Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) remains a clinically challenging malignancy, particularly in recurrent or metastatic disease where durable responses to chemoradiotherapy and immune checkpoint blockade are limited. The viral aetiology of NPC provides a strong biological rationale for immune-based treatment; however, translation of chimaeric antigen receptor (CAR) T-cell therapy into this solid tumour setting is constrained by poor tumour trafficking, antigen heterogeneity, limited surface accessibility of EBV latent antigens, T-cell exhaustion, and an immunosuppressive tumour microenvironment. This review critically evaluates the emerging therapeutic prospects of CRISPR-engineered CAR-T cell therapy for EBV-associated NPC. It synthesises evidence on EBV latency biology, NPC immune evasion, solid-tumour CAR-T limitations, and genome-engineering strategies including conventional CRISPR-Cas9, base editing, prime editing, and double-strand-break-sparing targeted integration. Particular attention is given to genotoxicity, chromosomal rearrangements, chromosome loss, bystander and off-target editing, manufacturing heterogeneity, and the regulatory and biological barriers that currently separate technical feasibility from NPC-specific clinical implementation. Available clinical evidence from checkpoint blockade, EBV-specific adoptive T-cell therapy, base-edited CAR-T cells in haematologic malignancy, and early CRISPR-edited T-cell trials supports the feasibility of immune and genetic redirection but does not establish efficacy of a clinically validated CRISPR-engineered CAR-T platform for NPC. Future development should prioritise surface-accessible antigen validation, fit-for-purpose selection of editing technology, genomic safety, scalable manufacturing, and biomarker-driven early-phase trials.
Respiratory syncytial virus (RSV) has long been underrecognized as a significant pathogen in older adults, despite accumulating evidence of its substantial morbidity and mortality burden in this population. While RSV vaccination is now well established as an effective intervention for preventing lower respiratory tract disease, this narrative review examines whether its public health value may extend beyond these primary clinical endpoints. A targeted search of Scopus and Web of Science from database inception to May 2026 was conducted to identify biological, epidemiological, observational, interventional, and modelling evidence relevant to potential downstream vaccine effects. The available evidence potentially supports hypotheses concerning possible reductions in cardiovascular complications and secondary bacterial infections, possible decreases in transmission to younger household contacts, and potential preservation of functional status and independence. However, the strength of evidence varies substantially across these outcomes. Cardiovascular protection has not been independently demonstrated in randomized trials, bacterial and antimicrobial-use outcomes have rarely been prespecified, real-world household transmission studies are unavailable, and functional trajectories may be strongly modified by baseline frailty and pre-existing disability. RSV vaccination in older adults therefore remains a well-validated strategy for preventing acute respiratory disease, whereas its proposed broader effects should be regarded as biologically plausible but incompletely demonstrated benefits. Future studies should incorporate prespecified cardiovascular, bacterial, transmission, geriatric, and functional outcomes, with particular attention to frailty, antimicrobial use, and longer-term follow-up.
Human cytomegalovirus (HCMV) is a globally prevalent virus that poses a significant public health concern, especially for newborns and immunocompromised patients, causing a wide range of infections. Clinical outcomes associated with HCMV infection include congenital disease, graft rejection in transplant recipients, and life-threatening systemic infections with significant morbidity and mortality. HCMV is a member of the Beta-herpesvirinae subfamily. Distinguishing characteristics of HCMV, in particular, and herpesviruses in general are their ubiquitous presence in nature and the initial infection that often results in lifelong latency. Over the past 40 years, the genetics of HCMV have been explored, leading to the isolation of various genotypes, including those of glycoprotein B, glycoprotein N, and UL144. Despite operational obstacles in isolating HCMV genotypes due to heterogeneity in the technologies used for genotyping the virus, studies have been able to describe their clinical implications across a variety of human hosts. This review summarises the genotypic variation of HCMV and discusses its clinical relevance and impact on antiviral resistance and vaccine development. Understanding the genetic diversity of HCMV genotypes is crucial for advancing drug development to combat resistant strains and for developing new vaccines and treatment modalities.
