Search Results (5,792)

Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies. Full article

In this paper we aimed to compare seasonality, clinical characteristics, and outcomes of Influenza A and COVID-19 in the context of influenza reemergence and ongoing Omicron circulation. We performed a retrospective comparative analysis at the Teaching Hospital of Infectious Diseases in Cluj-Napoca, Romania. We included adult patients hospitalized with Influenza A or COVID-19 between 1 November 2022 and 31 March 2024. Data were collected on demographics, clinical presentation, complications, and in-hospital mortality. We included 899 COVID-19 and 423 Influenza A patients. The median age was 74 years for COVID-19 and 65 for Influenza A (p < 0.001). The age-adjusted Charlson comorbidity index was higher in COVID-19 patients (5 vs. 3, p < 0.001). Despite this age gap, acute respiratory failure was more common in Influenza A (62.8% vs. 55.7%, p = 0.014), but ventilation rates did not differ significantly. Multivariate models showed Influenza A was associated with increased risk of intensive-care unit (ICU) admission or ventilation, whereas older COVID-19 patients had higher in-hospital mortality (5.67% vs. 3.3%, p = 0.064). Omicron COVID-19 disproportionately affected older patients with comorbidities, contributing to higher in-hospital mortality. However, Influenza A remained a significant driver of respiratory failure and ICU admission, underscoring the importance of preventive measures in high-risk groups. Full article

Background/Objectives: Cognitive impairment in older adults has emerged as a growing public health concern, particularly in relation to COVID-19 infection and its associated neuropsychiatric symptoms. The identification of modifiable risk factors may contribute to the development of targeted preventive strategies. This study aimed to assess predictors of cognitive impairment in older adults with and without recent SARS-CoV-2 infection. Methods: A prospective cohort study was conducted from June 2023 to March 2024 at a tertiary hospital in western Mexico. Adults aged 65 years or older with confirmed SARS-CoV-2 infection within the previous six months, along with uninfected controls, were enrolled. Cognitive function (Mini-Mental State Examination), depression (PHQ-9), anxiety (Geriatric Anxiety Inventory), insomnia (Insomnia Severity Index), functional status (Katz Index and Lawton–Brody Scale), and laboratory markers were evaluated at baseline, three months, and six months. The primary outcome was cognitive impairment at six months. Independent predictors were identified using a multivariable generalized linear mixed-effects model. Results: Among the 111 participants, 20 (18.8%) developed cognitive impairment within six months. Low serum magnesium (adjusted risk ratio [aRR] 2.73; 95% CI 1.04–7.17; p = 0.041) and depression (aRR 5.57; 95% CI 1.88–16.48; p = 0.002) were independently associated with a higher risk. A significant synergistic among COVID-19, depression, and hypomagnesemia was observed (RR 44.30; 95% CI 9.52–206.21; p < 0.001), corresponding to the group with simultaneous presence of all three factors compared to the group with none. Conclusions: Depression and hypomagnesemia appear to be independent predictors of cognitive impairment in older adults with recent COVID-19 infection. These findings suggest potential targets for prevention and support the implementation of routine neuropsychiatric and biochemical assessments in this population. Full article

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected. Full article

Early-career teachers (ECTs) entered the profession during the COVID-19 pandemic, a period that introduced unique stressors to an already-demanding career phase. This systematic review examines empirical studies published between 2020 and February 2025 to explore how the pandemic influenced ECT wellbeing, with particular attention to stressors and protective factors impacting long-term retention and professional sustainability. Guided by PRISMA protocols, databases including Web of Science, ERIC, Google Scholar, and Scopus were searched, screening 470 records and identifying 30 studies that met inclusion criteria: peer-reviewed, empirical, focused on early-career teachers (within the first five years), and situated in or explicitly addressing the pandemic and its ongoing impacts. The results of Braun and Clarke’s thematic analysis (2006) revealed that pandemic-related challenges such as increased workload, professional isolation, disrupted induction processes, and emotional strain have persisted into the post-pandemic era, contributing to sustained risks of burnout and attrition. Regardless, protective factors identified during the pandemic—including high-quality mentoring, structured induction programmes, collegial support, professional autonomy, and effective individual coping strategies—continue to offer essential support, enhancing resilience and professional wellbeing. These findings underscore the necessity of institutionalising targeted supports to address the enduring effects of pandemic-related stressors on ECT wellbeing. By prioritising sustained mental health initiatives and structural supports, education systems can effectively mitigate long-term impacts and improve retention outcomes for early-career teachers in a post-pandemic educational landscape. Full article

