Search Results (5,828)

Background/Objectives: Concern that COVID-19 vaccination causes pulmonary nodules persists because vaccination coincided with expanded computed tomography (CT), low-dose CT (LDCT) screening, post-COVID imaging and artificial intelligence (AI)-assisted detection. This review asks whether the current literature supports causality and how vaccination history should inform thoracic imaging. Methods: A focused search of PubMed, PubMed Central and the Cochrane Library was performed through 15 July 2026. Evidence was classified as direct or contextual; no PRISMA screening, risk-of-bias scoring or quantitative synthesis was performed. Results: Direct evidence remains sparse. One case report was too confounded for inference. A two-sample Mendelian randomization study found no broad lung disease risk signal, but nodules were not modeled and the heterogeneous endpoints were exploratory. An ecological study of 1,616,750 samples linked rising detection to SARS-CoV-2 infection waves and AI-assisted reading; lacking individual vaccination data, it cannot establish whether vaccination affected detection. Screening interruption produced the opposite pattern: Lung-RADS 4 nodules rose from 8% to 29%. The most reproducible post-vaccination thoracic finding is regional lymph-node activation on [18F]fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT), an expected immune response rather than a parenchymal nodule. Conclusions: Current evidence is insufficient to establish vaccination as an independent, population-level cause of pulmonary nodules. Vaccination history should guide [18F]FDG-PET/CT interpretation; CT-detected parenchymal nodules warrant standard risk stratification. Full article

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in substantial global morbidity and mortality since its emergence in late 2019. This retrospective study aims to determine the comorbidity patterns, co-occurrence networks, and associated demographic factors among 244 deceased COVID-19 cases in Grenada between 2021 and 2022. The prevalence of comorbid conditions varied considerably across diseases. Hypertension was the most frequently observed condition (41%) followed by diabetes (34.8%), and ARDS (27%). Our co-occurrence analysis revealed a densely interconnected core of cardiometabolic and respiratory conditions, particularly involving hypertension, diabetes, and ARDS. Stratified clustering analyses demonstrated that multimorbidity patterns were broadly consistent across gender but differed by age group and vaccination status, with older individuals showing more pronounced clustering of cardiometabolic conditions. Logistic regression analysis further identified age and gender as significant factors associated with the distribution of specific comorbidities, including higher odds of hypertension among older individuals. This study highlights the central role of cardiometabolic diseases and older age in COVID-19 mortality in Grenada in 2021–2022 and underscores the importance of multimorbidity structures rather than isolated conditions. We suggest early identification of high-risk multimorbidity profiles, particularly among older adults, to improve clinical management and preventive strategies during future infectious disease outbreaks. Full article

Population immune pressure from vaccination and prior infection continues to drive the evolution of SARS-CoV-2. Systematic characterization of RBD mutations under complex immune backgrounds is essential for understanding viral adaptation and evolutionary trajectories. Here, we applied a deep mutational scanning (DMS) to comprehensively map the neutralization escape landscape of the Omicron variant JN.1 and its descendant lineage XEC, under immune pressure from individuals who experienced Omicron breakthrough infections following three doses of inactivated vaccines. A neutralization escape map for the single amino acid substitutions in the RBD of JN.1 or XEC was generated, and the escape efficiency of each mutation was determined. The results show that RBD escape mutations are hierarchically organized: low-intensity signals are widespread, whereas high-intensity escape is confined to a few key sites. These escape mutations are not confined solely to the receptor-binding motif (RBM) but are broadly distributed across the entire RBD. Many escape sites could accommodate multiple amino acid substitutions. Integration of DMS data with genomic surveillance of circulating variants from 2024 to 2025 revealed significant overlap between experimentally identified escape sites and mutations observed in natural isolates. This overlap increased substantially in 2025, with site concordance rising from 27.17% and 26.81% to 45.09% and 47.10% for JN.1 and XEC, respectively. The natural prevalence of these escape mutations is further shaped by factors such as receptor-binding affinity, protein stability, and epistatic interactions. Overall, our findings suggest that SARS-CoV-2 antigenic evolution follows the pattern of multiple pathways within a constrained space, providing new insights into the adaptive mechanisms of Omicron-derived variants under hybrid immune pressure. Full article