Nipah virus (NiV) is a high-consequence zoonotic henipavirus characterised by severe encephalitis and respiratory distress, driving recurrent outbreaks with case fatality rates between 40% and 75% in India and Bangladesh. Within these outbreaks, 'super-spreading' dynamics play a critical role, where a small subset of individuals contributes to a disproportionately large share of secondary infections. To evaluate the relationship between human infectivity and viral load kinetics in Nipah virus infection and to define the role of the medical laboratory in identifying potential super-spreaders, a narrative review was conducted by executing a systematic search across PubMed, Scopus, and ScienceDirect for peer-reviewed literature published from 1998 to 2025. The qualitative synthesis demonstrated that NiV infectivity is highly dependent on specimen matrix efficiency and anatomical shedding patterns. Respiratory specimens yield the highest viral RNA copy numbers during the acute symptomatic phase, correlating strongly with active droplet transmission. Persistent real-time RT-PCR Cycle Threshold values below 25 (Ct < 25) in respiratory samples serve as an indirect laboratory indicator of high-risk shedders and should be interpreted alongside clinical and epidemiological findings. However, a comprehensive analysis indicates that super-spreading is inherently multifactorial. Early identification via frontline molecular diagnostics remains the cornerstone of breaking NiV transmission chains. Although a standalone viral load threshold is insufficient to predict a spreading event on its own, the medical laboratory provides an essential risk profile by combining longitudinal Ct kinetics with clinical and exposure data. Strengthening regional laboratory infrastructure and deploying standardized point-of-care molecular assays in endemic, resource-limited areas are urgent public health priorities.
Oncoviruses are responsible for a substantial fraction of human cancers and have emerged as critical modulators of host cellular pathways that also govern ageing. The convergence of viral oncogenesis, ageing, and cancer reflects shared molecular mechanisms, including genomic instability, epigenetic alterations, telomere attrition, and chronic inflammation. Increasing evidence indicates that oncoviruses such as human papillomavirus, Epstein-Barr virus, hepatitis B and C viruses, and Kaposi's sarcoma-associated herpesvirus actively reprogramme host signalling networks to promote persistent infection, immune evasion, and malignant transformation. This review synthesises current knowledge on how oncoviruses intersect with key hallmarks of ageing and cancer, with particular emphasis on the signalling pathways that bridge these processes. Central pathways, including p53, mTOR, NF-κB, PI3K/AKT, and Wnt/β-catenin, are frequently targeted by viral proteins, leading to dysregulated cell survival, proliferation, and senescence. These interactions not only facilitate tumourigenesis but also accelerate ageing-associated cellular dysfunctions, such as immunosenescence and inflammaging. Furthermore, we discuss how virus-induced modulation of the tumour microenvironment and host immune responses contributes to the dynamic interplay between ageing and cancer. Understanding these interconnected pathways provides valuable insights into the dual role of oncoviruses as drivers of both age-related decline and cancer development. Elucidating these mechanisms may reveal novel therapeutic targets and strategies for preventing and treating virus-associated malignancies in ageing populations.
Since May 2022, mpox has been reported across multiple nonendemic regions, with concurrent outbreaks in diverse geographic settings, raising concerns about broader international spread. However, evidence regarding the risk of airborne transmission remains limited. We conducted a systematic review to evaluate the risk of airborne transmission and the presence of viable viruses in air samples. PubMed, Web of Science, and the Cochrane Library were searched for studies published in English, including environmental studies, case reports, cross-sectional studies, and cohort studies. Data extraction included study characteristics (authors, year, design, and setting), sample size, diagnostic methods, participant characteristics, follow-up, type of respiratory particles assessed (droplets and/or aerosols), and key findings. Of 286 records identified, four studies met the inclusion criteria. All were environmental studies published between 2022 and 2023. MPXV DNA was detected in surface and air samples, with cycle threshold (Ct) values ranging from < 30 to < 45. However, none of the studies demonstrated consistent viral viability in aerosols or droplets sufficient to support airborne transmission. Overall, the available evidence is limited and does not support a clear risk of airborne infection. Further well-designed studies in human settings are needed to clarify the potential for mpox transmission through respiratory routes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42023391123.
