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1.
biorxiv; 2023.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2023.09.14.557399

ABSTRACT

Viral entry is mediated by oligomeric proteins on the virus and cell surfaces. The association is therefore open to multivalent interactions between these proteins, yet such recognition is typically rationalised as affinity between monomeric equivalents. As a result, assessment of the thermodynamic mechanisms that control viral entry has been limited. Here, we use mass photometry to overcome the analytical challenges consequent to multivalency. Examining the interaction between the spike protein of SARS-CoV-2 and the ACE2 receptor, we find that ACE2 induces oligomerisation of spike in a variant- dependent fashion. We also demonstrate that patient-derived antibodies use induced-oligomerisation as a primary inhibition mechanism or to enhance the effects of receptor-site blocking. Our results reveal that naive affinity measurements are poor predictors of potency, and introduce a novel antibody-based inhibition mechanism for oligomeric targets.

2.
J Ambient Intell Humaniz Comput ; 14(7): 9651-9665, 2023.
Article in English | MEDLINE | ID: covidwho-20237433

ABSTRACT

The COVID-19 outbreak has forced people to stay at home to prevent the spread of the virus. In this case, social media platforms have become the main communication venue for people. Online sales platforms have also become the main field for people's daily consumption. So, how to make full use of social media to carry out online advertising promotion, and then achieve better marketing, is one of the core issues that the marketing industry must pay attention to and solve. Therefore, this study takes the advertiser as the decision-maker, maximizes the number of full playing, likes, comments and forwarding, and minimizes the cost of advertising promotion as the decision-making goals, and Key Opinion Leader (KOL) selection as the decision vector. Based on this, a multi-objective uncertain programming model of advertising promotion is constructed. Among them, the chance-entropy constraint is proposed by combining the entropy constraint and the chance constraint. In addition, the multi-objective uncertain programming model is transformed into a clear single-objective model through mathematical derivation and linear weighting of the model. Finally, the practicability and effectiveness of the model are verified by numerical simulation, and decision-making suggestions for advertising promotion are put forward.

3.
Sustainability ; 15(11):9087, 2023.
Article in English | ProQuest Central | ID: covidwho-20238774

ABSTRACT

Plastic pollution is recognized as one of the most urgent global environmental concerns. China is the top producer and consumer of plastics and creates the most plastic waste globally. To evaluate policy options to control plastic pollution in China, we first reviewed the relevant policies and action plans in place. Then, we examined plastic-material flows and changes at the national level based on officially published data to evaluate the current situation and efficacy of policies at the macro-level. Results showed that 2016, the start of the 13th Five-Year Plan, was a pivotal year in the history of China's plastic policies tackling plastic issues nationally and internationally. Since 2016, the growth trend in the production and consumption of plastic products has slowed and the recycling rate has risen, surpassing 30% in 2021. To further tackle plastic pollution, key suggestions with important policy implications were provided, covering better integration of policies, the combined management of vertical–horizontal governance, tracking-system implementation, the introduction of a quality-certification system, the development of behaviour-based consumer-oriented solutions, the promotion of stakeholder collaboration, and the need for appropriate post-COVID-19 policies.

4.
American Journal of Clinical Pathology, suppl 1 ; 158:S9-S10, 2022.
Article in English | ProQuest Central | ID: covidwho-20236747

