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PubMed2026

Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection.

BACKGROUND: Monkeypox virus (MPXV) infects diverse human cell types, and human immunodeficiency virus (HIV) co-infection is common. The immunometabolic consequences of MPXV infection, and how it may be altered by HIV, remain poorly defined. METHODS: We performed quantitative plasma lipidomics and precise metabolomics in a discovery cohort (n = 81) comprising MPXV-monoinfected (MPLWOH), MPXV-HIV-coinfected (MPLWH), and HIV-monoinfected (PLWH) patients and healthy controls, integrating exosome proteomics, cytokine profiling, and transcriptomics of exosome-treated HepG2 and A549 cells for functional interpretation. An independent validation cohort (n = 65) was used to assess cross-cohort reproducibility. FINDINGS: MPXV infection induced broad lipid remodeling, with elevations in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and reductions in phosphatidylcholine (PC), lysophospholipids, cholesteryl ester (CE), and exosomal lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). These lipid alterations were correlated with tissue injury markers and inflammatory cytokines. The MPLWH group exhibited more severe metabolic disruption, including marked sulfatide (SL) depletion, lower cholesterol and high-density lipoprotein cholesterol (HDL-c), and extensive rewiring of lipid-cytokine associations. SL depletion in MPLWH correlated with abundances of COPI-mediated retrograde trafficking proteins in exosomes. Transcriptomic profiling of exosome-treated cells provided functional validation: MPLWOH exosomes induced lipid metabolism and repair-associated epithelial programs, while MPLWH exosomes drove phospholipid remodeling and acute inflammatory and mucosal barrier-stress responses. CONCLUSIONS: MPXV infection reprograms host lipid metabolism and exosome composition, with HIV co-infection amplifying inflammatory, metabolic, and trafficking disruptions. These convergent multi-omics signatures link systemic lipid dysregulation to exosome-mediated immunomodulation and identify potential targets for host-directed interventions. FUNDING: This study was funded by the Major Project of Guangzhou National Laboratory.

Adult↗
PubMed2026

Lesion viral burden, multidrug-resistant superinfection, and HIV-associated haematological vulnerability in hospitalised clade Ib mpox: a prospective cohort study in Uganda.

BACKGROUND: Mpox has shifted to sustained human-to-human transmission across Africa, yet integrated triage incorporating viral burden, bacterial co-infection, antimicrobial resistance (AMR), HIV status, and routine biomarkers remain scarce. METHODS: At Uganda's national mpox referral hospital, we prospectively enrolled 155 adults at 14 ± 2 days post-symptom onset; mpox was confirmed by lesion-swab qPCR (F3L), with clade assignment by whole-genome sequencing in a prespecified subset (March-April 2025). Lesion viral DNA burden was estimated using qPCR cycle threshold (Ct) values. Purulent lesions underwent EUCAST-standardised culture and susceptibility testing. Routine laboratory assessments included complete blood counts, C-reactive protein, serum chemistries, HIV serostatus, and plasma HIV-1 RNA. FINDINGS: Median age was 30 years, and 73/155 (47%) had HIV infection. Multisite pain, particularly anogenital, was highly prevalent. Among 80 participants with purulent lesions selected for clinically suspected bacterial superinfection, all yielded bacterial growth; 35/80 (43.8%) were polymicrobial and predominantly multidrug-resistant Gram-negative bacilli. Susceptibility to first-line β-lactams and fluoroquinolones was low, whereas meropenem retained activity (51/61, 84%). Lesion viral burden did not differ by HIV serostatus and showed weak correlation with HIV-1 viraemia; higher burden was associated with leucocytosis, neutrophilia with left shift, elevated CRP, and hypoalbuminaemia. Genomes clustered within Clade Ib, without segregation by HIV status or clinical severity. INTERPRETATION: Hospitalised adults with acute Clade Ib mpox in Uganda exhibited high lesion viral burden, frequent multidrug-resistant bacterial co-isolation, and an inflammatory haematological profile accentuated in participants living with HIV-1. These findings support consideration of integrating diagnostic microbiology, HIV viral load assessment, and antimicrobial stewardship into mpox case-management in endemic settings. FUNDING: This study was supported by the Coalition for Epidemic Preparedness Innovations (CEPI; Project ID PRJ-8284).

