Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection

Science Translational Medicine, Год журнала: 2025, Номер 17(783)

Опубликована: Янв. 29, 2025

At this stage in the COVID-19 pandemic, most infections are "breakthrough" that occur individuals with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure. To refine long-term vaccine strategies against emerging variants, we examined both innate and adaptive immunity breakthrough infections. We performed single-cell transcriptomic, proteomic, functional profiling of primary to compare immune responses from unvaccinated vaccinated during SARS-CoV-2 Delta wave. Breakthrough were characterized by a less activated transcriptomic profile monocytes natural killer cells, induction pathways limiting monocyte migratory potential cell proliferation. Furthermore, observed female-specific increase proteomic activation multiple subsets These insights suggest vaccination prevents overactivation discernible sex-specific patterns underscore harnessing vaccines mitigating pathologic resulting overactivation.

Язык: Английский

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Integrating Molecular Perspectives: Strategies for Comprehensive Multi-Omics Integrative Data Analysis and Machine Learning Applications in Transcriptomics, Proteomics, and Metabolomics

Biology, Год журнала: 2024, Номер 13(11), С. 848 - 848

Опубликована: Окт. 22, 2024

With the advent of high-throughput technologies, field omics has made significant strides in characterizing biological systems at various levels complexity. Transcriptomics, proteomics, and metabolomics are three most widely used each providing unique insights into different layers a system. However, analyzing data set separately may not provide comprehensive understanding subject under study. Therefore, integrating multi-omics become increasingly important bioinformatics research. In this article, we review strategies for transcriptomics, data, including co-expression analysis, metabolite-gene networks, constraint-based models, pathway enrichment interactome analysis. We discuss combined integration approaches, correlation-based strategies, machine learning techniques that utilize one or more types data. By presenting these methods, aim to researchers with better how integrate gain view system, facilitating identification complex patterns interactions might be missed by single-omics analyses.

Язык: Английский

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Next-generation treatments: Immunotherapy and advanced therapies for COVID-19

Heliyon, Год журнала: 2024, Номер 10(5), С. e26423 - e26423

Опубликована: Фев. 19, 2024

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 following prior outbreaks of coronaviruses like SARS and MERS recent decades, underscoring their high potential infectivity humans. Insights from previous have played a significant role developing effective strategies to mitigate the global impact SARS-CoV-2. As January 7, 2024, there been 774,075,242 confirmed cases worldwide. To date, 13.59 billion vaccine doses administered, 7,012,986 documented fatalities (https://www.who.int/)Despite progress addressing rapid evolution SARS-CoV-2 challenges human defenses, presenting ongoing challenges. emergence new lineages, shaped mutation recombination processes, has led successive waves infections. This scenario reveals need for next-generation vaccines as crucial requirement ensuring protection against demand calls formulations that trigger robust adaptive immune response without leading inflammation linked with infection.Key mutations detected Spike protein, critical target neutralizing antibodies design —specifically within Receptor Binding Domain region Omicron variant lineages (B.1.1.529), currently dominant worldwide, intensified concerns due association immunity evasion vaccinations infections.As world deals this evolving threat, narrative extends realm emerging variants, each displaying implications remain largely misunderstood. Notably, JN.1 lineage is gaining prevalence, early findings suggest it stands among immune-evading characteristic attributed its L455S. Moreover, detrimental consequences novel bear particularly on immunocompromised individuals older adults. Immunocompromised face such suboptimal responses vaccines, rendering them more susceptible disease. Similarly, adults an increased risk disease presence comorbid conditions, find themselves at heightened vulnerability develop Thus, recognizing these intricate factors effectively tailoring public health protect vulnerable populations. In context, review aims describe, analyze, discuss current treatments encompassing immunotherapeutic approaches advanced therapies complements will offer solutions counter disadvantages existing options. Preliminary outcomes show virus address immunomodulatory associated COVID-19. Furthermore, capacity promote tissue repair demonstrated, which can be noteworthy who stand actors landscape possess broader potential, offering wide range variants enhancing ability constant virus. are projected treatment alternatives managing Chronic Post-COVID-19 syndromeand long-term complications.

Язык: Английский

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A comparative cohort study of post-COVID-19 conditions based on physical examination records in China

EBioMedicine, Год журнала: 2025, Номер 112, С. 105549 - 105549

Опубликована: Янв. 5, 2025

Язык: Английский

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Deciphering the omicron variant: integrated omics analysis reveals critical biomarkers and pathophysiological pathways

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Фев. 29, 2024

The rapid emergence and global dissemination of the Omicron variant SARS-CoV-2 have posed formidable challenges in public health. This scenario underscores urgent need for an enhanced understanding Omicron's pathophysiological mechanisms to guide clinical management shape health strategies. Our study is aimed at deciphering intricate molecular underlying infections, particularly focusing on identification specific biomarkers.