Background/Objectives: Particulate vaccine formulations require delivery systems and immunostimulatory components that support antigen-presenting cell interaction while maintaining formulation stability and cytocompatibility. This study examines Guanine-α-D-Fructose (GDF), a guanine–fructose small-molecule immunostimulatory candidate, incorporated into poly(lactic acid-co-glycolic acid) (PLGA) microparticles and benchmarked in vitro against established adjuvant formulations containing Alum or AddaVax. Methods: GDF-loaded microparticles were prepared and characterized for particle size, morphology, surface charge, entrapment efficiency, and release behavior. Their in vitro immunostimulatory activity was evaluated using murine dendritic cells. To explore formulation compatibility, GDF MPs were tested in combination with multiple particulate antigen formulations, including measles, gonorrhea, SARS-CoV-2, influenza A (H3N2), and Zika. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to measure cell viability, while nitric oxide generation was measured with the Griess assay. Dendritic cell activation-associated surface marker expression was analyzed by flow cytometry using MHC I, MHC II, CD80, and CD40. Results: The particles showed consistent spherical morphology, sustained GDF release, and favorable cytocompatibility at concentrations up to 250 µg/mL, with reduced viability at higher concentrations. GDF MPs increased nitric oxide production and activation-associated marker expression, with responses benchmarked against Alum and AddaVax and comparable in several assay conditions. Increased autophagosome-associated fluorescence was also observed, suggesting modulation of autophagy-related cellular activity; however, direct antigen-processing or antigen-presentation assays are still required. Conclusions: Overall, these findings support GDF-loaded PLGA microparticles as an in vitro immunostimulatory particulate formulation suitable for further mechanistic and in vivo evaluation in vaccine-related systems. Full article

Coronaviruses are responsible for numerous diseases causing substantial morbidity and mortality to both humans and animals. In particular, they have caused three significant outbreaks in humans including severe acute respiratory syndrome 1 (SARS-CoV-1), Middle East respiratory syndrome (MERS-CoV), and, most recently, the severe acute respiratory syndrome 2 (SARS-CoV-2) pandemic. Two relevant veterinary diseases are porcine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV), which cause severe losses in the pork industry. While efficacious vaccines were developed in an unprecedented timeframe for COVID-19, vaccines have not been commercialized for other human coronaviruses and vaccines against animal coronaviruses have limited efficacy and logistical challenges in administration. There is a clear need for more efficacious vaccines with simpler methods of delivery and administration for both human and veterinary use. The production of subunit vaccines in plant systems holds great promise in addressing the current challenges and facilitate the preparation for future potential outbreaks and new viruses. This review will summarize the state of development of vaccines in plant systems including tobacco, rice, maize, and others. Full article