Adult↗
PubMed2025

Potential of MRNA vaccines for mpox prevention: current evidence and future directions.

In 2022, the presumption of monkeypox (mpox) to be of limited epidemiology shifted when a global outbreak was announced. Being a member of the Orthopoxvirus genus in the Poxviridae family, it'd been reported in over 82 countries with over 17 000 confirmed cases by July 2022, thus showing its capability for spreading rapidly. As the smallpox vaccine offers 85% cross-immunity against mpox, the outbreak highlighted the attenuation of global immunity against orthopoxviruses after the cessation of vaccination campaigns against smallpox. The mortality of this virus is higher in vulnerable populations such as children, pregnant women, the elderly, and immunosuppressed individuals. With treatment methods being limited to off-label use of antivirals, the need for urgent and efficient preventative measures is emphasized. At present, JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic), showing favorable safety, and ACAM2000, a live attenuated virus with a high risk of side effects, are two vaccines that are indicated for mpox immunization. However, neither of them has proven full safety, efficacy, and widespread accessibility against mpox. Hence, the use of mRNA vaccines has emerged as a better alternative to traditional vaccinations, as they leverage synthetic messenger RNA to instruct host cells to produce antigens, eliciting both humoral and cellular immune responses. Though they provided rapid scalability, adaptability to emerging viral variants, and an established safety profile after the COVID-19 pandemic, their usage in preventing mpox remains an area of research. This paper elucidates the potential of mRNA technology to address the unmet needs in mpox prevention. It also highlights the need for genomic surveillance, immunological insights, and innovative delivery systems.

COVID-19↗
PubMed2026

Saliva versus lesion swabs for PCR diagnosis of acute-phase clade Ib mpox in Uganda: a prospective matched hospital cohort study.

BACKGROUND: As clade Ib mpox expands through HIV-affected populations in east and central Africa, diagnostic specimen selection should balance accuracy, accessibility, and operational feasibility in outbreak settings. Here, we aimed to compare the diagnostic performance of matched plasma, saliva, genital, anal, and skin specimens during the acute rash phase of clade Ib mpox to identify clinically practical and high-yield sampling approaches for outbreak response and clinical care. METHODS: We conducted a prospective cohort study of 155 adults (median age 30 years, IQR 25-36) hospitalised at Uganda's national mpox referral hospital. The specimens were collected between March 3 and April 10, 2025, during the clade Ib outbreak. All participants were admitted with suspected mpox and were subsequently confirmed by MPXV PCR. We collected 836 clinical specimens (acid citrate dextrose plasma, saliva, genital swabs, anal swabs, and skin swabs) during the acute phase (visit 1; 14 days [SD 2] after systemic symptom onset) and at approximately 3 months (visit 2). A matched acute-phase subset (n=80) provided concurrent plasma, saliva, genital, and skin specimens for within-participant comparisons. MPXV DNA was quantified by F3L real-time quantitative PCR, and cycle threshold (Ct) values were compared using paired Wilcoxon signed-rank tests. Whole-genome sequencing of selected acute specimens confirmed clade assignment. FINDINGS: In the matched subset at visit 1, PCR positivity was high in saliva (78 [98%] of 80), skin swabs (78 [98%] of 80), and genital swabs (77 [96%] of 80). Results for the saliva closely mirrored genital and skin swab results, supporting saliva as a high-yield alternative when lesion sampling is painful, operationally difficult, or unacceptable. Plasma had substantially lower sensitivity (34 [43%] of 80) and showed poor agreement with mucocutaneous compartments. At 3 months, persistent MPXV DNA was rare (ten [9%] of 109) and clustered among people with HIV, including the only two participants with persistent plasma positivity. All sequenced genomes clustered within clade Ib. INTERPRETATION: During the established rash phase (14 days [SD 2] after onset), saliva provides diagnostic yield similar to that provided by lesion swabs for clade Ib mpox in this hospitalised cohort. These findings are restricted to this sampling window; further studies are needed to define performance in prodromal, pre-rash, and asymptomatic infection. FUNDING: CEPI through its Centralised Laboratory Network.