ABSTRACT

Objectives Human leukocyte antigens (HLA) are highly diverse transmembrane proteins that present viral peptides to T cells and launch pathogen-specific immune responses. We aim to investigate the correlation between HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of SARS-CoV-2 infection in a cohort from the St. Louis Metropolitan area. Methods We enrolled adult patients with SARS-CoV-2 infection confirmed by RT-PCR who were hospitalized at two tertiary hospitals in St. Louis between March and July 2020. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HLA alleles were assigned based on key-exon sequences (G group) and limited to the 2-field resolution. HED was calculated by Grantham distance, which considers the difference in composition, polarity, and molecular volume between each pair of amino acids from maternal and paternal HLA. The HED score was obtained for HLA class I (HLA-A, -B, and -C) genotypes using the HLAdivR package in R. Clinical data were collected retrospectively from electronic medical records. A poor outcome was defined as an admission to the intensive care unit (ICU), a need for mechanical ventilation, or death. A favorable outcome was defined as the absence of the above poor outcomes. Results A total of 234 patients were enrolled in this study, 96 being females (41%). The median age and BMI were 66 years old and 28.30 kg/m2, respectively. African Americans comprised 71.4% of the cohort. Only 19 patients (8.1%) presented with no comorbidity;the rest had one or more comorbidities, with cardiovascular diseases being the most common. A total of 137 (58.5%) patients had poor outcomes from SARS-CoV-2 infection, while 97 (41.5%) patients had a favorable outcome. We detected a significant association between higher HLA-B HED and favorable outcomes, with each 1-point increase in HLA-B HED associated with 8% increased probability for the composite endpoint (OR 1.08, 95% CI=1.01-1.16, P = 0.04). The HED scores calculated for HLA-A or HLA-C were not significantly different between patients with favorable or poor outcomes. In a multivariate logistic regression analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). Conclusion Our study shows a significant correlation between lower HLA-B HED scores and poor outcomes after SARS-CoV-2 infection. This finding suggests that maximizing the presentation of diverse SARS-CoV-2 peptides by HLA-B alleles may improve the clearance of SARS-CoV-2. Further studies are warranted to understand the functional and mechanistic implications of this finding.

5.
Electronics ; 12(11):2394, 2023.
Article in English | ProQuest Central | ID: covidwho-20236135

ABSTRACT

Sleep staging has always been a hot topic in the field of sleep medicine, and it is the cornerstone of research on sleep problems. At present, sleep staging heavily relies on manual interpretation, which is a time-consuming and laborious task with subjective interpretation factors. In this paper, we propose an automatic sleep stage classification model based on the Bidirectional Recurrent Neural Network (BiRNN) with data bundling augmentation and label redirection for accurate sleep staging. Through extensive analysis, we discovered that the incorrect classification labels are primarily concentrated in the transition and nonrapid eye movement stage I (N1). Therefore, our model utilizes a sliding window input to enhance data bundling and an attention mechanism to improve feature enhancement after label redirection. This approach focuses on mining latent features during the N1 and transition periods, which can further improve the network model's classification performance. We evaluated on multiple public datasets and achieved an overall accuracy rate of 87.3%, with the highest accuracy rate reaching 93.5%. Additionally, the network model's macro F1 score reached 82.5%. Finally, we used the optimal network model to study the impact of different EEG channels on the accuracy of each sleep stage.

6.
Int J Soc Psychiatry ; 69(4): 916-927, 2023 06.
Article in English | MEDLINE | ID: covidwho-20238631

ABSTRACT

BACKGROUND: Returning to social life after the lifting of COVID-19 lockdown may increase risk of social anxiety, which is highly co-morbid with depression. However, few studies have reported the association between them. AIMS: To explore the complex relationship between social anxiety and depression symptoms in left-behind children after the lifting of the COVID-19 lockdown. METHODS: A cross-sectional survey was conducted 6 months after the lockdown removal. A total of 3,107 left-behind children completed the survey with a mean age of 13.33 and a response rate of 87.77%. Depression and social anxiety severity were assessed by the DSM-5 Patient Health Questionnaire for Adolescents and the DSM-5 Social Anxiety Disorder Questionnaire, respectively. The symptom-level association between the two disorders was examined using network analysis. RESULTS: After the lifting of COVID-19 lockdown, the prevalence of depression and social anxiety in left-behind children was 19.57% and 12.36%, respectively, with a co-morbidity rate of 8.98%. Network analysis showed that "Social tension" and "Social avoidance" had the greatest expected influence; "Humiliation" and "Motor" were bridge symptom nodes in the network. The directed acyclic graph indicated that "Social fright" was at the upstream of all symptoms. CONCLUSION: Attention should be paid to social anxiety symptoms in left-behind children after the lifting of COVID-19 lockdown. Prevention and intervention measures should be taken promptly to reduce the comorbidity of social anxiety and depression symptoms in the left-behind children after the lifting of lockdown.


