As time has passed following the COVID-19 pandemic, individuals infected with SARS-CoV-2 have gradually exhibited a variety of symptoms associated with long COVID in the postacute phase of infection. Simultaneously, in many countries worldwide, the process of population aging has been accelerating. Within this context, the elderly population has not only become susceptible and high-risk during the acute phase of COVID-19 but also has considerable risks when confronting long COVID. Elderly individuals possess specific immunological backgrounds, and during the process of aging, their immune systems can enter a state known as “immunosenescence”. This further exacerbates “inflammaging” and the development of various comorbidities in elderly individuals, rendering them more susceptible to long COVID. Additionally, long COVID can inflict both physical and mental harm upon elderly people, thereby reducing their overall quality of life. Consequently, the impact of long COVID on elderly people should not be underestimated. This review seeks to summarize the infection characteristics and intrinsic factors of older adults during the COVID-19 pandemic, with a focus on the physical and mental impact of long COVID. Additionally, it aims to explore potential strategies to mitigate the risk of long COVID or other emerging infectious diseases among older adults in the future.

Data from EV-D68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. However, lack of a suitable animal model for EV-D68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. Ferrets have been widely used to evaluate respiratory virus infections. In the current study, we used EV-D68-infected ferrets as a potential animal to identify impersonal indices, involving clinical features and histopathological changes in the upper and lower respiratory tract (URT and LRT). The research results demonstrate that the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the viral load detection in the feces, nasal, and respiratory tracts, the infection and shedding of EV-D68 in the ferret model was confirmed, and these results were supported by the EV-D68 VP1 immunofluorescence confocal imaging with α2,6-linked sialic acid (SA) in lung tissues. Furthermore, we detected the inflammatory cytokine/chemokine expression level, which implied high expression levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs. These data indicate that systemic observation of responses following infection with EV-D68 in ferrets could be used as a model for EV-D68 infection and pathogenesis.

Multiple types of SARS-CoV-2 vaccines have been used worldwide, but summarizing their immunologic efficacy post-vaccination remains challenging. The BCR and TCR sequencing based on single-cell sorting makes it possible to evaluate the vaccine-induced immune responses of B or T cells. In this study, we compared the repertoire diversities of B cells and T cells between a whole-virus inactivated vaccine and an S1 protein subunit vaccine in rhesus macaques. We found that the inactivated vaccine could induce a large antigen-specific-BCR repertoire with longer VH CDR3 (21 aa), while the CD3+ TCR α chains of the two vaccine groups showed a similar TCRV/J usage frequency. Detailed analysis of the TCR and BCR repertoires might be of interest for further understanding of the mechanisms of vaccine-induced immune responses.

