Orthohantaviruses (also known as hantaviruses) are pathogens that cause two distinct, yet related forms of severe human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases pose a significant threat to global public health due to their high case fatality rates, which can range from 1% to 50%. In recent years, an increasing number of countries and regions have reported human cases, underscoring the urgent need for improved understanding, prevention, and treatment strategies. Given the severity of these diseases and the lack of specific post-exposure antiviral treatments, preventive measures are critical. For several decades, substantial efforts have been dedicated to developing orthohantavirus vaccines, leading to significant advancements. The first large-scale deployment involved inactivated vaccines, which played a crucial role in reducing HFRS incidence in South Korea and China. Subunit vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines have also been extensively researched. Nucleic acid vaccines, including both mRNA and DNA vaccines, hold the greatest potential for future development due to their rapid design and production cycles, ability to elicit robust immune responses, ease of storage and transportation, and adaptable production platforms. Ongoing advancements in computer technology and artificial intelligence promise to further enhance the development of more effective orthohantavirus vaccines.

A corrigendum on Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture by Jiang, H., Du, H., Wang, L. M., Wang, P. Z., and Bai, X. F. (2016). Front. Cell. Infect. Microbiol. 6:1. doi: 10.3389/fcimb.2016.00001 Due to an oversight the authors did not cite the original source for Figures 1, 2. Figure 1 was adapted from Figure 5 of Schönrich et al. (2008). The revised figure caption should read: Left side: Normal endothelial cells (EC), no vascular leakage occurs. Right side: EC were infected with hantaviruses. ZO-1, VEGFR2, VE-cadherin on EC were altered. High hantavirus RNA load result in severe vascular leakage. Virus-infected ECs be cleared by virus-specific CTLs leading to vascular damage. Owing to acute thrombocytopenia, there are not sufficient platelets available to repair “holes” in the EC barrier, resulting in vascular leakage. In addition, cytokines produced during the innate response against pathogenic hantaviruses like TNF-α could enhance vascular permeability. Adapted from Schönrich et al. (2008). Figure 2 was adapted from Figure 2 of Schönrich et al. (2015). The revised figure caption should read: Monocytes, macrophages, NK cells, and Lymphocytes produce various cytokines/chemokines which directly or indirectly increase vascular permeability. The humoral pattern recognition receptor PTX3 and antibodies activate complement. Activated complement components induce cytoskeletal rearrangement in EC further increasing dysfunction of the EC barrier. TLRs recognize Hantavirus and mediate the innate response. Virus-infected ECs were cleared by virus-specific CTLs leading to vascular leakage. B cells produce several subclass antibodies, while only the neutralizing antibodies against G1 and G2 is beneficial to decrease the viruses, then decrease vascular leakage. Adapted from Schönrich et al. (2015). This does not affect the scientific conclusions of this article in any way. The authors apologize for this oversight. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Schönrich, G., Krüger, D. H., and Raftery, M. J. (2015). Hantavirus-induced disruption of the endothelial barrier: neutrophils are on the payroll. Front. Microbiol. 6:222. doi: 10.3389/fmicb.2015.00222 PubMed Abstract | CrossRef Full Text | Google Scholar Schönrich, G., Rang, A., Lütteke, N., Raftery, M. J., Charbonnel, N., and Ulrich, R. G. (2008). Hantavirus-induced immunity in rodent reservoirs and humans. Immunol. Rev. 225, 163–189. doi: 10.1111/j.1600-065X.2008.00694.x PubMed Abstract | CrossRef Full Text | Google Scholar Keywords: hantavirus, hemorrhagic fever with renal syndrome, Bunyavirus, hantaan virus, pathogenesis Citation: Jiang H, Du H, Wang LM, Wang PZ and Bai XF (2016) Corrigendum: Hemorrhagic Fever with Renal Syndrome: Pathogenesis and Clinical Picture. Front. Cell. Infect. Microbiol. 6:178. doi: 10.3389/fcimb.2016.00178 Received: 05 April 2016; Accepted: 22 November 2016; Published: 08 December 2016. Edited and reviewed by: Shinichiro Kurosawa, Boston University School of Medicine, USA Copyright © 2016 Jiang, Du, Wang, Wang and Bai. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. *Correspondence: Ping Z. Wang, wangpz63@126.com Xue F. Bai, xfbai2011@163.com