Subject(s)
COVID-19 , Adolescent , Humans , Child , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , Depression/epidemiology , Cross-Sectional Studies , East Asian People , Communicable Disease Control , Anxiety/epidemiology
7.
Gut Microbes ; 15(1): 2223340, 2023.
Article in English | MEDLINE | ID: covidwho-20242837

ABSTRACT

The antibiotic resistome is the collection of all antibiotic resistance genes (ARGs) present in an individual. Whether an individual's susceptibility to infection and the eventual severity of coronavirus disease 2019 (COVID-19) is influenced by their respiratory tract antibiotic resistome is unknown. Additionally, whether a relationship exists between the respiratory tract and gut ARGs composition has not been fully explored. We recruited 66 patients with COVID-19 at three disease stages (admission, progression, and recovery) and conducted a metagenome sequencing analysis of 143 sputum and 97 fecal samples obtained from them. Respiratory tract, gut metagenomes, and peripheral blood mononuclear cell (PBMC) transcriptomes are analyzed to compare the gut and respiratory tract ARGs of intensive care unit (ICU) and non-ICU (nICU) patients and determine relationships between ARGs and immune response. Among the respiratory tract ARGs, we found that Aminoglycoside, Multidrug, and Vancomycin are increased in ICU patients compared with nICU patients. In the gut, we found that Multidrug, Vancomycin, and Fosmidomycin were increased in ICU patients. We discovered that the relative abundances of Multidrug were significantly correlated with clinical indices, and there was a significantly positive correlation between ARGs and microbiota in the respiratory tract and gut. We found that immune-related pathways in PBMC were enhanced, and they were correlated with Multidrug, Vancomycin, and Tetracycline ARGs. Based on the ARG types, we built a respiratory tract-gut ARG combined random-forest classifier to distinguish ICU COVID-19 patients from nICU patients with an AUC of 0.969. Cumulatively, our findings provide some of the first insights into the dynamic alterations of respiratory tract and gut antibiotic resistome in the progression of COVID-19 and disease severity. They also provide a better understanding of how this disease affects different cohorts of patients. As such, these findings should contribute to better diagnosis and treatment scenarios.


Subject(s)
COVID-19 , Gastrointestinal Microbiome , Humans , Anti-Bacterial Agents , Vancomycin , Leukocytes, Mononuclear , Respiratory System , Patient Acuity
8.
Nurs Open ; 2023 May 29.
Article in English | MEDLINE | ID: covidwho-20241889

ABSTRACT

AIM: To explore the nursing workforce allocation in intensive care units (ICUs) of COVID-19-designated hospitals during the epidemic peak in China. DESIGN: A nationwide cross-sectional online survey. METHODS: A total of 37 head nurses and 262 frontline nurses in 37 ICUs of COVID-19-designated tertiary hospitals located in 22 cities of China were surveyed. The self-reported human resource allocation questionnaire was used to assess the nursing workforce allocation. RESULTS: The average patient-to-nurse ratio was 1.89 ± 1.14, and the median working hours per shift was 5 h. The top four majors of front-line nurses in ICUs were respiratory (31.30%), lemology (27.86%), intensive care (21.76%) and emergency (17.18%). We also found that a smaller average patient-to-nurse ratio (odds ratio [OR]: 0.328, 95% CI: 0.108, 1.000), longer average weekly rest time per person (OR: 0.193, 95% CI: 0.051, 0.729) and larger proportion of 6-9 working years (OR: 0.002, 95% CI: 0.001, 1.121) decreased the occurrence of nursing adverse events.

