Rong Wang, Qilong Tan, Qiongyan Li, Shibo Li, Dandan Miao, Zhilei Mao
This study investigated the humoral immune response dynamics in patients with severe fever with thrombocytopenia syndrome (SFTS) to evaluate their prognostic value and construct an early warning model. A retrospective cohort of 36 laboratory-confirmed SFTS patients with ≥ 4 serial antibody measurements out of 153 patients recruited in the study were analyzed. Patients were categorized by outcome into mild, severe, and fatal groups. The results showed that, the fatal group was older, had more comorbidities, and showed no antibody seroconversion during follow-up, along with a significantly higher day-7 viral load. Early seroconversion (IgM/IgG ≤ 7 days post-admission) was associated with shorter recovery time and higher survival compared to delayed seroconversion (> 7 days) or antibody-deficient status. Antibody seroconversion time was strongly positively correlated with recovery time. Advanced age (≥ 70 years) was a significant risk factor for severe/fatal outcomes and was linked to delayed or absent seroconversion. A synergistic interaction was found between age and day-7 antibody status. A simple early warning model combining age and day-7 antibody status demonstrated good predictive performance with an AUC of 0.83. The findings indicate that antibody response timing and advanced age are key prognostic factors in SFTS. The proposed model shows promise for early identification of high-risk patients in resource-limited settings.
{"title":"Antibody Response Dynamics as an Early Predictor of Clinical Outcome in Severe Fever With Thrombocytopenia Syndrome (SFTS): A Retrospective Cohort Study for Prognostic Model Development","authors":"Rong Wang, Qilong Tan, Qiongyan Li, Shibo Li, Dandan Miao, Zhilei Mao","doi":"10.1002/jmv.70830","DOIUrl":"10.1002/jmv.70830","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigated the humoral immune response dynamics in patients with severe fever with thrombocytopenia syndrome (SFTS) to evaluate their prognostic value and construct an early warning model. A retrospective cohort of 36 laboratory-confirmed SFTS patients with ≥ 4 serial antibody measurements out of 153 patients recruited in the study were analyzed. Patients were categorized by outcome into mild, severe, and fatal groups. The results showed that, the fatal group was older, had more comorbidities, and showed no antibody seroconversion during follow-up, along with a significantly higher day-7 viral load. Early seroconversion (IgM/IgG ≤ 7 days post-admission) was associated with shorter recovery time and higher survival compared to delayed seroconversion (> 7 days) or antibody-deficient status. Antibody seroconversion time was strongly positively correlated with recovery time. Advanced age (≥ 70 years) was a significant risk factor for severe/fatal outcomes and was linked to delayed or absent seroconversion. A synergistic interaction was found between age and day-7 antibody status. A simple early warning model combining age and day-7 antibody status demonstrated good predictive performance with an AUC of 0.83. The findings indicate that antibody response timing and advanced age are key prognostic factors in SFTS. The proposed model shows promise for early identification of high-risk patients in resource-limited settings.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dongmei Lv, Xinxin Zhao, Xiao Li, Tao Meng, Wenlong Zhang
Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease that has received widespread attention. This study focused on the predictive value and trends of cytokines in SFTS patients. Information on 128 patients with SFTS was retrospectively collected from January 2019 to January 2023 at a large general hospital in Anhui Province, China. Of these, 34 died during the course of the disease. Compared to survivors, non-survivors exhibited significantly elevated cytokine levels and lower CD4⁺/CD8⁺ T-cell counts. Multivariate Cox analysis revealed that TNF-α (adjusted HR = 13.602, 95% CI = 1.197–154.539) was an independent predictor of death with area under the curve (AUC) values of 0.901. TNF-α, IL-6, IL-10, and IL-8 levels were found to be correlated with viral titers. Longitudinal monitoring revealed distinct cytokine dynamics during the disease course. Combining high-dose intravenous gamma globulin (IVIG) with ribavirin effectively reduced the levels of IL-6, IL-2R, and IL-10, suggesting a potential therapeutic strategy for clinical practice.
