COVID-19 in Autoimmune Rheumatic Diseases: Lessons Learned and Emerging Risk Stratification Approaches
Vasiliki E. Georgakopoulou1, Clio P. Mavragani1,2,3
1Department of Pathophysiology, Laiko General Hospital, National and Kapodistrian University of Athens, 11527, Athens, Greece
2 Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece
3Joint Academic Rheumatology Program, School of Medicine, National and Kapodistrian University of Athens, 11527, Athens, Greece
The coronavirus disease (COVID-19) pandemic has posed unique challenges for individuals with autoimmune and autoinflammatory rheumatic diseases (AARDs), raising critical concerns about susceptibility, disease severity, treatment outcomes, and vaccine response. This mini-review draws on data from a national Greek cohort and global studies. It summarizes current evidence on disease course and risk stratification in AARD patients with COVID-19.Most patients experienced mild disease; however, those with advanced age, interstitial lung disease (ILD), and treatment with rituximab, mycophenolate mofetil, or corticosteroids demonstrated increased risk for hospitalization and mortality. In contrast, biologics targeting pro-inflammatory cytokines such as tumor necrosis factor (TNF) and interleukin 6 (IL-6) were not associated with worse outcomes and, in some analyses, correlated with reduced hospitalization rates. Notably, long-term sequelae, particularly persistent fatigue, emerged as a common burden, underscoring the overlap between post-viral symptoms and underlying autoimmune dysfunction. The serologic response to SARS-CoV-2 infection and vaccination was attenuated in some AARD subgroups, especially in patients receiving B-cell depleting therapies, emphasizing the need for tailored immunization and preventive strategies. Additionally, anosmia was inversely associated with hospitalization and may represent a biomarker of milder disease and more effective early immune responses. This review highlights key predictors of adverse outcomes and discusses implications for immunosuppression management, vaccination timing, and long-term care. As the pandemic evolves, identifying high-risk AARD patients and implementing precision prevention and treatment strategies remain vital priorities.
DOI: 10.29245/2578-3009/2025/4.1262 View / Download PdfA Novel Point-of-Care Method for Measuring Human Salivary Immunoglobulin A
Kelsi Irvine*, David Vollmer and Xuesheng Han
4Life Research, LLC, Sandy, UT;
Purpose: The purpose of this study was to examine the potential of a novel method for quantifying salivary immunoglobulin A (sIgA) using a point of care device.
Method: This novel method included the use of a non-invasive oral fluid collector, lateral flow strips, and a cube reader device to collect and evaluate sIgA. Volunteers were recruited to collect saliva for analysis over three separate evaluations. These evaluations examined the precision, accuracy, and robustness of the method.
Result: Results indicated that this novel method could provide a reasonably reliable and fast option to monitor sIgA levels at an accessible price point.
Conclusion: This method could be a useful tool to improve individuals' ability to self-monitor important health biomarkers and gain insight into the status of their oral immunity with minimal effort and at a low cost compared to current standard methods.
DOI: 10.29245/2578-3009/2025/3.1260 View / Download PdfChimeric Antigen receptor-T cell Therapy for Solid Tumors with Antigen Heterogeneity.
Xing-Ning Li1, Chunfeng Qu1*
1Immunology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Chimeric antigen receptor-T (CAR-T) cell therapy in the treatment of solid tumors remains limited, though it has demonstrated remarkable success for hematological malignancies. One of the major restrictions is immune escape from the attack mediated by primary targeted CAR-T cells, driven by the heterogeneous cell components of solid tumors, including heterogeneous expression of tumor antigens. Here, we reviewed the specified challenges and corresponding strategies which are being developed, including the use of multi-targeted CAR-T cells and the activation of endogenous immune responses.
