Jiankai Ye, Rui Zhang, Jiahao Zhou, Tao Xu, Xiaoping Liu, Yunyu Chen
{"title":"Systematic Reevaluation of Repurposed Drugs Against the Main Protease of SARS-CoV-2 via Combined Experiments","authors":"Jiankai Ye, Rui Zhang, Jiahao Zhou, Tao Xu, Xiaoping Liu, Yunyu Chen","doi":"10.1002/jmv.70229","DOIUrl":"https://doi.org/10.1002/jmv.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>The main protease (Mpro) of SARS-CoV-2 is an attractive drug target for antivirals, as this enzyme plays a key role in virus replication. Drug repurposing is a promising option for the treatment of coronavirus disease 2019 (COVID-19). Recently, a number of FDA-approved drugs have been identified as Mpro inhibitors, but stringent hit validation is lacking. In this study, we rigorously reevaluated the in vitro inhibition of the Mpro enzyme by repurposed drugs via combined experiments, including the fluorescence resonance energy transfer (FRET) assay, fluorescence polarization (FP) assay, and protease biosensor cleavage assay. Our results from a set of in vitro assays revealed that boceprevir is a potential Mpro inhibitor, but other repurposed drugs, including atazanavir, dipyridamole, entrectinib, ethacridine, glecaprevir, hydroxychloroquine, ivermectin, meisoindigo, pelitinib, raloxifene, roxatidine acetate, saquinavir, teicoplanin, thonzonium bromide, and valacyclovir, are not. Our research highlights that the use of candidate Mpro inhibitors from primary screening warrants further comprehensive studies before the reporting of new findings.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380541","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}
Lawrence Henry Ofosu-Appiah, Manami Negoro, Jennifer Xolali Amexo, Dodzi Kofi Amelor, Prince Baffour Tonto, Dennis Odai Laryea, Keiko Yamasaki, Franklin Asiedu-Bekoe, Ken Sugata, Hiroki Hori, Narufumi Suganuma, Kiyosu Taniguchi
{"title":"Clinical Impact and Genetic Analysis of Enteric Viruses Associated With Acute Gastroenteritis in Greater Accra, Ghana: A Comprehensive Study of Five Viruses","authors":"Lawrence Henry Ofosu-Appiah, Manami Negoro, Jennifer Xolali Amexo, Dodzi Kofi Amelor, Prince Baffour Tonto, Dennis Odai Laryea, Keiko Yamasaki, Franklin Asiedu-Bekoe, Ken Sugata, Hiroki Hori, Narufumi Suganuma, Kiyosu Taniguchi","doi":"10.1002/jmv.70216","DOIUrl":"https://doi.org/10.1002/jmv.70216","url":null,"abstract":"<div>\u0000 \u0000 <p>Enteric viruses are significantly associated with acute gastroenteritis globally. Despite a decrease in severe rotavirus associated diarrhoea, Ghana still records high diarrhoea burden. Meanwhile aetiological investigations in hospital settings do not routinely include viral testing. Rotavirus vaccination is thought to alter enteric viral populations and impact evolution. To better understand virus-specific effects in acute gastroenteritis in both children and adults, we tested fecal samples from 228 patients at two hospitals in Accra from January to December 2019, using multiplex and singleplex PCR assays. The clinical impact of detected viruses was assessed using a modified Vesikari score system. Partial viral genome sequences were obtained by Sanger Sequencing and their genetic diversity and evolutionary history, traced by phylogenetic analyses. At least one enteric virus was found in 86 (37.7%) patient samples, with 36.9% of the population under five infected. Single infections of rotavirus, norovirus, adenovirus, sapovirus and astrovirus were 33, 14, 8, 6, and 1, respectively, while coinfections were 24. Rotavirus accounted for 33.3% of 24 clinically severe cases (modified Vesikari score > 7). Three out of 10 rotavirus cases with evidence of vaccination experienced severe gastroenteritis. Diverse genotypes, including RVA G2P[4], G1P[8], G12P[8] and G12P[6]; AdV F40 and F41; NoV GII.4 Sydney 2012, GII.6 and GI.3, several of which clustered with contemporary strains from the Americas, Europe and Asia, were detected. This study also provides the first report of SaV GI.1, GI.7 and GII.8 detection in humans in Ghana. RVA G2P[4] and AdV F were associated with higher proportions of hospitalizations. While RVA continues to have a profound clinical impact on gastroenteritis, AdV and SaV produce an equally severe disease. In contrast, NoV and AstV showed a generally mild to moderate impact on clinical disease severity.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388902","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}