{"title":"Evaluation and Dynamic Change Characteristics of Cytokines in Severe Fever With Thrombocytopenia Syndrome Infected Patients","authors":"Dongmei Lv, Xinxin Zhao, Xiao Li, Tao Meng, Wenlong Zhang","doi":"10.1002/jmv.70826","DOIUrl":"10.1002/jmv.70826","url":null,"abstract":"<div>\u0000 \u0000 <p>Severe fever with thrombocytopenia syndrome (SFTS) is a serious infectious disease that has received widespread attention. This study focused on the predictive value and trends of cytokines in SFTS patients. Information on 128 patients with SFTS was retrospectively collected from January 2019 to January 2023 at a large general hospital in Anhui Province, China. Of these, 34 died during the course of the disease. Compared to survivors, non-survivors exhibited significantly elevated cytokine levels and lower CD4⁺/CD8⁺ T-cell counts. Multivariate Cox analysis revealed that TNF-α (adjusted HR = 13.602, 95% CI = 1.197–154.539) was an independent predictor of death with area under the curve (AUC) values of 0.901. TNF-α, IL-6, IL-10, and IL-8 levels were found to be correlated with viral titers. Longitudinal monitoring revealed distinct cytokine dynamics during the disease course. Combining high-dose intravenous gamma globulin (IVIG) with ribavirin effectively reduced the levels of IL-6, IL-2R, and IL-10, suggesting a potential therapeutic strategy for clinical practice.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hand, foot, and mouth disease (HFMD) is a common infectious disease in children, primarily caused by human enteroviruses (EVs). This study describes the epidemiological characteristics of HFMD in Taiyuan, China (2017-2024), also the genetic features of Coxsackievirus A6 (CVA6). The incidence of HFMD showed significant variations during this period. Male cases outnumbered females, with children aged 0-6 years accounting for 81.88% of all cases and exhibiting a distinct seasonal distribution pattern. Real-time reverse transcription polymerase chain reaction was performed on 4389 clinical specimens, identifying 1,920 human EVs-positive specimens. Positive cases included 690 CVA6, 530 CVA16, 65 CVA10, 152 Enterovirus A71, and 483 other human EVs. Pathogen spectrum analysis revealed that CVA6 maintained high prevalence from 2017 to 2023 but declined in 2024. Phylogenetic analysis of 194 complete VP1 sequences revealed all strains belonged to sub-genotype D3 within genotype D. Nucleic acid homology ranged from 91.4% to 100%, and amino acid similarity from 97.0% to 100%. A persistent, continuously circulating lineage existed within the D3a branch. The GH loop within VP1 revealed high sequence conservation and structural stability, confirming its suitability as a vaccine target. These findings enhance genetic data on CVA6, thereby providing crucial scientific basis for prevention and vaccine development.
{"title":"Epidemiology of Hand, Foot, and Mouth Disease and Genetic Evolution Dynamics of Coxsackievirus A6 in Taiyuan, Shanxi, China From 2017 to 2024.","authors":"Jitao Wang, Chaojie Xu, Jihong Xu, Huangzan Yang, Li Gao, Ruihong Gao, Lifeng Zhao, Jiane Guo, Ping Zhang, Qiyu Zhao, Huijun Liu, Zhenzhi Han, Huibin Bai, Dongmei Yan, Jinbo Xiao, Yong Zhang","doi":"10.1002/jmv.70859","DOIUrl":"10.1002/jmv.70859","url":null,"abstract":"<p><p>Hand, foot, and mouth disease (HFMD) is a common infectious disease in children, primarily caused by human enteroviruses (EVs). This study describes the epidemiological characteristics of HFMD in Taiyuan, China (2017-2024), also the genetic features of Coxsackievirus A6 (CVA6). The incidence of HFMD showed significant variations during this period. Male cases outnumbered females, with children aged 0-6 years accounting for 81.88% of all cases and exhibiting a distinct seasonal distribution pattern. Real-time reverse transcription polymerase chain reaction was performed on 4389 clinical specimens, identifying 1,920 human EVs-positive specimens. Positive cases included 690 CVA6, 530 CVA16, 65 CVA10, 152 Enterovirus A71, and 483 other human EVs. Pathogen spectrum analysis revealed that CVA6 maintained high prevalence from 2017 to 2023 but declined in 2024. Phylogenetic analysis of 194 complete VP1 sequences revealed all strains belonged to sub-genotype D3 within genotype D. Nucleic acid homology ranged from 91.4% to 100%, and amino acid similarity from 97.0% to 100%. A persistent, continuously circulating lineage existed within the D3a branch. The GH loop within VP1 revealed high sequence conservation and structural stability, confirming its suitability as a vaccine target. These findings enhance genetic data on CVA6, thereby providing crucial scientific basis for prevention and vaccine development.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":"e70859"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Uyen Nguyen Phuong Le, Ruey-Hwang Chou, Chen-Sheng Lin, Hsueh-Chou Lai, Wen-Chi Su, Po-Ren Hsueh, Cheng-Wen Lin
Angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is critical for viral entry and pulmonary homeostasis, yet its regulation during infection remains unclear. Using SARS-CoV-2 single-round infectious particles (SRIPs), we found that ACE2 protein and mRNA were markedly reduced in human alveolar (A549) and bronchial (Calu-3) cells. This effect was reproduced by expression of the viral main protease (Mpro). Notably, ACE2 suppression was independent of Mpro enzymatic activity, as the catalytically inactive mutant (Mpro_C145A) downregulated ACE2 comparably to wild-type Mpro, and inhibition with nirmatrelvir or MG132 failed to restore expression. Mechanistically, Mpro enhanced STAT1 phosphorylation while suppressing STAT3 Tyr705 phosphorylation, impairing STAT3 nuclear localization and transcriptional activity. Overexpression of STAT3, but not STAT1, restored ACE2 expression in both Mpro-expressing and SARS-CoV-2-infected cells. Moreover, Mpro activated ERK1/2 through TRAF6-TAK1 signaling, which facilitated STAT3 interaction with the tyrosine phosphatase MEG2, leading to dephosphorylation of STAT3 at Tyr705. ERK1/2 inhibition restored STAT3 activity and ACE2 expression, while JNK inhibition had no effect. In infected cells, ERK1/2 inhibition increased ACE2 but also enhanced viral replication. These findings identify a non-enzymatic role of Mpro in suppressing ACE2 through the ERK1/2-MEG2-STAT3 axis, highlighting a mechanism that regulates host receptor availability and influences SARS-CoV-2 pathogenesis.
{"title":"SARS-CoV-2 Main Protease Activates ERK1/2 Signaling to Facilitate MEG2-STAT3-Mediated Suppression of ACE2.","authors":"Uyen Nguyen Phuong Le, Ruey-Hwang Chou, Chen-Sheng Lin, Hsueh-Chou Lai, Wen-Chi Su, Po-Ren Hsueh, Cheng-Wen Lin","doi":"10.1002/jmv.70855","DOIUrl":"https://doi.org/10.1002/jmv.70855","url":null,"abstract":"<p><p>Angiotensin-converting enzyme 2 (ACE2), the receptor for SARS-CoV-2, is critical for viral entry and pulmonary homeostasis, yet its regulation during infection remains unclear. Using SARS-CoV-2 single-round infectious particles (SRIPs), we found that ACE2 protein and mRNA were markedly reduced in human alveolar (A549) and bronchial (Calu-3) cells. This effect was reproduced by expression of the viral main protease (Mpro). Notably, ACE2 suppression was independent of Mpro enzymatic activity, as the catalytically inactive mutant (Mpro_C145A) downregulated ACE2 comparably to wild-type Mpro, and inhibition with nirmatrelvir or MG132 failed to restore expression. Mechanistically, Mpro enhanced STAT1 phosphorylation while suppressing STAT3 Tyr705 phosphorylation, impairing STAT3 nuclear localization and transcriptional activity. Overexpression of STAT3, but not STAT1, restored ACE2 expression in both Mpro-expressing and SARS-CoV-2-infected cells. Moreover, Mpro activated ERK1/2 through TRAF6-TAK1 signaling, which facilitated STAT3 interaction with the tyrosine phosphatase MEG2, leading to dephosphorylation of STAT3 at Tyr705. ERK1/2 inhibition restored STAT3 activity and ACE2 expression, while JNK inhibition had no effect. In infected cells, ERK1/2 inhibition increased ACE2 but also enhanced viral replication. These findings identify a non-enzymatic role of Mpro in suppressing ACE2 through the ERK1/2-MEG2-STAT3 axis, highlighting a mechanism that regulates host receptor availability and influences SARS-CoV-2 pathogenesis.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":"e70855"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jihyeon Kim, Hyeongki Park, Hoong Kai Chua, Yuqian Wang, Shingo Iwami, Yong Dam Jeong, Koya Ariyoshi, Po Ying Chia, Barnaby E. Young, Matthew E. Cove, Robin N. Thompson, William Hart, Il Hyo Jung, Kwang Su Kim, Hyojung Lee, Keisuke Ejima
Viral load data provide critical insights into host-pathogen interactions and guide clinical and public health decisions. Because frequent testing is often infeasible, viral dynamics models are used to reconstruct infection trajectories, but optimal sampling strategies remain unclear. We compared two approaches for collecting SARS-CoV-2 viral load data: cross-sectional sampling (one measurement at symptom onset) and longitudinal sampling (every 3 days after onset) under constraints on the total number of tests and tests per individual. A viral dynamics model was first fitted to data from the National Basketball Association cohort, and the estimated parameters were treated as ground truth. Synthetic data were then generated under each sampling design, refitted, and evaluated for accuracy in estimating viral load over 30 days, peak viral load, peak time, and viral shedding duration. Longitudinal sampling consistently yielded lower root mean squared error and narrower one standard deviation interval than cross-sectional sampling. Peak timing and viral shedding duration were unbiased under both designs, but cross-sectional designs underestimated peak viral load and produced wider one standard deviation intervals. Coverage of viral load estimates was markedly higher for longitudinal designs (> 0.90) compared with cross-sectional ones (~0.10). Accuracy and coverage exceeded 0.96 even with just two tests per individual, with little additional benefit from more tests. In conclusion, longitudinal sampling—despite limited data—substantially improves accuracy and precision of viral load estimation compared with cross-sectional designs. These findings highlight efficient strategies for study design and resource allocation in infectious disease research.
