Results: 747
(searched for: doi:10.1038/s41586-021-03944-y)
Yuan-Hao Xu, Hao-Jie Wang, Zhong-Wen Lu,
Published: 1 July 2023
by
Elsevier BV
Physica A: Statistical Mechanics and Its Applications, Volume 621; https://doi.org/10.1016/j.physa.2023.128723
, YuA. Savochkina,
, E.E. Glushchenko, A.R. Luparev, V.A. Polyakova, D.I. Danilov, E.E. Davydova, K.S. Vinogradov,
I.F. Stetsenko, et al.
,
,
, Graham C. Gibson, Briana Betke, José L. Herrera-Diestra, Spencer Woody, Kelly Pierce, Kaitlyn E. Johnson, Maureen Johnson-León, et al.
PLOS Computational Biology, Volume 19; https://doi.org/10.1371/journal.pcbi.1011149
Abstract:
COVID-19 has disproportionately impacted individuals depending on where they live and work, and based on their race, ethnicity, and socioeconomic status. Studies have documented catastrophic disparities at critical points throughout the pandemic, but have not yet systematically tracked their severity through time. Using anonymized hospitalization data from March 11, 2020 to June 1, 2021 and fine-grain infection hospitalization rates, we estimate the time-varying burden of COVID-19 by age group and ZIP code in Austin, Texas. During this 15-month period, we estimate an overall 23.7% (95% CrI: 22.5–24.8%) infection rate and 29.4% (95% CrI: 28.0–31.0%) case reporting rate. Individuals over 65 were less likely to be infected than younger age groups (11.2% [95% CrI: 10.3–12.0%] vs 25.1% [95% CrI: 23.7–26.4%]), but more likely to be hospitalized (1,965 per 100,000 vs 376 per 100,000) and have their infections reported (53% [95% CrI: 49–57%] vs 28% [95% CrI: 27–30%]). We used a mixed effect poisson regression model to estimate disparities in infection and reporting rates as a function of social vulnerability. We compared ZIP codes ranking in the 75th percentile of vulnerability to those in the 25th percentile, and found that the more vulnerable communities had 2.5 (95% CrI: 2.0–3.0) times the infection rate and only 70% (95% CrI: 60%-82%) the reporting rate compared to the less vulnerable communities. Inequality persisted but declined significantly over the 15-month study period. Our results suggest that further public health efforts are needed to mitigate local COVID-19 disparities and that the CDC’s social vulnerability index may serve as a reliable predictor of risk on a local scale when surveillance data are limited.
Zhongliang Wang, Bin Liu, Jie Luan, Shanshan Lu, Zhijie Zhang,
BMC Public Health, Volume 23, pp 1-13; https://doi.org/10.1186/s12889-023-15835-0
Abstract:
Background: Mathematical models to forecast the risk trend of the COVID-19 pandemic timely are of great significance to control the pandemic, but the requirement of manual operation and many parameters hinders their efficiency and value for application. This study aimed to establish a convenient and prompt one for monitoring emerging infectious diseases online and achieving risk assessment in real time. Methods: The Optimized Moving Average Prediction Limit (Op-MAPL) algorithm model analysed real-time COVID-19 data online and was validated using the data of the Delta variant in India and the Omicron in the United States. Then, the model was utilized to determine the infection risk level of the Omicron in Shanghai and Beijing. Results: The Op-MAPL model can predict the epidemic peak accurately. The daily risk ranking was stable and predictive, with an average accuracy of 87.85% within next 7 days. Early warning signals were issued for Shanghai and Beijing on February 28 and April 23, 2022, respectively. The two cities were rated as medium–high risk or above from March 27 to April 20 and from April 24 to May 5, indicating that the pandemic had entered a period of rapid increase. After April 21 and May 26, the risk level was downgraded to medium and became stable by the algorithm, indicating that the pandemic had been controlled well and mitigated gradually. Conclusions: The Op-MAPL relies on nothing but an indicator to assess the risk level of the COVID-19 pandemic with different data sources and granularities. This forward-looking method realizes real-time monitoring and early warning effectively to provide a valuable reference to prevent and control infectious diseases.
PLOS Global Public Health, Volume 3; https://doi.org/10.1371/journal.pgph.0001896
Abstract:
COVID-19 resulted in extensive morbidity and mortality worldwide. SARS-CoV-2 evolved rapidly, with increasing transmission due to Variants of Concern (VOC). Identifying VOC became important but genome submissions from low-middle income countries (LMIC) remained low leading to gaps in genomic epidemiology. We demonstrate the use of a specific mutation RT-PCR based approach to identify VOC in SARS-CoV-2 positive samples through the pandemic in Pakistan. We selected 2150 SARS-CoV-2 PCR positive respiratory specimens tested between April 2021 and February 2022, at the Aga Khan University Hospital Clinical Laboratories, Karachi, Pakistan. Commercially available RT-PCR assays were used as required for mutations in Spike protein (N501Y, A570D, E484K, K417N, L452R, P681R and deletion69_70) to identify Alpha, Beta, Gamma, Delta, and Omicron variants respectively. Three pandemic waves associated with Alpha, Delta and Omicron occurred during the study period. Of the samples screened, VOC were identified in 81.7% of cases comprising mainly; Delta (37.2%), Alpha (29.8%) and Omicron (17.1%) variants. During 2021, Alpha variants were predominant in April and May; Beta and Gamma variants emerged in May and peaked in June; the Delta variant peaked in July and remained predominant until November. Omicron (BA.1) emerged in December 2021 and remained predominant until February 2022. The CT values of Alpha, Beta, Gamma and Delta were all significantly higher than that of Omicron variants (p<0.0001). We observed VOC through the pandemic waves using spike mutation specific RT-PCR assays. We show the spike mutation specific RT-PCR assay is a rapid, low-cost and adaptable for the identification of VOC as an adjunct approach to NGS to effectively inform the public health response. Further, by associating the VOC with CT values of its diagnostic PCR we gain information regarding the viral load of samples and therefore the level of transmission and disease severity in the population.
, Weijing Wang, Neha Chauhan,
Yanyu Xiong, Nicholas Magazine, Owen Valdescruz, Dong Yeun Kim,
Tianjie Qiu,
,
, et al.