Adult↗
PubMed2025

Mpox: current knowledge and understanding-a scoping review.

Mpox in humans is a rash illness resulting from infection with monkeypox virus (MPXV). In 2022, a public health emergency of international concern (PHEIC) was declared with 115 countries reporting cases of Mpox. Most of these countries had not previously reported cases. This global outbreak was sustained primarily by human-to-human transmission within complex sexual networks. Whilst these cases were similar to previous clade II West African MPXV isolates, they were sufficiently genomically distinct to result in WHO recognizing two subclades within clade II: clade IIa and clade IIb. In 2024, a second PHEIC was declared, resulting from a marked increase in cases of clade I MPXV. In this scoping review, we compare the major clinical, epidemiological, and genomic features of the major mpox lineages and the implications for vaccination, transmission, infection control and treatment..

Humans↗
PubMed2026

Clinical, epidemiological, and genomic evidence on mpox in mainland China, 2022-2025: a scoping review.

BACKGROUND: Since 2022, mpox has expanded globally with sustained human-to-human transmission and increasing evidence of MPXV genomic diversification. In mainland China, mpox evidence has accumulated rapidly, but clinical, epidemiological, and genomic findings remain fragmented. METHODS: We conducted a scoping review of PubMed, CNKI, and WanFang databases up to March 2, 2026, and integrated literature-derived evidence with public MPXV sequences from GenBank, GenBase, and GISAID. Literature-derived data were used to map clinical-epidemiological characteristics, study-level genomic evidence, sequencing coverage, and reported lineage distribution. Curated public MPXV sequences were used for phylogenetic reconstruction, amino acid mutation profiling, and APOBEC-like substitution analysis. RESULTS: Fifty-eight studies were included: 32 addressed clinical or epidemiological evidence only, 25 addressed genomic evidence only, and one contributed to both domains. Fourteen hospital-based studies summarized 951 cases, showing that reported cases were concentrated among young adult men, with frequent MSM exposure (798/897, 89.0%; 95% CI 86.7-90.9%) and HIV co-infection (469/951, 49.3%; 95% CI 46.1-52.5%). Public sequence curation identified 231 unique mainland China MPXV sequences, of which 230 were used for phylogenetic and mutation analyses. Literature-based genomic evidence comprised 26 genomic studies, 37 study-level genomic records, and 31 reported-case units, including 414 sequenced cases among 530 reported cases (78.1%; 95% CI 74.4-81.4%). Clade IIb predominated among sequenced cases (412/414, 99.5%; 95% CI 98.3-99.9%), with C.1.1 and C.1 most frequently represented. Within the available dataset, public genomes represented multiple lineages and were unevenly distributed across regions and time. Mutation analysis revealed dispersed amino acid variation and a predominance of G>A and C>T transitions (73.0%). After collapsing recurrent substitutions to unique genomic sites, the proportion of G>A/C>T transitions decreased to 35.8% and further to 17.8% under a strict APOBEC3 motif definition, indicating that the observed mutation spectrum includes both shared lineage-associated substitutions and sequence-context-based APOBEC-like patterns. CONCLUSION: Available evidence indicates multi-lineage MPXV circulation and in mainland China, but interpretation remains constrained by uneven sequencing and lack of individual-level clinical-genomic linkage. Integrated genomic surveillance and standardized data linkage are needed to better characterize MPXV transmission and evolution.

APOBEC‑like substitutions↗
PubMed2026

Genomic Epidemiology and Clinical Characteristics of Mpox Lineage C.1 Outbreak in Thailand, 2023-2024.