Fan Zhang, Zuliang Shi, Yihan Wu, Jianbo Xia, Ling Wang
{"title":"Immunogenicity and Efficacy of an Accelerated Vaccination Schedule Against Hepatitis E Virus Infection in Rabbits","authors":"Fan Zhang, Zuliang Shi, Yihan Wu, Jianbo Xia, Ling Wang","doi":"10.1002/jmv.70218","DOIUrl":"https://doi.org/10.1002/jmv.70218","url":null,"abstract":"<div>\u0000 \u0000 <p>An important goal of the hepatitis E virus (HEV) vaccine is to prevent HEV in fragile, conflict-affected, and vulnerable (FCV) settings with documented HEV circulation, but the routine hepatitis E vaccination schedule (0, 1, and 6 months) might not provide adequate protection for them in time. Therefore, in this study, we aimed to evaluate the immunogenicity and efficacy of a HEV vaccine (HEV 239 vaccine, Hecolin) using an accelerated vaccination schedule (vaccine doses at 0 and 7 days). Two doses of accelerated vaccination schedule (0 and 7 days) induced high titers of anti-HEV protective antibodies in a short period of time in rabbits of the vaccine group, which could protect the rabbits from HEV infection compared with the infection group. Our results suggest that an accelerated vaccination schedule (0 and 7 days) could provide protective antibodies in a shorter time. The accelerated schedule should be further recommended for use as a backup in FCV settings or during a hepatitis E outbreak.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379961","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}
{"title":"Correction to “Fullerene (C60 & C70)-Meso-Tris-4-Carboxyphenyl Porphyrin Dyads Inhibit Entry of Wild-Type and Drug-Resistant HIV-1 Clades B and C”","authors":"","doi":"10.1002/jmv.70232","DOIUrl":"https://doi.org/10.1002/jmv.70232","url":null,"abstract":"<p>D. Sharma, M. Rai, A. Singh, R. Gaur, and D. Senguptaa, “Fullerene (C60 & C70)-Meso-Tris-4-Carboxyphenyl Porphyrin Dyads Inhibit Entry of Wild-Type and Drug-Resistant HIV-1 Clades B and C,” <i>Journal of Medical Virology</i> 97 (2025): e70181, https://doi.org/10.1002/jmv.70181.</p><p>In the originally published article, the family name of the corresponding author, Devashish Sengupta, was incorrectly spelled as “Senguptaa.” This has now been corrected to “Devashish Sengupta.”</p><p>We apologize for this error.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70232","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380723","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}
Rafiq Nabi, Vladimir N. Chouljenko, Farhana Musarrat, Megan E. Davis, Harikrishnan Mohan, Reza Ghavimi, Brent Stanfield, Ojasvi Dutta, Konstantin G. Kousoulas
{"title":"The Novel Oncolytic Herpes Simplex Virus Type-1 (HSV-1) Vaccine Strain VC2 Constitutively Expressing GM-CSF Causes Increased Intratumoral T Cell Infiltration and Inhibition of Tumor Metastasis in the 4T1/Balb/c Mouse Model of Stage Four Breast Cancer","authors":"Rafiq Nabi, Vladimir N. Chouljenko, Farhana Musarrat, Megan E. Davis, Harikrishnan Mohan, Reza Ghavimi, Brent Stanfield, Ojasvi Dutta, Konstantin G. Kousoulas","doi":"10.1002/jmv.70220","DOIUrl":"https://doi.org/10.1002/jmv.70220","url":null,"abstract":"<div>\u0000 \u0000 <p>Oncolytic virotherapy (OVT) aims to disrupt the tumor microenvironment and provide a unique therapeutic approach against solid tumors. Herpes simplex virus type-1 (HSV-1) has shown strong promise for treating various solid tumors and has been approved to treat melanoma and glioma in human patients. Previously, we reported the generation of an engineered HSV-1 vaccine strain VC2, which has shown exceptional promise as an oncolytic and immunotherapeutic virus. In the present work, we engineered VC2 to constitutively express the murine granulocyte-macrophage colony-stimulating factor (GM-CSF) gene inserted in place of HSV-1 Glycoprotein C (gC). We tested the efficacy of VC2-GMCSF for its ability to generate antitumor response in the 4T1 stage four metastatic breast cancer mouse model. GM-CSF expression enhanced VC2 viral replication and infectious virus production. Tumors formed after 7 days of engraftment in the mammary fat pad of Balb/CJ mice