Biosensors and Bioelectronics, Volume 229; https://doi.org/10.1016/j.bios.2023.115228
, Vijayakumar Jawalagatti,
Chamith Hewawaduge, Sivasankar Chandran, Ji-Young Park,
Microbes and Infection, Volume 25; https://doi.org/10.1016/j.micinf.2023.105101
Hazel Morrison, Susan Jackson,
Frontiers in Immunology, Volume 14; https://doi.org/10.3389/fimmu.2023.1211388
Abstract:
Controlled Human Infection Models (CHIMs) involve deliberately exposing healthy human volunteers to a known pathogen, to allow the detailed study of disease processes and evaluate methods of treatment and prevention, including next generation vaccines. CHIMs are in development for both tuberculosis (TB) and Covid-19, but challenges remain in their ongoing optimisation and refinement. It would be unethical to deliberately infect humans with virulent Mycobacteria tuberculosis (M.tb), however surrogate models involving other mycobacteria, M.tb Purified Protein Derivative or genetically modified forms of M.tb either exist or are under development. These utilise varying routes of administration, including via aerosol, per bronchoscope or intradermal injection, each with their own advantages and disadvantages. Intranasal CHIMs with SARS-CoV-2 were developed against the backdrop of the evolving Covid-19 pandemic and are currently being utilised to both assess viral kinetics, interrogate the local and systemic immunological responses post exposure, and identify immune correlates of protection. In future it is hoped they can be used to assess new treatments and vaccines. The changing face of the pandemic, including the emergence of new virus variants and increasing levels of vaccination and natural immunity within populations, has provided a unique and complex environment within which to develop a SARS-CoV-2 CHIM. This article will discuss current progress and potential future developments in CHIMs for these two globally significant pathogens.
, Mohsin Khan,
Sai Chaitanya Chiliveri, Xin Hu, Parker Irvin, Madeleine Leek, Ailis Grieshaber, Zongyi Hu, Eun Sun Jang, Ad Bax, et al.
Communications Biology, Volume 6, pp 1-14; https://doi.org/10.1038/s42003-023-04923-x
Abstract:
Since the emergence of the Omicron variants at the end of 2021, they quickly became the dominant variants globally. The Omicron variants may be more easily transmitted compared to the earlier Wuhan and the other variants. In this study, we aimed to elucidate mechanisms of the altered infectivity associated with the Omicron variants. We systemically evaluated mutations located in the S2 sequence of spike and identified mutations that are responsible for altered viral fusion. We demonstrated that mutations near the S1/S2 cleavage site decrease S1/S2 cleavage, resulting in reduced fusogenicity. Mutations in the HR1 and other S2 sequences also affect cell-cell fusion. Based on nuclear magnetic resonance (NMR) studies and in silico modeling, these mutations affect fusogenicity possibly at multiple steps of the viral fusion. Our findings reveal that the Omicron variants have accumulated mutations that contribute to reduced syncytial formation and hence an attenuated pathogenicity.
Frontiers in Immunology, Volume 14; https://doi.org/10.3389/fimmu.2023.1195299
Abstract:
Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant has rapidly spread around the globe. With a substantial number of mutations in its Spike protein, the SARS-CoV-2 Omicron variant is prone to immune evasion and led to the reduced efficacy of approved vaccines. Thus, emerging variants have brought new challenges to the prevention of COVID-19 and updated vaccines are urgently needed to provide better protection against the Omicron variant or other highly mutated variants.Materials and methods: Here, we developed a novel bivalent mRNA vaccine, RBMRNA-405, comprising a 1:1 mix of mRNAs encoding both Delta-derived and Omicron-derived Spike proteins. We evaluated the immunogenicity of RBMRNA-405 in BALB/c mice and compared the antibody response and prophylactic efficacy induced by monovalent Delta or Omicron-specific vaccine with the bivalent RBMRNA-405 vaccine in the SARSCoV-2 variant challenge.Results: Results showed that the RBMRNA-405 vaccine could generate broader neutralizing antibody responses against both Wuhan-Hu-1 and other SARS-CoV-2 variants, including Delta, Omicron, Alpha, Beta, and Gamma. RBMRNA-405 efficiently blocked infectious viral replication and lung injury in both Omicron- and Delta-challenged K18-ACE2 mice.Conclusion: Our data suggest that RBMRNA-405 is a promising bivalent SARS-CoV-2 vaccine with broad-spectrum efficacy for further clinical development.
, Anouk A. Leijs,
, Ali Tas, Jack L. Arbiser,
,
Microbiology Spectrum; https://doi.org/10.1128/spectrum.03273-22
Abstract:
Honokiol is a compound that shows both anti-inflammatory and antiviral effects, and therefore its effect on SARS-CoV-2 infection was assessed. This small molecule inhibited SARS-CoV-2 replication in various cell-based infection systems, with up to an ~1,000-fold reduction in virus titer.
Mingjun Su, Guanghui Zheng, Xiangwen Xu,
Animal Diseases, Volume 3, pp 1-8; https://doi.org/10.1186/s44149-023-00080-0
Abstract:
Coronaviruses are widespread in nature and can infect mammals and poultry, making them a public health concern. Globally, prevention and control of emerging and re-emerging animal coronaviruses is a great challenge. The mechanisms of virus-mediated immune responses have important implications for research on virus prevention and control. The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lymphocytes, playing an important role in antiviral immune responses. Thus, it can shed light on the development of diagnostic methods and novel vaccines. Here, we have reviewed advances in animal coronavirus antigenic epitope research, aiming to provide a reference for the prevention and control of animal and human coronaviruses.
Frontiers in Public Health, Volume 11; https://doi.org/10.3389/fpubh.2023.1139423
Abstract:
Wastewater surveillance has gained traction during the COVID-19 pandemic as an effective and non-biased means to track community infection. While most surveillance relies on samples collected at municipal wastewater treatment plants, surveillance is more actionable when samples are collected “upstream” where mitigation of transmission is tractable. This report describes the results of wastewater surveillance for SARS-CoV-2 at residence halls on a university campus aimed at preventing outbreak escalation by mitigating community spread. Another goal was to estimate fecal shedding rates of SARS-CoV-2 in a non-clinical setting. Passive sampling devices were deployed in sewer laterals originating from residence halls at a frequency of twice weekly during fall 2021 as the Delta variant of concern continued to circulate across North America. A positive detection as part of routine sampling in late November 2021 triggered daily monitoring and further isolated the signal to a single wing of one residence hall. Detection of SARS-CoV-2 within the wastewater over a period of 3 consecutive days led to a coordinated rapid antigen testing campaign targeting the residence hall occupants and the identification and isolation of infected individuals. With knowledge of the number of individuals testing positive for COVID-19, fecal shedding rates were estimated to range from 3.70 log10 gc ‧ g feces−1 to 5.94 log10 gc ‧ g feces−1. These results reinforce the efficacy of wastewater surveillance as an early indicator of infection in congregate living settings. Detections can trigger public health measures ranging from enhanced communications to targeted coordinated testing and quarantine.
