Search Results (4,989)

Although persistent neurological sequelae in long COVID are reportedly well associated with neuroinflammation, the underlying regulatory mechanisms remain poorly characterized. Previously, we identified dysregulated microRNA expression, including let-7a-5p, in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike S1-stimulated human microglial cells by RNA sequencing; however, how let-7a-5p regulates the S1-mediated neuroinflammatory processes remains undetermined. In the present study, we examined the functional role of let-7a-5p in alleviating S1-induced microglial inflammation in the CHME3 cell line as well as in human monocyte-derived microglia (MDMi) using a loss- and gain-of-function approach. Functional inhibition of let-7a-5p resulted in mitigating S1-induced inflammatory cytokine release and markers of pyroptosis. Mechanistically, we established SHIP-1 as a direct target of let-7a-5p using luciferase reporter assay validation. Interestingly, we noted upregulated expression of the TLR3 gene alongside TLR2/4 in S1-stimulated microglia. Although we could not establish exactly how TLR3 is stimulated in S1-induced neuroinflammatory processes, using siRNA-mediated inhibition and a pharmacological inhibitor in both CHME3 cells and MDMi, our study certainly provides evidence of TLR3 involvement during S1-induced microglial inflammation, which needs further investigation. Together, these in vitro findings demonstrate that the let-7a-5p/SHIP-1 axis regulates S1-induced inflammatory cascades in CHME3 and MDMi cells, providing mechanistic insight into its role in SARS-CoV-2-associated neuroinflammation and warranting further validation in appropriate in vivo/organoid models. Full article

Coronaviruses comprise a diverse group of enveloped, positive-sense single-stranded RNA viruses capable of causing high morbidity in humans and livestock. The repeated emergence of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 underscores the critical need for broad-spectrum countermeasures. Mounting evidence demonstrates that successful coronavirus infection depends on the manipulation of host cellular pathways governing translation, metabolism, autophagy, and survival. The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that functions via the mammalian target of rapamycin complex 1 (mTORC1) and complex 2 (mTORC2) to integrate extracellular and intracellular signals. Rather than remaining passive metabolic bystanders, coronaviruses actively exploit and rewrite host PI3K/Akt/mTOR networks to facilitate structural translation, assemble double-membrane replication organelles, suppress autophagic clearance, and reprogram protective innate and adaptive immune landscapes. This review provides a comprehensive synthesis of the molecular mechanisms dictating coronavirus–mTOR interactions across human pathogens and high-impact veterinary models. We detail the clinical consequences of dysregulated mTOR signaling—including immunometabolic perturbations, long-term metabolic memory, and tissue-specific complications—and evaluate the therapeutic potential of allosteric rapalogs, dual ATP-competitive inhibitors, and natural compounds as host-directed platforms designed to complement conventional antiviral regimens and enhance global pandemic preparedness. Full article

Background: This study aims to characterise the clinical and radiological features of Posterior reversible encephalopathy syndrome (PRES) in the context of multisystem inflammatory syndrome in children (MIS-C), consolidating reported cases to aid clinicians in diagnosis, management, and future research. Methods: A systematic review was conducted, adhering to PRISMA guidelines and registered under PROSPERO (CRD420251011869). Four academic databases and grey literature sources were searched up to April 2025. Inclusion criteria were cases with confirmed MIS-C and a diagnosis of PRES supported by compatible clinical and radiological findings or reported by the original investigators when detailed imaging information was unavailable. Results: Sixteen studies encompassing sixteen pediatric cases were identified. The majority were female, with a median age of 9 years. Among patients with available data, hypertension was reported in 8 cases, seizures in 9 cases, and visual disturbances in 4 cases. MRI findings predominantly showed cortical-subcortical hyperintensities in the parieto-occipital, posterior temporal, and frontal lobes. CT was frequently normal. Radiological regression was observed in most follow-up MRIs. Reported management was heterogeneous and variably described, including treatment of hypertension and seizures when present, alongside treatment of MIS-C and other potential precipitating conditions. Favourable clinical outcomes were reported in the published cases in which outcome information was available, with a median length of hospital stay of 26 days (range: 8–45 days). PRES is a rare but clinically important neurological condition reported in children with MIS-C. MRI remains the imaging modality of choice due to its sensitivity in detecting characteristic vasogenic edema, which is often missed on CT. Conclusions: PRES has been reported in a small number of children with MIS-C, but the available evidence is heterogeneous and subject to substantial diagnostic, selection, and publication biases. The relationship between MIS-C and PRES and the prognosis of affected patients still remain to be further elucidated. Full article

