Reviews in Medical Virology最新文献

{"title":"Beyond the Usual Suspects: Emerging Associations Between Epstein-Barr Virus Infection/Infectious Mononucleosis and Cancers.","authors":"Marisa D Muckian, Graham S Taylor, John Diaz-Decaro, Enejda Senko, Helen R Stagg","doi":"10.1002/rmv.70153","DOIUrl":"10.1002/rmv.70153","url":null,"abstract":"<p><p>Epstein-Barr virus (EBV) is a ubiquitous herpesvirus and a causal factor for Burkitt Lymphoma (BL), Hodgkin Lymphoma (HL), gastric carcinoma (GC) and nasopharyngeal carcinoma (NPC). Whether EBV contributes to a wider spectrum of cancers remains uncertain. We reviewed MEDLINE, Embase and Web of Science on 30^th July 2024 to identify observational studies that examined the association between EBV infection or EBV-infectious mononucleosis (IM) and cancers beyond BL, HL, GC and NPC. Evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. For cancers meeting minimum thresholds we assessed etiologic fractions (EFs), biological plausibility, epidemiological burden, latency after IM, and predictive biomarkers. Thirty-three eligible studies were identified, yielding 13 hypotheses (i.e., specific potential reported associations between EBV infection or IM and individual cancer types) that advanced through GRADE. Breast cancer and NHL had the greatest weight of biological plausibility, cervical and prostate the least. Despite an array of tests, testicular cancer studies provided limited evidence. EFs ranged between 12.3% (IM-breast) and 85.1% (EBV infection-NHL). Breast and prostate cancers had the highest global incidence. Only one study (for NHL) provided data on time from IM to cancer onset, and prostate-specific antigen was the only biomarker identified. In this review, we highlight eight cancers across six cancer groups (breast, cervical, leukaemia/other haematologic, NHL, prostate, testicular) with some evidence of EBV involvement. These results reinforce the potential long-term value of EBV vaccine development, while emphasising the need for high-quality prospective studies with robust methods of viral detection to establish causality.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70153"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109813/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 Variants and Immune Evasion: Mapping the Future of Vaccine Design.","authors":"Fatih Uzer, Fulya Erendor, Salih Sanlioglu","doi":"10.1002/rmv.70157","DOIUrl":"10.1002/rmv.70157","url":null,"abstract":"<p><p>The evolutionary trajectory of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has progressed through several distinct phases since its zoonotic emergence, transitioning from initial human adaptation to an era of rapid antigenic drift and complex immune evasion. As of early 2026, the global landscape is dominated by highly evolved sublineages of the Omicron (B.1.1.529) variant, including the JN.1-descendent subvariants NB.1.8.1 and XFG. This review provides a comprehensive overview of the molecular mechanisms driving viral fitness, with a primary focus on the structural transformations within the spike (S) protein's receptor-binding domain (RBD), N-terminal domain (NTD), and S2 subunit. We examine the biophysical impacts of pivotal mutations, such as E484 K, K417 N, and F486P, alongside the phenomenon of convergent evolution and epistatic compensation. Furthermore, we provide an integrated analysis of current knowledge regarding the evolving dynamics of humoral and cellular immunity, exploring the challenges posed by immune imprinting and the decline of neutralizing antibody titers against antigenically distant strains. A comparative discussion of SARS-CoV-2 and seasonal influenza highlights divergent evolutionary paces but converging regulatory frameworks for annual vaccine updates. Finally, the current status of next-generation vaccine platforms is evaluated, specifically mosaic nanoparticles and mucosal delivery systems, which aim to provide pan-sarbecovirus protection and interrupt transmission. These insights are integrated into a policy framework focused on annual strain selection and enhanced genomic surveillance for sustainable long-term pandemic management.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70157"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Cytomegalovirus Infection in Haematopoietic Stem Cell Transplant Recipients and CAR-T Cell Recipients-PART 2: Antiviral Therapy and Virus-Specific T Cell Therapy for HCMV in Allo-HSCT.","authors":"Gaurav Sutrave, Michelle K Yong, Danya Kaplan, David J Gottlieb, Allison Abendroth, Barry Slobedman, Emily Blyth, Lauren Stern","doi":"10.1002/rmv.70135","DOIUrl":"10.1002/rmv.70135","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) reactivation is a common and significant complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT), causing potentially life-threatening disease. Antiviral therapy approaches for HCMV are often limited by toxicities and the risk of developing antiviral drug resistance. This review article (Part 2) provides an overview of current antiviral pharmacotherapies for HCMV and the application of virus-specific adoptive T cell therapies for the prevention or treatment of HCMV reactivation in allo-HSCT recipients. The number of available antiviral drugs for HCMV is expanding, and letermovir primary prophylaxis is increasingly