Background/Objective: Persistent infection with human papillomavirus type 16 (HPV-16) is the principal cause of cervical high-grade squamous intraepithelial lesions (cHSIL) and cervical cancer, yet the established treatments remain limited to ablative or excisional procedures that carry reproductive risk and do not eliminate the underlying infection. We report the preclinical development of ARV-2001, a messenger RNA (mRNA)–lipid nanoparticle (LNP) immunotherapeutic encoding mutated, non-oncogenic HPV-16 E6 and E7 fused to a SARS-CoV-2 spike S2 subdomain enriched in human CD4 helper epitopes, formulated in a novel cholesterol-derived ionizable lipid (ARV-T1). Methods: Interactions of ARV-2001-expressed antigens with p53 and retinoblastoma (Rb) were evaluated in human cervical carcinoma cell line C33A, in lentiviral constructs in primary human keratinocytes, and in soft-agar colony-formation assays. ARV-2001 was administrated by intramuscular (IM) or intradermal (ID) injection in naive mice or in the TC-1 tumor models. Tumor size and survival were monitored over time and tumor-infiltrated lymphocytes were characterized by flow cytometry. Intracellular cytokine staining and Elispot were used to evaluate immunogenicity. Results: In vitro, the mutated E6/E7–S2 antigen lost the ability to degrade p53, to deregulate the retinoblastoma (Rb) pathway, and to support anchorage-independent growth, suggesting abrogation of oncogenic activity. The S2 domain and imiquimod administration each augmented antitumor activity and intratumoral CD8⁺ T-cell infiltration while reducing myeloid-derived suppressor cells in the syngeneic HPV-16 E6/E7 TC-1 tumor models. In addition, ID administration of ARV-2001 into TC-1 tumor-bearing mice was superior to IM administration in terms of both tumor growth inhibition and survival. ID vaccination with ARV-2001 in mice consistently elicited a more potent E6/E7-specific T-cell response than the same dose given IM. Dose-escalation studies showed a dose-dependent T cell response against E6/E7 in ID-injected mice. Conclusions: This study supports future human evaluation of intradermally administrated ARV-2001 for treatment of HPV-16+ cHSIL in clinical trials. Full article

The approval of safe and effective lipid nanoparticles-encapsulated mRNA (LNP-mRNA) vaccines during the SARS-CoV-2 pandemic is catalysing the development of the next generation of mRNA therapeutics. Accurate characterisation methods are crucial for assessing the quality and efficacy of these complex formulations. Several analytical techniques exist for the quantification of the mRNA drug substance, including UV spectroscopy, capillary electrophoresis, high-performance liquid chromatography (HPLC), and digital PCR (dPCR). Here, we compare these methods, highlight their limitations, and discuss critical considerations for experimental design to improve the agreement between different analytical methods. Full article

Background and Objectives: The pandemic caused by the SARS-CoV-2 infection has been named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO). Cancer patients may have been more adversely affected during the COVID-19 Pandemic due to their receipt of immunosuppressive treatments, higher burden of comorbidities, and greater nutritional vulnerability compared to the general population. The aim of our study is to identify potential measures by detecting changes in the nutritional statuses of patients with an oncological diagnosis who presented to our hospital during the COVID-19 pandemic, using the globally accepted NRS-2002 questionnaire. Materials and Method: Our study included 324 patients diagnosed with malignancy who applied to the outpatient clinic of Gaziantep University, Şahinbey Training and Research Hospital, Gaziantep/Türkiye, between December 2021 and January 2022 or were hospitalized in the service. Patients included in the study were evaluated in terms of clinical–demographic information and COVID-19-related characteristics using a sociodemographic data form we developed, and then the NRS-2002 questionnaire was administered. Results: Our study included 324 patients. Overall, 49.07% (159 patients) of the patients were male, and 50.93% (165 patients) were female. A total of 20.37% of our patients (66 patients) had COVID-19 disease. While those living with their families constituted 96.91% of the patients, at least one of the family members of 36.42% of the patients had COVID-19 disease. While 76.23% (247 patients) of the patients were vaccinated, 23.77% (77 patients) were not vaccinated. When NRS analyses were examined according to the type of malignancy, a statistically significant difference was found between NRS analyses according to the type of diagnosis. When NRS analyses were examined according to the stages of the diseases, it was determined that stage 4 patients were in the risk group in terms of nutrition. When NRS analyses according to age were examined, it was determined that patients over the age of 65 were in the risk group in terms of nutrition. When NRS analyses by gender were examined, it was found that male patients were in the risk group in terms of nutrition. When the NRS analyses were examined according to whether or not radiotherapy was administered, it was determined that the patients who received radiotherapy were in the risk group in terms of nutrition. Contrary to the literature, no statistically significant difference was found according to whether or not chemotherapy was administered. Conclusions: According to NRS analysis, no statistically significant differences were found in terms of nutritional status according to COVID-19 transmission and vaccination status. When NRS analyses were examined according to the delay of treatment during the pandemic period, it was found that patients who postponed treatment were in the risk group in terms of nutrition, while patients who did not postpone treatment were mostly in the follow-up group. In multivariable analyses, however, no independent relationship was identified between this parameter and NRS-2002 risk. Full article