were treated by injecting ~5 × 10<sup>4</sup> plaque forming units (PFU) of VC2/VC2-GMCSF once. Intratumor treatment did not appreciably reduce average primary tumor sizes. However, metastatic foci were significantly reduced in mice lungs treated with VC2-GMCSF compared to VC2 or mock treatment. VC2-GMCSF intratumoral treatment induced a stronger intratumor T cell infiltration but not an increased cytotoxic activity. A significant T cell infiltration was observed in the metastatic areas in VC2-GMCSF treated animals, which was associated with reduced pro-tumor marker PDL1 and VEGF gene expression. These results show that constitutive expression of GM-CSF enhanced the overall efficacy of VC2 for OVT. VC2-GMCSF holds promise as oncolytic and immunotherapeutic virotherapy for breast and other cancers.</p>\u0000 </div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380722","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}
Adrian Oo, Angel Borge, Regina Ching Hua Lee, Cyrill Kafi Salim, Wenyu Wang, Michael Ricca, Deborah Yuhui Fong, Sylvie Alonso, Lauren E. Brown, John A. Porco Jr., Justin Jang Hann Chu
{"title":"In Vitro Discovery of a Therapeutic Lead for HFMD From a Library Screen of Rocaglates/Aglains","authors":"Adrian Oo, Angel Borge, Regina Ching Hua Lee, Cyrill Kafi Salim, Wenyu Wang, Michael Ricca, Deborah Yuhui Fong, Sylvie Alonso, Lauren E. Brown, John A. Porco Jr., Justin Jang Hann Chu","doi":"10.1002/jmv.70228","DOIUrl":"https://doi.org/10.1002/jmv.70228","url":null,"abstract":"<p>The lack of effective antiviral treatments for enteroviruses, including human enterovirus A71 (EV-A71), have resulted in an immense global healthcare burden associated with hand-foot-and-mouth disease (HFMD). Rocaglates and aglains belong to a family of compounds produced by <i>Aglaia</i> genus plants. Since the initial discovery of rocaglates in 1982, various rocaglates and aglains have been synthesized and extensively studied mainly as anticancer agents. Here, we report the discovery of a novel aglain derivative as a potential EV-A71 inhibitor. From an immunofluorescence-based phenotypic screen of a library of 296 rocaglate and aglain derivatives, we identified a lead aglain which effectively suppressed EV-A71 replication by 2.3 log fold at a non-cytotoxic concentration, with a host cell CC<sub>50</sub> of 21.78 µM, an EV-A71 infection EC<sub>50</sub> of 3.57 µM, and a selectivity index of 6.1. Further validation revealed inhibition of EV-A71 across multiple human cell types and a pan-enterovirus inhibitory spectrum against other enteroviruses. Subsequent mechanistic investigation revealed interference with EV-A71 intracellular post-entry events including viral RNA transcription and translation. Findings from this study have established a strong foundation for development of aglain scaffolds as much needed antiviral agents for HFMD, paving the way for future medicinal chemistry optimization and <i>in vivo</i> studies.</p>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmv.70228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362890","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}
Huanhuan Lu, Jinbo Xiao, Jingdong Song, Yang Song, Hai Li, Hu Ren, Jichen Li, Ruyi Cong, Hangwen Li, Yi Fang, Dongmei Yan, Shuangli Zhu, Qiang Sun, Ying Liu, Yong Zhang
{"title":"The Immunogenicity of Coxsackievirus A6 (D3a Sub-Genotype) Virus-Like Particle and mRNA Vaccines","authors":"Huanhuan Lu, Jinbo Xiao, Jingdong Song, Yang Song, Hai Li, Hu Ren, Jichen Li, Ruyi Cong, Hangwen Li, Yi Fang, Dongmei Yan, Shuangli Zhu, Qiang Sun, Ying Liu, Yong Zhang","doi":"10.1002/jmv.70201","DOIUrl":"https://doi.org/10.1002/jmv.70201","url":null,"abstract":"<div>\u0000 \u0000 <p>In recent years, coxsackievirus A6 (CVA6) has surpassed enterovirus A71 to become the main pathogen causing severe Hand, Foot, and Mouth disease (HFMD) in China with a substantial disease burden. However, there is currently no commercial CVA6 vaccine. The D3a genotype of CVA6 is the predominant genotype in China. In this study, virus-like particles (VLPs) and mRNA vaccines based on the CVA6 sub-genotype D3a were successfully developed. The immunogenicity and protective effects of the VLP of CVA6 combined with Al(OH)<sub>3</sub> and CpG adjuvant indicated that VLP-induced