling. Color differences (ΔE 00) and relative translucency parameters (RTP) were calculated. Specimens were then subjected to BFS test. Statistical analysis was performed by using 1- (ΔE 00 and BFS) and 2-way (RTP) ANOVA tests (α = 0.05). Results ΔE 00 values of tested materials were similar (df = 3, F = 0.150, p = 0.929). Two-way ANOVA showed the significant effect of material type, coffee thermocycling, and the interaction between these parameters on RTP values (p < 0.001). Both before and after thermocycling, LDS had the highest (p ≤ 0.001) and ZLS had the lowest (p < 0.001) RTP values, while ALDS-N had higher RTP than ALDS-S (p ≤ 0.001). Among tested materials, only LDS had similar RTP values before and after thermocycling (p = 0.865) as the other materials had lower RTP values after thermocycling (p < 0.001). ALDS-N had higher BFS values than ALDS-S (p = 0.005), while LDS had similar values to ALDS specimens (p ≥ 0.201). ZLS had the highest BFS (p ≤ 0.007). Conclusions ALDS had comparable values to those of other materials. However, reduced glazing duration resulted in decreased translucency and BFS of ALDS. Clinical significance ALDS may be an appropriate restorative material for those patients with increased coffee consumption considering its color stability and ability to maintain translucency, particularly when glazed by using a conventional porcelain furnace. View on Web

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Helicobacter pylori infection and risk of multiple sclerosis: An updated meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Helicobacter pylori infection and risk of multiple sclerosis: An updated meta‐analysis via Helicobacter Abstract Background There is considerable controversy around the question as to whether Helicobacter pylori (H. pylori) infection has a protective or causative role in the development of multiple sclerosis (MS). This study evaluated published information to assess the association between H. pylori infection and MS. Methods We conducted a comprehensive systematic review of relevant observational studies in international databases. A random-effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). I 2 statistic was used to assess the between-study heterogeneity. Subgroup and meta-regression analyses were applied to identify the source of heterogeneity. Results In total, 22 studies (25 datasets) were eligible for the meta-analysis: 17 datasets had prevalence data and eight datasets had data on the mean titer of anti-H. pylori IgG. The pooled prevalence of H. pylori was 44.1% (908/2606) in the MS patients and 46.1% (1016/2200) in the controls, indicating a non-significant protective effect of H. pylori on MS (OR, 0.82; 95%CI, 0.58–1.17). In the subgroup analysis, studies that used ELISA yielded a significant protective association (OR, 0.59; 95%CI, 0.46–0.77), while a positive non-significant association (OR, 1.33; 95%CI, 0.83–2.15) was found from studies that used other serological methods; interestingly, a significant positive association (OR, 6.64; 95%CI, 2.40–13.76) was found from studies that used histological methods to detect H. pylori infection. Conclusions Our findings do not support the hypothesis that H. pylori infection represents a protective factor against the development of MS; however, the results varied depending on the diagnostic method(s). Particularly, a significant positive association was identified when studies introduced results based on histological examination, suggesting that active H. pylori infection might be a risk factor for development of MS. Thus, further studies are needed utilizing accurate diagnostic methods to elucidate the association between active H. pylori infection and MS. View on Web

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Disease Burden, Risk Factors, and Trends of Primary Central Nervous System (CNS) Cancer: a global study of registries data

alexandrossfakianakis shared this article with you from Inoreader Disease Burden, Risk Factors, and Trends of Primary Central Nervous System (CNS) Cancer: a global study of registries data via Neuro-Oncology Advance Access Abstract Background This study aimed to evaluate the global incidence, mortality, associated risk factors, and temporal trends of central nervous system (CNS) cancer by sex, age, and country. Methods We extracted incidence and mortality of CNS cancer from the GLOBOCAN (2020), Cancer Incidence in Five Continents series I-X, WHO mortality database, the Nordic Cancer Registries, and the Surveillance, Epidemiology, and End Results Program. We searched the Global Health data exchanges for the prevalence of its associated risk factors. We tested the trends by Average Annual Percentage Change (AAPC) from Joinpoint regression analysis with 95% confidence intervals in different age groups. Results The age-standardized rates (ASRs) of CNS cancer incidence and mortality were 3.5 and 2.8 per 100,000 globally. Southern Europe (ASR=6.0) and Western Asia (ASR=4.2) had the highest incidence and mortality, respectively. The incidence was associated with Human Development Index, Gross Domestics Products per capita, prevalence of traumatic brain injuries, occupational carcinogens exposure, and mobile phone use at the country level. There was an overall stable and mixed trend in the CNS cancer burden. However, increasing incidence was observed in younger male population from five countries, with Slovakia (AAPC=5.40; 95% CI=1.88, 9.04; p=0.007) reporting the largest increase. Conclusions While the overall global trends of cancer have been largely stable, significant increasing trends were found in the younger male population. The presence of some higher-HDI countries with increasing mortality suggested an ample scope for further research and exploration of the reasons behind these epidemiological trends. View on Web

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