Search Results (6,016)

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Background/Objectives: Due to the significant overlap in symptoms between COVID-19 and other respiratory infections, a multiplex PCR-based platform was developed to simultaneously detect 22 respiratory pathogens. Target sequences were retrieved from the GenBank database and aligned using Clustal Omega 2.1 to identify conserved regions prioritized for primer design. Primers were designed using Primer Express^® 3.0.1 and evaluated in Primer Explorer to ensure specificity and minimize secondary structures. A multiplex strategy organized primers into three groups, each labeled with distinct fluorophores (FAM, VIC, or NED), allowing for detection by conventional PCR or capillary electrophoresis (CE). Methods: After reverse transcription for RNA targets, amplification was performed in a single-tube reaction. A total of 340 clinical samples—nasopharyngeal and saliva swabs—were collected from patients, during the COVID-19 pandemic period. The automated analysis of electropherograms enabled precise pathogen identification. Results: Of the samples analyzed, 57.1% tested negative for all pathogens. SARS-CoV-2 was the most frequently detected pathogen (29%), followed by enterovirus (6.5%). Positive results were detected in both nasopharyngeal and saliva swabs, with SARS-CoV-2 predominating in saliva samples. Conclusion: This single-tube multiplex PCR-CE assay represents a cost-effective and robust approach for comprehensive respiratory pathogen detection. It enables rapid and simultaneous diagnosis, facilitating targeted treatment strategies and improved patient outcomes. Full article

Background/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. 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

Background: The implementation of intravenous thrombolysis (IVT) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) has proven effective, offering significant benefits for patient outcomes. We therefore investigated trends in the implementation of IVT and MT in Germany between 2015 and 2023. Methods: We conducted a retrospective analysis using German Diagnosis-Related Group (DRG) statistics from 2015 to 2023. Treatment numbers were analyzed annually based on OPS codes. We examined the age and sex distribution of patients undergoing these treatments. Additionally, we analyzed all hospital cases coded with ICD-10 for acute ischemic stroke (AIS). Results: Between 2015 and 2023, the number of AIS cases in Germany slightly declined from 250,802 to 248,107 (−1.1%), with the largest annual decrease (−4.3%) occurring during the COVID-19 pandemic (2019–2020). Despite this, the use of IVT increased from 40,766 cases (16.25%) in 2015 to 48,378 (19.50%) in 2023. MT usage rose even more sharply, from 7840 cases (3.13%) to 22,445 (9.05%). Among MT recipients, the proportion of patients aged ≥80 years rose significantly, from 27.2% to 42.1%. In this age group, women consistently comprised the majority of MT patients—65.4% in 2015 and 65.5% in 2023. Conclusions: Despite a stable stroke incidence, the use of IVT—and particularly MT—continued to increase in Germany from 2015 to 2023, even during the COVID-19 pandemic. MT usage nearly tripled, especially among patients aged ≥80 years. These trends highlight a resilient stroke care system and underscore the need for future planning to meet the rising demand for endovascular treatment in an aging population. 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

Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of COVID-19, it is not known whether these drugs directly affect SMCs. Accordingly, the present study investigated the ability of three approved COVID-19 antiviral drugs to influence SMC function. Treatment of SMCs with remdesivir (RDV), but not molnupiravir or nirmatrelvir, inhibited cell proliferation, DNA synthesis, and migration without affecting cell viability. RDV also stimulated an increase in heme oxygenase-1 (HO-1) expression that was not observed with molnupiravir or nirmatrelvir. The induction of HO-1 by RDV was abolished by mutating the antioxidant responsive element of the promoter, overexpressing dominant-negative NF-E2-related factor-2 (Nrf2), or treating cells with an antioxidant. Finally, silencing HO-1 partly rescued the proliferative and migratory response of RDV-treated SMCs, and this was reversed by carbon monoxide and bilirubin. In conclusion, the induction of HO-1 via the oxidant-sensitive Nrf2 signaling pathway contributes to the antiproliferative and antimigratory actions of RDV by generating carbon monoxide and bilirubin. These pleiotropic actions of RDV may prevent occlusive vascular disease in COVID-19. Full article

Purpose: Exercise is recommended for survivors of breast cancer to alleviate adverse reactions and reduce the psychological burden. In recent years, however, environmental factors (e.g., pandemics and climate change) have made it difficult to exercise outdoors. Therefore, this study focused on the COVID-19 pandemic in Japan and evaluated the relationship between changes in physical activity (PA) and mental and physical health in breast cancer survivors. Methods: A questionnaire survey was conducted among 345 outpatient female breast cancer survivors aged between 29 and 69 years. The questionnaire was based on the International Physical Activity Questionnaire, the Patient Health Questionnaire-9, the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire, and the Fear of COVID-19 Scale and included patient characteristics, changes in PA during pandemic restrictions, and needs for exercise support. The analysis categorized PA changes into two groups according to activity levels. The relationship between changes in PA and physical and mental health was evaluated using logistic regression analysis. Results: Patients with decreased PA accounted for 65.5% of the study population. Regardless of their activity level, these patients were aware of an increased susceptibility to COVID-19, showed a fear of the disease and a tendency for depression, and reported low life satisfaction and declined physical function. Of the patients who stopped exercising, 82.9% reported a decline in PA. Compared with those who had never exercised, those who stopped exercising saw their risk of depression increase by 15.6%. There was a high demand for personalized exercise support from healthcare professionals. Conclusions: Regardless of their activity level, decreasing PA during the pandemic decreased mental health and physical function in breast cancer survivors. There was a higher risk of depression among patients who stopped exercising. Because it is possible that similar situations may occur in the future, interventions by healthcare professionals must be considered in order to continue exercise. Full article

