Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis

BMJ, Journal Year: 2022, Volume and Issue: unknown, P. e068632 - e068632

Published: March 2, 2022

Abstract Objective To compare the efficacy of covid-19 vaccines between immunocompromised and immunocompetent people. Design Systematic review meta-analysis. Data sources PubMed, Embase, Central Register Controlled Trials, COVID-19 Open Research Dataset Challenge (CORD-19), WHO databases for studies published 1 December 2020 5 November 2021. ClinicalTrials.gov International Clinical Trials Registry Platform were searched in 2021 to identify registered but as yet unpublished or ongoing studies. Study selection Prospective observational comparing vaccination participants. Methods A frequentist random effects meta-analysis was used separately pool relative absolute risks seroconversion after first second doses a vaccine. without SARS-CoV-2 antibody titre levels performed first, second, third vaccine rate dose. Risk bias certainty evidence assessed. Results 82 included Of these studies, 77 (94%) mRNA vaccines, 16 (20%) viral vector 4 (5%) inactivated whole virus vaccines. 63 assessed be at low risk 19 moderate bias. After one dose, about half likely patients with haematological cancers (risk ratio 0.40, 95% confidence interval 0.32 0.50, I 2 =80%; 0.29, 0.20 =89%), immune mediated inflammatory disorders (0.53, 0.39 0.71, =89%; 0.11 0.58, =97%), solid (0.55, 0.46 0.65, =78%; 0.44, 0.36 0.53, =84%) compared controls, whereas organ transplant recipients times less seroconvert (0.06, 0.04 0.09, =0%; 0.06, 0.08, =0%). remained least (0.39, 0.46, =92%; 0.35, 0.26 0.46), only achieving seroconversion. Seroconversion increasingly (0.63, 0.57 0.69, =88%; 0.62, 0.54 0.70, =90%), (0.75, 0.69 0.82, 0.77, 0.66 0.85, =93%), (0.90, 0.88 0.93, =51%; 0.89, 0.86 0.91, =49%). similar people HIV controls (1.00, 0.98 1.01, 0.97, 0.83 1.00, =89%). 11 showed that dose associated among non-responders cancers, disorders, although response variable inadequately studied those receiving non-mRNA Conclusion rates significantly lower patients, especially recipients. consistently improved across all patient groups, albeit magnitude Targeted interventions including (booster) should performed. registration PROSPERO CRD42021272088.

Language: Английский

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Safety profile of upadacitinib over 15 000 patient-years across rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and atopic dermatitis

RMD Open, Journal Year: 2023, Volume and Issue: 9(1), P. e002735 - e002735

Published: Feb. 1, 2023

To evaluate the long-term safety profile for upadacitinib across rheumatoid arthritis (RA), psoriatic (PsA), ankylosing spondylitis (AS) and atopic dermatitis (AD).Safety data from clinical trials of 15 mg 30 (AD only) treating RA, PsA, AS AD as June 2021 were analysed; some RA PsA studies included adalimumab methotrexate active comparators. Treatment-emergent adverse events (TEAEs) presented by disease exposure-adjusted event rates per 100 patient years (E/100 PY).The analysis 6991 patients (RA, n=3209; n=907; AS, n=182; AD, n=2693) who received at least one dose upadacitinib, representing 425 PY exposure (maximum duration 2.75-5.45 years) diseases. Rates PY) any TEAE (205.5-278.1) leading to discontinuation (4.5-5.4) similar diseases; serious TEAEs numerically higher in with PsA. herpes zoster (1.6-3.6), non-melanoma skin cancer (0-0.8) elevations creatine phosphokinase levels (4.4-7.9) than comparators populations. Deaths (0-0.8), infections (0-3.9), major cardiovascular (0-0.4), venous thromboembolism (<0.1-0.4) malignancies (0.3-1.4) observed, generally lowest AD. Increased acne observed only.Findings this demonstrate that is well tolerated differences profiles likely reflective varying characteristics populations.NCT02675426, NCT02706951, NCT02706847, NCT02629159, NCT02706873, NCT03086343, NCT03104374, NCT03104400, NCT03178487, NCT03569293, NCT03568318 NCT03607422.

Language: Английский

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Mesenchymal Stem Cell-Derived Secretome: A Potential Therapeutic Option for Autoimmune and Immune-Mediated Inflammatory Diseases

Cells, Journal Year: 2022, Volume and Issue: 11(15), P. 2300 - 2300

Published: July 26, 2022

Immune-mediated inflammatory diseases (IMIDs) encompass several entities such as “classic” autoimmune disorders or immune-mediated with autoinflammatory characteristics. Adult stem cells including mesenchymal (MSCs) are by far the most commonly used type in clinical practice. However, due to possible side effects of MSC-based treatments, there is an increase interest MSC-secretome (containing large extracellular vesicles, microvesicles, and exosomes) alternative therapeutic option IMIDs. A wide spectrum MSC-secretome-related biological activities has been proven thus anti-inflammatory, anti-apoptotic, immunomodulatory properties. In comparison MSCs, secretome less immunogenic but exerts similar actions, so it can be considered ideal cell-free alternative. Additionally, since composition engineered, for a future perspective, could also viewed part potential delivery system within nanomedicine, allowing us specifically target dysfunctional tissues. Although many encouraging results from pre-clinical studies have recently obtained that strongly support application IMIDs, human administration still their infancy. This article reviews IMIDs provides insight into interpretation its beneficial actions.