To develop and validate a simple and effective death risk stratification scale for hemorrhagic fever with renal syndrome (HFRS). In this ambispective cohort study, we investigated the epidemiological and clinical data of 2245 patients with HFRS (1873 enrolled retrospectively and constituting the training cohort, 372 prospectively recruited as the validation cohort) from September 2008 to December 2021, and identified independent risk factors for 30-day death of HFRS. Using logistic regression analysis, a nomogram prediction model was established and was further simplified into a novel scoring scale. Calibration plot, receiver operating characteristic curve, net reclassification index, integrated discrimination index, and decision curve analysis were used to assess the calibration, discrimination, precision, and clinical utility in both training and validation cohorts. Of 2245 patients with HFRS, 132 (5.9%) died during hospitalization. The nomogram prediction model and scoring scale were developed using six predictors: comorbid hypertension, hypotensive shock, hypoxemia, neutrophils, aspartate aminotransferase, and activated partial thromboplastin time. Both the scale and nomogram were well calibrated (near-diagonal calibration curves) and demonstrated significant predictive values (areas under receiver operating characteristic curves >0.9, sensitivity and specificity >90% in the training cohort and >84% in the validation cohort). The simplified scoring scale demonstrated equivalent discriminative ability to the nomogram, with net reclassification index and integrated discrimination index of 0.022 and 0.007 in the training cohort, 0.126 and 0.022 in the validation cohort. Decision curve analysis graphically represented significant clinical utility and comparable net benefits of the nomogram and scoring scale across a range of threshold probabilities. This evidence-based, factor-weighted, accurate score could help clinicians swiftly stratify HFRS mortality risk and facilitate the implementation of patient triage and tiered medical services during epidemic peaks.

Until now, there is non-specific treatment, and exploring early and novel biomarkers to determine the disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS) would be of importance for clinician to take systematic and timely intervention. This study observed the expression of plasma sCD138, a soluble component shedding from the glycocalyx (GCX) to the circulating blood, and evaluated its predictive value on disease severity and prognosis of HFRS. One hundred and seventy-six patients with HFRS who were treated at our center between January 2011 and December 2013 were randomly enrolled in this study. The patients were divided into a mild-type group, a moderate-type group, a severe-type group and a critical-type group according to the HFRS criteria for clinical classification. Thirty-five blood samples from healthy subjects were obtained as the controls. The concentrations of sCD138 were detected using enzyme linked immunosorbent assay (ELISA). The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), albumin (ALB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), white blood cells (WBC), platelets (PLT), glucose (GLU), blood urea nitrogen (BUN) and serum creatinine (Scr) in the samples were routinely tested. The levels of sCD138 among the different types were compared; the correlation among sCD138 and the laboratory parameters mentioned above were analyzed. The predictive effectiveness for prognosis of sCD138 was evaluated using the receiver operating characteristic (ROC) curve analysis. Except for the mild-type, the levels of sCD138 in the moderate-, severe- and critical-type patients during the acute stage were significantly higher than that of the convalescent stage and the control (P0.05). sCD138 was negatively correlated with Fib, PLT and ALB, and was positively correlated with WBC and AST (P<0.05). sCD138 demonstrated predictive effectiveness for prognosis with the area under the curve (AUC) of 0.778 (P<0.001). Dynamic detection of plasma sCD138 might be benefit to evaluating the disease severity and prognosis of the patients with HFRS.

Influenza viruses remain a major global public health concern, causing significant morbidity and mortality annually despite widespread vaccination efforts. The limitations of current seasonal vaccines, including strain-specific efficacy and manufacturing delays, have accelerated the development of next-generation candidates aiming for universal protection. This review comprehensively summarizes the recent progress in universal influenza vaccine research. We first outline the key conserved antigenic targets, such as the hemagglutinin (HA) stem, neuraminidase (NA), and matrix proteins (M2e, NP, and M1), which are crucial for eliciting broad cross-reactive immunity. We then delve into advanced antigen design strategies, including immunofocusing, multi-antigen combinations, computationally optimized broadly reactive antigens (COBRA), and nanoparticle-based platforms. Furthermore, we evaluate evolving vaccine delivery systems, from traditional inactivated and live-attenuated vaccines to modern mRNA and viral vector platforms, alongside the critical role of novel adjuvants in enhancing immune responses. The convergence of these disciplines—structural biology, computational design, and nanotechnology—is driving the field toward a transformative goal. We conclude that the successful development of a universal influenza vaccine will likely depend on the strategic integration of these innovative approaches to overcome existing immunological and logistical challenges, ultimately providing durable and broad-spectrum protection against diverse influenza virus strains.