Human herpesvirus-8 (HHV-8) is an oncogenic herpesvirus that poses unique challenges in solid-organ transplantation. Although uncommon, HHV-8-associated diseases including Kaposi sarcoma (KS), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and the KSHV inflammatory cytokine syndrome (KICS) can lead to significant morbidity, graft loss, and death. The clinical spectrum ranges from indolent cutaneous lesions to fulminant systemic inflammation, yet recognition is often delayed because of nonspecific presentations and the lack of standardized screening or monitoring strategies. Regional differences in HHV-8 seroprevalence and immunosuppressive regimens further complicate prevention and management. This review summarises current understanding of HHV-8 infection in solid-organ transplant recipients, focussing on epidemiology, transmission pathways, pathogenesis, clinical manifestations, diagnostic approaches, and management principles for each major syndrome. It also highlights knowledge gaps, therapeutic challenges, and priorities for research and standardized surveillance to improve outcomes in this rare but important group of transplant-related complications. We propose a risk-stratified donor and recipient screening algorithm and a practical management framework for recipients with HHV-8 PCR positivity but without symptoms, to guide clinical practice in the absence of standardized guidelines.
Due to their complex anatomy, high heterogeneity, and immunosuppressive tumour microenvironment, gastrointestinal cancers severely restrict the effective delivery and function of oncolytic viruses (OVs). This review summarises current multidimensional strategies to improve OV delivery efficiency. First, genetic engineering with deletion of viral genes and insertion of therapeutic genes, markedly enhance viral targeting, safety, and therapeutic capacity. Second, combination therapies with radiotherapy, chemotherapy and immunotherapy can execute microenvironmental preconditioning and either concurrent or sequential administration to improve viral distribution inside tumours, increase local accumulation and enhance immune activation. In addition, modulation of the tumour immune microenvironment helps enhance viral replication and spread in 'cold' tumours, thereby inducing systemic antitumour responses. Finally, carrier-mediated delivery using stem cells, extracellular vesicles, and viral envelope reconstitution provides innovative approaches to overcome systemic delivery barriers. Despite persisting challenges such as rapid clearance, physical barriers, and viral inactivation, the strategies discussed in this review demonstrate significant advances in delivery mechanisms, immune synergy, and targeted accumulation, providing a solid foundation and new directions for the clinical translation of OVs in gastrointestinal tumours.
The efficacy of convalescent plasma (CP) in COVID-19 has been contested, with large randomized trials producing conflicting results that led to recommendations against routine use. We performed a systematic review with design-stratified narrative synthesis (PRISMA 2020; SWiM; OSF: https://osf.io/tjcuq) to test whether these conflicting outcomes can be reconciled through three interacting determinants-timing, antibody titre, and host characteristics-using a standardized 91-field extraction matrix applied to each study. PubMed, Web of Science, and Scopus were searched through May 2026. Thirty-one studies (20,793 patients; 8 RCTs, 23 observational) were included. The synthesis indicates that CP is effective, but only under a specific convergence of conditions: when administered early in the disease course, with sufficient antibody titre, to seronegative or immunocompromised hosts who have not yet mounted an endogenous antibody response. Among RCTs analysing timing, 4 of 6 found benefit with earlier administration; for titre, 3 of 4 RCTs with explicit comparisons found benefit with higher-titre CP; and two large RCTs (combined n = 12,522) demonstrated preferential benefit in seronegative recipients. This interpretation is consistent with modelling estimates that CP, deployed largely to hospitalised patients, nonetheless saved tens of thousands of lives in the United States during the first pandemic year, an effect attributed to the subset treated early enough to modify disease progression. A second, previously unquantified finding concerns antibody class: characterisation of non-IgG immunoglobulins was nearly absent, with only 2 of 31 studies-both from our group-reporting IgA or IgM data, despite evidence that IgA and IgM are among the most potent neutralising classes against SARS-CoV-2. This hypothesis-generating observation identifies a systematic gap in CP product assessment. These findings reframe CP efficacy from a binary question to a conditional one and provide a template for the precision deployment of passive immunotherapy in future pandemics.