being adopted due to its favourable safety profile. Treatment resistant/refractory infections, end-organ disease, and late HCMV reactivations after antiviral therapy withdrawal continue to pose challenges. Adoptive HCMV-specific T cell therapies are a promising strategy for promoting immune-mediated control of HCMV reactivation in allo-HSCT recipients. The administration of HCMV-specific T cell products, generated through ex vivo expansion of donor-derived or partially HLA matched, third party HCMV-specific T cells, have demonstrated efficacy in combatting clinically significant HCMV infection in clinical trials. Adoptive HCMV-specific T cell therapies represent a powerful alternative approach for managing drug resistant HCMV infections in allo-HSCT recipients and reducing the reliance on antiviral pharmacotherapies.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70135"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13036708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147582401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatitis B Non-Vaccination Rate and Associated Factors Among Healthcare Workers in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.","authors":"Alphonce Ignace Marealle, Goodluck G Nyondo, Martine Aron Manguzu, Castory G Munishi, George Msema Bwire","doi":"10.1002/rmv.70169","DOIUrl":"10.1002/rmv.70169","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) remains a significant occupational hazard for healthcare workers (HCWs), especially in low- and middle-income countries (LMICs) where vaccination coverage is often suboptimal. This review examined the non-vaccination rate against HBV among HCWs in LMICs. We conducted a systematic search across multiple databases, including PubMed/MEDLINE, Embase, Web of Science, and Scopus, for studies published from the inception up to 04 Feb 2024. Non-vaccination (NV) was defined as the absence of any hepatitis B vaccination dose as reported by individual studies. Pooled NV rates were calculated using a random-effects model. This review was registered in PROSPERO (CRD42024510223). The search retrieved 2990 studies, of which 62 met the eligibility criteria for the final analysis, including data from over 23,000 HCWs. The pooled prevalence of unvaccinated (zero-dose) HBV individuals was 36.2% (95% CI: 27.7%-45.5%; I² = 98.9%). Subgroup analysis revealed marked disparities, with the highest prevalence in low-income countries (61.4%; 95% CI: 30.6%-85.1%; I² = 98.7%) compared to upper-middle-income countries (20.4%; 95% CI: 7.8%-43.9%; I² = 98.8%). Regionally, the burden was greatest in Africa (45.3%; 95% CI: 32.7%-58.4%; I² = 98.9%) and lowest in Latin America (8.8%; 95% CI: 0.0%-99.9%; I² = 92.7). This review found that more than one-third of healthcare workers remain unvaccinated against HBV, with marked disparities across income levels and geographic regions. The consistently high heterogeneity suggests these gaps are context-specific, highlighting the need for targeted strategies to improve vaccine uptake and equity.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70169"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of High-Dose and Standard-Dose Influenza Vaccines for Hospitalisation and Mortality in Adults Aged 65 and Older: An Updated Systematic Review and Meta-Analysis.","authors":"Bilal Wazir Khan, Muhammad Huzaifa Khattak, Muhammad Maaz Amjad, Shahreena Athar Siddiqui, Tayyaba Ikram Qazi, Hamdullah Rehmat, Muhammad Faaz Khan, Haris Wazir Khan, Affan Masaud Mian, Mohsin Ullah, Umer Zaryab Khan, Muhammad Abdur Rafay, Sajjad Ghanim Al-Badri, Zaryab Bacha","doi":"10.1002/rmv.70158","DOIUrl":"10.1002/rmv.70158","url":null,"abstract":"<p><p>This updated systematic review and meta-analysis evaluated the relative vaccine effectiveness (rVE) of high-dose inactivated influenza vaccine (HD-IV) versus standard-dose (SD-IV) in adults ≥ 65 years for key clinical outcomes, including hospitalisations and mortality. Conducted in accordance with PRISMA guidelines, PubMed, Embase, and the Cochrane Library were searched for randomised controlled trials. Primary outcomes were pneumonia and influenza (P&I) hospitalisation, all-cause hospitalisation, and all-cause mortality, while secondary outcomes included hospitalisation for cardiorespiratory disease, influenza-related hospitalisation, laboratory-confirmed influenza hospitalisation, and serious adverse events (SAEs). Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using fixed-effect models. Across 586,188 participants, HD-IV reduced P&I hospitalisation (rVE 12.0%), increasing to 22.0% in sensitivity analysis. For all-cause hospitalisation (∼600,000 participants), rVE was 4.0%, while no significant reduction was observed for all-cause mortality (rVE = 2.0%). Subgroup analyses suggested greater benefits in individuals without cardiovascular disease and those aged 65-79 years. HD-IV also showed strong protection against influenza-specific outcomes (rVE 39% for influenza hospitalisation; 32% for laboratory-confirmed influenza hospitalisation), with no significant difference in SAEs between groups. Overall, HD-IV provides superior protection compared with SD-IV against P&I and all-cause hospitalisation in older adults, with the greatest benefits among younger seniors and those without cardiovascular disease. These findings support prioritising HD-IV to reduce influenza burden in the elderly, although benefits appear limited in adults aged > 80 years.