Vaccines, Volume 11; https://doi.org/10.3390/vaccines11050991
Abstract:
Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with comorbidities has recently been questioned, and increasing evidence has shown that, as with many other vaccines, they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Additionally, recent investigations have found abnormally high levels of IgG4 in people who were administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.
Journal of Medical Microbiology, Volume 72; https://doi.org/10.1099/jmm.0.001685
Abstract:
Introduction. As the world was still recovering from the 2020 pandemic, the devastating impact of Covid-19 driven by the Delta variant shook the world in 2021. As the second wave was declining, there was an unusual surge in Covid-19 positive cases by the end of 2021 which led to global concern about the change in virus characteristics. Hypothesis/gap statement. Whole genome sequencing is critical for understanding a rapidly progressing pandemic. Aim. To provide an insight into the major differences encountered in the changing characteristics between the second and third waves of the pandemic at a tertiary care hospital in India. Methods. A retrospective observational cohort analysis was conducted on Covid-positive patients during the second wave of the Covid-19 pandemic (from March 2021 to April 2021) and the third wave of the Covid-19 pandemic (from December 2021 to January 2022). Results. Out of 303 Covid-19 positive cases, 52 samples were tested by whole genome sequencing during the second wave and 108 during the third wave. A decline of 18.5 % was observed in the case fatality rate from the second wave to the third wave. There was a 5 % decline in the number of patients admitted with ARDS and a 16.3 % decline in the number of patients with co-morbidities. In total, 51.9 percent of cases were due to the Delta variant during the second wave and 95 percent due to the Omicron variant during the third wave. We found that 36.5 % of Covid-positive patients during the second wave had been vaccinated compared to 40 % in the third wave. Conclusion. Whole genome sequencing of clinical samples from a wide range of individuals during a viral epidemic will enable us to develop a more rapid public health response to new variants and identify the required vaccine modifications more quickly.
Peifang Li, Huiliang Yang, Jinyu Wu, Yanfei Ma, Ailin Hou, Jiali Chen,
Published: 12 May 2023
Abstract:
Background With the emergence of new COVID-19 variants (Omicron BA.5.2.48 and B.7.14), predicting the mortality of infected patients has become increasingly challenging due to the continuous mutation of the virus. Existing models have shown poor performance and limited clinical utility. This study aims to identify the independent risk factors and develop a practical predictive model for mortality among patients infected with new COVID-19 variants.Methods Demographic, clinical, and laboratory data of COVID-19 patients were retrospectively collected at our hospital between December 22, 2022, and February 15, 2023. Logistic regression (LR), decision tree (DT), and Extreme Gradient Boosting (XGBoost) models were developed to predict mortality. Those models were separately visualized via nomogram, decision trees, and Shapley Additive Explanations (SHAP). To evaluate those models, accuracy, sensitivity, specificity, precision, Youden’s index, and area under curve (AUC, 95% CI) were calculated.Results A total of 987 cases with new COVID-19 variants (Omicron BA.5.2.48 and B.7.14) were eventually included, among them, 153 (15.5%) died. Noninvasive ventilation, intubation, myoglobin, INR, age, number of diagnoses, respiratory, pulse, neutrophil, and albumin were the most important predictors of mortality among new COVID-19 variants. The AUC of LR, DT, and XGBoost models were 0.959, 0.878, and 0.961, respectively. The diagnostic accuracy was 0.926 for LR, 0.913 for DT, and 0.977 for XGBoost. XGBoost model had the highest sensitivity (0.983) and specificity (0.940).Conclusion Our study developed and validated three practical models for predicting mortality in patients with new COVID-19 variants. All models performed well, and XGBoost was the best-performing model.
, Rohini Dwivedi, Poonam Sharma, Deepak Kumar, Ritesh Tandon,
PLoS ONE, Volume 18; https://doi.org/10.1371/journal.pone.0285539
Abstract:
Fucosylated chondroitin sulfate (FucCS) is a unique glycosaminoglycan found primarily in sea cucumbers. This marine sulfated glycan is composed of a chondroitin sulfate backbone decorated with fucosyl branches attached to the glucuronic acid. FucCS exhibits potential biological actions including inhibition of blood clotting and severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. These biological effects have been attributed to certain structural features, including molecular weight (MW), and/or those related to fucosylation, such as degrees of fucosyl branches, sulfation patterns and contents. In a previous work, we were able to generate oligosaccharides of the FucCS from Pentacta pygmaea (PpFucCS) with reduced anticoagulant effect but still retaining significant anti-SARS-CoV-2 activity against the delta strain. In this work, we extended our study to the FucCS extracted from the species Holothuria floridana (HfFucCS). The oligosaccharides were prepared by free-radical depolymerization of the HfFucCS via copper-based Fenton reaction. One-dimensional 1H nuclear magnetic resonance spectra were employed in structural analysis. Activated partial thromboplastin time and assays using protease (factors Xa and IIa) and serine protease inhibitors (antithrombin, and heparin cofactor II) in the presence of the sulfated carbohydrates were used to monitor anticoagulation. Anti-SARS-CoV-2 effects were measured using the concentration–response inhibitory curves of HEK-293T-human angiotensin-converting enzyme-2 cells infected with a baculovirus pseudotyped SARS-CoV-2 wild-type and delta variant spike (S)-proteins. Furthermore, the cytotoxicity of native HfFucCS and its oligosaccharides was also assessed. Like for PpFucCS, we were able to generate a HfFucCS oligosaccharide fraction devoid of high anticoagulant effect but still retaining considerable anti-SARS-CoV-2 actions against both variants. However, compared to the oligosaccharide fraction derived from PpFucCS, the average MW of the shortest active HfFucCS oligosaccharide fraction was significantly lower. This finding suggests that the specific structural feature in HfFucCS, the branching 3,4-di-sulfated fucoses together with the backbone 4,6-di-sulfated N-acetylgalactosamines, is relevant for the anti-SARS-CoV-2 activity of FucCS molecules.