Background: Seasonal influenza is typically a self-limiting illness in healthy young adults, but severe and potentially life-threatening complications can occur. Influenza A infection may predispose patients to secondary bacterial infections, including Staphylococcus aureus pneumonia and bacteremia, which can rapidly progress to necrotizing pneumonia, acute respiratory distress syndrome (ARDS), and cardiovascular dysfunction. Case Presentation: We report the case of a young adult with influenza A(H3) infection complicated by Staphylococcus aureus bacteremia, necrotizing pneumonia, ARDS, and biventricular dysfunction. The patient experienced rapid cardiopulmonary deterioration requiring advanced critical care support, including extracorporeal membrane oxygenation (ECMO) and left ventricular unloading. Serial point-of-care ultrasound (POCUS) was central to clinical management, enabling early recognition of worsening respiratory and cardiac function and guiding timely escalation of supportive strategies. Conclusions: This case highlights the potential severity of influenza-associated complications even in young and previously healthy individuals. Repeated POCUS assessment can play a pivotal role in detecting rapid cardiopulmonary deterioration and guiding advanced interventions. Efficient hub-and-spoke organization may further support timely referral and management of critically ill patients requiring ECMO and specialized care. Full article

Background: Pediatric inflammatory multisystem syndrome (PIMS), also referred to as multisystem inflammatory syndrome in children (MIS-C), is a rare but serious post-infectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection characterized by systemic hyperinflammation and multiorgan involvement. New-onset neurological and psychiatric symptoms have emerged as critical clinical features, occurring in approximately 12–27% of pediatric patients aged 2–15 years (median age, 10 years) and often indicating a more severe disease course. This narrative review aims to provide a comprehensive overview of the current literature regarding the neurological and psychiatric manifestations of PIMS/MIS-C, focusing on epidemiology, pathophysiology, clinical presentation, neuroimaging findings, biomarkers, treatment strategies, and outcomes. Methods: A narrative literature review was conducted to synthesize current evidence on the neurological and psychiatric spectrum of PIMS/MIS-C. Evaluated parameters included clinical presentations ranging from common symptoms (such as headache, encephalopathy, altered mental status, and seizures) to rare complications (such as ischemic stroke, acute disseminated encephalomyelitis, Guillain–Barré syndrome, and cerebral edema), alongside associated psychiatric disturbances, diagnostic findings, and therapeutic approaches. Results: Neurological and psychiatric manifestations significantly impact the clinical trajectory of PIMS/MIS-C. Acute symptoms include headache, encephalopathy, seizures, and psychiatric disturbances like behavioral changes, hallucinations, delirium, anxiety, and sleep disorders. Neuroimaging in many cases reveals reversible lesions of the splenium of the corpus callosum, while electroencephalography typically demonstrates diffuse slowing consistent with encephalopathy. Early recognition and prompt administration of immunomodulatory therapy—primarily intravenous immunoglobulin and corticosteroids—correlate with favorable neurological recovery in the majority of patients. However, current evidence remains largely observational and heterogeneous, precluding definitive causal conclusions regarding this treatment–outcome relationship. Affected children more frequently require intensive care unit admission and remain at risk for persistent cognitive, behavioral, and psychiatric sequelae. Conclusions: Neurological and psychiatric complications in PIMS/MIS-C are clinically significant indicators of disease severity that require vigilant monitoring and early immunomodulatory intervention. Continued multidisciplinary follow-up and prospective studies are essential to elucidate the long-term neurodevelopmental and psychiatric consequences and to optimize therapeutic strategies for these patients. Full article