Seasonal influenza remains a major global public health challenge despite decades of vaccine development, underscoring the need for more effective and adaptable immunization strategies. The recently approved mRNA-1010 vaccine represents a promising advance by applying messenger RNA technology to a pathogen characterized by continuous antigenic drift. Recent Phase 3 clinical trials conducted in support of regulatory review have demonstrated robust immunogenicity and superior protective efficacy against seasonal influenza compared with standard influenza vaccines in adults aged 50 years and older. However, increased reactogenicity, particularly among younger adults, together with the need for continued post-marketing safety surveillance, highlights the balance between enhanced immune responses and tolerability. Beyond seasonal influenza, mRNA-1010 provides a foundation for next-generation respiratory vaccines, including combination formulations targeting influenza, SARS-CoV-2, and respiratory syncytial virus (RSV), while illustrating the broader potential of mRNA vaccine technology. At the same time, challenges related to manufacturing scalability, cost, cold-chain requirements, and global accessibility remain important considerations for widespread implementation. This perspective examines whether mRNA-1010 represents an incremental advance in influenza vaccination or a potential transformative milestone in respiratory immunization, while considering the continuing roles of alternative vaccine platforms in achieving optimal effectiveness, safety, and equitable global access. Full article

Background/Objectives: Messenger RNA vaccines can induce strong immune responses, but delivery, biodistribution, and storage stability remain important considerations. We evaluated the safety and immunogenicity of SW-BIC-213, a Lipo-Polyplex (LPP)-based mRNA vaccine against SARS-CoV-2, in healthy adults in Laos. Methods: We conducted a seamless phase 1/2 clinical trial in healthy adults. Phase 1 enrolled adults aged 18–60 years in an open-label, single-arm dose-escalation study; phase 2 enrolled adults aged ≥18 years in a randomized, double-blind, placebo-controlled study. Participants received two doses 21 days apart. The primary endpoints were safety in phase 1 and safety and immunogenicity in phase 2. Results: In phase 1, 41 participants received 25 or 45 μg of SW-BIC-213. In phase 2, 480 participants were randomized in a 2:2:1 ratio to receive 25 μg, 45 μg, or placebo. All phase 1 adverse reactions were grade 1 or 2; grade 3 reactions in phase 2 were limited to transient fever. At 14 days after the second dose, pseudovirus neutralizing-antibody seroconversion exceeded 99% against wild-type virus, 98% against Delta, 84% against Omicron BA.1, and 88% against BA.2. Neutralizing-antibody titers were higher in both vaccine groups than in the placebo group (p < 0.0001). Conclusions: Two doses of SW-BIC-213 showed an acceptable safety profile and substantial humoral immunogenicity in healthy adults aged ≥18 years. Full article

Vaccination ranks among the most consequential interventions in medicine, yet cold-chain dependence, sharps hazards, needle phobia, and reliance on trained vaccinators limit coverage where vaccine-preventable mortality is highest. Microneedle patches deposit antigen into the antigen-presenting-cell-rich epidermis and upper dermis through projections that penetrate the stratum corneum without reaching dermal nociceptors. Such targeting yields immunogenicity matching or exceeding intramuscular injection at a fraction of the antigen mass, with dose-sparing up to six-fold recorded for influenza, polio, and SARS-CoV-2 antigens. Solid-state formulation converts that immunological advantage into a logistical one, since polymeric matrices preserve potency for as long as two years at ambient temperature, removing the refrigeration infrastructure that consumes significant delivery cost. Six microneedle types have reached preclinical or clinical maturity, with dissolving microneedle patches the most advanced. Two trials provide the clinical evidence: a Phase I influenza study showing non-inferior antibody responses and successful self-application, and a Phase I/II measles–rubella trial in The Gambia reaching 93% measles and 100% rubella seroconversion in infants without related serious adverse events. Engineering advances currently include an automated printer producing thermostable mRNA–lipid nanoparticle patches that retain bioactivity for six months at ambient temperature, the first intradermal self-amplifying RNA patch, and quantum-dot on-body immunization records. Sterility assurance, dose uniformity, nucleic acid integrity within solid matrices, and fragmented regulatory guidance remain the challenging obstacles, alongside a clinical pipeline concentrated on few antigens. This review integrates the mechanistic, materials, manufacturing, clinical, regulatory, and global health dimensions of the field to guide translation and equitable deployment. Full article

