Weiqiang Chen

Introduction: Periprosthetic joint infection (PJI) remains one of the most challenging complications of total joint arthroplasty, often complicated by limitations in diagnostic sensitivity. Standard clinical culture methods fail to identify pathogens in 20%-50% of cases, leading to potential under- or overtreatment. This pilot study aimed to compare the microbial detection capabilities of standard clinical culture methods with enhanced research laboratory techniques, and to explore whether additional microbial findings might have the potential to influence antibiotic treatment planning. Materials and methods: Thirteen patients undergoing surgery for PJI, as defined by the 2018 International Consensus Meeting (ICM) on Infection criteria, were prospectively enrolled at a single academic medical center between August 2023 and September 2024. Intraoperative synovial fluid, periprosthetic tissue, and implant swabs were collected and processed using both standard clinical workflows and optimized research protocols. Culture results and treatment decisions were reviewed in collaboration with Infectious Disease specialists. Results: Both methods identified primary organisms. However, research techniques detected additional organisms not captured by clinical cultures ( p = 0.013). Despite these differences, overall detection rates were comparable (57.1% vs. 59.5%; p = 0.963), with the research workflow achieving similar yield with fewer samples. The potential impact of additional isolate identification on antibiotic selection, if deemed clinically significant, did not appear to result in meaningful changes to antibiotic regimens, although this may have been influenced by the empiric use broad-spectrum antibiotics. Conclusions: Clinical culture methods may not detect all organisms in PJI, highlighting possible limitations in current diagnostic approaches. Although this pilot study did not directly assess the impact of enhanced microbial detection on antibiotic prescribing and treatment decisions were largely unchanged, these findings suggest that a more comprehensive microbial detection could potentially inform antibiotic selection and warrants further investigation.

Viral infections are increasingly recognized as triggers of autoimmunity, yet the mechanisms linking viral infection to breakdown of B-cell tolerance remain incompletely understood. B-cell tolerance is maintained through sequential central and peripheral checkpoints that normally eliminate or silence self-reactive clones. Viral infections converge on shared mechanisms, including inflammatory cytokines, innate immune activation, molecular mimicry, and persistent antigen exposure, while also promoting polyreactivity, thereby enhancing the survival, activation, and expansion of autoreactive B cells. In this review, we propose that autoimmune outcomes are determined less by viral identity than by the immunological and anatomical context in which tolerance fails. We integrate mechanistic and clinical evidence across systemic, localized, and neurotropic viral infections to present a unifying framework for virus-induced B-cell tolerance breakdown. This framework identifies conserved principles underlying post-viral autoimmunity and provides a foundation for developing therapeutic strategies to preserve B-cell tolerance.

Autoimmune rheumatic diseases (AIRDs), such as rheumatoid arthritis and systemic lupus erythematosus, substantially affect quality of life, with viral infections increasingly recognized as potential but underappreciated triggers of worsening preexisting AIRD symptoms. Despite growing evidence that post-viral infections are associated with heightened autoimmune activity and disease flares, the precise mechanisms underlying the complex virus–autoimmune response remain poorly understood. As AIRD is most prevalent in women, hormonal factors might have a role in AIRD pathogenesis. Hormones can influence immune regulation, potentially affecting the risk and severity of viral-induced AIRD flares. Given the global rise of viral disease outbreaks with increasing evidence of viral persistence in AIRD pathology, this Review addresses a critical knowledge gap in understanding the immune crosstalk during viral-induced AIRD flares. We place an emphasis on emerging viruses and their potential role in AIRD flares, exploring mechanisms of immune dysregulation, chronic inflammation, molecular mimicry, viral persistence and emerging therapeutic strategies to mitigate virus-induced AIRD exacerbations. This Review is aimed at shedding light on the mechanisms by which emerging viruses promote AIRD flares, serving as a practical guide to improve clinical management and therapeutic innovations.