{"title":"Comparing Cross-Sectional and Longitudinal Study Designs for Accurate Viral Dynamics Estimation: Insights From the NBA Cohort Data","authors":"Jihyeon Kim, Hyeongki Park, Hoong Kai Chua, Yuqian Wang, Shingo Iwami, Yong Dam Jeong, Koya Ariyoshi, Po Ying Chia, Barnaby E. Young, Matthew E. Cove, Robin N. Thompson, William Hart, Il Hyo Jung, Kwang Su Kim, Hyojung Lee, Keisuke Ejima","doi":"10.1002/jmv.70823","DOIUrl":"10.1002/jmv.70823","url":null,"abstract":"<p>Viral load data provide critical insights into host-pathogen interactions and guide clinical and public health decisions. Because frequent testing is often infeasible, viral dynamics models are used to reconstruct infection trajectories, but optimal sampling strategies remain unclear. We compared two approaches for collecting SARS-CoV-2 viral load data: cross-sectional sampling (one measurement at symptom onset) and longitudinal sampling (every 3 days after onset) under constraints on the total number of tests and tests per individual. A viral dynamics model was first fitted to data from the National Basketball Association cohort, and the estimated parameters were treated as ground truth. Synthetic data were then generated under each sampling design, refitted, and evaluated for accuracy in estimating viral load over 30 days, peak viral load, peak time, and viral shedding duration. Longitudinal sampling consistently yielded lower root mean squared error and narrower one standard deviation interval than cross-sectional sampling. Peak timing and viral shedding duration were unbiased under both designs, but cross-sectional designs underestimated peak viral load and produced wider one standard deviation intervals. Coverage of viral load estimates was markedly higher for longitudinal designs (> 0.90) compared with cross-sectional ones (~0.10). Accuracy and coverage exceeded 0.96 even with just two tests per individual, with little additional benefit from more tests. In conclusion, longitudinal sampling—despite limited data—substantially improves accuracy and precision of viral load estimation compared with cross-sectional designs. These findings highlight efficient strategies for study design and resource allocation in infectious disease research.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146099963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Current dengue vaccines remain limited by serotype-dependent efficacy and interference from preexisting anti-dengue immunity. We developed a novel multivalent fusion protein vaccine composed of three engineered dengue virus (DENV) components: a C-terminal truncated nonstructural protein 1 (ΔcNS1) to block NS1-mediated pathologic effects without harmful cross-reactivity, a consensus envelope protein domain III (cEDIII) to induce broad neutralizing antibodies, and an N-terminal truncated NS3 (ΔnNS3) to enhance cellular immune responses. In a murine dengue disease model, three-dose immunization with ΔcNS1–cEDIII–ΔnNS3 adjuvanted with Alum provides protection against all four DENV serotypes by significantly reducing viremia and prolonged bleeding time, with elicited robust antibody responses, enhanced cytotoxic activity of CD8+ T cells upon NS1/NS3 restimulation, and increased memory B and T cell populations. Notably, CpG oligodeoxynucleotides 1826 (CpG) plus Alum further enhanced immunogenicity, showing higher neutralizing activity, antigen-specific plasmablast expansion, and enhanced T cell functional activity, which was associated with more consistent improvement in protection-relevant outcomes compared with Alum alone. Importantly, two-dose immunization with CpG plus Alum-adjuvanted fusion protein conferred durable protection against the virulent DENV2 strain TW2015. These findings support this vaccine as a promising subunit candidate that addresses current limitations, offering both cross-serotype coverage and potential long-term efficacy.