Since 2022, human monkeypox virus (hMPXV) has emerged in non-endemic regions, including Thailand. However, the genomic dynamics and clinical correlates of local transmission remain incompletely defined. Whole-genome sequencing was performed on hMPXV from 16 patients in Thailand (2023-2024) using targeted amplicon NGS. Phylogenetic analyses integrated global reference sequences. Mutational profiles, specifically non-synonymous substitutions and APOBEC3-associated signatures, were analyzed in relation to clinical data. Phylogenetic reconstruction identified three temporal phases. Early 2022 cases (clade IIb lineages A and B) were interspersed with global sequences, consistent with multiple introductions. In contrast, 2023-2024 cases were dominated by lineage C.1. All 16 genomes belonged to C.1 (one C.1.1), and formed a distinct mid-2023 cluster, designated C.1/Thai/Cluster, supporting sustained local transmission. APOBEC3-associated mutations were pervasive across the C.1 lineage overall, including within C.1/Thai/Cluster, without evidence of significant enrichment specific to this cluster. The cohort comprised exclusively male patients (81% HIV-positive, MSM), with predominantly genital painful lesions and a median recovery time of 23 days. No significant associations were detected between viral genetic variation and clinical outcomes. Mpox transmission in Thailand evolved from multiple introductions to sustained C.1-dominated local spread, underscoring the importance of continued genomic surveillance.

Humans↗
PubMed2026

Integrated molecular, epidemiological, and bioinformatics perspectives on the Mpox virus: Implications for surveillance and Global Health preparedness.

Mpox has re-emerged as a significant global zoonotic threat, driven mainly by two large waves the 2022 worldwide Clade IIb outbreak and the 2024 Clade Ib epidemic in Central Africa. This review examines the challenges of interpreting this evolving virus from molecular, epidemiological, and bioinformatics perspectives, with a focus on global health workforce preparedness. Clade IIb largely moved through sexual transmission across countries, but Clade Ib has appeared in a wider population-women, children, and individuals infected through household spread without any sexual contact. Early case series suggest that Clade Ib may cause a more severe disease burden, but more research is needed to directly compare severity and fatality rates with Clade IIb due to the limited number of current studies. The review examines the virus's strategies for evading the host's immune defenses throughout its ∼197 kbp genome, including how it disrupts interferon signaling and creates decoy receptors. This review summarizes the clinical findings of PALM007 and STOMP, noting that neither trial achieved its main efficacy endpoint making routine tecovirimat use less compelling-while leaving open whether it helps particular high-risk groups. A further point is that immunity from the MVA-BN vaccine wanes with time, leading to the growing adoption of booster vaccinations. In conclusion, the review calls for a One Health approach pairing genomic tracking with ecological intelligence and including wastewater surveillance to fill existing gaps in knowledge and enhance the global handling of new orthopoxvirus threats.

Animals↗
PubMed2026

Early epidemiologic and genomic insights from Sierra Leone's first mpox cases, 2025.

INTRODUCTION: early characterization of outbreak cases supports rapid decisions. We conducted real-time analysis during the initial outbreak phase in mid-March 2025 of Sierra Leone's first 44 laboratory-confirmed Mpox cases (10th January to 5th March 2025) to generate epidemiologic and genomic intelligence for response. METHODS: we summarized surveillance data and sequenced 18 early cases with Oxford Nanopore. Firth-penalized logistic regression was employed to explore risk factors for severe disease. RESULTS: median age was 27 years (interquartile range 22 to 35); 68.2% were male. Most cases reported no recent international travel (95.5%). All cases presented with rash; fever occurred in 72.7%. Six cases (13.6%) met severe criteria; no deaths occurred (0 of 44; 95% confidence interval 0 to 8.0). Household secondary attack rate was 7.3% during the study window and 8.2% after completion of follow-up. Sequencing identified two co-circulating sub-lineages consistent with A.2.2 and B.1.6 and a strong APOBEC3 pattern (142 of 212 guanine-to-adenine in thymine-cytosine versus 70 of 212 cytosine-to-thymine in guanine-adenine; exact binomial p approximately 8.6x10-7; X2= 24.5, df = 1, p≈ 7.6x10-7). Root-to-tip analysis showed weak temporal signal (R2=0.31; date randomization p= 0.18), so we did not interpret clock estimates. CONCLUSION: real-time analysis during the initial outbreak phase showed community transmission, quantified household spread, documented two sub-lineages with an APOBEC3 signature, and generated severity hypotheses that immediately informed surveillance and vaccine prioritization. Findings require validation in larger cohorts.