,
,
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, Bhavya Singh, Patrick T. Garrett,
,
,
Published: 9 May 2023
Abstract:
It has been three years since SARS-CoV-2 emerged and the world plunged into a “once in a century” pandemic. Since then, multiple waves of infection have swept through the human population, led by variants that were able to evade any acquired immunity. The co-evolution of SARS-CoV-2 variants with human immunity provides an excellent opportunity to study the interaction between viral pathogens and their human hosts. The heavilyN-glycosylated spike-protein of SARS-CoV-2 plays a pivotal role in initiating infection and is the target for host immune response, both of which are impacted by host-installedN-glycans. We compared theN-glycan landscape of recombinantly expressed, stabilized, soluble spike-protein trimers representing seven of the most prominent SARS-CoV-2 variants and found thatN-glycan processing is conserved at most sites. However, in multiple variants, processing ofN-glycans from high mannose-to complex-type is reduced at sites N165, N343 and N616, implicated in spike-protein function.
Viruses, Volume 15; https://doi.org/10.3390/v15051129
Abstract:
The COVID-19 pandemic resulted from the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first appearance in 2019, new SARS-CoV-2 variants of concern (VOCs) have emerged frequently, changing the infection’s dynamic. SARS-CoV-2 infects cells via two distinct entry routes; receptor-mediated endocytosis or membrane fusion, depending on the absence or presence of transmembrane serine protease 2 (TMPRSS2), respectively. In laboratory conditions, the Omicron SARS-CoV-2 strain inefficiently infects cells predominantly via endocytosis and is phenotypically characterized by decreased syncytia formation compared to the earlier Delta variant. Thus, it is important to characterize Omicron’s unique mutations and their phenotypic manifestations. Here, by utilizing SARS-CoV-2 pseudovirions, we report that the specific Omicron Spike F375 residue decreases infectivity, and its conversion to the Delta S375 sequence significantly increases Omicron infectivity. Further, we identified that residue Y655 decreases Omicron’s TMPRSS2 dependency and entry via membrane fusion. The Y655H, K764N, K856N and K969N Omicron revertant mutations, bearing the Delta variant sequence, increased the cytopathic effect of cell–cell fusion, suggesting these Omicron-specific residues reduced the severity of SARS-CoV-2. This study of the correlation of the mutational profile with the phenotypic outcome should sensitize our alertness towards emerging VOCs.
Microbiology Spectrum; https://doi.org/10.1128/spectrum.03450-22
Abstract:
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genome changes constantly. It is estimated that there are thousands of variants of SARS-CoV-2 by now.
Published: 4 May 2023
Signal Transduction and Targeted Therapy, Volume 8, pp 1-10; https://doi.org/10.1038/s41392-023-01422-7
Abstract:
The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide. A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages, while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells. However, specific T-cell responses remain largely unaffected by the mutations, indicating that T-cell-mediated cellular immunity can still provide protection. Moreover, the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo, which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1. These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies. The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health. The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants. Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.
Published: 2 May 2023
Abstract:
The continuous emergence of highly immune evasive SARS-CoV-2 variants, like XBB.1.5 and XBB.1.16, highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by wildtype (WT)-based vaccination would compromise the antibody response to Omicron-based boosters. Vaccination strategies that can counter immune imprinting are critically needed. In this study, we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. Our results show that in mice, the efficacy of single Omicron-boosting is heavily limited by immune imprinting, especially when using variants antigenically distinct from WT, like XBB, while the concerning situation could be largely mitigated by a second Omicron booster. Similarly, in humans, we found that repeated Omicron infections could also alleviate WT-vaccination-induced immune imprinting and generate high neutralizing titers against XBB.1.5 and XBB.1.16 in both plasma and nasal mucosa. By isolating 781 RBD-targeting mAbs from repeated Omicron infection cohorts, we revealed that double Omicron exposure alleviates immune imprinting by generating a large proportion of highly matured and potent Omicron-specific antibodies. Importantly, epitope characterization using deep mutational scanning (DMS) showed that these Omicron-specific antibodies target distinct RBD epitopes compared to WT-induced antibodies, and the bias towards non-neutralizing epitopes observed in single Omicron exposures due to imprinting was largely restored after repeated Omicron stimulation, together leading to a substantial neutralizing epitope shift. Based on the DMS profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated the combinations of these mutations could further boost XBB.1.5's immune-evasion capability while maintaining high ACE2 binding affinity. Our findings suggest the WT component should be abandoned when updating COVID-19 vaccine antigen compositions to XBB lineages, and those who haven't been exposed to Omicron yet should receive two updated vaccine boosters.
, Cuicui Liu, Xiaowei Xie, Mingming Niu, Yingrui Wang, Xuelian Cheng, Biao Zhang, Dong Zhang, Mengyao Liu, Rui Sun, et al.
Abstract:
While host responses to the ancestral SARS-CoV-2 strain are well-described, those to the new Omicron variants are less resolved. We profiled the clinical phenomes, transcriptomes, proteomes, metabolomes, and immune repertoires of >1,000 blood cell or plasma specimens from SARS-CoV-2 Omicron patients. Using in-depth integrated multi-omics, we dissected the host response dynamics during multiple disease phases to reveal the molecular and cellular landscapes in the blood. Specifically, we detected enhanced interferon-mediated antiviral signatures of platelets in Omicron infected patients and platelets preferentially formed widespread aggregates with leukocytes to modulate immune cell functions. In addition, patients who were tested re-positive for viral RNA showed marked reductions in B cell receptor clones, antibody generation and neutralizing capacity against Omicron. Finally, we developed a machine-learning model that accurately predicted the probability of re-positivity in Omicron patients. Our study may inspire a paradigm shift for studying systemic diseases and emerging public health concerns.
Cell Reports, Volume 42, pp 112503-112503; https://doi.org/10.1016/j.celrep.2023.112503
Abstract:
Striking antibody evasion by emerging circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants drives the identification of broadly neutralizing antibodies (bNAbs). However, how a bNAb acquires increased neutralization breadth during antibody evolution is still elusive. Here, we identify a clonally related antibody family from a convalescent individual. One of the members, XG005, exhibits potent and broad neutralizing activities against SARS-CoV-2 variants, while the other members show significant reductions in neutralization breadth and potency, especially against the Omicron sublineages. Structural analysis visualizing the XG005-Omicron spike binding interface reveals how crucial somatic mutations endow XG005 with greater neutralization potency and breadth. A single administration of XG005 with extended half-life, reduced antibody-dependent enhancement (ADE) effect, and increased antibody product quality exhibits a high therapeutic efficacy in BA.2- and BA.5-challenged mice. Our results provide a natural example to show the importance of somatic hypermutation during antibody evolution for SARS-CoV-2 neutralization breadth and potency.