{"title":"A Multivalent Dengue Fusion Protein ΔcNS1–cEDIII–ΔnNS3 Confers Cross-Serotype Protection and Durable Immunity in Mice","authors":"Mu-Fan Pi, Wei-Chiao Liao, Xin-Yan Li, Miao-Huei Cheng, Chu-En Tsai, Yen-Chung Lai, Hsing-Han Lin, Yung-Chun Chuang, Chin-Kai Tseng, Yee-Shin Lin, Chih-Peng Chang, Tzong-Shiann Ho, Guan-Da Syu, Trai-Ming Yeh, Jen‑Ren Wang, Justin Jang Hann Chu, Chia-Yi Yu, Shu-Wen Wan","doi":"10.1002/jmv.70822","DOIUrl":"10.1002/jmv.70822","url":null,"abstract":"<div>\u0000 \u0000 <p>Current dengue vaccines remain limited by serotype-dependent efficacy and interference from preexisting anti-dengue immunity. We developed a novel multivalent fusion protein vaccine composed of three engineered dengue virus (DENV) components: a C-terminal truncated nonstructural protein 1 (ΔcNS1) to block NS1-mediated pathologic effects without harmful cross-reactivity, a consensus envelope protein domain III (cEDIII) to induce broad neutralizing antibodies, and an N-terminal truncated NS3 (ΔnNS3) to enhance cellular immune responses. In a murine dengue disease model, three-dose immunization with ΔcNS1–cEDIII–ΔnNS3 adjuvanted with Alum provides protection against all four DENV serotypes by significantly reducing viremia and prolonged bleeding time, with elicited robust antibody responses, enhanced cytotoxic activity of CD8<sup>+</sup> T cells upon NS1/NS3 restimulation, and increased memory B and T cell populations. Notably, CpG oligodeoxynucleotides 1826 (CpG) plus Alum further enhanced immunogenicity, showing higher neutralizing activity, antigen-specific plasmablast expansion, and enhanced T cell functional activity, which was associated with more consistent improvement in protection-relevant outcomes compared with Alum alone. Importantly, two-dose immunization with CpG plus Alum-adjuvanted fusion protein conferred durable protection against the virulent DENV2 strain TW2015. These findings support this vaccine as a promising subunit candidate that addresses current limitations, offering both cross-serotype coverage and potential long-term efficacy.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wang Chun Kwok, Isaac Sze Him Leung, Chun Ka Emmanuel Wong, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Shuk Man Ngai, Kelvin Kai Wang To, Desmond Yat Hin Yap
Human metapneumovirus (hMPV) causes mild and self-limiting disease in adults. However, the risk factors for serious adverse outcomes following hMPV infection in adult patients without preexisting chronic airway diseases remain poorly understood. We conducted a territory-wide retrospective study on adult patients (aged ≥ 18 years) without chronic airway diseases hospitalized for hMPV infections between January 1, 2016 and June 30, 2023 in Hong Kong. We assessed the incidence and risk factors for in-patient mortality, severe respiratory failure (SRF), secondary bacterial pneumonia and acute kidney injury (AKI) were assessed. A total of 1552 eligible adult patients without chronic airway diseases hospitalized for hMPV infections were analyzed. Within the index admission, 92 (5.9%) patients died. Ischemic heart disease (IHD) was associated with increased risks of SRF [adjusted odds ratio (aOR) 2.00 (95% CI 1.48–2.71), p < 0.001]. IHD, heart failure (HF), and history of ischemic stroke were significant predictors for AKI [aOR 1.51 (95% CI 1.12–2.04), 2.87 (95% CI 2.14–3.85), and 1.47 (95% CI = 1.12–1.93), p = 0.007, < 0.001, and 0.005, respectively). Patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) were at increased risk of in-patient mortality [aOR 6.36 (95% CI 2.34–17.26), p < 0.001] and SRF [aOR 8.80 (95% CI 3.84–20.16), p < 0.001]. The presence of cardiovascular diseases and ESKD requiring RRT is a strong predictor of severe in-hospital outcomes among adult patients without chronic airway diseases who are hospitalized for hMPV infections.