Hantaviruses are emerging zoonotic pathogens of increasing global public health significance. Their epidemiological landscape is rapidly changing due to ecological disruption, climate variability, urbanisation, and evolving human-animal interfaces. This narrative review synthesises current knowledge on hantavirus virology, epidemiology, pathogenesis, clinical management, and emerging countermeasures, with a focus on developments from the past 5 years. Traditionally classified into Old World viruses causing haemorrhagic fever with renal syndrome (HFRS) and New World viruses causing hantavirus cardiopulmonary syndrome (HCPS), this dichotomy has become increasingly blurred, with overlapping renal and pulmonary manifestations now recognized. Among the most consequential recent advances is the consolidated evidence for person-to-person transmission of Andes virus, documented among household contacts and during the prodromal phase, with viral shedding in respiratory secretions. Endothelial dysfunction remains the pathological hallmark of severe disease, driven by VEGF sensitisation, Src kinase and RhoA pathway activation, pericyte infection, and dysregulated inflammatory responses including IL-6 trans-signalling. Concurrently, environmental and ecological studies have linked climate change, rodent population dynamics, land-use modification, and urbanisation to increased human disease risk across multiple continents. Diagnostic strategies continue to rely on serology and molecular testing, while management remains predominantly supportive, with extracorporeal membrane oxygenation (ECMO) improving survival in fulminant HCPS. Importantly, recent structural virology advances have enabled the development of broadly neutralising monoclonal antibodies targeting conserved quaternary epitopes, as well as next-generation vaccine platforms including DNA, mRNA, and prefusion-stabilised glycoprotein candidates. Hantaviruses represent a paradigmatic One Health challenge at the intersection of environmental change, viral evolution, and global interconnectedness. Despite major progress in understanding transmission dynamics and endothelial pathogenesis, critical gaps remain regarding determinants of person-to-person spread, long-term post-infection sequelae, and the absence of licenced broadly protective vaccines or specific antiviral therapies. Future preparedness will require integrated surveillance frameworks combining ecological monitoring, genomic epidemiology, and clinical readiness within coordinated international public health strategies.
Anti-Spike monoclonal antibodies (mAbs) progressively lost efficacy during the COVID-19 pandemic due to the emergence and predominance of resistant SARS-CoV-2 variants. By contrast, high-titre COVID-19 convalescent plasma (CCP) collected from vaccinated donors recently recovered from infection provides a polyclonal source of antibodies that remains effective in clearing SARS-CoV-2 in immunosuppressed patients, unable to mount an adequate immune response against the virus. We conducted a systematic review and individual participant data meta-analysis to examine the effect of CCP in immunocompromised patients persistently positive for SARS-CoV-2 viraemia following mAb therapy, and to evaluate possible biological factors associated with a favourable outcome. Electronic databases were searched for studies published from January 2020 to January 2026. All studies including eligible cases were considered in the systematic review. Unpublished cases were also collected from investigators of the selected studies. The protocol was registered at PROSPERO (CRD420251142891). Forty-seven cases (30 cases from 12 published studies and 17 unpublished cases) were included. In 33 out of 47 patients (70.2%) with a mAb-resistant infection, SARS-CoV-2 clearance occurred following CCP transfusion, with a mean of 2.7 CCP units administered. In logistic regression, total CCP volume transfused was positively associated with SARS-CoV-2 clearance. In conclusion, CCP transfusion was associated with SARS-CoV-2 clearance in persistently positive immunocompromised patients following failure of anti-Spike mAb therapy.