Язык: Английский

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An allelic atlas of immunoglobulin heavy chain variable regions reveals antibody binding epitope preference resilient to SARS-CoV-2 mutation escape

Frontiers in Immunology, Год журнала: 2025, Номер 15

Опубликована: Янв. 7, 2025

Although immunoglobulin (Ig) alleles play a pivotal role in the antibody response to pathogens, research understand their humoral immune is still limited. We retrieved germline sequences for IGHV from IMGT database illustrate amino acid polymorphism present within of genes. aassembled IgM and IgD repertoire 130 people investigate genetic variations population. A dataset comprising 10,643 SARS-CoV-2 spike-specific antibodies, obtained COV-AbDab, was compiled assess impact infection on allelic gene utilization. Binding affinity neutralizing activity were determined using bio-layer interferometry pseudovirus neutralization assays. Primary docking performed ZDOCK (3.0.2) generate initial conformation antigen-antibody complex, followed by simulations complete conformations Rosetta SnugDock software. The original simulated structural visualized presented ChimeraX (v1.5). an atlas heavy chain (IgH) variable regions, illustrating diversity variants across 33 family sequencing IgH Our comprehensive analysis antibodies revealed preferential use specific Ig among these antibodies. observed association between binding epitopes. Different genotypes same RBD epitope spike show different potency breadth. found that carrying IGHV1-69*02 allele tended bind E2.2 epitope. G50 L55 residues exhibit potential enhancements containing L452R mutation RBD, whereas R50 F55 tend have reduced potency. IGHV2-5*02 D56 D2 with greater due interaction HCDR2 K444 most Omicron subvariants. In contrast, IGHV2-5*01 N56 increased resistance K444T RBD. This study provides valuable insights into responses perspective population genetics. These findings underscore importance vaccine design therapeutic development.

Язык: Английский

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4D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection

Journal of Proteome Research, Год журнала: 2025, Номер 24(2), С. 499 - 514

Опубликована: Янв. 13, 2025

Since late 2021, Omicron variants have dominated the epidemiological scenario as most successful severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineages, driving new and breakthrough infections globally over past two years. In this study, we investigated for first time host salivary response of COVID-19 patients infected with (BA.1, BA.2, BA.4/5) by using an untargeted four-dimensional data-independent acquisition (4D-DIA)-based proteomics approach. We identified 137 proteins whose abundance levels differed between positive negative groups. Salivary signatures were mainly enriched in ribosomal proteins, linked to mRNAviral translation, protein synthesis processing, immune innate, antiapoptotic signaling. The higher 14-3-3 (YWHAG, YWHAQ, YWHAE, SFN) saliva, reported here, may be associated increased infectivity improved viral replicative fitness. also seven (ACTN1, H2AC2, GSN, NDKA, CD109, GGH, PCYOX) that yielded comprehension into infection performed outstandingly screening a hospital setting. This panel presented enhanced anti-COVID-19 anti-inflammatory signature, providing insights disease severity, supported comparisons other proteome data sets. signature provided valuable host's SARS-CoV-2 infection, shedding light on pathophysiology COVID-19, particularly cases mild disease. It underscores potential clinical applications saliva settings. Data are available via ProteomeXchange identifier PXD054133.

Язык: Английский

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Antiviral Activity and Underlying Mechanism of Moslae Herba Aqueous Extract for Treating SARS-CoV-2

Molecules, Год журнала: 2025, Номер 30(2), С. 387 - 387

Опубликована: Янв. 17, 2025

Despite the widespread use of COVID-19 vaccines, there is still a global need to find effective therapeutics deal with variants SARS-CoV-2. Moslae herba (MH) herbal medicine credited antiviral effects. This study aims investigate effects and underlying mechanism aqueous extract (AEMH) for treating The in vitro anti-SARS-CoV-2 activity AEMH was evaluated using cell viability viral load. Component analysis performed by HPLC-ESI-Q-TOF/MS. connection between constructed integrating network pharmacology transcriptome profiles seek core targets. components activities were analyzed molecular docking pharmacological verification. exerted inhibiting replication reducing death caused infection (IC50 170 μg/mL omicron strain). A total 27 identified from AEMH. Through matching 119 intersection targets ‘disease drug’ 1082 differentially expressed genes patients, nine screened. Of nine, PNP TPI1 as treatment significantly regulated mRNA expression level two on infected cells. Three components, caffeic acid, luteolin, rosmarinic displayed Molecular also demonstrated they could form stable bonds explored possible SARS-CoV-2, which provide basic data reference clinical application MH.

Язык: Английский

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Inhibition of platelet activation process upon tris (2-chloroethyl) phosphate exposure: Role of PFKP-mediated glycolysis and the pentose phosphate pathway

Environmental Pollution, Год журнала: 2025, Номер unknown, С. 125714 - 125714

Опубликована: Янв. 1, 2025

Язык: Английский

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Short-term antiretroviral therapy may not correct the dysregulations of plasma virome and cytokines induced by HIV-1 infection

Virulence, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

An expansion of plasma anelloviruses and dysregulation inflammation was associated with HIV-1 infection. However, how antiretroviral therapy (ART) affects the dynamics virome cytokine profile remains largely unknown. To characterize cytokines in HIV-1-infected individuals before during first year ART, a cohort 26 19 healthy controls recruited. Blood samples were collected subjected to metagenomic analysis measurement 27 cytokines. Metagenomic revealed an increased abundance prevalence human pegivirus type 1 (HPgV-1) slightly decreased diversity anellovirus after ART. No obvious impact observed on other commensal viruses. Increased HPgV-1 further confirmed by RT-qPCR assay larger 114 individuals. Notably, most dysregulated not fully restored extremely abnormal levels IL-10, GM-CSF, VEGF, eotaxin, significantly level I-FABP. Anelloviruses showed negative correlations viruses except HPgV-1, but had positive corrections several anti-inflammatory Th1 These results suggest that short-term ART may correct dysregulations induced The highlight need for investigation into long-term effect

Язык: Английский

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