人偏肺病毒（hMPV）在成人中引起轻度和自限性疾病。然而，对于没有既往存在的慢性气道疾病的成人hMPV感染后严重不良后果的危险因素仍然知之甚少。我们对2016年1月1日至2023年6月30日期间在香港因hMPV感染住院的无慢性气道疾病的成人患者（年龄≥18岁）进行了一项区域性回顾性研究。我们评估了住院患者死亡率、严重呼吸衰竭（SRF）、继发性细菌性肺炎和急性肾损伤（AKI）的发生率和危险因素。对1552例因hMPV感染住院的无慢性气道疾病的成人患者进行分析。在指标入院期间，92例（5.9%）患者死亡。缺血性心脏病（IHD）与SRF的风险增加相关[校正优势比（aOR） 2.00 (95% CI 1.48-2.71), p
{"title":"Cardio–Renal Diseases Are Independent Risk Factors of Severe Human Metapneumovirus Infection Among Patients Without Chronic Airway Diseases","authors":"Wang Chun Kwok, Isaac Sze Him Leung, Chun Ka Emmanuel Wong, James Chung Man Ho, David Chi Leung Lam, Mary Sau Man Ip, Shuk Man Ngai, Kelvin Kai Wang To, Desmond Yat Hin Yap","doi":"10.1002/jmv.70812","DOIUrl":"10.1002/jmv.70812","url":null,"abstract":"<p>Human metapneumovirus (hMPV) causes mild and self-limiting disease in adults. However, the risk factors for serious adverse outcomes following hMPV infection in adult patients without preexisting chronic airway diseases remain poorly understood. We conducted a territory-wide retrospective study on adult patients (aged ≥ 18 years) without chronic airway diseases hospitalized for hMPV infections between January 1, 2016 and June 30, 2023 in Hong Kong. We assessed the incidence and risk factors for in-patient mortality, severe respiratory failure (SRF), secondary bacterial pneumonia and acute kidney injury (AKI) were assessed. A total of 1552 eligible adult patients without chronic airway diseases hospitalized for hMPV infections were analyzed. Within the index admission, 92 (5.9%) patients died. Ischemic heart disease (IHD) was associated with increased risks of SRF [adjusted odds ratio (aOR) 2.00 (95% CI 1.48–2.71), <i>p</i> < 0.001]. IHD, heart failure (HF), and history of ischemic stroke were significant predictors for AKI [aOR 1.51 (95% CI 1.12–2.04), 2.87 (95% CI 2.14–3.85), and 1.47 (95% CI = 1.12–1.93), <i>p</i> = 0.007, < 0.001, and 0.005, respectively). Patients with end-stage kidney disease (ESKD) requiring renal replacement therapy (RRT) were at increased risk of in-patient mortality [aOR 6.36 (95% CI 2.34–17.26), <i>p</i> < 0.001] and SRF [aOR 8.80 (95% CI 3.84–20.16), <i>p</i> < 0.001]. The presence of cardiovascular diseases and ESKD requiring RRT is a strong predictor of severe in-hospital outcomes among adult patients without chronic airway diseases who are hospitalized for hMPV infections.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catalina A. Andrade, Mario A. Ramírez, Tays Troncoso-Bravo, Karen Bohmwald, Jorge A. Soto, Alexis M. Kalergis
The human metapneumovirus (HMPV) is a major respiratory pathogen mainly affecting infants under 5 years old. The interferon (IFN) response varies among patients, animal models, and HMPV strains, and this variation is crucial because the initial IFN response controls viral replication. Therefore, it is important to study the different profiles of IFN secretion during the same HMPV infection across various animal models. In this study, BALB/c and C57BL/6 mice were infected with a clinical A1 strain of HMPV-CZ0107, and at the endpoint, the expression of different types of IFN was measured. BALB/c mice showed significant weight loss and viral replication, while C57BL/6 mice exhibited notable neutrophil infiltration. Mice infected with BALB/c displayed significant secretion of all tested IFN types in all samples, whereas C57BL/6-infected mice showed significant secretion of IFN-α and IFN-γ only in the lungs. Additionally, infected BALB/c and C57BL/6 mice demonstrated different activation patterns of IFN-α- and IFN-γ-secreting natural killer (NK) cells, including both immature and mature cells. These findings characterize the IFN response induced by HMPV-CZ0107 and suggest that this infection results in higher secretion of IFNs in BALB/c mice compared to C57BL/6 mice, which may help explain the less severe clinical parameters observed in C57BL/6 mice.