Language: Английский

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Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

EClinicalMedicine, Journal Year: 2023, Volume and Issue: 64, P. 102193 - 102193

Published: Sept. 9, 2023

The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific rarely studied. study aims to investigate pattern trend 1990 2019.We collected detailed information on six major IMIDs, including asthma, bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, atopic dermatitis, between 2019, derived Global Burden Disease in 2019. average annual percent change (AAPC) number incidents age standardized rate (ASR) by sex, age, region, causes, were calculated quantify temporal trends.In disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% overall new cases, respectively. ASR showed substantial regional global variation with highest High SDI High-income North America, United States America. Throughout human lifespan, distribution incident cases was quite different. Globally, increased an AAPC 0.68 decreased -0.34 across arthritis (0.21, 95% CI 0.18, 0.25), while asthma (AAPC = -0.41), -0.72), sclerosis -0.26), psoriasis -0.77), dermatitis -0.15) decreased. individual IMID at level. Countries higher experienced a more rapid decrease ASR.The patterns varied considerably world. Innovative prevention integrative management strategy urgently needed mitigate increasing upsurging other five respectively.The Study is funded Bill Melinda Gates Foundation. project Scientific Research Fund Sichuan Academy Medical Sciences & Provincial People's Hospital (2022QN38).

Language: Английский

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Protein kinases: drug targets for immunological disorders

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(12), P. 787 - 806

Published: May 15, 2023

Language: Английский

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From periphery to center stage: 50 years of advancements in innate immunity

Cell, Journal Year: 2024, Volume and Issue: 187(9), P. 2030 - 2051

Published: April 1, 2024

Over the past 50 years in field of immunology, something a Copernican revolution has happened. For long time, immunologists were mainly concerned with what is termed adaptive immunity, which involves exquisitely specific activities lymphocytes. But other arm so-called "innate immunity," had been neglected. To celebrate Cell's 50th anniversary, we have put together review processes and components innate immunity trace seminal contributions leading to modern state this field. Innate joined center interest for all those who study body's defenses, as well homeostasis pathology. We are now entering era where therapeutic targeting immune receptors downstream signals hold substantial promise infectious inflammatory diseases cancer.

Language: Английский

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Reframing sepsis immunobiology for translation: towards informative subtyping and targeted immunomodulatory therapies

The Lancet Respiratory Medicine, Journal Year: 2024, Volume and Issue: 12(4), P. 323 - 336

Published: Feb. 23, 2024

Language: Английский

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GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Inflammatory diseases are often chronic and recurrent, current treatments do not typically remove underlying disease drivers1. T cells participate in a wide range of inflammatory such as psoriasis2, Crohn's disease3, oesophagitis4 multiple sclerosis5,6, clonally expanded antigen-specific may contribute to chronicity recurrence, part by forming persistent pathogenic memory. Chronic rhinosinusitis asthma airway that present comorbidities7. affects more than 10% the general population8. Among these patients, 20–25% would develop nasal polyps, which require repeated surgical resections owing high incidence recurrence9. Whereas abundant infiltrate polyps tissue10,11, cell subsets drive pathology promote recurrence fully understood. By comparing repertoires polyp tissues obtained from consecutive surgeries, here we report CD8+ clones carrying effector memory-like features colonize mucosal tissue during characteristically express tryptase Granzyme K (GZMK). We find GZMK cleaves many complement components, including C2, C3, C4 C5, collectively activation cascade. GZMK-expressing organized tertiary lymphoid structures, levels predict severity comorbidities better well-established biomarkers eosinophilia interleukin-5. Using mouse model, further show exacerbate manner dependent on proteolytic activity complements. Genetic ablation or pharmacological inhibition after onset markedly alleviates restores lung function. Our work identifies memory subset promotes inflammation recurrent molecule suggests potential therapeutic target. Comparing surgeries shows producing K, complement-activating tryptase, is

Language: Английский

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Obesity and Chronic Inflammation: Implications for Rheumatoid Arthritis, Spondyloarthritis, and Ulcerative Colitis

Immunity Inflammation and Disease, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 1, 2025

Immune-mediated inflammatory diseases (IMIDs) are a group of chronic conditions characterized by dysregulated immune responses and persistent inflammation. Rheumatoid arthritis (RA), spondyloarthritis (SpA), ulcerative colitis (UC) exemplify prominent IMIDs, each presenting unique challenges for their management, that impact patient's quality life (QoL). Obesity, marked low-grade inflammation, influences the progression, response to treatment, clinical management patients with RA, SpA, UC. Besides, emerging role sarcopenic obesity, special subtype obesity malnutrition, should be considered in definition appropriated therapeutic interventions.

Language: Английский

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Advances in antiviral strategies targeting mosquito-borne viruses: cellular, viral, and immune-related approaches

Virology Journal, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 4, 2025

Mosquito-borne viruses (MBVs) are a major global health threat, causing significant morbidity and mortality. MBVs belong to several distinct viral families, each with unique characteristics. The primary families include Flaviviridae (e.g., Dengue, Zika, West Nile, Yellow Fever, Japanese Encephalitis), transmitted predominantly by Aedes Culex mosquitoes; Togaviridae, which consists of the genus Alphavirus Chikungunya, Eastern Western Equine Encephalitis viruses), also Culex; Bunyaviridae (recently reorganized), containing like Rift Valley Fever Oropouche virus, mosquitoes sometimes sandflies; Reoviridae, includes Orbivirus Nile Bluetongue primarily affecting animals sandflies. Despite extensive research, effective antiviral treatments for remain scarce, current therapies mainly provide symptomatic relief supportive care. This review examines components cellular immune factors involved in life cycle MBVs. It highlights recent advances strategies targeting host such as lipid metabolism, ion channels, proteasomes, well targets NS2B-NS3 proteases nonstructural proteins. Additionally, it explores immunomodulatory enhance responses emphasizes potential drug repurposing, bioinformatics, artificial intelligence, deep learning identifying novel candidates. Continued research is crucial mitigating MBVs' impact preventing future outbreaks.

Language: Английский

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