New mouse model for inducible hACE2 expression enables to dissect SARS-CoV-2 pathology beyond the respiratory system DOI Creative Commons

Federica Gambini,

Dominik Arbon, Petr Nickl

et al.

Mammalian Genome, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 22, 2025

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection is not limited to the respiratory tract as receptors, including angiotensin-converting enzyme 2 (ACE2), are expressed across many tissues. This study employed a new conditional mouse model, Rosa26creERT2/chACE2, which expresses human ACE2 (hACE2) multiple organs, investigate effects of SARS-CoV-2 beyond system. strain demonstrated susceptibility in dose and sex-dependent manner, showing that infected male mice exhibited more severe disease outcomes, significant weight loss, pronounced lung pathology dysfunction, increased mortality, compared females. In contrast intratracheal infection, intranasal virus administration facilitated viral spread brain, thereby underscoring nasal route's role pathogenesis neurological manifestations. Intranasal also led innate immune system activation administration, even though both routes activated adaptive response. model provides valuable tool individual tissues or use multisystemic approach, it advances possibilities for preclinical evaluation antiviral therapies vaccine strategies.

Language: Английский

Long COVID science, research and policy DOI Creative Commons
Ziyad Al‐Aly, Hannah Davis, Lisa McCorkell

et al.

Nature Medicine, Journal Year: 2024, Volume and Issue: 30(8), P. 2148 - 2164

Published: Aug. 1, 2024

Long COVID represents the constellation of post-acute and long-term health effects caused by SARS-CoV-2 infection; it is a complex, multisystem disorder that can affect nearly every organ system be severely disabling. The cumulative global incidence long around 400 million individuals, which estimated to have an annual economic impact approximately $1 trillion-equivalent about 1% economy. Several mechanistic pathways are implicated in COVID, including viral persistence, immune dysregulation, mitochondrial dysfunction, complement endothelial inflammation microbiome dysbiosis. devastating impacts on individual lives and, due its complexity prevalence, also has major ramifications for systems economies, even threatening progress toward achieving Sustainable Development Goals. Addressing challenge requires ambitious coordinated-but so far absent-global research policy response strategy. In this interdisciplinary review, we provide synthesis state scientific evidence assess human health, systems, economy metrics, forward-looking roadmap.

Language: Английский

Citations

106
Long COVID: a clinical update DOI
Trisha Greenhalgh, Manoj Sivan,

Alice Perlowski

et al.

The Lancet, Journal Year: 2024, Volume and Issue: 404(10453), P. 707 - 724

Published: July 31, 2024

Language: Английский

Citations

78
Mechanisms of long COVID and the path toward therapeutics DOI Creative Commons

Michael J. Peluso,

Steven G. Deeks

Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

32
Mapping the effectiveness and risks of GLP-1 receptor agonists DOI Creative Commons
Yan Xie,

Taeyoung Choi,

Ziyad Al‐Aly

et al.

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

Published: Jan. 20, 2025

Language: Английский

Citations

15
Interventions for the management of long covid (post-covid condition): living systematic review DOI Creative Commons
Dena Zeraatkar, King‐Hwa Ling, Sarah Kirsh

et al.

BMJ, Journal Year: 2024, Volume and Issue: unknown, P. e081318 - e081318

Published: Nov. 27, 2024

Abstract Objective To compare the effectiveness of interventions for management long covid (post-covid condition). Design Living systematic review. Data sources Medline, Embase, CINAHL, PsycInfo, Allied and Complementary Medicine Database, Cochrane Central Register Controlled Trials from inception to December 2023. Eligibility criteria that randomised adults (≥18 years) with drug or non-drug interventions, placebo sham, usual care. Results 24 trials 3695 patients were eligible. Four (n=708 patients) investigated eight (n=985) physical activity rehabilitation, three (n=314) behavioural, four (n=794) dietary, (n=309) medical devices technologies, one (n=585) a combination exercise mental health rehabilitation. Moderate certainty evidence suggested that, compared care, an online programme cognitive behavioural therapy (CBT) probably reduces fatigue (mean difference −8.4, 95% confidence interval (CI) −13.11 −3.69; Checklist Individual Strength subscale; range 8-56, higher scores indicate greater impairment) improves concentration −5.2, −7.97 −2.43; problems 4-28; impairment). online, supervised, combined rehabilitation leads improvement in overall health, estimated 161 more per 1000 (95% CI 61 292 more) experiencing meaningful recovery, symptoms depression −1.50, −2.41 −0.59; Hospital Anxiety Depression Scale 0-21; impairment), quality life (0.04, 0.00 0.08; Patient-Reported Outcomes Measurement Information System 29+2 Profile; −0.022-1; less intermittent aerobic 3-5 times weekly 4-6 weeks function continuous 3.8, 1.12 6.48; SF-36 component summary score; 0-100; No compelling was found support other including, among others, vortioxetine, leronlimab, probiotics-prebiotics, coenzyme Q10, amygdala insula retraining, L-arginine vitamin C, inspiratory muscle training, transcranial direct current stimulation, hyperbaric oxygen, mobile application providing education on covid. Conclusion suggests CBT improve Systematic review registration Open Science Framework https://osf.io/9h7zm/ . Readers’ note This article is living will be updated reflect emerging evidence. Updates may occur up two years date original publication.