Acute liver injury (ALI) is a severe clinical syndrome characterized by systemic inflammation and mitochondrial oxidative stress. This study investigated the hepatoprotective effects of paeonol (PA) in LPS/D-GalN-induced ALI and explored the potential involvement of macrophage mitochondrial function and NDUFS7. Proteomic analysis showed that the expression of mitochondrial respiratory chain-related proteins was suppressed in the liver of ALI mice, while PA treatment was associated with increased expression of several of these proteins. Integrated metabolomic analysis further indicated that PA modulated metabolites associated with energy metabolism and redox processes. In vitro experiments suggested that inflammatory RAW264.7 macrophages contributed to hepatocyte injury, whereas PA attenuated inflammatory responses and reduced macrophage-mediated injury to AML12 cells. In RAW264.7 cells, PA attenuated ROS accumulation and modulated multiple mitochondrial functional parameters, including mitochondrial membrane potential, ATP levels, the NAD⁺/NADH ratio, and complex I activity. Metabolic studies in human liver microsomes and primary human hepatocytes identified three major PA glucuronide metabolite products with five possible structural assignments. Molecular docking and microscale thermophoresis further indicated that several proposed PA metabolite structures exhibited more favorable predicted interactions and stronger binding to recombinant NDUFS7 than the parent PA. Collectively, these findings support the hepatoprotective effects of PA and its modulation of macrophage mitochondrial function, as well as the potential involvement of PA metabolites and NDUFS7, while further functional validation is required to establish their causal roles. Full article

Background/Objectives: Severe acute respiratory syndrome (SARS) remains an important cause of hospitalization and mortality, particularly among vulnerable populations. Understanding the factors associated with previous hospitalization may support more effective prevention and vaccination strategies. This study aimed to analyze the epidemiological profile of previous hospitalization among patients with SARS in the state of Pernambuco, Brazil. Methods: A quantitative, retrospective, cross-sectional study was conducted using data from the Influenza Epidemiological Surveillance System (SIVEP-Gripe), including 79,852 adult patients (≥18 years) notified with SARS in Pernambuco between 2021 and 2024. Sociodemographic, clinical, and vaccination-related variables were analyzed to identify factors associated with previous hospitalization. Results: The prevalence of previous hospital admission (readmission history) was 6.6%. Patients with previous hospitalization had a significantly higher median age compared to those without previous hospitalization (66 vs. 63 years; p < 0.001). The prevalence of previous hospitalization was higher among individuals with chronic comorbidities, particularly hematologic diseases (prevalence ratio [PR] = 1.95; 95% confidence interval [CI]: 1.51–2.51; p < 0.001) and asthma (PR = 1.67; 95% CI: 1.42–1.96; p < 0.001). Influenza vaccination was associated with a lower prevalence of previous SARS hospitalization (PR = 1.29; 95% CI: 1.03–1.61; p = 0.023). In contrast, COVID-19 vaccination status showed no significant association with previous hospitalization. A history of previous SARS hospitalization was associated with a higher prevalence of death in subsequent hospitalizations (PR = 1.09; 95% CI: 1.01–1.18; p = 0.022). Conclusions: Older adults and individuals with chronic comorbidities showed a higher prevalence of previous SARS hospitalization in Pernambuco. The findings show an association between influenza vaccination and a lower prevalence of previous SARS hospitalization and highlight the importance of post-discharge follow-up and epidemiological surveillance. Full article

Acute respiratory distress syndrome (ARDS) represents a major cause of morbidity and mortality in critically ill patients and is most frequently triggered by severe respiratory infections, including nosocomial pneumonia. Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) are highly prevalent in intensive care units and share overlapping pathophysiological mechanisms with ARDS. Despite this close interrelationship, the proportion of patients with nosocomial pneumonia who subsequently develop ARDS remains poorly defined, underscoring the need to identify potential predisposing factors and improve early recognition of patients at risk. While the development of pneumonia in patients with an established diagnosis of ARDS has been extensively investigated, limited data are available on patients who develop ARDS as a complication of HAP/VAP. This narrative review summarizes the limited direct evidence on this topic and discusses potential clinical characteristics, risk factors, and predictive tools, while considering indirect evidence from CAP and broader ARDS populations. Full article