Pediatrics in Review, Volume 44, pp 243-254; https://doi.org/10.1542/pir.2022-005686
Heliyon, Volume 9; https://doi.org/10.1016/j.heliyon.2023.e15587
Abstract:
The COVID-19 pandemic continues to threaten human health worldwide as new variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge. Currently, the predominant circulating strains around the world are Omicron variants, which can evade many therapeutic antibodies. Thus, the development of new broadly neutralizing antibodies remains an urgent need. In this work, we address this need by using the mRNA-lipid nanoparticle immunization method to generate a set of Omicron-targeting monoclonal antibodies. Five of our novel K-RBD-mAbs show strong binding and neutralizing activities toward all SARS-CoV-2 variants of concern (Alpha, Beta, Gamma, Delta and Omicron). Notably, the epitopes of these five K-RBD-mAbs are overlapping and localized around Y453 and F486 of the spike protein receptor binding domain (RBD). Chimeric derivatives of the five antibodies (K-RBD-chAbs) neutralize Omicron sublineages BA.1 and BA.2 with low IC50 values ranging from 5.7 to 12.9 ng/mL. Additionally, we performed antibody humanization on broadly neutralizing chimeric antibodies to create K-RBD-hAb-60 and -62, which still retain excellent neutralizing activity against Omicron. Our results collectively suggest that these five therapeutic antibodies may effectively combat current and emerging SARS-CoV-2 variants, including Omicron BA.1 and BA.2. Therefore, the antibodies can potentially be used as universal neutralizing antibodies against SARS-CoV-2.
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Sudhir Babji, Anna George, Ramya Madhavan, Julian Vivek Leander Xavier, Jenita Sharon David Chelladurai, Origanti Sharon Nikitha, Arpitha Anbu Deborah, Shalini Vijayakumar, et al.
The Lancet Regional Health - Southeast Asia, Volume 12; https://doi.org/10.1016/j.lansea.2023.100141
Indian Journal of Medical Microbiology, Volume 43, pp 58-65; https://doi.org/10.1016/j.ijmmb.2022.10.011
Acta Pharmaceutica Sinica. B, Volume 13, pp 2219-2233; https://doi.org/10.1016/j.apsb.2022.07.004
Rui Gao, Xinxin Xu,
, Ye Liu, Hongyu Zhang, Xiao Guo, Maozhong Sun, Felippe Colombari, André de Moura, Changlong Hao, et al.
Published: 27 April 2023
Abstract:
The emergence of new viral threats, wide applications of viruses in biotechnology and challenges associated with viral contamination necessitate multiple types of virustatic agents. Here, we show that highly biocompatible tapered CuS nanoparticles efficiently agglutinate COVID virus with binding affinity dependent on chirality of surface ligands and particle shape. L-penicillamine-stabilized nanoparticles with left-handed curved apexes display half-maximal inhibitory concentration as low as 0.57 pM for authentic SARS-CoV-2 viruses, which is ca 15 times greater than for antibodies. Exposure to elevated temperatures causes no change in activity or biocompatibility of nanoparticles while completely deactivating antibodies. Testing with mice indicates that the chirality-optimized nanoparticles can serve as analogs of high antiviral molecular weight biologics complementing the current spectrum of virustatic agents. Their thermal and chemical stability simplifies their applications in biomedical and biotechnological processes.
Hongyang Shu, Chunxia Zhao,
Cardiology Plus; https://doi.org/10.1097/cp9.0000000000000046
Abstract:
Coronavirus disease 2019 (COVID-19) disease has infected nearly 600 million people, resulting in > 6 million deaths, with many of them dying from cardiovascular diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is caused by a combination of the virus surface spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. In addition to being highly expressed in the lungs, ACE2 is widely distributed in the heart, mainly in myocardial cells and pericytes. Like other types of viruses, SARS-CoV-2 can cause myocarditis after infecting the myocardial tissue, which is attributed to the direct damage of the virus and uncontrolled inflammatory reactions. Patients with chest tightness, palpitation, abnormal electrocardiogram, and cardiac troponin elevation, should be suspected of myocarditis within 1–3 weeks of COVID-19 infection. When the hemodynamics change rapidly, fulminant myocarditis should be suspected. Cardiac ultrasound, myocardial biopsy, cytokine detection, cardiac magnetic resonance imaging, 18F-fluorodeoxyglucose positron emission tomography, and other examination methods can assist in the diagnosis. Although scientists and clinicians have made concerted efforts to seek treatment and prevention measures, there are no clear recommendations for the treatment of COVID-19-related myocarditis. For most cases of common myocarditis, general symptomatic and supportive treatments are used. For COVID-19-related fulminant myocarditis, it is emphasized to achieve “early identification, early diagnosis, early prediction, and early treatment” based on the “life support-based comprehensive treatment regimen.” Mechanical circulatory support therapy can rest the heart, which is a cure for symptoms, and immune regulation therapy can control the inflammatory storms which is a cure for the disease. Furthermore, complications of COVID-19-related myocarditis, such as arrhythmia, thrombosis, and infection, should be actively treated. Herein, we summarized the incidence rate, manifestations, and diagnosis of COVID-19-related myocarditis and discussed in detail the treatment of COVID-19-related myocarditis, especially the treatment strategy of fulminant myocarditis.