Background/Objectives: Seasonal influenza vaccination (SIV) coverage remains suboptimal among adults aged ≥50 years, and the COVID-19 pandemic might influence the determinants of SIV uptake. This systematic review aimed to identify determinants of SIV uptake among adults aged ≥50 years during and after the COVID-19 pandemic. Methods: We searched PubMed, MEDLINE, Embase, Web of Science, Global Health, CINAHL, Cochrane Library, APA PsycINFO, and APA PsycArticles for studies published between 1 December 2019 and 1 January 2026. The pooled prevalence of SIV uptake was synthesized using random-effects models in meta-analysis. Results: A total of 50 studies were included in the systematic review. COVID-19-related factors, such as perceived risk of co-infection with SARS-CoV-2 and seasonal influenza and concerns about potential interactions between COVID-19 vaccines and SIV, were determinants of SIV uptake. Other modifiable determinants included those that existed before the pandemic (e.g., knowledge and perceptions of seasonal influenza and SIV). Subgroup analysis showed that cost and inaccessibility were barriers to receiving SIV in places without a fully subsidized SIV, and perceived susceptibility and vaccine safety concerns were commonly identified as facilitators and barriers in studies with data collected after the pandemic. The pooled prevalence of SIV uptake among adults aged 50 years or above was 53% (95% confidence interval: 44–62%). Such uptake appeared lower among adults aged 50–64 years, in regions without a fully subsidized SIV, and after the COVID-19 pandemic. Conclusions: These findings could inform service planning and interventions promoting SIV uptake among adults aged ≥50 years in the post-pandemic era. More studies are needed to explore determinants specific to people aged 50–64 years to inform health promotion tailored to their needs. Full article

Background and Objectives: Oral antiviral agents nirmatrelvir/ritonavir (NMV/r) and molnupiravir are recommended for the early treatment of non-hospitalized adults with COVID-19 who are at increased risk of disease progression. Real-world comparative data on these two agents remain limited. The aim of this study was to evaluate the efficacy and safety of NMV/r and molnupiravir in non-hospitalized patients with COVID-19. Materials and Methods: We conducted a retrospective, single-center study with a sample size of 122 initially non-hospitalized adults with confirmed SARS-CoV-2 infection treated at the Clinic for Infectious Diseases, University Clinical Center of Vojvodina (UCCV), Novi Sad, Serbia, during 2022. Patients were treated within the first five days of symptom onset with either NMV/r (n = 48) or molnupiravir (n = 74) for five days. Demographic characteristics, clinical presentation, comorbidities, vaccination status, laboratory parameters at baseline and on day 3, chest radiography findings, hospitalization, and mortality were analyzed. Statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS), version 21 (IBM Corp., Armonk, NY, USA). Results: The groups did not differ significantly in age, sex, vaccination status, or vaccine type. Between baseline and day 3, the increase in lymphocyte count (p < 0.001) was significantly greater in the molnupiravir group. Chest radiography showed no significant between-group differences. Overall, 6 patients (4.9%) were hospitalized, with no significant difference between antiviral agents (p = 1.000), and no deaths occurred. Among patient-reported symptoms effects, the incidence of dysgeusia was significantly higher in patients treated with NMV/r (p = 0.001). Conclusions: Both antivirals showed similarly low progression, hospitalization, and mortality rates. Full article