neutralizing antibodies against three CVA6 sub-genotype (D2, D3a, and D3b) strains in Institute of Cancer Research (ICR) mice, and the combination of the two adjuvants enhanced cellular immunity. Passive immunization with serum from mice immunized with VLPs protected suckling mice against CVA6 lethal challenge in both antiserum transfer and maternal immunization experiments. The immunogenicity and protective effects of the mRNA vaccine of CVA6 indicate that it induces robust T-cell immunity. T-cell immunity was found to cross-protect against coxsackievirus A10 infection in mice. This is the first trial of a CVA6 mRNA vaccine worldwide and the first comparison of the immunogenicity and protective effects of VLP and mRNA vaccines based on D3a CVA6. The study provides a theoretical basis for the development of enteroviruses vaccines and the formulation of immunization strategies.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362891","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}
Hanbai Liang, Ying Zhang, Wenhao Sun, Xiaomei Xiao, Xiwen Zhao, Bin Tan, Jian Zhang, Xun Song, Zhengdan He, Liang Ye
{"title":"Identification of a Novel Alkaloid Zj6-11 as a Potent Inhibitor of Influenza Virus Infection via Repression of Virus-Induced Mitochondria-Dependent Apoptosis","authors":"Hanbai Liang, Ying Zhang, Wenhao Sun, Xiaomei Xiao, Xiwen Zhao, Bin Tan, Jian Zhang, Xun Song, Zhengdan He, Liang Ye","doi":"10.1002/jmv.70230","DOIUrl":"https://doi.org/10.1002/jmv.70230","url":null,"abstract":"<div>\u0000 \u0000 <p>Influenza A virus (IAV) remains a major global public health threat, especially with the emergence of antiviral resistance, highlighting the urgent need for novel therapeutics. Alkaloids are known for their antiviral properties, and chemical synthesis has become a key strategy in developing new alkaloid compounds. In this study, we synthesized a series of novel alkaloids using the Ugi reaction and assessed their antiviral potential and mechanisms. Through screening and validation, Zj6-11 was identified as a promising compound that effectively inhibits IAV infection in vitro. Molecular docking and binding affinity assays showed that Zj6-11 binds with high affinity to IAV nucleoprotein (NP) and inhibits its interaction with nucleic acids. Further, in vitro nuclear translocation assays confirmed that Zj6-11 suppresses NP nuclear import. Mechanistically, Zj6-11 significantly inhibits IAV-induced apoptosis and mitigates mitochondrial membrane potential dysfunction. Zj6-11 also inhibits cytochrome c release, reduces the expression of cleaved Caspase-9 and Caspase-3, and suppresses IAV-induced apoptosis-inducing factor (Aif) expression, suppressing IAV-induced mitochondrial apoptosis. More importantly, Zj6-11 plays a crucial role in protecting mice from IAV infection and reducing IAV pathogenicity. Our study provides mechanistic insights into Zj6-11's control of IAV infection in vitro and in vivo, offering new perspectives for antiviral therapy development.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362892","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}
Shuxia Wang, Jin Sun, Yazhuo Hu, Wei Zhang, Bangguo Qin, Man Li, Nan Zhang, Shengshu Wang, Tingyu Zhou, Miao Liu, Cong Ma, Xinli Deng, Yongyi Bai, Geping Qu, Lin Liu, Hui Shi, Bo Zhou, Ke Li, Bo Yang, Suxia Li, Fan Wang, Jinling Ma, Lu Zhang, Yajuan Wang, Li An, Wenhui Liu, Qing Chang, Ru Zhang, Xi Yin, Yang Yang, Qiangguo Ao, Qiang Ma, Shuangtong Yan, Haili Huang, Peng Song, Shu Zhao, Linggen Gao, Wenning Lu, Lining Xu, Li Lei, Keyu Wang, Qing Song, Zhijian Zhang, Xiangqun Fang, Yao He, Qi Zhang, Jianjun Jia, Ping Zhu