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies. Full article

Background/Objectives: COVID-19 is a systemic viral infection that may lead to serious complications including acute kidney injury that requires kidney replacement therapy. The primary aim of this study was to evaluate urinary SerpinA3 (uSerpinA3) excretion as a biomarker of kidney recovery at 90 days, and the mortality in patients with critical COVID-19 and AKI requiring kidney replacement therapy (KRT). Methods: The study included patients with critical COVID-19 on invasive mechanical ventilation (IMV) requiring KRT. Blood and urine samples were obtained when KRT was initiated (day zero), and thereafter on days 1, 3, 7, and 14 post-replacement. uSerpinA3, kidney injury molecule-1 (uKIM-1), and neutrophil gelatinase-associated lipocalin (uNGAL) were measured in urine, and interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) in peripheral blood. In addition, metabolomics in sample days zero and 3, and in the survivors on sample day 90 was performed by employing gas chromatography coupled with mass spectrometry. Results: A total of 60 patients were recruited, of whom 29 (48%) survived hospitalization and recovered kidney function by day 90. In the survivors, 79% presented complete recovery (CRR) and the remaining (21%) recovered partially (PRR). In terms of uSerpinA3, levels on days 7 and 14 predicted CRR, with AUC values of 0.68 (p = 0.041) and 0.71 (p = 0.030), respectively, as well as mortality, with AUC values of 0.75 (p = 0.007) and 0.76 (p = 0.015), respectively. Among the other biomarkers, the excretion of uKIM-1 on day zero of KRT had a superior performance as a CRR predictor [(AUC, 0.71 (p = 0.017)], and as a mortality predictor [AUC, 0.68 (p = 0.028)]. In the metabolomics analysis, we identified four distinct profiles; the metabolite that maintained statistical significance in predicting mortality was p-cresol glucuronide. Conclusions: This study strongly suggests that uSerpinA3 and uKIM-1 can predict CRR and mortality in patients with critical COVID-19 and AKI requiring KRT. Metabolic analysis appears promising for identifying affected pathways and their clinical impact in this population. Full article

Objective: This study aimed to evaluate physical training protocols for alleviating long COVID symptoms, especially dyspnea and fatigue, through a systematic review with meta-analysis. Method: Data were collected from EMBASE, LILACS, PubMed, Scopus, CINAHL, Web of Science, and grey literature (Google Scholar, medRxiv). Studies evaluating dyspnea and/or fatigue before and after physical rehabilitation, using validated questionnaires, were included. Studies lacking pre- and post-assessments or physical training were excluded. Two reviewers independently extracted data on intervention type, duration, frequency, intensity, and assessment methods for dyspnea and fatigue. Bias risk was evaluated using the Cochrane tool. Results: Combined methods, such as respiratory muscle training with strength and aerobic exercise, were common for long COVID symptoms. Aerobic exercise notably improved dyspnea and/or fatigue. Among 25 studies, four had a low risk of bias. Meta-analysis of two studies found no significant reduction in fatigue. Conclusion: Combined training methods, particularly aerobic exercise, alleviate dyspnea and fatigue in long COVID. More high-quality studies are needed to confirm these findings. Full article

Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (M^pro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of M^pro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of M^pro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 M^pro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the M^pro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under M^pro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 M^pro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article