Colorectal cancer (CRC) remains a leading cause of cancer-related death worldwide, prompting ongoing research into infectious agents that may contribute to colorectal carcinogenesis. Among candidate oncogenic viruses, JC polyomavirus (JCPyV), a ubiquitous human polyomavirus, has attracted considerable attention due to its potential involvement in tumour initiation and progression. Although several studies have reported the presence of JCPyV viral DNA, transcripts, and proteins in colorectal adenomas and carcinomas, the prevalence and clinical significance of these findings vary considerably across populations and diagnostic methods. Mechanistically, the viral Large T Antigen (TAg) is implicated in several oncogenic processes through its interactions with key cellular regulators, including p53, retinoblastoma protein (pRb), and components of the Wnt/β-catenin signalling pathway. These interactions may cause genomic instability, aberrant cell cycle progression, impaired DNA repair, and aberrant cell proliferation, thereby creating an environment conducive to malignant transformation. In addition, emerging evidence suggests that JCPyV may contribute to chromosomal instability and epigenetic changes that facilitate tumour progression. Despite these observations, the causal role of JCPyV in colorectal cancer remains controversial. Inconsistent epidemiological data, discrepancies in virus detection, geographic variation, and the inability to confirm direct causation of carcinogenesis have generated ongoing debates about the involvement of JCPyV as a stimulator factor or cofactor in colorectal tumourigenesis. This review critically evaluates the current evidence linking JCPyV to colorectal cancer, summarises the proposed molecular mechanisms of viral carcinogenesis, and highlights key unresolved questions that need to be addressed to clarify the biological and clinical significance of JCPyV in colorectal carcinogenesis.
Human sapovirus (HuSaV) has long occupied a peripheral position in etiological research on acute gastroenteritis. However, in the context of widespread rotavirus vaccination, the pathogen spectrum of childhood diarrhoea has been reshaped; molecular diagnostics have continued to evolve; and evidence from birth cohorts and environmental surveillance has accumulated. Together, these developments have prompted a systematic reassessment of the public health significance of HuSaV in childhood diarrhoea, outbreaks in childcare facilities and schools, asymptomatic infection, and persistent infection in immunocompromised hosts. Here, we review key advances in HuSaV research across disease burden and epidemiological patterns, genome organization and evolution, natural history and immune responses, experimental models and host interactions, complex clinical phenotypes, and surveillance-to-public-health translation. We further propose priority directions for the next 5 years, including the establishment of standardized antigen panels and reference strain repositories, integration of serological and genotyping data within longitudinal cohorts, elucidation of viral receptor recognition, cell entry and immune-evasion mechanisms, and the development of closed-loop linkages between experimental-model research and population-level surveillance systems. Overall, HuSaV has evolved from a historically underestimated pathogen associated with acute gastroenteritis in infants and young children into a key enteric viral pathogen that requires dedicated surveillance, mechanistic investigation and translational intervention strategies in the post-rotavirus vaccine era. The research paradigm is likewise shifting from descriptive epidemiology towards an integrated framework that combines disease burden, host immunity, experimental systems and transmission surveillance.
Cruise ships and other confined travel settings remain highly vulnerable to infectious disease outbreaks. During 2025-2026, multiple norovirus outbreaks and the rare Andes hantavirus outbreak associated with the MV Hondius cruise highlighted the continuing public health challenges posed by both highly transmissible enteric viruses and emerging zoonotic pathogens. This review summarises recent cruise-associated viral outbreaks with particular emphasis on indirect transmission pathways, environmental persistence, and the limitations of conventional outbreak-control strategies. Norovirus outbreaks continued to occur despite implementation of enhanced sanitation and infection-control measures, highlighting the difficulty of interrupting transmission in environments where contaminated surfaces, aerosolised particles, and shared spaces may contribute to viral spread. In contrast, the Andes virus outbreak emphasised the additional risks associated with expedition-style travel, delayed symptom onset, zoonotic exposure, and complex international surveillance requirements. Current outbreak responses remain largely dependent on reactive measures such as cleaning, disinfection, passenger isolation, and contact tracing. However, the repeated occurrence of these outbreaks suggests that these approaches alone may be insufficient for long-term prevention in highly interconnected environments. Emerging environmental intervention strategies, including advanced air decontamination systems, antiviral surface coatings, self-disinfecting smart materials, and peptide-based antiviral technologies, have demonstrated promising antiviral activity against a range of respiratory and enteric viruses. These technologies may offer complementary passive protection approaches capable of reducing environmental contamination and minimising indirect viral transmission. Collectively, this review highlights the need to move beyond conventional reactive sanitation measures towards integrated and multidisciplinary preparedness strategies for future outbreak prevention in cruise ships and other crowded, closed, and interconnected settings.