Background: Individuals with autoimmune disease, inflammatory bowel disease (IBD), and transplants face a higher risk of severe COVID-19 and breakthrough hospitalizations. It is essential to understand the magnitude and durability of vaccine-induced humoral immune response in these populations. Methods: We evaluated SARS-CoV-2 spike IgG antibody levels and avidity in autoimmune, IBD, transplant, and healthy cohorts following multiple COVID-19 mRNA vaccine doses. Serum samples were collected approximately 1 month (8–52 days) and 6 months (158–202 days) post-vaccination. Antibody levels and avidity were measured using validated ELISA and chaotropic-based avidity assays. Results: Individuals with IBD and individuals with autoimmune disease, especially systemic autoimmune disease, exhibited lower antibody levels and avidity compared with healthy individuals at certain doses and time points. Transplant recipients demonstrated substantial impairments in both antibody levels and avidity, with avidity reduced across all doses and time points. Significantly lower avidity levels were observed in transplant recipients, suggesting challenges in developing or maintaining antibody quality. For example, geometric mean anti-spike IgG levels were substantially lower in transplant recipients than in healthy individuals at both 1 month (635 vs. 7685 BAU/mL; p < 0.0001) and 6 months (1146 vs. 3277 BAU/mL; p = 0.0057) post third dose. Similarly, transplant recipients had lower antibody avidity than healthy individuals after the third dose, with geometric mean AI80 values of 4.5 M vs. 5.5 M at 1 month (p < 0.0001) and 4.6 M vs. 5.4 M at 6 months (p < 0.0001). Age, sex, and vaccine manufacturer may further influence humoral immune responses in the transplant cohort. Conclusions: Vaccine-induced humoral immunity varies across autoimmune, IBD, and transplant cohorts, with the most persistent impairment observed in transplant recipients across vaccine dose groups and at both post-vaccination time points. These findings reveal immune response patterns that may guide future studies evaluating vaccination schedules, immune monitoring, and clinical outcomes in these populations. Full article

Introduction: The development of bivalent mucosal vaccines capable of providing protection against both influenza and SARS-CoV-2 is a major public health focus. While most COVID-19 vaccines target the spike (S) protein, the highly conserved nucleocapsid (N) protein represents a strategic target for cross-reactive, cell-mediated immunity. This study evaluates Corfluvec, an intranasal vaccine candidate based on an attenuated NS1-truncated influenza vector expressing a fragment of the SARS-CoV-2 N protein. Methods: Protective efficacy, including viral load and pathomorphological changes in the lungs and vessels, was evaluated in Syrian hamsters challenged with high and low doses of SARS-CoV-2 (lineage B.1.1). Cross-protective efficacy against homologous and heterologous influenza A strains (H1N1pdm09, H3N2, and A/PR/8/1934) was tested in a lethal murine model. Additionally, immunogenicity of Corfluvec applied via human-compatible delivery device was tested in cynomolgus macaques (Macaca fascicularis). Results: In Syrian hamsters, vaccination significantly reduced viral loads in the lungs and nasal turbinates. Histopathological analysis revealed a preservation of lung vascular integrity: vaccinated animals showed stable CD31 expression and controlled Ki-67 proliferative activity, accompanied by a marked reduction in vasculitis and perivascular edema compared to placebo controls. In mice, the vaccine provided 100% protection against homologous and heterologous influenza virus challenges. In macaques, the two-dose intranasal immunization was well-tolerated and induced significant systemic IgG and mucosal sIgA responses, alongside robust N-specific IFNγ+ T-cell activation. Conclusions: Corfluvec is a promising bivalent vaccine candidate that provides dual protection against influenza and COVID-19. Its ability to limit viral shedding from the upper respiratory tract and to mitigate SARS-CoV-2-induced pulmonary pathology, contributing to the preservation of lung vascular integrity, underscores the utility of mucosal immunization with Corfluvec as a valuable intranasal complement to current systemic vaccination strategies. Full article