The COVID-19 pandemic triggered unprecedented economic disruptions, raising critical questions about the resilience and adaptability of macroeconomic productivity across countries. This study examines the impact of COVID-19 on macroeconomic efficiency and productivity dynamics in 37 OECD countries using quarterly data from 2018Q1 to 2024Q4. By employing a Slack-Based Measure Data Envelopment Analysis (SBM-DEA) and the Malmquist Productivity Index (MPI), we decompose total factor productivity (TFP) into efficiency change (EC) and technological change (TC) across three periods: pre-pandemic, during-pandemic, and post-pandemic. Our framework incorporates both desirable (GDP) and undesirable outputs (inflation, unemployment, housing price inflation, and interest rate distortions), offering a multidimensional view of macroeconomic efficiency. Results show broad but uneven productivity gains, with technological progress proving more resilient than efficiency during the pandemic. Post-COVID recovery trajectories diverged, reflecting differences in structural adaptability and innovation capacity. Regression analysis reveals that stringent lockdowns in 2020 were associated with lower productivity in 2023–2024, while more adaptive policies in 2021 supported long-term technological gains. These findings highlight the importance of aligning crisis response with forward-looking economic strategies and demonstrate the value of DEA-based methods for evaluating macroeconomic performance beyond GDP. Full article

Background/Objectives: This study aimed to evaluate sociodemographic factors, features of the acute infection, and post-infection health status in survivors of COVID-19, assessing their association with post-acute COVID-19 syndrome (PACS). Methods: A multidisciplinary public clinic in Brazil assessed COVID-19 survivors between June 2020 and February 2022. Patients were classified as having PACS or subacute infection (SI). Data on the history of the acute infection, current symptoms, physical examination, and laboratory findings were collected and analyzed using multivariate models with PACS as the outcome. Results: Among the 113 participants, 63.71% were diagnosed with PACS at a median of 130 days (IQR: 53–196) following acute symptom onset. Admission to the intensive care unit was more frequent among individuals with PACS than those with SI (83.3% vs. 65.0% respectively; p = 0.037). Symptoms significantly more prevalent in the PACS group when compared to the SI cohort included hair loss (44.4% vs. 17.1% respectively; p = 0.004), lower limb paresthesia (34.7% vs. 9.8% respectively; p = 0.003), and slow thinking speed (28.2% vs. 0.0% respectively; p < 0.001). Logistic regression revealed that only the time interval between the onset of acute symptoms and the clinical evaluation was independently associated with a PACS diagnosis (β = 0.057; 95% CI: 1.03–1.08; p < 0.001). Conclusions: Patients with PACS had a higher frequency of intensive care unit admission compared to those with subacute infection. However, in the multivariate analysis, the severity of the acute infection did not predict the final diagnosis of PACS, which was associated only with the time elapsed since symptom onset. Full article

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the etiologic agent that causes the coronavirus disease (COVID-19) identified in Wuhan, in 2019. Men are more prone to developing severe manifestations than women, suggesting a possible crucial role of sex hormones. 17,β-Estradiol (E2) and 1,25 α dihydroxyvitamin D₃ (calcitriol) act upon gene pathways as immunomodulators in several infectious respiratory diseases. In this study, we aimed to evaluate the influence of E2 and calcitriol on the VSV-based pseudovirus SARS-CoV-2 and SARS-CoV-2 infection in vitro. We infected Vero E6 cells with the recombinant VSV-based pseudovirus SARS-CoV-2 and the SARS-CoV-2 viruses according to the pre-treatment and pre–post-treatment models. The Angiotensin-Converting Enzyme 2 (ACE2) and Vitamin D Receptor (VDR) gene expression did not change under different treatments. The VSV-based pseudovirus SARS-CoV-2 infection showed a significant decrease in the focus-forming unit count in the presence of E2 and calcitriol (either alone or in combination) in the pre-treatment model, while in the pre–post-treatment model, the infection was inhibited only in the presence of E2. Th SARS-CoV-2 infection highlighted a decrease in viral titres in the presence of E2 and calcitriol only in the pre–post-treatment model. 17,β-Estradiol and calcitriol can exert an inhibitory effect on SARS-CoV-2 infections, demonstrating their protective role against viral infections. Full article