Chronic viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) remains a leading global public health burden, driving progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) through complex interactions between viral replication, host immune responses, and extracellular matrix (ECM) remodelling. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that serve as central regulators of ECM homoeostasis and immune modulation in the liver. While physiological MMP activity is essential for tissue repair and immune surveillance, dysregulation of the MMP/TIMP (tissue inhibitors of metalloproteinases) axis during viral hepatitis promotes hepatic fibrogenesis, immune evasion, and malignant transformation, positioning MMPs as both drivers of disease progression and promising therapeutic targets. This review comprehensively examines the molecular and cellular mechanisms governing MMP/TIMP dysregulation across the spectrum of viral hepatitis, with particular focus on HCV and HBV. We address the reciprocal interactions between these viruses and MMP/TIMP expression, the roles of MMPs in liver fibrosis, viral replication, hepatocarcinogenesis, and immunomodulation of the tumour microenvironment, and the accelerated fibrogenic mechanisms in HIV-HCV and HIV-HBV coinfection. The review also extends to acute viral hepatitis (HAV and HEV), where direct MMP/TIMP data remain scarce but mechanistic and indirect ECM evidence indicate significant involvement. Finally, we critically evaluate current and emerging MMP-targeted therapeutic strategies including selective inhibitors, nanoparticle delivery systems, and RNA-based approaches and highlight key unresolved questions to guide future research towards disease-tailored interventions against viral hepatitis-driven liver damage and malignant progression.
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are seasonal respiratory viruses that can cause severe outcomes, particularly in older adults; however, their burden remains under-captured. The World Health Organisation (WHO) recommends expanding surveillance over pathogens, such as RSV and hMPV, through the Mosaic Respiratory Surveillance Framework. Although COVID-19 accelerated RSV surveillance, similar advancements for hMPV are lacking. This study evaluated and compared RSV and hMPV surveillance across multiple countries. A comparative qualitative analysis of RSV and hMPV surveillance was conducted in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States using a framework based on the WHO guidance. Surveillance systems were mapped across seven modules: non-medically attended community, virological, community, outbreak, primary care, hospital, and mortality surveillance. Each was assessed using five criteria: granularity, timing, representativeness, sampling strategy, and communication. Sources included public health institution webpages, surveillance subsystems, and peer-reviewed publications. Most countries have dedicated RSV surveillance frameworks, with the United States and Spain having the most comprehensive systems. Key areas for potential improvement included limited adult-centric data and severe outcome reporting. No country had robust surveillance for hMPV (Germany reported hMPV-specific hospital data, whereas France, Germany, and the United Kingdom published sentinel positivity rates), and detection was mainly through influenza or COVID-19 virological surveillance. The absence of hMPV reporting from active sentinel surveillance, year-round monitoring, demographic and severity data, and restricted public information dissemination are common limitations. Significant limitations persist in RSV and particularly hMPV surveillance, highlighting the need for more robust, comprehensive systems.
Nipah virus (NiV) has emerged as a high-consequence zoonotic pathogen, posing a significant threat to global health security. Characterised by extreme virulence and case-fatality rates that can exceed 70%, it is recognized as a WHO priority pathogen. This review examines the multifaceted challenges posed by recurring NiV outbreaks, spanning the complex dynamics of unpredictable zoonotic spillover from Pteropus fruit bats, the rising risk of sustained human-to-human transmission, and the profound gaps in medical countermeasures. The epidemiological shift from events mediated by intermediate hosts to those involving direct spillover and efficient person-to-person spread in South Asia highlights the virus's evolving pandemic potential. In the absence of any licenced vaccines or therapeutics, public health responses are limited to supportive care and stringent infection control. Ultimately, this review concludes that mitigating the NiV threat is fundamentally a One Health challenge, requiring an integrated strategy that unites ecological surveillance, accelerated medical research, and coordinated global policy to secure against this formidable pathogen.