Language: Английский

Citations

9
Deterministic optimal control compartmental model for COVID-19 infection DOI

Barbara Fosua Afful,

Godfred Agyemang Safo,

D. Marri

et al.

Modeling Earth Systems and Environment, Journal Year: 2025, Volume and Issue: 11(2)

Published: Jan. 20, 2025

Language: Английский

Citations

1
Rates of infection with other pathogens after a positive COVID-19 test versus a negative test in US veterans (November, 2021, to December, 2023): a retrospective cohort study DOI
Miao Cai, Evan Xu, Yan Xie

et al.

The Lancet Infectious Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

1
Translating insights into therapies for Long Covid DOI Open Access
Annukka A.R. Antar, Andrea L. Cox

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(773)

Published: Nov. 13, 2024

Long Covid is defined by a wide range of symptoms that persist after the acute phase severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Commonly reported include fatigue, weakness, postexertional malaise, and cognitive dysfunction, with many other reported. Symptom range, duration, severity are highly variable partially overlap myalgic encephalomyelitis/chronic fatigue post-acute infectious syndromes, highlighting opportunities to define shared mechanisms pathogenesis. Potential diverse, including persistence viral reservoirs, dysregulated immune responses, direct damage tissues targeted SARS-CoV-2, inflammation driven reactivation latent infections, vascular endothelium activation or subsequent thromboinflammation, autoimmunity, metabolic derangements, microglial activation, microbiota dysbiosis. The heterogeneity baseline characteristics people Covid, as well varying states immunity therapies given at time infection, have made etiologies difficult determine. Here, we examine progress on preclinical models for review being in clinical trials, need large human studies further development better understand Covid. Such will inform trials treatments benefit those living this condition.

Language: Английский

Citations

4
Cell-Autonomous and Non-Cell-Autonomous Antiviral Immunity via siRNA-Directed RNAi in Drosophila melanogaster DOI Creative Commons

Haojiang Luan

Immune discovery., Journal Year: 2025, Volume and Issue: 1(1), P. 10001 - 10001

Published: Jan. 1, 2025

In Drosophila melanogaster, the siRNA-directed RNAi pathway provides crucial antiviral defenses. Cell-autonomously, Dicer-2 (Dcr-2) recognizes and cleaves viral dsRNA into siRNAs, which are incorporated RNA-induced silencing complex (RISC). Argonaute 2 (Ago2) then targets RNA, preventing replication. Non-cell-autonomously, infected hemocytes secrete exosomes containing spreading signals to other cells. Additionally, tunneling nanotubes can transfer components between neighboring cells, further enhancing systemic immunity. These findings highlight sophisticated strategies in Drosophila, offering insights for broader research.

Language: Английский

Citations

0
Prevalence and factors associated with severe fatigue 2 years into the COVID-19 pandemic: a cross-sectional population-based study in Geneva, Switzerland DOI Creative Commons
Clément Graindorge, Stephanie Schrempft, Nick Pullen

et al.

BMJ Open, Journal Year: 2025, Volume and Issue: 15(1), P. e089011 - e089011

Published: Jan. 1, 2025

Objectives This study aims (1) to assess the prevalence of severe fatigue among general population Geneva, 2 years into COVID-19 pandemic and (2) identify non-pandemic factors associated with fatigue. Design Cross-sectional population-based survey conducted in Spring 2022. Setting General adult Switzerland. Participants 6870 participants, randomly selected from population, included Specchio-COVID-19 cohort study, were invited answer an online health survey. Outcome cofactor measure Prevalence was measured by Chalder Fatigue Questionnaire a cut-off score≥4 out 11. We assessed ratios considering sociodemographic factors, behavioural characteristics (body mass index, depression, recent diagnosis chronic disease or allergy, acute event, smoking status, physical activity sleep quality) self-reported infections. Results A total 4040 individuals participated (participation rate 59%, 58% women, mean age 53.2 (SD=14.1 years)). Overall 30.7% (95% CI=29.2%–32.1%). After adjusting for age, sex, educational level pre-existing comorbidities, following fatigue: aged 18–24 (adjusted ratio (aPR)=1.39 (1.10–1.76)) 25–34 (aPR=1.23 (1.05–1.45)), female sex (aPR=1.28 (1.16–1.41)), depression (aPR=2.78 (2.56–3.01)), occurrence events unrelated (aPR=1.51 (1.38–1.65)) infection past 12 months (aPR=1.41 (1.28–1.56)). further adjustment previous associations maintained except young age. Conclusions About one-third Geneva experienced fatigue, pandemic. Heightened adults is partly explained depressive symptoms. Recent substantially regardless severity co-occurrence disorder. Trial registration number CCER project ID 2020-00881.

Language: Английский

Citations

0