Published: 13 April 2023
by
MDPI
International Journal of Environmental Research and Public Health, Volume 20; https://doi.org/10.3390/ijerph20085503
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that evolves over time, leading to new variants. In the current study, we assessed the genomic epidemiology of SARS-CoV-2 in the Dominican Republic. A total of 1149 SARS-CoV-2 complete genome nucleotide sequences from samples collected between March 2020 and mid-February 2022 in the Dominican Republic were obtained from the Global Initiative on Sharing All Influenza Data (GISAID) database. Phylogenetic relationships and evolution rates were analyzed using the maximum likelihood method and the Bayesian Markov chain Monte Carlo (MCMC) approach. The genotyping details (lineages) were obtained using the Pangolin web application. In addition, the web tools Coronapp, and Genome Detective Viral Tools, among others, were used to monitor epidemiological characteristics. Our results show that the most frequent non-synonymous mutation over the study period was D614G. Of the 1149 samples, 870 (75.74%) were classified into 8 relevant variants according to Pangolin/Scorpio. The first Variants Being Monitored (VBM) were detected in December 2020. Meanwhile, in 2021, the variants of concern Delta and Omicron were identified. The mean mutation rate was estimated to be 1.5523 × 10−3 (95% HPD: 1.2358 × 10−3, 1.8635 × 10−3) nucleotide substitutions per site. We also report the emergence of an autochthonous SARS-CoV-2 lineage, B.1.575.2, that circulated from October 2021 to January 2022, in co-circulation with the variants of concern Delta and Omicron. The impact of B.1.575.2 in the Dominican Republic was minimal, but it then expanded rapidly in Spain. A better understanding of viral evolution and genomic surveillance data will help to inform strategies to mitigate the impact on public health.
Renata Gili,
Published: 10 April 2023
Journal: Journal of Translational Medicine
Journal of Translational Medicine, Volume 21, pp 1-6; https://doi.org/10.1186/s12967-023-04095-6
Abstract:
For the first time in the history of medicine, it has been possible to describe—after a spillover—the evolution of a new human virus spreading in a non-immune population. This allowed not only to observe the subsequent emersion of variants endowed with features providing the virus with an evolutionary advantage, but also the shift of the pathways of virus replication and the acquisition of immunoevasive features. These characteristics had a remarkable influence on the diffusion of the SARS-CoV-2 and on the clinical presentation and prognosis of COVID-19, aspects that are described and commented in this review.
Diagnostics, Volume 13; https://doi.org/10.3390/diagnostics13081364
Abstract:
Shortly after its emergence, Omicron and its sub-variants have quickly replaced the Delta variant during the current COVID-19 outbreaks in Vietnam and around the world. To enable the rapid and timely detection of existing and future variants for epidemiological surveillance and diagnostic applications, a robust, economical real-time PCR method that can specifically and sensitively detect and identify multiple different circulating variants is needed. The principle of target- failure (TF) real-time PCR is simple. If a target contains a deletion mutation, then there is a mismatch with the primer or probe, and the real-time PCR will fail to amplify the target. In this study, we designed and evaluated a novel multiplex RT real-time PCR (MPL RT-rPCR) based on the principle of target failure to detect and identify different variants of SARS-CoV-2 directly from the nasopharyngeal swabs collected from COVID-19 suspected cases. The primers and probes were designed based on the specific deletion mutations of current circulating variants. To evaluate the results from the MPL RT-rPCR, this study also designed nine pairs of primers for amplifying and sequencing of nine fragments from the S gene containing mutations of known variants. We demonstrated that (i) our MPL RT-rPCR was able to accurately detect multiple variants that existed in a single sample; (ii) the limit of detection of the MPL RT-rPCR in the detection of the variants ranged from 1 to 10 copies for Omicron BA.2 and BA.5, and from 10 to 100 copies for Delta, Omicron BA.1, recombination of BA.1 and BA.2, and BA.4; (iii) between January and September 2022, Omicron BA.1 emerged and co-existed with the Delta variant during the early period, both of which were rapidly replaced by Omicron BA.2, and this was followed by Omicron BA.5 as the dominant variant toward the later period. Our results showed that SARS-CoV-2 variants rapidly evolved within a short period of time, proving the importance of a robust, economical, and easy-to-access method not just for epidemiological surveillance but also for diagnoses around the world where SARS-CoV-2 variants remain the WHO’s highest health concern. Our highly sensitive and specific MPL RT-rPCR is considered suitable for further implementation in many laboratories, especially in developing countries.
,
,
, Rockib Uddin, Zoe Levine, Ben Kotzen, Katelyn S. Messer, Sabrina T. Dobbins, Katherine C. DeRuff, Christine M. Loreth, et al.
Published: 6 April 2023
Journal: The New England Journal of Medicine
The New England Journal of Medicine, Volume 388, pp 1335-1337; https://doi.org/10.1056/nejmc2216153
Dongchun Ni, Priscilla Turelli, Bertrand Beckert, Sergey Nazarov, Emiko Uchikawa, Alexander Myasnikov, Florence Pojer, Didier Trono,
,
PLOS Pathogens, Volume 19; https://doi.org/10.1371/journal.ppat.1011206
Abstract:
Investigation of potential hosts of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is crucial to understanding future risks of spillover and spillback. SARS-CoV-2 has been reported to be transmitted from humans to various animals after requiring relatively few mutations. There is significant interest in describing how the virus interacts with mice as they are well adapted to human environments, are used widely as infection models and can be infected. Structural and binding data of the mouse ACE2 receptor with the Spike protein of newly identified SARS-CoV-2 variants are needed to better understand the impact of immune system evading mutations present in variants of concern (VOC). Previous studies have developed mouse-adapted variants and identified residues critical for binding to heterologous ACE2 receptors. Here we report the cryo-EM structures of mouse ACE2 bound to trimeric Spike ectodomains of four different VOC: Beta, Omicron BA.1, Omicron BA.2.12.1 and Omicron BA.4/5. These variants represent the oldest to the newest variants known to bind the mouse ACE2 receptor. Our high-resolution structural data complemented with bio-layer interferometry (BLI) binding assays reveal a requirement for a combination of mutations in the Spike protein that enable binding to the mouse ACE2 receptor.
Ikechukwu B Jacob, Amanda Gemmiti, Weichuan Xiong, Erin Reynolds, Brian Nicholas,
, Hongpeng Jia,
Published: 3 April 2023
Abstract:
SARS coronavirus 2 (SARS-CoV-2) infects human angiotensin-converting enzyme 2 (hACE2)-expressing lung epithelial cells through its spike (S) protein. The S protein is highly glycosylated and could be a target for lectins. Surfactant protein A (SP-A) is a collagen-containing C-type lectin, expressed by mucosal epithelial cells and mediates its antiviral activities by binding to viral glycoproteins. This study examined the mechanistic role of human SP-A in SARS-CoV-2 infectivity. The interactions between human SP-A and SARS-CoV-2 S protein and hACE2 receptor, and SP-A level in COVID-19 patients were assessed by ELISA. The effect of SP-A on SARS-CoV-2 infectivity was analyzed by infecting human lung epithelial cells (A549-ACE2) with pseudoviral particles and infectious SARS-CoV-2 (Delta variant) pre-incubated with SP-A. Virus binding, entry, and infectivity were assessed by RT-qPCR, immunoblotting, and plaque assay. The results showed that human SP-A can bind SARS-CoV-2 S protein/RBD and hACE2 in a dose-dependent manner (p<0.01). Human SP-A inhibited virus binding and entry, and reduce viral load in lung epithelial cells, evidenced by the dose-dependent decrease in viral RNA, nucleocapsid protein, and titer (p<0.01). Increased SP-A level was observed in the saliva of COVID-19 patients compared to healthy controls (p<0.05), but severe COVID-19 patients had relatively lower SP-A levels than moderate COVID-19 patients (p<0.05). Therefore, SP-A plays an important role in mucosal innate immunity against SARS-CoV-2 infectivity by directly binding to the S protein and inhibiting its infectivity in host cells. SP-A level in the saliva of COVID-19 patients might serve as a biomarker for COVID-19 severity.