Between mosquitoes and birds, West Nile virus (WNV) is a neurotropic flavivirus, an arthropod-borne pathogen involved in an enzootic cycle. Additionally, it can infect both people and horses, leading to severe illness. Since 1999, WNV has spread across North and South America, including Mexico and the Caribbean. It is endemic in several regions of Europe, Africa, the Middle East, and Asia. WNV affects the central nervous system (CNS), causing severe disease in a small percentage of infected individuals, especially in immunocompromised or elderly hosts. This re-emerging pathogen was identified during an outbreak in July 2025 in the Lazio region of Italy, rekindling interest in an area where the virus had not circulated for some time and raising several questions about the WNV vector and its spread. Gammadelta T (γδ T) lymphocytes are innate cells that can respond rapidly and non-specifically to viral infections and other pathogens, thereby linking innate and adaptive immunity. Several studies in mice and humans suggest they play distinct roles in controlling WNV infection by communicating with other immune cells, underscoring their antiviral role, which is essential for containing viral dissemination in the host. This review will discuss recent studies on the role of γδ T cells in viral pathogenesis and in protective immunity during WNV infection.
Metformin has been shown to reduce hospitalisation and symptom duration among adults with COVID-19, but the effect has not been studied. We conducted this meta-analysis to assess the efficacy and safety of metformin in patients with COVID-19. Randomized controlled trials (RCTs) comparing metformin with placebo in COVID-19 were identified through major databases through November 2025. We performed statistical analyses using RevMan 5.4, employing the random-effects model, along with Risk Ratio (RR) and Mean Difference (MD) as the effect measures. Our meta-analysis of four RCTs showed that metformin did not significantly reduce the composite outcome of hospitalisation, emergency department (ED) visits, or death, compared with placebo (RR 0.60, 95% CI 0.40-0.90.21). The incidence of all-cause mortality (RR 1.00; 95% CI 0.06-15.91) and serious adverse events (RR 2.86; 95% CI 0.76-10.76) was also comparable between the two groups. Our meta-analysis, with low to moderate certainty, found that metformin may provide modest benefit in reducing hospitalisation, ED visits, or mortality in patients with COVID-19 without an association with increased serious adverse events. However, these findings should be interpreted cautiously, given the limited number of trials, low event rates, and clinical heterogeneity across studies. Further large RCTs are needed before metformin can be considered for use in COVID-19.
Oncogenic viruses cause approximately 20% of cancers globally burden, with Epstein-Barr virus and high-risk Human papillomavirus recognized as major contributors to epithelial malignancies. Increasing evidence suggests that EBV-HPV co-infection may enhance tumour progression through overlapping molecular and immunological mechanisms, particularly in cervical, oropharyngeal, and nasopharyngeal cancers. This review critically summarizes current evidence regarding the cooperative role of EBV and HPV in carcinogenesis while distinguishing viral co-presence from biologically active co-infection. EBV latent proteins, including LMP1, LMP2A, and EBNA1, activate oncogenic signalling pathways such as NF-κB, PI3K/Akt, and JAK/STAT, whereas HPV oncoproteins E6 and E7 disrupt p53 and retinoblastoma (Rb) tumour suppressor pathways. Together, these alterations may promote genomic instability, chronic inflammation, immune evasion, epigenetic dysregulation, and epithelial-mesenchymal transition (EMT), thereby enhancing invasive and metastatic potential. Epidemiological studies report higher frequencies of EBV-HPV co-detection in advanced lesions and aggressive tumours; however, causal synergy remains insufficiently validated because of methodological heterogeneity and variability in viral detection techniques, including PCR, in situ hybridization, and immunohistochemistry. Emerging technologies such as spatial transcriptomics and single-cell profiling may improve characterization of biologically meaningful co-infection. In addition, circulating viral DNA, viral microRNAs, and HPV genotyping are being explored as biomarkers for disease monitoring and prognosis. Therapeutic strategies targeting viral oncogenes, immune checkpoints, and gene-editing technologies also represent promising investigational approaches. Overall, EBV-HPV co-infection represents a biologically plausible but incompletely understood contributor to tumour aggressiveness, emphasizing the need for standardized diagnostics, longitudinal studies, and functional experimental models.
