Search Results (19,594)

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^TM 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

Post-exertional malaise (PEM) and cognitive dysfunction (hereafter “cognitive dysfunction”, including the patient-reported syndrome often described as “brain fog”) are among the most disabling features of Long COVID; yet, approved disease-modifying treatments remain lacking. Emerging evidence implicates interacting disturbances in mitochondrial bioenergetics, redox regulation and neurovascular inflammation, although much of the supporting evidence remains indirect and derives from acute COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), primary mitochondrial disease, inflammatory biology and mechanistic pharmacology rather than from direct Long COVID intervention trials. This hypothesis-generating narrative review develops a mechanism-based translational framework: that a pathway-targeted nutraceutical programme may modulate selected elements of these three axes, subject to prior demonstration of formulation quality, pharmacokinetic feasibility, target engagement and safety. Candidate modules comprise coenzyme Q10 and alpha-lipoic acid for bioenergetic/redox support; selenium, sulforaphane and resveratrol for Nrf2–thioredoxin-related redox regulation; and Boswellia serrata, luteolin and eicosapentaenoic acid for putative prostaglandin/resolution-pathway modulation. Sonlicromanol provides a conceptual mechanistic precedent for combined redox and prostaglandin-directed pharmacology, but it is not considered pharmacologically equivalent to an eight-agent nutraceutical combination. We summarise the mechanistic rationale, distinguish direct from indirect evidence, define qualitative evidence-grading criteria, outline safety and interaction considerations, and propose a staged translational research programme. This framework is intended to generate falsifiable hypotheses for future Long COVID studies, not to imply established clinical efficacy. Full article

Background/Objectives: Although SARS-CoV-2 infection is usually mild in children, some develop severe respiratory disease (RD) or multisystem inflammatory syndrome in children (MIS-C). We evaluated long-term respiratory symptoms, pulmonary function, and cardiopulmonary exercise performance in children recovering from SARS-CoV-2-related RD and MIS-C. Methods: This single-center prospective observational study included children hospitalized for SARS-CoV-2-related RD or MIS-C. Pulmonary function tests (PFTs) and cardiopulmonary exercise testing (CPET) were performed at a mean follow-up of 22.8 ± 9.8 months after hospitalization and compared between groups. Results: Forty-two children (25 RD, 17 MIS-C) were included. Persistent post-COVID symptoms were reported by 38.1% of participants and were more frequent in the RD group (56.0% vs. 11.8%; p < 0.01), with fatigue being the predominant symptom (p = 0.02). Pulmonary function and CPET parameters were comparable between groups, with no evidence of clinically significant ventilatory limitation or impaired aerobic capacity. VO₂peak did not differ between groups. Multivariable regression identified the breathing reserve index and OUES normalized to body weight as strong positive predictors of aerobic capacity in both groups. Despite differences in follow-up duration, stratified analyses using a 24-month cut-off showed comparable physiological findings. Conclusions: Children demonstrated preserved pulmonary function and exercise capacity nearly two years after hospitalization for severe SARS-CoV-2-related RD or MIS-C. Despite these favorable objective findings, subjective symptoms persisted in a substantial subset of patients, particularly those recovering from RD, suggesting that symptom resolution may lag behind objective physiological recovery. OUES normalized to body weight and the breathing reserve index may serve as complementary markers of aerobic capacity. Full article

The mitigation measures adopted to reduce the spread of COVID-19 have not only impacted the transmission of respiratory infections but also other infectious diseases. In this study, we explored the effect of the pandemic on the epidemiology of Central Nervous System (CNS) infections by conducting a retrospective analysis of diagnostic data obtained from cerebrospinal fluids (CSFs) collected before, during, and after the pandemic from patients with acute-suspected neuro-infectious syndrome. The samples were analyzed using a meningitis/encephalitis molecular syndromic panel. A total of 4203 CSFs were split into three groups: pre-pandemic (August 2018–February 2020), pandemic (March 2020–March 2022) and post-pandemic (April 2022–March 2024). Each pathogen was statistically assessed individually, comparing one group vs. another. Results showed that viral pathogens were the most frequently detected across all groups; however, Streptococcus pneumoniae was the single most identified pathogen. Comparison of the pre-pandemic and pandemic groups by statistical analysis showed a significant reduction in neuro-infections caused by enterovirus, S. pneumoniae and N. meningitidis, while the other pathogens were not affected. In conclusion, a reduction in CNS infections caused by respiratory and close-contact-transmitted pathogens, including both viral and bacterial agents, was observed during the period when COVID-19 containment measures were in effect. 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

In May 2025, a new and welcome Pandemic Treaty was signed. The success of this treaty for the management of future pandemics depends on a re-evaluation of the importance of previous well-established treaty-based international human rights norms in controlling health crises. During the COVID-19 pandemic, public health responses globally were characterised by poor preparation, uncertainty, and hasty and sometimes perverse decisions. International human rights norms, especially health rights, and other treaty obligations were honoured more in their breach than their observance. The lessons learned from public health strategies that had integrated international human rights norms into the control and management of the HIV/AIDS pandemic were either ignored or forgotten. Early public health attempts to control the HIV/AIDs pandemic were hobbled by data breaches, travel restrictions, compulsory reporting, stigma, and misinformation about how the virus spread. This was replaced by a more successful human rights-based approach (HRBA) that used health rights indicators to identify groups susceptible to the disease but difficult to reach with conventional public health policies. The efficacy of health rights indicators and HRB methodology to remove barriers to treatment and suppress pandemics should have been seriously considered in strategies to control COVID-19. The article claims that failure to do this meant that more lives were lost than necessary and more people were left with serious long-term health effects. This article explores the practical significance of the international human rights legal framework, especially health rights, as trialled during the HIV/AIDS pandemic, for the management of COVID-19 and other pandemics. Full article