Four review articles provide an integrated perspective on antiviral immunity and vaccine innovation. Wang et al synthesize current knowledge on neutralizing antibody responses against major non-polio enteroviruses (NPEVs), including EV-A71, CVA16, EV-D68, and echoviruses. It outlines key mechanisms underlying antibody efficacy, such as interference with receptor binding, internalization, and uncoating, and discusses the application prospects of bispecific or multivalent antibodies. These structural and mechanistic insights provide a scientific foundation for the rational design of future antiviral therapeutics (Frontiers | Neutralizing antibody landscape of the non-polio Enteroviruses and future strategy). Zhou et al highlight Coxsackievirus A6 (CVA6) vaccine development across diverse platforms, including inactivated, virus-like particle (VLP), and subunit vaccines. Comparative animal data reveal substantial variation in immunogenicity, protective efficacy, and cross-reactive responses among candidates. Given the frequent recombination events of CVA6 and the continuous evolution of its pathogen spectrum, the authors emphasize the importance of developing multivalent and mRNA vaccines to better control emerging dominant serotypes (Frontiers | Recent advances on coxsackievirus A6 vaccine research). Alandijany et al systematically evaluated the efficacy, safety, and immunogenicity of the three FDA-approved RSV vaccines-Arexvy, Abrysvo, and mResvia. Collectively, these vaccines are capable of providing sustained immune protection with favorable safety profiles in high-risk populations, thereby offering crucial evidence for global RSV prevention and control strategies. (Frontiers | Evaluating the efficacy, safety, and immunogenicity of FDA-approved RSV vaccines: a systematic review of Arexvy, Abrysvo, and mResvia). Hartnell et al present a comprehensive review that explores the dynamic changes in Type I interferon (T1IFN) signaling across the human lifespan. They highlight how these shifts shape populationlevel susceptibility to viral infections. By examining the evolution of immune responses throughout life, the authors provide a theoretical framework for developing individualized treatment strategies, fostering more inclusive research designs, and ultimately improving outcomes for both the youngest and oldest patients. (Frontiers | Together, these reviews illustrate how antibody-mediated protection, vaccine design, and innate immune regulation converge to shape host defense against diverse viral pathogens.Beyond the review articles, several studies in this issue expand our understanding of viral and bacterial pathogenesis. These include molecular epidemiology of adenoviruses in children, cellular-level analysis of SARS-CoV-2 subgenomic RNAs, and the use of animal models such as C57BL/6J mice for Mycobacterium abscessus infection and tree shrews for EV-A71 neuropathogenesis. Chen et al conducted a study in Yancheng, China (2023-2024) and identified HAdV-B3 as the dominant strain, with occasional detection of B21, C1, and C5, thereby providing valuable data for public health interventions. (Frontiers | Epidemiological characteristics of adenovirus in children in Yancheng, China, 2023-2024). At the cellular level, Zhang et al reported the discovery of a fusion ORF3a-E-sgRNA in SARS-CoV-2, which enhances ribosomal protein S3 expression, supports viral assembly and release, and aids immune evasion. Differences in transcriptional levels may explain distinct infection processes between Wuhan and XBB strains (Frontiers | A fusion ORF3a-E subgenomic RNA involved in SARS-CoV-2 infection efficacy by influencing cellular protein synthesis). Wang et al further elucidate viral neuropathogenesis and antibacterial immune regulation. In tree shrews, EV -A71 infection resulted in marked neurotropism and blood-brain barrier disruption, characterized by downregulation of Claudin-5 and junctional adhesion molecule A, and identified SCARB2 and Annexin A2 as potential entry receptors (Frontiers | EV-A71 invades the central nervous system and affects the blood-brain barrier in a tree shrew model).Li et al conducted a study using a C57BL/6J mouse model of Mycobacterium abscessus infection, showing that the cardiac glycoside ouabain mitigated pulmonary inflammation by suppressing pro-inflammatory cytokine production, inhibiting NLRP3 inflammasome activation, and limiting M1 macrophage polarization, thereby suggesting therapeutic potential against drug-resistant infections. (Frontiers | Ouabain alleviates Mycobacterium abscessus-triggered inflammatory responses through dual regulation of NLRP3 inflammasome activity and M1 macrophage polarization). Collectively, these findings underscore the pathogenic roles of Claudin-5, adhesion molecules, and NLRP3, and highlight the value of diverse experimental systems in translational research.Clinical studies in this issue provide translational relevance. Using single-cell sequencing and CyTOF, researchers analyzed immune cell mobilization during viral infection and vaccination. Bodin et al conducted a study using high-dimensional single-cell mass cytometry, showing that severe influenza patients have fewer regulatory MAIT and memory T/B cells but expanded inhibitory monocyte and NK cell subsets. These alterations persist into convalescence and are linked to older age and comorbidities. Through advanced single-cell technologies, Bodin et al provides valuable biomarkers of disease severity and informs future risk assessment and therapeutic strategies. (Frontiers | High-dimensional single-cell phenotyping unveils persistent differences in immune cell profiles between severe and moderate seasonal influenza).Wang et al used single-cell RNA sequencing to demonstrate that macrophages are activated early during EV-A71 infection, initiating specific immune responses closely linked to severe HFMD. They further showed that these activated macrophages not only drive persistent...