Patients with immune-mediated inflammatory diseases (IMIDs) like rheumatoid arthritis (RA) are at higher risk for severe COVID-19 and long-term complications in bone health. Emerging clinical evidence demonstrated that SARS-CoV-2 infection reduces bone turnover and promotes bone loss, but the mechanism underlying worsened bone health remains elusive. This study sought to identify specific immune mediators that exacerbated preexisting IMIDs after SARS-CoV-2 exposure. Plasma samples from 4 groups were analyzed: healthy, IMID only, COVID-19 only, and COVID-19 + IMID. Using high-throughput multiplexed proteomics, we profiled 1,500 protein biomarkers and identified 148 unique biomarkers in COVID-19 patients with IMIDs, including elevated inflammatory cytokines (e.g., IL-17F) and bone resorption markers. Long-term circulating SARS-CoV-2 ORF8, a virulence factor for COVID-19, was detected in the COVID + IMID group. RA was one of the most common IMIDs in our study. ORF8 treatment of RA-derived human osteoblasts (RA-hOBs) increased levels of inflammatory ( TNF , IL6 , CCL2 ) and bone resorption ( RANKL /osteoprotegerin ratio) markers compared with healthy controls. Supernatants from ORF8-treated RA-hOBs drove the differentiation of macrophages into osteoclast-like cells. These findings suggest that SARS-CoV-2 exposure can exacerbate IMIDs through ORF8-driven inflammation and osteoclastogenesis, highlighting potential therapeutic targets for managing COVID-19–induced bone pathologies.

Prenatal SARS-CoV-2 infection is associated with higher rates of pregnancy and birth complications, despite that vertical transmission rates are thought to be low. Here, multi-omics analyses of human placental tissues, cord tissues/plasma, and amniotic fluid from 23 COVID-19 mother-infant pairs revealed robust inflammatory responses in both maternal and fetal compartments. Pronounced expression of complement proteins (C1q, C3, C3b, C4, C5) and inflammatory cytokines (TNF, IL-1α, and IL-17A/E) was detected in the fetal compartment of COVID-19-affected pregnancies. While ~26% of fetal tissues were positive for SARS-CoV-2 RNA, more than 60% of fetal tissues contained SARS-CoV-2 ORF8 proteins, suggesting transplacental transfer of this viral accessory protein. ORF8-positive fetal compartments exhibited increased inflammation and complement activation compared to ORF8-negative COVID-19 pregnancies. In human placental trophoblasts in vitro, exogenous ORF8 exposure resulted in complement activation and inflammatory responses. Co-immunoprecipitation analysis demonstrated that ORF8 binds to C1q specifically by interacting with a 15-peptide region on ORF8 (C37-A51) and the globular domain of C1q subunit A. In conclusion, an ORF8-C1q-dependent complement activation pathway was identified in COVID-19-affected pregnancies, likely contributing to fetal inflammation independently of fetal virus exposure.

Thioredoxin-interacting protein (TXNIP) has emerged as a key player in cancer and diabetes since it targets thioredoxin (TRX)-mediated redox regulation and glucose transporter (GLUT)-mediated metabolism. TXNIP consists of two arrestin (ARR, N-ARR and C-ARR) domains at its amino-terminus and two PPxY (PY) motifs and a di-leucine (LL) motif for endocytosis at its carboxyl-terminus. Here, we report that TXNIP shuffles between TRX and GLUTs to regulate homeostasis of intracellular oxidative stress and glucose metabolism. While TXNIP functions as a gatekeeper of TRX by default, it robustly interacted with class I GLUTs through its C-ARR domain upon increase of intracellular reactive oxygen species. This interaction prompted the surface expression downregulation and lysosomal degradation of GLUTs by its carboxyl-terminal LL endocytic signaling motif to attenuate glucose uptake. Consequently, TXNIP expression significantly limited glucose uptake, leading to the suppression of glycolysis, hexosamine biosynthesis, and the pentose phosphate pathway. Our findings establish a fundamental link between ROS and glucose metabolism through TXNIP and provide a promising target for the drug development against GLUT-related metabolic disorders.

Bone-related diseases (osteopathologies) associated with human virus infections have increased around the globe. Recent findings have highlighted the intricate interplay between viral infection, the host immune system and the bone remodelling process. Viral infections can disrupt bone homeostasis, contributing to conditions such as arthritis and soft tissue calcifications. Osteopathologies can occur after arbovirus infections such as chikungunya virus, dengue virus and Zika virus, as well as respiratory viruses, such as severe acute respiratory syndrome coronavirus 2 and enteroviruses such as Coxsackievirus B. Here we explore how human viruses dysregulate bone homeostasis, detailing viral factors, molecular mechanisms, host immune response changes and bone remodelling that ultimately result in osteopathologies. We highlight model systems and technologies to advance mechanistic understanding of viral-mediated bone alterations. Finally, we propose potential prophylactic and therapeutic strategies, introduce ‘osteovirology’ as a research field highlighting the underestimated roles of viruses in bone-related diseases, and discuss research avenues for further investigation.