{"title":"Variability in IFN Secretion in Response to the Human Metapneumovirus CZ0107 Strain: A Comparative Study in BALB/c and C57BL/6 Mouse Models","authors":"Catalina A. Andrade, Mario A. Ramírez, Tays Troncoso-Bravo, Karen Bohmwald, Jorge A. Soto, Alexis M. Kalergis","doi":"10.1002/jmv.70818","DOIUrl":"10.1002/jmv.70818","url":null,"abstract":"<div>\u0000 \u0000 <p>The human metapneumovirus (HMPV) is a major respiratory pathogen mainly affecting infants under 5 years old. The interferon (IFN) response varies among patients, animal models, and HMPV strains, and this variation is crucial because the initial IFN response controls viral replication. Therefore, it is important to study the different profiles of IFN secretion during the same HMPV infection across various animal models. In this study, BALB/c and C57BL/6 mice were infected with a clinical A1 strain of HMPV-CZ0107, and at the endpoint, the expression of different types of IFN was measured. BALB/c mice showed significant weight loss and viral replication, while C57BL/6 mice exhibited notable neutrophil infiltration. Mice infected with BALB/c displayed significant secretion of all tested IFN types in all samples, whereas C57BL/6-infected mice showed significant secretion of IFN-α and IFN-γ only in the lungs. Additionally, infected BALB/c and C57BL/6 mice demonstrated different activation patterns of IFN-α- and IFN-γ-secreting natural killer (NK) cells, including both immature and mature cells. These findings characterize the IFN response induced by HMPV-CZ0107 and suggest that this infection results in higher secretion of IFNs in BALB/c mice compared to C57BL/6 mice, which may help explain the less severe clinical parameters observed in C57BL/6 mice.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146086149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In recent years, coronavirus, a kind of virus with a wide host range and high variability, has a large and complex genome. Research on the reverse genetics of coronaviruses has always been a hot spot. Coronavirus cannot only infect mammals, but also infect humans, showing its wide host adaptability. The mutation ability of the coronavirus is extremely strong. Recently, the rapid mutation rate of SARS-CoV-2 has made the development of vaccines and therapeutic methods face great challenges. At present, reverse genetics technology is a molecular biology tool. This process primarily involves cloning the full-length genome cDNA of the virus onto a vector, and then reproducing the modified progeny virus in the cell to achieve accurate modification of the virus's genetic characteristics. This technology can explore the external characteristics of mutants and the evolution of their traits through artificial operations, such as knockout and site-directed mutagenesis of specific genes, and then reveal the biological functions of genes. This article will review the research progress of the coronavirus reverse genetic operating system. In the past research, reverse genetics technology has made remarkable progress in the field of coronavirus research. Researchers have successfully constructed various reverse genetic systems for coronaviruses, including IBV, SARS-CoV-2, and MERS-CoV. In addition, the reverse genetic system has also been used to study the cross-species transmission capacity of the virus, which is of great significance for preventing possible future novel coronavirus epidemics.
{"title":"Research Progress of Coronavirus Reverse Genetics Technology","authors":"Ziqi Han, Jiaxu Han, Yan Zhao, Chao Xu, Xue Leng, Boyin Jia, Naichao Diao, Fei Liu, Chunmei Cui, Jian Liang, Yuhang Jiang, Rui Du","doi":"10.1002/jmv.70792","DOIUrl":"https://doi.org/10.1002/jmv.70792","url":null,"abstract":"<div>\u0000 \u0000 <p>In recent years, coronavirus, a kind of virus with a wide host range and high variability, has a large and complex genome. Research on the reverse genetics of coronaviruses has always been a hot spot. Coronavirus cannot only infect mammals, but also infect humans, showing its wide host adaptability. The mutation ability of the coronavirus is extremely strong. Recently, the rapid mutation rate of SARS-CoV-2 has made the development of vaccines and therapeutic methods face great challenges. At present, reverse genetics technology is a molecular biology tool. This process primarily involves cloning the full-length genome cDNA of the virus onto a vector, and then reproducing the modified progeny virus in the cell to achieve accurate modification of the virus's genetic characteristics. This technology can explore the external characteristics of mutants and the evolution of their traits through artificial operations, such as knockout and site-directed mutagenesis of specific genes, and then reveal the biological functions of genes. This article will review the research progress of the coronavirus reverse genetic operating system. In the past research, reverse genetics technology has made remarkable progress in the field of coronavirus research. Researchers have successfully constructed various reverse genetic systems for coronaviruses, including IBV, SARS-CoV-2, and MERS-CoV. In addition, the reverse genetic system has also been used to study the cross-species transmission capacity of the virus, which is of great significance for preventing possible future novel coronavirus epidemics.