Early, rapid, and accurate detection is essential for clinical management and epidemiological control of acute respiratory infections caused by pathogens. Traditional testing methods such as microbial culture, serological testing, and PCR are restrictive in terms of operation and logistics and are therefore not easily used in point-of-care settings. The CRISPR/Cas system is an adaptive prokaryotic immune system composed of clustered regularly interspaced short palindromic repeats and their associated proteins, which has been used as a nucleic acid diagnostic platform with programmable sequence-specific target recognition and signal-amplifying collateral cleavage activity. Existing reviews have mostly focused on the classification of Cas enzymes or amplification strategies; in this review, a pathogen-centric approach was taken, covering viral pathogens (SARS-CoV-2, influenza virus, RSV, HAdV and VZV), bacterial pathogens (Mycobacterium tuberculosis, Streptococcus pneumoniae, Mycoplasma pneumoniae and Staphylococcus aureus) and fungal pathogens (Aspergillus fumigatus and Pneumocystis jirovecii). Key technological advances, such as isothermal amplification coupling, single-vessel integrated reaction designs, amplification-free digital detection, and electrochemical biosensor integration, are evaluated for Cas9-, Cas12-, and Cas13-based systems, with their mechanistic bases outlined. The current challenges that hinder clinical translation, such as sample matrix interference, multiple signal cross-talk, crRNA off-target effects, and the lack of large-scale validation studies, are critically assessed. At the same time, future pathways for portable, integrated, and inexpensive diagnostic platforms are suggested. 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

Coronavirus disease 2019 (COVID-19) is increasingly recognized as a multisystem disorder associated with persistent metabolic complications extending beyond the acute phase of infection. Accumulating evidence suggests that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may disrupt glucose homeostasis through mechanisms involving pancreatic β-cell dysfunction, insulin resistance, chronic inflammation, oxidative stress, mitochondrial dysfunction, and hypoxia-related signalling. This review summarizes current evidence regarding the molecular and cellular mechanisms linking SARS-CoV-2 infection to impaired insulin secretion and post-COVID metabolic disturbances. Particular emphasis is placed on the regulation of insulin secretion, β-cell compensation and failure, oxidative stress, inflammatory signalling, mitochondrial dysfunction, and the development of the post-COVID metabolic phenotype. Emerging evidence indicates that persistent metabolic abnormalities after COVID-19 may range from transient dysglycaemia to new-onset diabetes mellitus and metabolic syndrome. The review also discusses clinical implications, biomarkers, therapeutic perspectives, and unresolved questions regarding the reversibility of post-COVID β-cell dysfunction. A better understanding of the mechanisms underlying post-COVID metabolic dysfunction may improve risk stratification, facilitate early intervention, and support development of targeted therapeutic strategies aimed at preserving β-cell function and long-term metabolic health. Full article

Background: Sex-related differences in SARS-CoV-2 viral susceptibility, severity, and recovery are prevalent. Factors such as age and biological variation provide some explanation for immune response, yet the use of biological sex as a variable may limit understanding of underlying individual mechanisms related to endocrine–immune function involved in long-term immune memory. Endogenous sex hormone concentrations provide a means to assess the magnitude or durability of antibody persistence and disease recovery. Objective: This study examined salivary concentrations of 17β-estradiol and testosterone, as well as the number of weeks since prior SARS-CoV-2 viral infection. The study aimed to determine whether endogenous sex hormones contributed additional explanatory value to antibody persistence beyond biological sex. Methods: A cross-sectional study included 75 college students (63% female) who reported weeks since previous SARS-CoV-2 infection (M = 15.41, SD = 7.13), confirmed through a positive SARS-CoV-2 anti-N rapid antibody test. Participants provided saliva samples, which were tested for concentration of 17β-estradiol and testosterone. Hierarchical multiple regression analyses examined the effects of biological sex and endogenous sex hormones on the persistence of SARS-CoV-2 antibodies following natural infection. Results: 17β-estradiol was the strongest positive predictor of SARS-CoV-2 antibody persistence (β = 0.63, p < 0.001). Departing from previous findings, biological sex was not a significant predictor of antibodies targeting the SARS-CoV-2 N protein. Conclusions: Findings underscored the role of estradiol on immune recovery in a healthy young adult population. Individual hormone variation appears more informative than sex classification for understanding antibody persistence and immune response. Full article

SARS-CoV-2 transmission between humans and animals is an important One Health concern, particularly in settings where close human–animal interactions are difficult to avoid. We developed and applied a qualitative likelihood ranking framework for SARS-CoV-2 transmission between people and captive lions (Panthera leo) in an urban zoological setting. Following a structured review, scenario trees were constructed to rank direct and indirect transmission pathways using five domains: activity duration, proximity and frequency, SARS-CoV-2 survival on fomites, and environmental conditions. The framework was applied to a case study of a lion exhibit at an urban zoo in Australia. Pathway ranking depended on the combined effects of baseline exposure attributes and subsequent modifiers reflecting exposure frequency and level of natural disinfection. Although direct pathways, such as veterinary procedures, had the highest likelihood of transmission, they were differentiated by interaction duration and proximity, with frequency modification distinguishing rare, high-intensity interactions from repeated lower-intensity activities. Therefore, routine husbandry or visitor-associated exposures could increase in relative importance. Environmental modification further differentiated pathway likelihood, in particular due to solar exposure and temperature. The framework provides a transparent, practical approach for ranking transmission likelihood when data are scarce, supports consistent prioritisation of biosecurity resources, and is applicable to other emerging infectious disease threats in zoological settings. Full article