Fabien Le Chevalier, Pierre Authié, Sébastien Chardenoux,
, Benjamin Vesin, Delphine Cussigh, Yohann Sassier,
,
, Kirill Nemirov, et al.
Microbes and Infection; https://doi.org/10.1016/j.micinf.2023.105142
Abstract:
Human Angiotensin-Converting Enzyme 2 (hACE2) is the major receptor enabling host cell invasion by SARS-CoV-2 via interaction with Spike. The murine ACE2 does not interact efficiently with SARS-CoV-2 Spike and therefore the laboratory mouse strains are not permissive to SARS-CoV-2 replication. Here, we generated new hACE2 transgenic mice, which harbor the hACE2 gene under the human keratin 18 promoter, in "HHD-DR1" background. HHD-DR1 mice are fully devoid of murine Major Histocompatibility Complex (MHC) molecules of class-I and -II and express only MHC molecules from Human Leukocyte Antigen (HLA) HLA 02.01, DRA01.01, DRB1.01.01 alleles, widely expressed in human populations. We selected three transgenic strains, with various hACE2 mRNA expression levels and distinctive profiles of lung and/or brain permissiveness to SARS-CoV-2 replication. These new hACE2 transgenic strains display high permissiveness to the replication of SARS-CoV-2 Omicron sub-variants, while the previously available B6.K18-ACE22Prlmn/JAX mice have been reported to be poorly susceptible to infection with Omicron. As a first application, one of these MHC- and ACE2-humanized strains was successfully used to show the efficacy of a lentiviral-based COVID-19 vaccine.
iScience, Volume 26; https://doi.org/10.1016/j.isci.2023.106540
Abstract:
SARS-CoV-2 variants evade current monoclonal antibody therapies. Bispecific antibodies (bsAbs) combine the specificities of two distinct antibodies taking advantage of the avidity and synergy provided by targeting different epitopes. Here we used controlled Fab-arm exchange to produce bsAbs that neutralize SARS-CoV and SARS-CoV-2 variants, including Omicron and its subvariants, by combining potent SARS-CoV-2-specific neutralizing antibodies with broader antibodies that also neutralize SARS-CoV. We demonstrated that the parental antibodies rely on avidity for neutralization using bsAbs containing one irrelevant Fab arm. Using mass photometry to measure the formation of antibody:spike complexes, we determined that bsAbs increase binding stoichiometry compared to corresponding cocktails, without a loss of binding affinity. The heterogeneous binding pattern of bsAbs to spike, observed by negative-stain electron microscopy and mass photometry provided evidence for both intra- and inter-spike crosslinking. This study highlights the utility of cross-neutralizing antibodies for designing bivalent agents to combat circulating and future SARS-like coronaviruses.
Negar Firouzabadi, Parisa Ghasemiyeh, Fatemeh Moradishooli,
International Immunopharmacology, Volume 117; https://doi.org/10.1016/j.intimp.2023.109968
Anouschka Akerman,
Vanessa Milogiannakis, Tyra Jean,
,
Mariana Ruiz Silva, Timothy Ison, Christina Fichter, Joseph A. Lopez, Deborah Chandra, Zin Naing, et al.
Ebiomedicine, Volume 90; https://doi.org/10.1016/j.ebiom.2023.104545
The publisher has not yet granted permission to display this abstract.
Published: 29 March 2023
by
IntechOpen
Abstract:
In the genomic medicine era, the emergence of SARS-CoV-2 was immediately followed by viral genome sequencing and world-wide sequences sharing. Almost in real-time, based on these sequences, resources were developed and applied around the world, such as molecular diagnostic tests, informed public health decisions, and vaccines. Molecular SARS-CoV-2 variant surveillance was a normal approach in this context yet, considering that the viral genome modification occurs commonly in viral replication process, the challenge is to identify the modifications that significantly affect virulence, transmissibility, reduced effectiveness of vaccines and therapeutics or failure of diagnostic tests. However, assessing the importance of the emergence of new mutations and linking them to epidemiological trend, is still a laborious process and faster phenotypic evaluation approaches, in conjunction with genomic data, are required in order to release timely and efficient control measures.
, Carolina Lucas, Bridget Menasche, Mallery I Breban, Inci Yildirim, Melissa Campbell, Saad B Omer,
, Albert I Ko, Nathan D Grubaugh, et al.
Genome Biology and Evolution, Volume 15; https://doi.org/10.1093/gbe/evad052
Abstract:
Developing a timely and effective response to emerging SARS-CoV-2 variants of concern (VOCs) is of paramount public health importance. Global health surveillance does not rely on genomic data alone to identify concerning variants when they emerge. Instead, methods that utilize genomic data to estimate the epidemiological dynamics of emerging lineages have the potential to serve as an early warning system. However, these methods assume that genomic data are uniformly reported across circulating lineages. In this study, we analyze differences in reporting delays among SARS-CoV-2 VOCs as a plausible explanation for the timing of the global response to the former VOC Mu. Mu likely emerged in South America in mid-2020, where its circulation was largely confined. In this study, we demonstrate that Mu was designated as a VOC ∼1 year after it emerged and find that the reporting of genomic data for Mu differed significantly than that of other VOCs within countries, states, and individual laboratories. Our findings suggest that nonsystematic biases in the reporting of genomic data may have delayed the global response to Mu. Until they are resolved, the surveillance gaps that affected the global response to Mu could impede the rapid and accurate assessment of future emerging variants.
