Search Results (19,605)

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

Background: COVID-19 is a multisystem disorder associated with inflammatory, metabolic, electrolyte, and endocrine disturbances. However, the clinical relevance of dysnatremia and acute hormonal alterations remains uncertain, particularly when assessed alongside established clinical risk factors. Methods: This prospective cohort study included 252 adults hospitalized with confirmed COVID-19. Clinical, laboratory, hormonal, and metabolic parameters were assessed at admission, and their associations with disease severity, intensive care unit (ICU) admission, and in-hospital mortality were analyzed. Results: The median age was 73 years, 50.4% of patients were female, and severe or critical disease was present in 81.7%. Dysnatremia and/or endocrine alterations were detected in 55.2% of patients, including hyponatremia in 16.7%, while thyroid-function alterations were observed in 40.9%. Dysnatremia was associated with higher glucose levels and inflammatory-cell changes. Several hormonal and metabolic parameters showed statistically significant univariate associations with adverse outcomes; however, their discriminative performance was weak, with AUC values below clinically meaningful thresholds. After adjustment for major clinical confounders, dysnatremia and endocrine alterations were not independent predictors of disease severity, ICU admission, or mortality. Conclusions: These findings suggest that electrolyte and endocrine abnormalities in hospitalized COVID-19 patients primarily reflect systemic stress physiology and acute disease burden rather than functioning as independent prognostic biomarkers. Full article

The SARS-CoV-2 pandemic has significantly impacted global health, politics, medicine, finance, and society. Since 2020, various mutations have been reported, leading to drug resistance in current treatments against different SARS-CoV-2 strains and a drastic increase in cases of long-COVID. This situation underscores the urgent need to develop targeted and effective drugs to combat the spread of SARS-CoV-2 strains and their mutants, manage long-COVID symptoms and prepare for future pandemics. Currently, the treatment of SARS-CoV-2 focuses on targeting the virus’s entry and replication mechanisms to disrupt its life cycle. This review examines approved drugs, clinical candidates, and inhibitors under development, along with their bioassay data, while highlighting associated challenges. It illustrates how inhibitors bind to active sites, providing insights and emphasizing the importance of in silico studies, such as molecular docking, molecular dynamics simulation, FEP+, WaterMap, and quantitative structure–activity relationship (QSAR) analyses, and their correlation with experimental studies in expediting the drug discovery process. The review aims to provide researchers with insights into the gaps that need to be addressed concerning mutations affecting viral entry and to prepare for future pandemics. Full article

SARS-CoV-2 relies on a virus-encoded RNA capping pathway to produce 5′ cap structures that are essential for mRNA stability, efficient translation, and evasion of host innate immune surveillance. Within this pathway, nonstructural protein 14 (nsp14) catalyzes N7 methylation of the guanine cap, a key step that converts the cap core into a functional Cap-0 structure and enables subsequent maturation. Owing to its essential role in viral replication and its high conservation across coronaviruses, nsp14 has emerged as an attractive antiviral target. Recent structural and biochemical studies have elucidated the architecture of the nsp14 N7-methyltransferase domain, revealing an S-adenosyl-L-methionine (SAM)-dependent fold with a defined cofactor-binding site and an adjacent cap-binding pocket that orients the RNA substrate for methyl transfer. These insights have guided the development of diverse inhibitor classes, including SAM-competitive analogs, bisubstrate-like compounds, and non-nucleoside inhibitors identified through screening approaches. While early SAM-like inhibitors demonstrated target tractability, their therapeutic potential has been limited by challenges in selectivity and cellular permeability. More recent inhibitors that target the cap-binding pocket or exploit product-assisted ternary complex mechanisms highlight alternative strategies for achieving improved potency and specificity. Despite these advances, current structural models rely on truncated RNA substrates and isolated protein constructs, which may not fully capture the native catalytic environment. Future efforts to resolve nsp14 within the replication–transcription complex and develop novel inhibition strategies will be critical for advancing mechanistic understanding and antiviral development. 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

The emergence of SARS-CoV-2 variants and antiviral resistance highlights the need for improved therapeutic strategies against COVID-19 and other coronavirus infections. By pairing direct-acting antivirals with repurposed host-modulating drugs, combination therapy approaches may enhance antiviral efficacy while mitigating inflammation. In this study, we evaluated the effects of combining Nirmatrelvir (a SARS-CoV-2 main protease inhibitor) with Ivermectin, Azithromycin or Doxycycline—using a murine hepatitis virus (MHV) infection model of RAW264.7 macrophages. Checkerboard assays demonstrated that the Nirmatrelvir–Ivermectin combination exhibited strongly synergistic antiviral activity. This combination achieved potent inhibition of live virus titer of at least 5 to 6 log₁₀ and reduction in viral RNA load of 3 log₁₀, at drug concentrations much lower than the respective monotherapies. The Nirmatrelvir–Ivermectin combination treatment affected the coronavirus replication cycle at the same time-point of 8 h as Nirmatrelvir monotherapy. Moreover, multiplex cytokine protein profiling revealed that Nirmatrelvir–Ivermectin markedly suppressed key pro-inflammatory cytokines and chemokines associated with the cytokine storm, including IL-6, TNF-α, IL-1β, and MCP-1. Conversely, the combinations of Nirmatrelvir with Azithromycin or Doxycycline exhibited only additive or mildly additive effects, with alterations in certain cytokine levels. These findings support the potential of Nirmatrelvir–Ivermectin as a promising novel combination therapy with both antiviral and anti-inflammatory benefits, warranting further in vivo validation and clinical investigation. Full article