Adult↗
PubMed2025

Genomic epidemiology of clade Ia monkeypox viruses circulating in the Central African Republic in 2022-24: a retrospective cross-sectional study.

BACKGROUND: The spread of monkeypox virus (Orthopoxvirus monkeypox) clade Ib from the Democratic Republic of the Congo to neighbouring countries has raised global concerns, leading to WHO declaring mpox a public health emergency on Aug 14, 2024. We applied genomic epidemiology to investigate the causes of recurrent mpox outbreaks in the Central African Republic. We aimed to determine whether frequent zoonotic spillovers or increased human-to-human transmissions are driving mpox epidemiology. METHODS: We performed a retrospective cross-sectional study of monkeypox virus genomic sequences among PCR-confirmed mpox cases detected in the Central African Republic between Feb 17, 2022, and Sept 17, 2024. We used hybridisation capture coupled to high throughput sequencing to analyse 46 samples from mpox outbreaks that occurred in eight of the 20 prefectures (14 of 35 health districts). Near-complete genomes were used for phylogenomic analyses. FINDINGS: Between Jan 10, 2022, and Sept 15, 2024, 89 mpox cases were confirmed, including 53 cases in the first 9 months of 2024. We generated 41 near-complete genomes from this period, including 33 from 2024. All new and already published monkeypox virus genomes from the Central African Republic belonged to clade Ia. These genomes spanned the phylogenetic diversity of clade Ia viruses, and most likely represented several dozen independent transmission events to humans. The monkeypox virus phylogenetic diversity was geographically structured within the country. Plausibly linked cases often showed indistinguishable genomes. Conversely, we detected identical genomes in cases that epidemiological information would suggest were independent outbreaks. Finally, we found that three distinct viruses caused cases in the capital city of Bangui in July, 2024, with all three detected on the same day (July 24, 2024). We did not detect substantial enrichment of APOBEC3 editing, suggesting limited human-to-human transmission. INTERPRETATION: The data indicate that mpox epidemiology in the Central African Republic is primarily driven by short-lived outbreaks resulting from many independent zoonotic spillover events, particularly in rural areas. Although evidence remains limited, in Bangui additional factors such as movement of people and importation of bushmeat from other regions might be introducing the virus into urban settings. Similar spillover patterns have been observed in the Democratic Republic of the Congo. The poorly understood nature of monkeypox virus reservoirs in both countries is a regional concern, as frequent spillovers increase the risk of outbreaks leading to sustained human transmission. Beyond strengthening surveillance and developing countermeasures, it is important to better understand the reservoirs and focus on reducing transmission opportunities to prevent further outbreaks. FUNDING: Pasteur Institute of Bangui, Africa CDC, AFROSCREEN, WHO, the Helmholtz Institute for One Health, and the Deutsche Forschungsgemeinschaft.

Humans↗
PubMed2026

A comprehensive overview of monkeypox virus disease.

BACKGROUND: Monkeypox (mpox), caused by monkeypox virus (MPXV), re-emerged as a major global public health concern in 2022, resulting in widespread transmission beyond traditionally endemic regions. As of March 2026, 181,164 confirmed cases and 492 deaths had been reported across 144 countries globally. The unprecedented geographic spread of the outbreak highlighted important knowledge gaps in disease surveillance, prevention, and control. Given the ongoing global circulation of MPXV and the risk of future outbreaks, this review provides a comprehensive synthesis of current evidence on MPXV and mpox. METHODS: The literature, surveillance data, and public health reports available up to March 2026 were systematically reviewed and synthesized. The review comprehensively assesses viral biology, genetic diversity, epidemiology, transmission dynamics, clinical manifestations, pathogenesis, laboratory diagnosis, infection during pregnancy, host immune responses, immune evasion mechanisms, therapeutic interventions, and prevention strategies. FINDINGS AND CONCLUSIONS: Globally, the decline in public immunity following the cessation of routine smallpox vaccination, together with ongoing viral evolution, may have contributed to the resurgence of mpox. Advances in genomic surveillance, diagnostics, and public health preparedness have strengthened outbreak response; however, important gaps remain in understanding long-term immunity and optimal treatment strategies. This review summarizes current evidence on MPXV and mpox and highlights priorities for future research and public health interventions.