Diagnostics, Volume 13; https://doi.org/10.3390/diagnostics13071280
Abstract:
Immune memory to SARS-CoV-2 is key for establishing herd immunity and limiting the spread of the virus. The duration and qualities of T-cell-mediated protection in the settings of constantly evolving pathogens remain an open question. We conducted a cross-sectional study of SARS-CoV-2-specific CD4+ and CD8+ T-cell responses at several time points over 18 months (30–750 days) post mild/moderate infection with the aim to identify suitable methods and biomarkers for evaluation of long-term T-cell memory in peripheral blood. Included were 107 samples from 95 donors infected during the periods 03/2020–07/2021 and 09/2021–03/2022, coinciding with the prevalence of B.1.1.7 (alpha) and B.1.617.2 (delta) variants in Bulgaria. SARS-CoV-2-specific IFNγ+ T cells were measured in ELISpot in parallel with flow cytometry detection of AIM+ total and stem cell-like memory (TSCM) CD4+ and CD8+ T cells after in vitro stimulation with peptide pools corresponding to the original and delta variants. We show that, unlike IFNγ+ T cells, AIM+ virus-specific CD4+ and CD8+ TSCM are more adequate markers of T cell memory, even beyond 18 months post-infection. In the settings of circulating and evolving viruses, CD8+ TSCM is remarkably stable, back-differentiated into effectors, and delivers immediate protection, regardless of the initial priming strain.
RSC Advances, Volume 13, pp 9800-9810; https://doi.org/10.1039/d3ra00198a
Abstract:
SARS-CoV-2 has continuously evolved as changes in the genetic code occur during replication of the genome, with some of the mutations leading to higher transmission among human beings.
PLoS ONE, Volume 18; https://doi.org/10.1371/journal.pone.0283473
Abstract:
SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.
Published: 23 March 2023
Journal: DÜMF Mühendislik Dergisi
DÜMF Mühendislik Dergisi, Volume 14, pp 17-26; https://doi.org/10.24012/dumf.1195600
Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to coronaviridae family and a change in the genetic sequence of SARS-CoV-2 is named as a mutation that causes to variants of SARS-CoV-2. In this paper, we propose a novel and efficient method to predict SARS-CoV-2 variants of concern from whole human genome sequences. In this method, we describe 16 dinucleotide and 64 trinucleotide features to differentiate SARS-CoV-2 variants of concern. The efficacy of the proposed features is proved by using four classifiers, k-nearest neighbor, support vector machines, multilayer perceptron, and random forest. The proposed method is evaluated on the dataset including 223,326 complete human genome sequences including recently designated variants of concern, Alpha, Beta, Gamma, Delta, and Omicron variants. Experimental results present that overall accuracy for detecting SARS-CoV-2 variants of concern remarkably increases when trinucleotide features rather than dinucleotide features are used. Furthermore, we use the whale optimization algorithm, which is a state-of-the-art method for reducing the number of features and choosing the most relevant features. We select 44 trinucleotide features out of 64 to differentiate SARS-CoV-2 variants with acceptable accuracy as a result of the whale optimization method. Experimental results indicate that the SVM classifier with selected features achieves about 99% accuracy, sensitivity, specificity, precision on average. The proposed method presents an admirable performance for detecting SARS-CoV-2 variants.
Xi-Ru Zhang, Qi Fu, Jin-Dong Wang, Qing-Mei Huang, Wei-Qi Song, Xiao-Yu Xu, Zhi-Hao Li,
BMC Public Health, Volume 23, pp 1-10; https://doi.org/10.1186/s12889-023-15294-7
Abstract:
Background: COVID-19, which is caused by SARS-CoV-2, is a major global health threat. The dominant variant of SARS-CoV-2 has changed over time due to continuous evolution. We aimed to evaluate the coverage of SARS-CoV-2 vaccination among employees in China, explore their willingness to receive the SARS-CoV-2 variant vaccine and examine the potential factors influencing vaccination coverage and willingness. Methods: A cross-sectional epidemiological survey was conducted online from January 1, 2022, to January 30, 2022. The information collected in the survey included sociodemographic characteristics, lifestyle habits, vaccination coverage, willingness to be vaccinated against SARS-CoV-2 variants and the reasons for vaccination and willingness. Multivariable logistic regression models were used to assess the associations of potential factors with the rate of vaccination and the willingness to be vaccinated. Results: Among 62,395 eligible participants, the coverage of SARS-CoV-2 vaccination was 98.9% for at least one dose and 70.1% for a booster. The great majority of vaccinated individuals (94.4%) voluntarily received the vaccine. A total of 60,694 respondents (97.7%) were willing to be vaccinated against SARS-CoV-2 variants, mainly due to confidence in the effectiveness of vaccines (92.8%). A total of 1431 respondents were unwilling to be vaccinated, mainly because of concerns about the adverse effects of vaccines (77.6%). Longer education duration was associated with a higher rate of SARS-CoV-2 vaccination and willingness to be vaccinated. General or poor health status and having no history of influenza vaccination were associated with a lower rate of SARS-CoV-2 vaccination and willingness to be vaccinated. Additionally, we observed a significant positive association of abuse experience with the willingness to be vaccinated. Conclusion: Although the rate of SARS-CoV-2 vaccination and the willingness to be vaccinated were relatively high in the study population, there were still some respondents with vaccine hesitancy. Relevant strategies based on significant related factors should be developed and implemented to encourage vaccination.
Muhannad Alruwaili, Stuart Armstrong, Tessa Prince, Maximilian Erdmann,
, Andrew Davidson, Waleed Aljabr,
Published: 20 March 2023
Abstract:
Summary: SARS-CoV-2 emerged into the human population in late 2019 and human to human transmission has dominated the evolutionary landscape and driven the selection of different lineages. The first major change that resulted in increased transmission was the D614G substitution in the spike protein. This was accompanied by the P323L substitution in the viral RNA dependent RNA polymerase (RdRp) (NSP12). Together, with D614G these changes are the root of the predominant global SARS-CoV-2 landscape. Here, we found that NSP12 formed an interactome with cellular proteins. The functioning of NSP12 was dependent on the T-complex protein Ring Complex, a molecular chaperone. In contrast, there was differential association between NSP12 variants and components of a phosphatase complex (PP2/PP2A and STRN3). Virus expressing NSP12L323was less sensitive to perturbations in PP2A and supports the paradigm that ongoing genotype to phenotype adaptation of SARS- CoV-2 in humans is not exclusively restricted to the spike protein.