Since the onset of the COVID-19 pandemic, remarkable progress has been made in the development of antiviral therapies for SARS-CoV-2. Several direct-acting antivirals, such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir, offer clinical benefits. These agents have significantly contributed to reducing the viral loads and duration of the illness, as well as the disease’s severity and mortality. However, despite these advances, important limitations remain. The continued emergence of resistant SARS-CoV-2 variants highlights the urgent need for adaptable and durable therapeutic strategies. Therefore, this review aims to provide an updated overview of the main antiviral strategies that are used and the discovery of new drugs against SARS-CoV-2, as well as the therapeutic limitations that have shaped clinical management in recent years. The major challenges include resistance associated with viral mutations, limited treatment windows, and unequal access to treatment. Moreover, there is an ongoing need to identify novel compounds with broad-spectrum activity, improved pharmacokinetics, and suitable safety profiles. Combination treatment regimens represent a promising strategy to increase the efficacy of treating COVID-19 while minimizing the potential for resistance. Ideally, these interventions should be safe, affordable, and easy to administer, which would ensure broad global access and equitable treatment and enable control of COVID-19 cases and preparedness for future threats. Full article

Background: Emerging evidence indicates that some individuals recovering from COVID-19 develop persistent symptoms, including fatigue, pain, cognitive difficulties, and psychological distress, commonly known as Long COVID. These symptoms often overlap with those seen in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), underscoring the need for integrative, non-pharmacological interventions. This Phase II controlled trial aimed to evaluate the feasibility and preliminary efficacy of Heart Rate Variability Biofeedback (HRV-BF) in individuals with Long COVID who meet the diagnostic criteria for CFS/ME. Specific objectives included assessing feasibility indicators (drop-out rates, side effects, participant satisfaction) and changes in fatigue, depression, anxiety, pain, and health-related quality of life. Methods: Participants were assigned alternately and consecutively to the HRV-BF intervention or Treatment-as-usual (TAU), in a predefined 1:1 sequence (quasirandom assignment). The intervention consisted of 10 HRV-BF sessions, held twice weekly over 5 weeks, with each session including a 10 min respiratory preparation and 40 min of active training. Results: The overall drop-out rate was low (5.56%), and participants reported a generally high level of satisfaction. Regarding side effects, the mean total Simulator Sickness Questionnaire score was 24.31 (SD = 35.42), decreasing to 12.82 (SD = 15.24) after excluding an outlier. A significantly greater improvement in severe fatigue was observed in the experimental group (H = 4.083, p = 0.043). When considering all outcomes collectively, a tendency toward improvement was detected in the experimental group (binomial test, p < 0.0001). Conclusions: HRV-BF appears feasible and well tolerated. Findings support the need for Phase III trials to confirm its potential in mitigating fatigue in Long COVID. Full article

Various SARS-CoV-2 remdesivir resistance-associated substitutions (RAS) have been reported, but a comprehensive comparison of their resistance levels is lacking. We identified novel RAS and performed head-to-head comparisons with known RAS in Vero E6 cells. A remdesivir escape polyclonal virus exhibited a 3.6-fold increase in remdesivir EC₅₀ and mutations throughout the genome, including substitutions in nsp12 (E796D) and nsp14 (A255S). However, in reverse-genetics infectious assays, viruses harboring both these substitutions exhibited only a slight decrease in remdesivir susceptibility (1.3-fold increase in EC₅₀). The nsp12-E796D substitution did not impair viral fitness (Vero E6 cells or Syrian hamsters) and was reported in a remdesivir-treated COVID-19 patient. In replication assays, a subgenomic replicon containing nsp12-E796D+nsp14-A255S led to a 16.1-fold increase in replication under remdesivir treatment. A comparison with known RAS showed that S759A, located in the active site of nsp12, conferred the highest remdesivir resistance (106.1-fold increase in replication). Nsp12-RAS V166A/L, V792I, E796D or C799F, all adjacent to the active site, caused intermediate resistance (2.0- to 11.5-fold), whereas N198S, D484Y, or E802D, located farther from the active site, showed no resistance (≤2.0-fold). In conclusion, our classification system, correlating replication under remdesivir treatment with RAS location in nsp12, shows that most nsp12-RAS cause moderate resistance. Full article

Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context of the COVID-19 pandemic, contradictory findings from previous studies that also addressed sex differences in cerebrovascular diseases demonstrate the need for further focused research. This study aimed to evaluate the sex discrepancies in the clinical presentation of IS and its outcomes in patients admitted to Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS), Lithuania. Materials and Methods: This is a retrospective record-based single-center study. All the study patients—727 men and 1082 women—enrolled between 1 January 2020, and 27 February 2022; suffered from acute IS; and had absolute contraindications against interventional IS treatment. These patients received a conservative non-interventional IS treatment at the neurological department of the LUHS’s Kaunas Hospital. The sociodemographic data; laboratory findings; comorbidities, including COVID-19; in-hospital complications; and outcome factors were obtained from the patients’ medical records and evaluated by deploying appropriate statistical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazards regression for in-hospital lethality. Results: The mean age of IS patients was significantly higher in women compared to men (p < 0.001), as was the proportion of in-hospital deaths (19.10% and 15.36%, respectively; p < 0.05). The mean total number of in-hospital complications was again significantly higher in the group of women compared to men (p < 0.05). The prevalence of COVID-19 was higher in men compared to women (p < 0.05). COVID-19 diagnosis (HR = 1.53; p = 0.02) and acute in-hospital pulmonary complications (HR = 1.91; p = 0.008) significantly increased the risk of in-hospital lethality in men. The risk of in-hospital lethality was significantly higher in women with comorbid diabetes mellitus type 2 (DM) compared to those with comorbid isolated arterial hypertension (AH) (HR = 2.25, p = 0.007). Increased C-reactive protein elevated the risk of in-hospital lethality by more than twice in both men and women (HR = 2.46; p < 0.001 and HR = 2.28; p < 0.001, respectively). Conclusions: The following differences between men and women with IS were determined: Acute in-hospital pulmonary complications, including COVID-19, significantly increased the risk of in-hospital lethality in the male group, but not in women. However, women suffering from DM had a significantly increased risk of in-hospital lethality compared with those women IS patients with AH or chronic ischemic heart disease (IHD). Increased C-reactive protein was associated with an elevated risk of in-hospital lethality both in male and female groups. Full article

Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article

Background/Objectives: Given the heterogeneous nature of long COVID, its treatment and management remain challenging. This study aimed to investigate whether poor pre-pandemic sleep quality, its deterioration during the peak of the pandemic, and circadian preference increase the risk of long COVID symptoms. Methods: An online survey was conducted between 9 October and 12 December 2022, with 384 participants who had recovered from COVID-19 at least three months prior to data collection. Participants were categorized based on the presence of at least one long COVID symptom. Logistic regression models assessed associations between sleep-related variables and long COVID symptoms. Results: Participants with long COVID symptoms reported significantly poorer sleep quality, higher perceived stress, greater somatic and cognitive pre-sleep arousal, and elevated levels of post-traumatic stress symptoms, anxiety, depression, and aggression. Fatigue (39.8%) and memory problems (37.0%) were the most common long COVID symptoms. Sleep deterioration during the pandemic peak was reported by 34.6% of respondents. Pre-pandemic poor sleep quality, its deterioration during the pandemic, and poor sleep at the time of the survey were all significantly associated with long COVID. An extreme morning chronotype consistently predicted long COVID symptoms across all models, while an extreme evening chronotype was predictive only when accounting for sleep quality changes during the pandemic. COVID-19 frequency, severity, financial impact, and somatic pre-sleep arousal were significant predictors in all models. Conclusions: Poor sleep quality before the pandemic and its worsening during the pandemic peak are associated with a higher likelihood of long COVID symptoms. These findings underscore the need to monitor sleep health during pandemics and similar global events to help identify at-risk individuals and mitigate long-term health consequences, with important clinical and societal implications. Full article

This report presents two cases of herpes simplex keratitis recurrence after COVID-19 mRNA vaccination in patients on herpetic prophylaxis due to recurrent herpetic keratitis. A 58-year-old man with a history of a previous penetrating keratoplasty presented with blurred vision and evidence of corneal endothelitis 48 h after the first dose of the m-RNA vaccination, and a 24-year-old male student came with a dendritic ulcer 72 h post first vaccination dose. The original prophylactic treatment of 400 mg of acyclovir twice daily was increased to five times per day for a week for both patients. The grafted patient additionally received an increase in Dexamethasone 0.1% from twice daily to four times a day. Improvement was noted within two days and documented at the weekly review, during which both patients returned to their prophylactic antiviral regime without further recurrence. At the time of their second dose of vaccination, both patients followed the same regime with an increase in treatment as per the first dose of vaccination without recurrence. Our findings suggest that patients with recurrent herpetic disease receiving prophylactic treatment need close monitoring when experiencing even subtle symptoms of recurrence and may benefit from an increase in their dose to therapeutic levels during the first days after the COVID-19 mRNA vaccination. Full article