{"title":"Clinical and Multiorgan Proteomics Characteristics of the Diverse Fatal Phase in Super Elderly Patients With SARS-CoV-2 Infection: A Descriptive Study","authors":"Shuxia Wang, Jin Sun, Yazhuo Hu, Wei Zhang, Bangguo Qin, Man Li, Nan Zhang, Shengshu Wang, Tingyu Zhou, Miao Liu, Cong Ma, Xinli Deng, Yongyi Bai, Geping Qu, Lin Liu, Hui Shi, Bo Zhou, Ke Li, Bo Yang, Suxia Li, Fan Wang, Jinling Ma, Lu Zhang, Yajuan Wang, Li An, Wenhui Liu, Qing Chang, Ru Zhang, Xi Yin, Yang Yang, Qiangguo Ao, Qiang Ma, Shuangtong Yan, Haili Huang, Peng Song, Shu Zhao, Linggen Gao, Wenning Lu, Lining Xu, Li Lei, Keyu Wang, Qing Song, Zhijian Zhang, Xiangqun Fang, Yao He, Qi Zhang, Jianjun Jia, Ping Zhu","doi":"10.1002/jmv.70207","DOIUrl":"https://doi.org/10.1002/jmv.70207","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aims to identify the risk factors associated with clinical outcomes and the proteomic changes in organs related to fatal SARS-CoV-2 infection within the super-elderly population. This retrospective analysis included all elderly individuals with COVID-19 admitted to the Second Medical Center of PLA General Hospital from December 2022 to January 2023. The follow-up period ended on March 30, 2023. During this time, epidemiological, demographic, laboratory, and outcome data were analyzed descriptively. Proteomic sequencing was performed on super-elderly patients who died from COVID-19 at different stages of the disease. A total of 352 elderly COVID-19 patients, with a mean age of 89.84 ± 8.54 years, were included in this study. During a median follow-up period of 98 days, 79 patients died. Deceased patients were older and more likely to have cardiovascular and cerebrovascular diseases, with a lower prevalence of lipid-lowering therapy. The number of deaths in the acute and post-acute phases were 34 and 45, respectively. Proteomics data suggest that the immune systems of patients who died in the acute phase underwent a more rapid and severe onslaught. Patients in the post-acute phase showed higher levels of viral genome replication and a more robust immune response. However, the over-activation of the immune system led to systemic organ dysfunction. Effective management of comorbidities may improve the prognosis of COVID-19 in super-elderly patients. The continuous replication of the SARS-CoV-2 virus and its subsequent impact on the immune system are critical determinants of survival time in this demographic.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362889","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}
Ana Rita Torres, Vânia Gaio, Aryse Melo, Miguel Lança, Marta Barreto, Licínia Gomes, Inês Azevedo, Teresa Bandeira, David Lito, Raquel Guiomar, Ana Paula Rodrigues, VigiRSV group
{"title":"RSV-Bacterial Co-Infection Is Associated With Increased Illness Severity in Hospitalized Children - Results From a Prospective Sentinel Surveillance Study","authors":"Ana Rita Torres, Vânia Gaio, Aryse Melo, Miguel Lança, Marta Barreto, Licínia Gomes, Inês Azevedo, Teresa Bandeira, David Lito, Raquel Guiomar, Ana Paula Rodrigues, VigiRSV group","doi":"10.1002/jmv.70209","DOIUrl":"https://doi.org/10.1002/jmv.70209","url":null,"abstract":"<div>\u0000 \u0000 <p>During the autumn/winter respiratory syncytial virus (RSV) epidemics, bacterial co-infection is common and affects the disease severity. We aimed to understand the relationship between RSV-bacterial co-infections and clinical severity since the RSV seasonality change after COVID-19 pandemic. We conducted a prospective, sentinel surveillance study at 20 sites in Portugal in children under 2 years hospitalized with RSV, between April 21 and January 23. Effect of co-infection with potentially pathogenic bacteria (PPB) on the length of hospitalization and disease severity was investigated using multivariate linear and log-binomial regression models. Among 678 RSV hospitalizations, 67.4% occurred in children under 6 months and 15.3% in preterm; 20.4% tested positive for PPB; median length of hospitalization was 5 days (IQR: 3–7days). Children coinfected with PPB had a higher rate of ICU admission (29.7% vs. 3.5%, <i>p</i> < 0.001), resulting in more prolonged hospitalizations (7 vs. 5 days, <i>p</i> < 0.001) and a 13-fold risk of having severe disease (RR: 13.2, 95% CI:7.3–23.9). RSV-bacterial co-infection was associated with increased length of hospitalization and severe illness during off-season epidemics. This risk is probably overestimated, as laboratory testing for bacterial infections is usually higher in severely ill-appearing children. Measures to prevent outgrowth of pathogenic bacteria within the respiratory tract should be discussed.</p></div>","PeriodicalId":16354,"journal":{"name":"Journal of Medical Virology","volume":"97 2","pages":""},"PeriodicalIF":6.8,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143362800","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}