Viral infections are a widely recognized cause of mortality. Recently it has been demonstrated that vitamin D plays an important immuno-modulatory role in both innate and adaptive immune responses against infections, by reducing excessive inflammation and enhancing defense mechanisms. Specifically, exacerbation of infections may cause sepsis, characterized by a dysregulated immune response with hyperinflammation and immune exhaustion. Vitamin D can modulate these processes through various mechanisms, such as enhancing antiviral protection, promoting anti-inflammatory responses, protecting endothelial barriers, and modulating T-cells. This has been demonstrated for various viral infections, including influenza viruses, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus. Although vitamin D deficiency has been associated with increased susceptibility to viral infections and immune cells of infected patients are highly responsive to vitamin D, the clinical benefits of its supplementation to vitamin D-deficient infected individuals are uncertain and, most importantly, direct evidence linking vitamin D to viral sepsis specifically remains particularly limited, with most mechanistic inference extrapolated from non-septic viral infection and bacterial sepsis literature. Based on these assumptions, this review will outline the present understanding about vitamin D regulatory effects on immune system and the possible connection between its serum levels and viral infections, while also addressing controversial issues. Full article

Introduction: Cognitive dysfunction (“brain fog”) is a common manifestation of post-acute COVID-19 syndrome (PACS) and may persist long after the acute infection. While cross-sectional studies have described cognitive deficits, longitudinal evidence on recovery trajectories remains limited. Methods: We conducted a longitudinal observational study of neurocognitive performance and neuropsychiatric symptoms in patients with PACS. Participants underwent assessment with 20 standardized tests covering five cognitive domains (memory, attention, language, executive functions, psychomotor processing speed); anxiety, depression, and sleep quality were assessed at three time points. Changes were analysed using the Friedman test. Results: Forty-two patients were included (median age 57 years; 35.7% female) from a predominantly hospitalized cohort (81% hospitalised; 66.7% requiring respiratory support). Patients who completed all three assessments (completers, n = 42) were compared with those who attended the first evaluation but did not complete follow-up (non-completers, n = 544); completers were more severely ill during the acute phase rather than healthier or more motivated. At the group level, statistically significant improvements over time were observed across the whole sample in verbal short-term learning, visuospatial memory, working memory, constructional praxis, phonological verbal fluency, and psychomotor processing speed (all p ≤ 0.05); after Benjamini–Hochberg adjustment across the twenty cognitive outcomes, visuospatial span forward and backward and psychomotor processing speed remained significant (all FDR-adjusted p ≤ 0.013), with the change confined to the first six months. Sleep quality also improved (p < 0.0001). Conclusion: In this cohort, group-level performance improved in six of the twenty tests administered, of which three remained significant after correction for multiple comparisons, while 28 of 42 patients (66.7%) still scored in the impaired range on at least one test at 12 months, and 17 (40.5%) on two or more. These findings highlight the importance of long-term neuropsychological monitoring and integrated cognitive-psychiatric evaluation in post-COVID care. Given the small, predominantly hospitalized sample, improvements should be interpreted cautiously and confirmed in larger controlled studies, although the use of alternate forms for part of the battery makes task-specific learning an incomplete explanation. Full article