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70158"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147779754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global Vaccine Confidence at a Crossroads: Immunisation Coverage Declines, Misinformation, and the Future of Vaccine Policy.","authors":"Alfi Sophian, Normasari, Andhika Harumanto, Abinawanto","doi":"10.1002/rmv.70149","DOIUrl":"10.1002/rmv.70149","url":null,"abstract":"<p><p>Vaccination remains one of the most effective public health interventions; however, recent global trends indicate a reversal in routine immunisation coverage alongside resurgent outbreaks of vaccine-preventable diseases. This review synthesises current evidence on declining immunisation coverage, the re-emergence of diseases such as measles and poliomyelitis, and the growing influence of vaccine hesitancy and misinformation on vaccine uptake. A systematic search of PubMed, Scopus, and WHO/UNICEF databases was conducted using terms including 'vaccine hesitancy', 'immunisation coverage', 'vaccine-preventable diseases', 'misinformation', and 'vaccine policy', covering literature published between 2000 and 2024. We examine how pandemic-related disruptions, structural inequities, and evolving information ecosystems have collectively weakened immunisation system resilience across diverse settings. Beyond epidemiological consequences, declining coverage reflects broader challenges related to trust, governance, and equity in vaccine delivery. The review highlights the limitations of reactive, outbreak-driven approaches and emphasises the central role of strong routine immunisation systems embedded within primary healthcare. We discuss policy implications for integrating behavioural and social science insights, strengthening risk communication, and advancing equity-oriented immunisation governance. We conclude that sustaining and extending global immunisation gains will depend on aligning scientific innovation with public trust and system resilience. Addressing vaccine confidence as a core component of immunisation performance is essential to safeguarding global health security in the coming decade.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70149"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Possible Effects of C-Reactive Protein in the Central Nervous System During Venezuelan Equine Encephalitis Virus Infection.","authors":"Nereida Valero-Cedeño, Anyelo Durán, Jesus A Mosquera","doi":"10.1002/rmv.70165","DOIUrl":"10.1002/rmv.70165","url":null,"abstract":"<p><p>Venezuelan equine encephalitis virus (VEEV) is an alphavirus vectored by mosquitos. It can cause disease in equines and humans characterised by a febrile illness that may progress into encephalitis. Replication of VEEV in the central nervous system induces activation of glial cells and neurons, compromising the blood-brain barrier (BBB) and inducing a state of neuroinflammation. This inflammation can lead to symptoms such as confusion, seizures, and coma, and sustained inflammation contributes to neurodegeneration. C-reactive protein (CRP) is a biomarker that has previously been associated with inflammation and infection. It is now known that its functions are related to various brain disorders. Circulating increased CRP levels correlate with alterations in brain structure and metabolism associated with cognitive vulnerability, suggesting the effect of CRP on brain cell biology. However, the fact that alphavirus (including VEEV) infection is accompanied by increased CRP production makes it likely that VEEV infection induces the production of this protein systemically and/or mediated by the activation of brain cells. This review highlights a role of CRP in the brain parenchyma, influencing various aspects of VEEV brain infection such as general inflammation, BBB permeability, hypoxia, apoptosis, interaction with different brain cells, and brain metabolism. The influence of CRP in the brain may exacerbate the inflammatory process induced by VEEV. The existence of several drugs with anti-CRP effects opens their use in the treatment of VEEV brain infection.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 3","pages":"e70165"},"PeriodicalIF":5.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147960185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chandipura Virus: A Neglected Sandfly-Borne Neurotropic Virus in Children - Insights From Seven Decades of Evidence.","authors":"Ravi Rai Dangi, Vipin Vageriya, Anil Sharma, Pragna Dabhi","doi":"10.1002/rmv.70119","DOIUrl":"10.1002/rmv.70119","url":null,"abstract":"<p><p>Chandipura virus, a neurotropic RNA virus transmitted by Phlebotomus sandflies, remains an under-recognised cause of acute paediatric encephalitis in India. The 2024 outbreak, with 245 confirmed cases and 82 deaths, underscores its ongoing public health relevance. This review provides an integrated analysis of CHPV, encompassing its epidemiological distribution in India, host-agent-environment transmission dynamics, molecular and cellular pathogenesis, clinical presentation, diagnostic modalities, therapeutic options, and vaccine research. Evidence from 1950 to 2025, drawn from peer-reviewed studies, outbreak reports, and