Pelargonium graveolens L’Hér. is a widely distributed aromatic plant that has been utilized in traditional medicine for an extended period. It is currently experiencing a surge in popularity in modern phytotherapy. The ethnopharmacological uses of this species include treatment of respiratory tract infections, digestive disorders, and analgesia. The plant’s multifaceted biological activity is attributed to the presence of monoterpenes, such as citronellol and geraniol, as well as non-volatile polyphenolic fractions and organic acids. Research has demonstrated the efficacy of PGEO (P. graveolens essential oil) in mitigating inflammation, a phenomenon attributable to the suppression of NF-κB and MAPK signaling pathways, as well as the inhibition of inflammatory mediators such as histamine, prostaglandins (PGs), and nitric oxide (NO). Furthermore, a broad spectrum of antimicrobial activity has been demonstrated against pathogens such as MRSA and Mycobacterium tuberculosis, whilst myricetin derivatives have been shown to enable the effective eradication of bacterial biofilms. It is also noteworthy that the oil’s components can reduce ACE2 receptor expression, indicating their potential to inhibit SARS-CoV-2 infection. Active compounds, such as geraniol, have been shown to modulate metabolic processes through interaction with LXR and FXR nuclear receptors. In addition, these compounds have been observed to exhibit spasmolytic effects within the gastrointestinal tract by blocking calcium channels. The influence on the HPA axis and the GABAergic system provides a scientific rationale for the plant’s traditional use in reducing stress and anxiety. Nevertheless, variations in chemical composition, determined by geographical origin, and an insufficient number of rigorous clinical data hinder the full medical implementation of this plant. It is imperative that further standardization of extracts and their verification in clinical trials is undertaken. Full article

COVID-19 affects the olfactory system and the hippocampus, leading to severe olfactory and cognitive impairments. This study aimed to quantify volumetric changes in the olfactory bulbs and hippocampus in patients with COVID-19, and to investigate these differences in relation to loss of smell and taste. This stereological MRI study included 60 COVID-19 (+) participants and 54 non-COVID-19 participants. Using OsiriX software, the volumes of the olfactory bulb and hippocampus were manually measured from 3T MRI images. Compared with controls, participants with loss of smell and taste had smaller olfactory bulb volumes. This decrease was especially noticeable in the left olfactory bulb of female patients. Furthermore, the right hippocampal volume in male patients with loss of smell and taste was significantly decreased. These findings suggest that atrophy of the olfactory bulb and hippocampus may be specific to certain regions and sexes following SARS-CoV-2 infection. Stereological MRI assessments can effectively identify these changes. Prospective longitudinal studies are needed to determine the clinical significance of these changes and their impact on patient management. Full article

Pre-analytical variables, including specimen transport media, may influence the performance of molecular assays used for respiratory pathogen detection. Universal Biomolecular Medium (UBM™) has been developed to support nucleic acid preservation and molecular testing, but evidence regarding its analytical compatibility with routinely used molecular platforms remains limited. We conducted a retrospective paired comparison of UBM™ against conventional transport and lysis media across multiple molecular platforms to evaluate the post-collection analytical compatibility of UBM. Residual respiratory specimens positive for SARS-CoV-2, influenza A virus, influenza B virus, respiratory syncytial virus, human rhinovirus, human metapneumovirus, Haemophilus influenzae, Mycoplasma pneumoniae, and Bordetella pertussis were analyzed. Paired aliquots generated from the same specimen were tested using the Allplex™ SARS-CoV-2/FluA/FluB/RSV Assay, Xpert^® Xpress CoV-2/Flu/RSV plus, Panther Fusion^® SARS-CoV-2/Flu A/B/RSV Assay, and selected Allplex™ respiratory panels. Analytical agreement and cycle threshold (Ct) values were compared using paired statistical analyses and Bland–Altman methods. UBM demonstrated complete qualitative concordance with comparator media across all evaluated targets and platforms, yielding 100% positive, negative and overall agreement. Although statistically significant Ct differences were observed for selected target–platform combinations, these shifts were generally small and did not affect qualitative result interpretation. Internal control performance remained stable across media. These findings support the post-collection analytical compatibility of UBM™ with the evaluated molecular workflows. Full article

Background/Objectives: Host genetic variation contributes to the heterogeneous clinical outcomes of coronavirus disease 2019 (COVID-19), yet evidence from Southeast Asian populations remains limited. Methods: We investigated host genetic factors associated with COVID-19 severity in Vietnamese patients infected with the SARS-CoV-2 Delta variant using whole-exome sequencing. A total of 48 unvaccinated patients were enrolled. During sample-level quality control, one sample was excluded because the genetically inferred sex was discordant with the information recorded in the clinical medical record, leaving 47 samples (23 severe/critical and 24 mild/asymptomatic) for downstream genetic analyses. Gene-based association analysis was performed using MAGMA, followed by functional enrichment and interaction network analyses with Metascape and GeneMANIA. Results: Population structure analysis showed that the study participants clustered closely with the East Asian (EAS) reference population. No individual variant reached the prespecified multiple-testing-adjusted threshold, and no gene-level association survived Benjamini–Hochberg correction. Using a nominal MAGMA gene-based p < 0.01 threshold solely for exploratory prioritization, 44 genes were selected for downstream functional analyses. Functional enrichment highlighted RNA processing and mRNA maturation, together with mitochondrial, metabolic, immune-regulatory, and cellular homeostasis pathways. Network topology analysis further identified several highly connected genes, including CPSF4, MRPS34, ATP5MF, BUD31, SNRPD3, and HDAC1. Conclusions: These hypothesis-generating findings are consistent with a potentially polygenic contribution to severe COVID-19 and provide an exploratory systems-level framework for understanding host genetic susceptibility in the Vietnamese population, while identifying biologically plausible candidate genes and pathways for future validation. 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