DOI: 10.29245/2578-3009/2025/2.1261 View / Download PdfAdvancing Brain Tumor Immunotherapy: The Role of Nanomedicine in Primary and Metastatic Brain Tumor
Sandbhor Puja1*, Mathur Ishita1, John Geofrey2, and Goda Jayant2
1Translational Nanomedicine and Bioengineering Lab, Department of Radiation Oncology, Advanced Centre for Treatment, Research, and Education in Cancer-Tata Memorial Centre (ACTREC-TMC), Navi-Mumbai 410210, India
2Radiobiology Lab, Department of Radiation Oncology & Homi Bhabha National Institute, Tata Memorial Hospital (TMH), Mumbai, 400012, India
The present mini-review explore the therapeutic potential of nanomedicine in advancing immunotherapy for primary and metastatic brain tumors, addressing existing challenges and paving the way for transformative precision therapy. Primary brain tumors including glioblastoma and metastases from other cancers like breast, lung etc., experiences limitation in treatment outcomes due to the tumor heterogeneity, immunosuppressive tumor microenvironment (TME), the blood-brain-barrier (BBB), and therapy resistance. Although, immunotherapies have shown promising benefits, however are hindered by immune escape, organ toxicities, and variable patient responses. Major unresolved challenges include insufficient therapeutic penetration across the BBB, the inability to reprogram the immunosuppressive TME, limited strategies to counteract dynamic tumor antigen escape, and systemic toxicities associated with conventional therapies. To address these challenges, multifunctional nanomedicines offer promising solutions through precise and controlled delivery, immunosuppressive TME modulation, and/or recalibration of immune system. Advanced nanomaterials including lipid/polymer-based system, dendrimers, and quantum dots, can co-deliver immunomodulators and chemotherapeutic/radiosensitizers, enhances BBB permeability, and activate favorable immune responses. Nanomedicines with multimodality such as localized hyperthermia (e.g. photothermal ablation), and immunogenic cell death stimulate immunological memory and improve therapeutic benefits. Furthermore, innovation in gene therapy (e.g. CRISPR-Cas9) and personalized cancer vaccines enhance targeted anti-tumor immune responses. Despite these groundbreaking advancements challenges persist, including nanoparticles-biological interactions (protein corona effects), stability, scalability, and regulatory hurdles. However, emerging trends such as 3D organoids, organ-on-a-chip system, patient-derived xenografts, and integration of AI/ML platforms, offer physiologically relevant platforms to optimize nanotherapy with better response predictions. Moreover, surface functionalization such as solid-lipid nanoparticles targeting programmed death–ligand 1 (PD-L1)-epidermal growth factor receptor (PD-L1/EGFR), have demonstrated success in augmenting the abscopal effect of radiotherapy. Radiotherapy enhances tumor antigen cross-presentation by inducing immunogenic cell death (ICD), leading to the release of tumor-associated antigens (TAAs). This process is accompanied by the release of damage-associated molecular patterns (DAMPs), such as calreticulin, HMGB1, and ATP. These signals recruit and activate dendritic cells (DCs), which engulf tumor antigens and process them via the major histocompatibility complex (MHC) class I, facilitating the activation of cytotoxic T lymphocytes (CTLs) against the tumor (S. Zhu et al., 2022). Nanoparticles (NPs) can improve antigen delivery by encapsulating tumor antigens and immune-modulatory agents, ensuring prolonged antigen presentation. Furthermore, radio-enhancing NPs, such as gold or hafnium oxide nanoparticles, intensify the effects of radiation by increasing DNA damage and reactive oxygen species (ROS) production, which strengthens the ICD response and improves antigen release (He et al., 2025). In order to further enhance immune activation, some NPs are also designed to modulate the tumor microenvironment by promoting pro-inflammatory signaling.
DOI: 10.29245/2578-3009/2025/1.1259 View / Download PdfHot to Cold Tumors: Regulations of MEX-3 Family Proteins
DOI: 10.29245/2578-3009/2025/1.1258 View / Download PdfKanglong Yang1#*, Lulu Zhu1#, Liang Zhang1*
1Center for Advanced Interdisciplinary Science and Biomedicine of IHM; Ministry of Education Key Laboratory for Membraneless Organelles and Cellular Dynamics; Hefei National Research Center for Cross-disciplinary Science; Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230027, China
Human Leukocyte Antigen (HLA) at the Root of Persistent Antigens and Long COVID
Apostolos P. Georgopoulos1,2*, Lisa M. James1,2,3 and Phillip K. Peterson4
1Brain Sciences Center, Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA
2Department of Neuroscience, University of Minnesota Medical School, Minneapolis, MN, USA
3Department of Psychiatry, University of Minnesota Medical School, Minneapolis, MN, USA
4Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
Here we offer a perspective on recent findings of persistent SARS-CoV-2 antigens in Long COVID1 through the lens of immunogenetic risk and protection, namely in the context of the fundamental role of Human Leukocyte Antigen (HLA) in eliminating viral infections. Specifically, we attribute the persistence of viral antigens to the lack or weak protection conferred by HLA against SARS-CoV-2 in individuals carrying HLA alleles with low binding affinities to the virus. We suggest that determining the HLA Class I and II makeup of Long COVID patients will provide valuable new information in elucidating the cause for antigen persistence underlying the development of Long COVID and pave the way for successful interventions.
DOI: 10.29245/2578-3009/2025/1.1257 View / Download Pdf