national surveillance databases, shows that CHPV primarily affects children younger than 15 years and causes abrupt fever, seizures, and coma within 24-48 h. The virus breaches the blood-brain barrier through cytokine-mediated permeability and induces neuronal apoptosis via Fas- and NF-κB-linked pathways, while genomic studies demonstrate overall stability across outbreaks. Diagnosis depends on RT-PCR and IgM ELISA, available only in reference laboratories. Experimental antivirals such as favipiravir and recombinant glycoprotein vaccines show promise in animal models but remain untested in humans. Strengthening molecular surveillance, integrating CHPV detection into India's Integrated Disease Surveillance Programme, and investing in antiviral and vaccine development are crucial to reducing the recurring burden of this neglected childhood neurotropic arbovirus.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 2","pages":"e70119"},"PeriodicalIF":5.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Azvudine and Nirmatrelvir-Ritonavir in Hospitalised Patients With COVID-19: A Systematic Review and Meta-Analysis.","authors":"Tahoora Mousavi, Mahmood Moosazadeh, Hossein Jalali","doi":"10.1002/rmv.70114","DOIUrl":"10.1002/rmv.70114","url":null,"abstract":"<p><p>Azvudine is a nucleoside reverse transcriptase inhibitor (NRTI) and belongs to the family of 2', 3'-dideoxynucleoside (ddNs) that can mimic natural nucleosides and block viral DNA or RNA chain synthesis and prevent viral replication. Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, Azvudine has been used to treat patients with COVID-19. Therefore, the objective of this meta-analysis study was to compare Azvudine and Nirmatrelvir-Ritonavir in hospitalised patients. The global online databases were used to identify relevant studies published between January 2019 and October 2024. The quality of all articles was determined using the Newcastle-Ottawa Scale (NOS) checklist. In this study, heterogeneity assay was assessed using the Cochran's Q-test and the I2 index, and STATA software version.14 (StataCorp) was used for statistical analysis. Egger's test, Begg's test, and funnel plot were performed to estimate of the publication bias, and the impact of each study on the overall estimate was assessed using sensitivity analysis. In this study, 19 studies were included in this meta-analysis. The results of the meta-analysis showed that the relative risk of death in the Azvudine treatment group compared with the Nirmatrelvir-Ritonavir treatment group was 0.64 (95% CI: 0. 44, 0. 93). These results suggest that treatment with Azvudine may provide significant clinical benefit in patients hospitalised with COVID-19.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 2","pages":"e70114"},"PeriodicalIF":5.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Study Size on COVID-19 Treatment Outcomes: A Meta-Epidemiological Study Comparing Large and Small Randomized Controlled Trials: A Systematic Review and Meta-Analyses.","authors":"Dong Hyun Kim, Soojin Lim, Michael Eisenhut, Andreas Kronbichler, Eunyoung Kim, Min Seo Kim, Stefania I Papatheodorou, Justin Stebbing, Yonghong Peng, Sarah Soyeon Oh, Jae Il Shin, Lee Smith","doi":"10.1002/rmv.70125","DOIUrl":"10.1002/rmv.70125","url":null,"abstract":"<p><p>Small randomized controlled trials (RCTs) in COVID-19 meta-analyses have been associated with more favourable treatment effects and reduced result stability. This study assessed how trial size impacts effect estimates, statistical stability, and risk of bias. Following PRISMA guidelines, we identified meta-analyses of COVID-19 treatments included in WHO, NIH, and the LIVING Project. Trials were classified by log-scale sample size, and separate pooled meta-analyses were conducted for large-only, small-only, and combined trials. Comparative metrics included the Ratio of Odds Ratios (ROR), Kappa statistics, Fragility Index (FI), Reverse Fragility Index (RFI), and Cochrane Risk of Bias assessments. Sensitivity analyses applied alternative size thresholds (≥ 1000 participants and median-based cutoffs) and stratified results by treatment and outcome type. Across 25 meta-analyses including 221 RCTs (46 large, 175 small), small trials produced more extreme estimates in 19 analyses and wider confidence intervals in 23. The pooled ROR was 0.85 (95% CI: 0.76-0.95; P = 0.004), decreasing to 0.81 (95% CI: 0.68-0.95; P = 0.011) when limited to small trials published before the first large trial. RORs remained below 1 across treatment and outcome types. Agreement between small and large trials was minimal, while large trials showed substantial agreement with overall estimates. Stability and bias profiles favoured large trials (FI: 14.0 vs. 4.0; RFI: 10.0 vs. 5.0). In conclusion, small RCTs tend to overestimate treatment effects and yield less precise, less stable results. Meta-analyses should prioritise large, high-quality trials and interpret small-study findings with caution, particularly in rapidly evolving research contexts.</p>","PeriodicalId":21180,"journal":{"name":"Reviews in Medical Virology","volume":"36 2","pages":"e70125"},"PeriodicalIF":5.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12966952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147370109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}