9.
Nat Commun ; 14(1): 3334, 2023 06 07.
Article in English | MEDLINE | ID: covidwho-20241659

ABSTRACT

COVID-19 patients at risk of severe disease may be treated with neutralising monoclonal antibodies (mAbs). To minimise virus escape from neutralisation these are administered as combinations e.g. casirivimab+imdevimab or, for antibodies targeting relatively conserved regions, individually e.g. sotrovimab. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to detect emerging drug resistance in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the antibody epitopes and for casirivimab+imdevimab multiple mutations are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , Antibodies, Monoclonal/therapeutic use , Immunotherapy , Mutation , Antibodies, Neutralizing , Antibodies, Viral
10.
Front Immunol ; 13: 952650, 2022.
Article in English | MEDLINE | ID: covidwho-2326989

ABSTRACT

Given pandemic risks of zoonotic SARS-CoV-2 variants and other SARS-like coronaviruses in the future, it is valuable to perform studies on conserved antigenic sites to design universal SARS-like coronavirus vaccines. By using antibodies obtained from convalescent COVID-19 patients, we succeeded in functional comparison of conserved antigenic sites at multiple aspects with each other, and even with SARS-CoV-2 unique antigenic sites, which promotes the cognition of process of humoral immune response to the conserved antigenic sites. The conserved antigenic sites between SARS-CoV-2 and SARS-CoV can effectively induce affinity maturation of cross-binding antibodies, finally resulting in broadly neutralizing antibodies against multiple variants of concern, which provides an important basis for universal vaccine design, however they are subdominant, putatively due to their lower accessibility relative to SARS-CoV-2 unique antigenic sites. Furthermore, we preliminarily design RBDs to improve the immunogenicity of these conserved antigenic sites. Our study focusing on conserved antigenic sites provides insights for promoting the development of universal SARS-like coronavirus vaccines, thereby enhancing our pandemic preparedness.


Subject(s)
COVID-19 , SARS-CoV-2 , Antibodies, Viral , Broadly Neutralizing Antibodies , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Spike Glycoprotein, Coronavirus/genetics
11.
Diabetes Res Clin Pract ; 201: 110723, 2023 Jul.
Article in English | MEDLINE | ID: covidwho-2324508

ABSTRACT

AIMS: Reports have suggested that COVID-19 vaccination may cause Type 1 diabetes (T1D), particularly fulminant T1D (FT1D). This study aimed to investigate the incidence of T1D in a general population of China, where>90% of the people have received three injections of inactivated SARS-Cov-2 vaccines in 2021. METHODS: A population-based registry of T1D was performed using data from the Beijing Municipal Health Commission Information Center. Annual incidence rates were calculated by age group and gender, and annual percentage changes were assessed using Joinpoint regression. RESULTS: The study included 14.14 million registered residents, and 7,697 people with newly diagnosed T1D were identified from 2007 to 2021. T1D incidence increased from 2.77 in 2007 to 3.84 per 100,000 persons in 2021. However, T1D incidence was stable from 2019 to 2021, and the incidence rate did not increase when people were vaccinated in January-December 2021. The incidence of FT1D did not increase from 2015 to 2021. CONCLUSIONS: The findings suggest that COVID-19 vaccination did not increase the onset of T1D or have a significant impact on T1D pathogenesis, at least not on a large scale.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 1 , Humans , Diabetes Mellitus, Type 1/epidemiology , Incidence , COVID-19 Vaccines/adverse effects , COVID-19/epidemiology , COVID-19/prevention & control , SARS-CoV-2 , China/epidemiology , Vaccination
12.
Journal of Statistical Computation and Simulation ; 93(8):1318-1336, 2023.
Article in English | ProQuest Central | ID: covidwho-2316644

ABSTRACT

The INAR(1) processes with coefficients , where c>0 is a fixed constant and is a deterministic sequence growing to infinity at a slower rate than n, which are often referred to as nearly unstable INAR processes with moderate deviations from a unit root. We consider some basic properties of the processes and obtain the conditional least squares estimation of the coefficient , which converges to a normal distribution at speed . The simulation study provides numerical support for the theoretical results. The practical utility is illustrated in the data sets about liquor offences, claims of short-term disability and COVID-19, respectively.