Antiviral therapy↗
PubMed2026

Insights into the Life Cycle and Therapeutic Agents for Monkeypox Virus Infection.

Since the first confirmed case in 1970, the monkeypox virus (MPXV) has emerged as a significant threat to global public health. The World Health Organization (WHO) has declared it a Public Health Emergency of International Concern (PHEIC) on two occasions. Despite decades of research, only tecovirimat has been approved by the European Medicines Agency (EMA) for the treatment of MPXV infection. The genome and structure are similar between MPXV and other orthopoxviruses (OPXVs), suggesting that the strategies used for other OPXVs may be applicable to MPXV. This review systematically summarizes the genome, structure, and critical stages in the life cycle of OPXVs, especially MPXV. A variety of antiviral agents against MPXV and other OPXVs are discussed according to their distinct mechanisms of action: 1) blocking viral entry and fusion, 2) inhibiting DNA replication and processing, 3) disrupting transcription and mRNA processing, 4) preventing virion assembly, maturation and release, 5) modulating immune responses, and 6) mechanism unknown. Overall, this article provides a systematic review of current research progress on potential therapeutic targets and agent for MPXV, aiming to offer innovative insights and strategies for the development of effective therapeutic agents against mpox.

Animals↗
PubMed2025

Orthopoxvirus Genome Sequencing, Assembly, and Analysis.

Poxviruses have exceptionally large genomes compared to most other viruses, which represent unique challenges to sequencing and assembly due to complex features such as repeat elements and low complexity sequences. The 2022 global mpox outbreak led to an unprecedented level of poxvirus sequencing as public health and research institutions faced with large sample numbers and demand for fast turnaround, merged NGS protocols designed for small RNA viruses with poxvirus expertise. Traditional manual assembly, checking, and editing of genomes was not feasible. Here, we present a protocol for metagenomic sequencing and orthopoxvirus genome assembly directly from DNA extracted from a patient lesion swab with no viral enrichment or host depletion. This sequencing approach is cost effective when using high throughput sequencing instruments and allows for detection of genomic insertions, deletions, and large rearrangement with confidence. We describe usage of two publicly available bioinformatic pipelines for genome assembly, quality control, annotation, and submission to sequence repositories.

Orthopoxvirus↗
PubMed2026

Project ODIN: advancing environmental genomic surveillance for public health across sub-Saharan Africa.

Persistent SARS-CoV-2 transmission, ongoing mpox outbreaks, and the continued spread of endemic diseases such as typhoid fever and cholera underscore the urgent need for global, multiomics surveillance. In this Personal View, we present Project ODIN, a consortium of European and African partners launched in 2023 that aims to meet this challenge by deploying innovative systems for near real-time pathogen detection and actionable public health insights. The project is a collaboration between high-income and low-income countries in northern Europe and sub-Saharan Africa. Focusing on low-income and middle-income countries, ODIN integrates metagenomics with mobile laboratory systems for comprehensive pathogen monitoring across diverse environments. ODIN emphasises standardised sampling, bioinformatics pipelines, and data-sharing protocols to ensure reliable, interoperable results while addressing infrastructure and resource limitations. By bridging gaps in genomic surveillance, these initiatives seek to strengthen outbreak preparedness, improve pathogen detection, monitor antimicrobial resistance, and provide a holistic approach to One Health challenges. Together, these innovations could advance global surveillance capacity-particularly in under-resourced regions-paving the way for effective disease control and evidence-based policy making.

Humans↗