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146155181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mike Horton, Adam B. Smith, Ruairidh Milne, Darren Winch, Clare Rayner, Stephen Halpin, Rory O'Connor, Roman Rocha Lawrence, Darren C. Greenwood, Nawar D. Bakerly, Rachael Evans, Joseph Kwon, Helen Dawes, Conor Wood, Paul Williams, Harsha Master, Mae Mansoubi, Johannes H. De Kock, Jordan Mullard, Mike Ormerod, Ghazala Mir, Stavros Petrou, Daryl B. O'Connor, Manoj Sivan, LOCOMOTION Consortium
The C19-YRS was the first condition-specific for long COVID/post-COVID syndrome. Although the original C19-YRS evolved to the modified version (C19-YRSm) based on psychometric evidence, clinical content relevance, as well as feedback from patients and healthcare professionals, it has not been validated through Rasch analysis. The study aim was to psychometrically assess and validate the C19-YRSm using newly collected data from a large-scale, multicenter study (LOCOMOTION). In total, 1278 patients (67% Female; mean age = 48.6, SD 12.7) digitally completed the C19-YRSm. The psychometric properties of the C19-YRSm Symptom Severity (SS) and Functional Disability (FD) subscales were assessed using a Rasch Measurement Theory framework, assessing for individual item model fit, targeting, internal consistency reliability, unidimensionality, local dependency (LD), response category functioning and differential item functioning (DIF) by age group, sex and ethnicity. Rasch analysis revealed robust psychometric properties of both subscales, with each demonstrating unidimensionality, appropriate response category structuring, no floor or ceiling effects, and minimal LD and DIF. Both subscales also displayed good targeting and reliability (SS: Person Separation Index (PSI) = 0.81, Cronbach's α = 0.82; FD: PSI = 0.76, Cronbach's α = 0.81). Although some minor anomalies are apparent, the modifications to the original C19-YRS have strengthened its measurement characteristics and its clinical and conceptual relevance.
{"title":"Large-Scale Psychometric Assessment and Validation of the Modified COVID-19 Yorkshire Rehabilitation Scale Patient-Reported Outcome Measure for Long COVID or Post-COVID Syndrome","authors":"Mike Horton, Adam B. Smith, Ruairidh Milne, Darren Winch, Clare Rayner, Stephen Halpin, Rory O'Connor, Roman Rocha Lawrence, Darren C. Greenwood, Nawar D. Bakerly, Rachael Evans, Joseph Kwon, Helen Dawes, Conor Wood, Paul Williams, Harsha Master, Mae Mansoubi, Johannes H. De Kock, Jordan Mullard, Mike Ormerod, Ghazala Mir, Stavros Petrou, Daryl B. O'Connor, Manoj Sivan, LOCOMOTION Consortium","doi":"10.1002/jmv.70816","DOIUrl":"10.1002/jmv.70816","url":null,"abstract":"<p>The C19-YRS was the first condition-specific for long COVID/post-COVID syndrome. Although the original C19-YRS evolved to the modified version (C19-YRSm) based on psychometric evidence, clinical content relevance, as well as feedback from patients and healthcare professionals, it has not been validated through Rasch analysis. The study aim was to psychometrically assess and validate the C19-YRSm using newly collected data from a large-scale, multicenter study (LOCOMOTION). In total, 1278 patients (67% Female; mean age = 48.6, SD 12.7) digitally completed the C19-YRSm. The psychometric properties of the C19-YRSm Symptom Severity (SS) and Functional Disability (FD) subscales were assessed using a Rasch Measurement Theory framework, assessing for individual item model fit, targeting, internal consistency reliability, unidimensionality, local dependency (LD), response category functioning and differential item functioning (DIF) by age group, sex and ethnicity. Rasch analysis revealed robust psychometric properties of both subscales, with each demonstrating unidimensionality, appropriate response category structuring, no floor or ceiling effects, and minimal LD and DIF. Both subscales also displayed good targeting and reliability (SS: Person Separation Index (PSI) = 0.81, Cronbach's <i>α </i>= 0.82; FD: PSI = 0.76, Cronbach's <i>α</i> = 0.81). Although some minor anomalies are apparent, the modifications to the original C19-YRS have strengthened its measurement characteristics and its clinical and conceptual relevance.</p><p><b>Trial Registration:</b> NCT05057260, ISRCTN15022307</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"98 2","pages":""},"PeriodicalIF":4.6,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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