13.
Hum Immunol ; 83(12): 803-807, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2296407

ABSTRACT

We examined the correlation between class I HLA evolutionary divergence (HED), a surrogate for the capacity to present different peptides, and the outcomes of 234 adult inpatients with confirmed SARS-CoV-2 infection. Genomic DNA was extracted from peripheral blood and genotyped by next-generation sequencing (NGS). HED scores for HLA class I (HLA-A, -B, and -C) genotypes were calculated using Grantham's distance. Higher HED scores for HLA-B, but not HLA-A or -C, are significantly associated with a decreased probability of poor outcomes including ICU admission, mechanical ventilation, and death (OR = 0.93; P = 0.04) in the univariate analysis. In the multivariate analysis, increased HLA-B HED score, younger age, and no comorbidity were independently associated with favorable outcomes (P = 0.02, P = 0.01, and P = 0.05, respectively). This finding is consistent with the notion that broader peptide repertoires presented by class I HLA may be beneficial in infection control.


Subject(s)
COVID-19 , Adult , Humans , COVID-19/genetics , SARS-CoV-2 , Genotype , Hospitalization , HLA-B Antigens/genetics
14.
Smart Mater Med ; 4: 514-521, 2023.
Article in English | MEDLINE | ID: covidwho-2298947

ABSTRACT

Alleviating excessive inflammation while accelerating chronic wound healing to prevent wound infection has remained challenging, especially during the coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 when patients experienced difficulties with receive appropriate healthcare. We addressed this issue by developing handheld electrospun aloe-nanofiber membranes (ANFMs) with convenient, environmentally friendly properties and a therapeutic capacity for wound closure. Our results showed that ANFMs fabricated with high molecular weight polyvinyl alcohol (PVA) to form fibers during electrospinning had uniform fibrous architecture and a porous structure. Given the value of aloe gel in accelerating wound healing, liquid extracts from ANFMs significantly downregulated the expression of the pro-inflammatory genes, interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), and markedly suppress the generation of reactive oxygen species (ROS) induced by lipopolysaccharide in RAW264.7 macrophages. These results indicated the excellent antioxidant and anti-inflammatory effects of ANFMs. After implantation into a mouse diabetic wound model for 12 days in situ, ANFMs notably expedited chronic wound healing via promoting angiogenesis and enhancing cell viability. Our ANFMs generated by handheld electrospinning in situ healed chronic wounds offer a convenient and promising alternative for patients to heal their own wounds under variable conditions.

15.
Cell reports ; 2023.
Article in English | EuropePMC | ID: covidwho-2306169

ABSTRACT

Most existing studies characterising SARS-CoV-2-specific T cell responses are peptide based. This does not allow evaluation of whether tested peptides are processed and presented canonically. In this study, we use recombinant vaccinia virus (rVACV)-mediated expression of SARS-CoV-2 spike protein and SARS-CoV-2 infection of ACE-2-transduced B cell lines to evaluate overall T cell responses in a small cohort of recovered COVID-19 patients and uninfected donors vaccinated with ChAdOx1 nCoV-19. We show that rVACV expression of SARS-CoV-2 antigen can be used as an alternative to SARS-CoV-2 infection to evaluate T cell responses to naturally processed spike antigens. In addition, rVACV system can be used to evaluate the cross-reactivity of memory T cells to variants of concern (VOCs) and to identify epitope escape mutants. Finally, our data show that both natural infection and vaccination could induce multi-functional T cell responses with overall T cell responses remaining despite the identification of escape mutations. Graphical Yin et al. utilize two informative systems for evaluating overall T cell responses to SARS-CoV-2 and variants, enabling greater understanding of T cell responses to the virus, cross-reactivity to viral variants and the differences between vaccine- and infection-induced immunity to SARS-CoV-2, and other emerging viruses in the future.