Background: Severe COPD–OSA overlap syndrome remains challenging to manage, and existing approaches rarely combine guideline-directed OSA therapy with sustained pulmonary rehabilitation, leaving patients vulnerable to recurrent acute exacerbations. Case Presentation: A 71-year-old male with severe overlap syndrome had been hospitalized three times for hypercapnic encephalopathy requiring invasive ventilation. Following admission in 2021, we implemented a four-year, three-stage closed-loop rehabilitation program combined with multimodal OSA management guided by the American Academy of Sleep Medicine (AASM) and 2023 GOLD recommendations. The program included personalized BiPAP titration, quarterly pressure adjustments, positional therapy, and targeted weight control. Management and Outcomes: Over four years of follow-up, this combined approach improved arterial blood gas values and exercise tolerance and markedly improved sleep-disordered breathing parameters, with no readmissions for respiratory failure. Conclusions: Guideline-conformant multimodal OSA therapy combined with staged closed-loop respiratory rehabilitation may offer an effective long-term strategy for severe overlap syndrome. However, as the findings of a single case report are hypothesis-generating, they require validation in larger prospective studies. Full article

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

Airborne viruses are a key driver of infectious disease transmission, highlighting the importance of reliable detection in public health surveillance. As atmospheric viral concentrations are very low, a sampler with a high viral collection efficiency is essential. Although multiple approaches for evaluating collection efficiency have been applied using various samplers, no standardized sampler has yet been developed. We previously developed a wet-type electrostatic precipitator (WT-ESP) and successfully collected severe acute respiratory syndrome coronavirus 2 from the public environment. However, its efficiency for quantitative collection of airborne viruses remains unclear. This study aimed to clarify the collection efficiency of the WT-ESP. We evaluated collection efficiency via two different approaches: direct spray, where virus-containing aerosols were sprayed directly into the WT-ESP inlet, and indirect spray, where aerosols were dispersed into a closed space and then collected using the sampler. The direct spray tests achieved 20.1–50.2% collection efficiency, whereas the indirect spray test achieved an efficiency <12%. These findings highlight that electrostatic precipitation has an advantage of enhancing collection efficiency compared with values reported for impingers in previous studies and provide preliminary insights into the collection efficiencies under direct and indirect spray conditions, providing foundational data that bridge the gap between both methods. Full article

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

Background/Objectives: Mechanical power (MP) quantifies the energy delivered to the respiratory system during ventilation and serves as a promising marker for ventilator-induced lung injury (VILI). According to its original definition by Gattinoni, MP reflects the energy transferred from the ventilator to the respiratory system under conditions of deep sedation, passive breathing, neuromuscular blockade, and volume-controlled ventilation. Its role in coronavirus disease 2019 (COVID-19)-associated acute respiratory distress syndrome (ARDS) remains under investigation. This systematic review aimed to synthesize the available evidence on the association between MP and VILI, complications related to mechanical ventilation (MV), and mortality in adult patients with COVID-19 undergoing invasive mechanical ventilation (IMV). Methods: A systematic review was conducted using PubMed-MEDLINE (Medical Literature Analysis and Retrieval System Online) for studies published in recent years, focusing on adult COVID-19 patients undergoing IMV. Inclusion criteria centered on studies reporting MP and its association with VILI, complications, or mortality. Ten studies met eligibility criteria after screening 356 retrieved articles. Results: Most included studies were retrospective and observational, encompassing critically ill COVID-19 patients. Elevated MP was correlated with more severe outcomes, including increased 28-day mortality, prolonged MV, and weaning failure. Franck et al. demonstrated strong correlations between MP and driving pressure, elastance, and positive end-expiratory pressure, emphasizing the importance of calculation methods. González-Castro et al. identified a threshold of 17 J/min, above which mortality risk increased. Stalla et al. highlighted that dynamic MP reductions during prone positioning were associated with survival. Registry-based analyses confirmed that both magnitude and cumulative exposure above 18 J/min increased intensive care unit mortality. Novel indices combining MP with oxygenation parameters improved prognostic accuracy. While absolute MP at initiation provided limited predictive value, temporal trends and individual components were strongly linked to VILI. Conclusions: Higher MP has been associated with adverse clinical outcomes in patients with COVID-19 receiving invasive mechanical ventilation, supporting its potential role as a prognostic indicator. Its dynamic assessment, thresholds, and integration with ventilatory strategies such as prone positioning enhance risk stratification and may guide individualized, lung-protective ventilation. Continuous monitoring and standardized calculation are recommended to optimize clinical decision-making. Full article