Nasal irrigation (NI) is an effective, safe, low-cost strategy for treating and preventing upper respiratory tract diseases. High-volume, low-pressure saline irrigations are the most efficient method for removing infectious agents, allergens, and inflammatory mediators. This article reviews clinical evidence supporting NI use in various conditions: nasal congestion in infants, recurrent respiratory infections, acute and chronic rhinosinusitis, allergic and gestational rhinitis, empty nose syndrome, and post-endoscopic sinus surgery care. NI improves symptoms, reduces recurrence, enhances the efficacy of topical drugs, and decreases the need for antibiotics and decongestants. During the COVID-19 pandemic, NI has also been explored as a complementary measure to reduce viral load. Due to the safe profile and mechanical cleansing action on inflammatory mucus, nasal irrigations represent a valuable adjunctive treatment across a wide range of sinonasal conditions. Full article

Non-polio enteroviruses continue to cause numerous epidemics world-wide that range from mild to severe disease, including acute flaccid paralysis, meningitis, severe respiratory infections and encephalitis. Using publicly available data we present a comprehensive global and regional temporal distribution of non-polio enteroviruses, with a focus on highly prevalent genotypes. We found that regional distribution did vary compared to global prevalence where the top prevalent genotypes included CVA6 and EV-A71 in Asia, EV-D68 in North America and CVA13 in Africa, while E-30 was prevalent in Europe, South America and Oceania. In 2020, the COVID-19 pandemic did interrupt non-polio enterovirus detections globally, and cases rebounded in subsequent years, albeit at lower prevalence and with decreased genotype diversity. Environmental surveillance for non-polio enteroviruses does occur and has been used in some regions as an early-warning system; however, further development is needed to effectively supplement potential gaps in clinical surveillance data. Overall, monitoring for non-polio enteroviruses is critical to identify true incidence, improve understanding of genotype circulation, provide an early warning system for emerging/re-emerging genotypes and allow for better outbreak control. Full article

Background and Objectives: Preterm birth and stillbirth are primary adverse pregnancy outcomes. Research during the COVID-19 pandemic revealed reductions in preterm birth in some countries, while stillbirth rates increased or remained unchanged. These findings suggest the presence of preventable risk factors associated with changes in physical activity and lower exposure to community-acquired infections due to lockdown measures, altered social interaction patterns or reduced access to antenatal care. Assessing seasonal variation may offer insights into whether lifestyle changes during the COVID-19 lockdown period influenced preterm birth rates. Materials and Methods: This retrospective cohort study used data from the electronic medical records of Bihor and Sibiu counties. Preterm deliveries (<37 weeks) and stillbirths during the COVID-19 pandemic (2020 and 2021) were compared with the corresponding pre-pandemic (2018 and 2019) and post-pandemic (2022 and 2023) period. Preterm birth rates during summer and winter in the pre-pandemic, pandemic, and post-pandemic years were analyzed. A comparison with rates during strict lockdown was made. Results: Out of 52,021 newborn infants, 4473 were born preterm. Preterm birth rates remained stable across all three periods (p = 0.13), and no significant seasonal pattern was identified (p = 0.65). In contrast, stillbirth rates increased notably during the strict lockdown period, with the median incidence almost doubling compared to other periods (0.87%, p = 0.05), while remaining unchanged during the rest of the pandemic (p = 0.52). Conclusions: Our study found that preterm birth rates remained unaffected by the pandemic and lockdown periods, while stillbirths increased significantly during the strict lockdown. These findings highlight the importance of maintaining access to timely antenatal care during public health emergencies to prevent adverse perinatal outcomes. Full article