16.
Sustainability ; 15(8):6424, 2023.
Article in English | ProQuest Central | ID: covidwho-2298885

ABSTRACT

As brand equity (BE) is a valuable, but intangible, asset of any firm, understanding BE represents a primary task for many organizations. Factors that influence the development of BE are of inordinate academic and practical significance and a source of continuous investigation. While the current literature on social media communication (SMC) and BE provides a wealth of information, our study pioneers the most recent processes of mediation and moderation of electronic word-of-mouth and product involvement (PI) in BE research. Accordingly, the results of this work will likely become one of the key sources of information in sustainable marketing planning and in the development of strategies. To accomplish this goal, we assessed the structural relationships among SMC, electronic word of mouth (e-WOM), PI, and BE. A questionnaire survey was administered concerning consumer brands in China. In this survey, due to the need for social distancing during the COVID-19 pandemic, the questionnaire was distributed and collected via the internet. A total of 369 data sets were analyzed by partial least squares structural equation modeling (PLS-SEM). The results of our investigation reveal that: (a) social media firm- and user-generated content have a positive impact on e-WOM, (b) social media firm- and user-generated content have a positive impact on BE, (c) e-WOM has a positive impact on BE and serves as an intermediary role between SMC and BE, and (d) PI exerts specific moderating effects between SMC and BE.

17.
Journal of Operations Management ; 69(3):450-476, 2023.
Article in English | ProQuest Central | ID: covidwho-2295421

ABSTRACT

The COVID‐19 pandemic has disrupted firms' operations. To cope with the crisis, many firms have allowed their employees to work from home (WFH). We examine whether a firm's WFH capacity has increased its resilience during the pandemic. We test the hypotheses using a unique data set that combines listed firms' financial statements, supply chain partners, and job postings on a leading online platform that provides hiring services. We find that imposing COVID‐19 anti‐contagion policies on firms and their suppliers or customers significantly increases their operating revenue volatility, slows their recovery, and has repercussions on their supply chains. WFH enhances firms' resistance capacity by reducing the effect of COVID‐19 on their operating revenue volatility and disruptions to their supply chain partners;however, it also decreases their recovery capacity by extending the time taken to return to normal. Firm attributes, along with workers' occupations, education, and experience, have an impact on the effect of WFH on firm resilience. This study enhances our understanding of shock transmission across supply chains and WFH as a source of firm resilience.

18.
Sci Rep ; 13(1): 4033, 2023 03 10.
Article in English | MEDLINE | ID: covidwho-2283657

ABSTRACT

In order to reduce infection risk of novel coronavirus (SARS-CoV-2), we developed nano-photocatalysts with nanoscale rutile TiO2 (4-8 nm) and CuxO (1-2 nm or less). Their extraordinarily small size leads to high dispersity and good optical transparency, besides large active surface area. Those photocatalysts can be applied to white and translucent latex paints. Although Cu2O clusters involved in the paint coating undergo gradual aerobic oxidation in the dark, the oxidized clusters are re-reduced under > 380 nm light. The paint coating inactivated the original and alpha variant of novel coronavirus under irradiation with fluorescent light for 3 h. The photocatalysts greatly suppressed binding ability of the receptor binding domain (RBD) of coronavirus (the original, alpha and delta variants) spike protein to the receptor of human cells. The coating also exhibited antivirus effects on influenza A virus, feline calicivirus, bacteriophage Qß and bacteriophage M13. The photocatalysts would be applied to practical coatings and lower the risk of coronavirus infection via solid surfaces.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/metabolism , Protein Denaturation , Spike Glycoprotein, Coronavirus/metabolism
19.
Cell Rep ; 42(4): 112271, 2023 Mar 07.
Article in English | MEDLINE | ID: covidwho-2257202

ABSTRACT

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent mAb binding shifting to 3 clusters, 2 corresponding to early-pandemic binding hotspots. The RBD mutations in recent variants map close to these binding sites and knock out or severely knock down neutralization activity of all but 1 potent mAb. This recent mAb escape corresponds with large falls in neutralization titer of vaccine or BA.1, BA.2, or BA.4/5 immune serum.

20.
Front Immunol ; 14: 1123913, 2023.
Article in English | MEDLINE | ID: covidwho-2254677

ABSTRACT

Background: COVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI. Materials and methods: A total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique. Results: We identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve > 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups. Conclusion: The present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.


Subject(s)
COVID-19 , MicroRNAs , Humans , Male , SARS-CoV-2 , Pandemics , Semen
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