Search Results (257)

The development of severe SARS-CoV-2 pneumonia is characterized by extensive lung inflammation, which, in turn, leads to respiratory distress and a decline in blood oxygen levels. Hospital admission, along with intensive care or ventilator usage, becomes necessary because this condition leads to serious respiratory problems. This review aims to provide a comprehensive overview of the pathophysiological mechanisms, diagnostic methods, and current therapeutic options for pneumonia caused by the SARS-CoV-2 virus. The pathophysiological process of severe pneumonia due to SARS-CoV-2 infection is characterized by direct lung damage from viral replication, an excessive immune system response, inflammation, impaired gas exchange, and multi-organ failure. The coexistence of various medical conditions leads to substantial lung impairment, resulting in hypoxia and respiratory failure, which can ultimately lead to fatal outcomes. The diagnosis of severe SARS-CoV-2 pneumonia is made through a combination of clinical, radiologic, and laboratory findings. A multifaceted approach integrating antiviral therapy, corticosteroids, oxygen supplementation, ventilatory management, and immunomodulation is imperative to control inflammation and enhance clinical outcomes. Early intervention, meticulous monitoring, and personalized care are paramount for enhancing survival and mitigating complications in critically ill patients with COVID-19 pneumonia. Full article

Background and Objectives: Coronavirus Disease 2019 (COVID-19) may cause extensive multi-organ pathology, particularly in the lungs, heart, kidneys, and liver. While hypercoagulability—often signaled by elevated D-dimer—has been thoroughly investigated, the concurrent pathological findings across organs and their interrelation with distinct D-dimer levels remain incompletely characterized. This study aimed to evaluate the pathological changes observed in autopsied or deceased COVID-19 patients, focusing on the prevalence of organ-specific lesions, and to perform subgroup analyses based on three D-dimer categories. Methods: We conducted a retrospective review of 69 COVID-19 patients from a Romanian-language dataset, translating all clinical and pathological descriptions into English. Pathological findings (pulmonary microthrombi, bronchopneumonia, myocardial fibrosis, hepatic steatosis, and renal tubular necrosis) were cataloged. Patients were grouped into three categories by admission D-dimer: <500 ng/mL, 500–2000 ng/mL, and ≥2000 ng/mL. Laboratory parameters (C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and clinical outcomes (intensive care unit [ICU] admission, mechanical ventilation, and mortality) were also recorded. Intergroup comparisons were performed with chi-square tests for categorical data and one-way ANOVA or the Kruskal–Wallis test for continuous data. Results: Marked organ pathology was significantly more frequent in the highest D-dimer group (≥2000 ng/mL). Pulmonary microthrombi and bronchopneumonia increased stepwise across ascending D-dimer strata (p < 0.05). Myocardial and renal lesions similarly showed higher prevalence in patients with elevated D-dimer. Correlation analysis revealed that severe lung and heart pathologies were strongly associated with high inflammatory markers and a greater risk of ICU admission and mortality. Conclusions: Our findings underscore that COVID-19-related organ damage is magnified in patients with significantly elevated D-dimer. By integrating pathology reports with clinical and laboratory data, we highlight the prognostic role of hypercoagulability and systemic inflammation in the pathogenesis of multi-organ complications. Stratifying patients by D-dimer may inform more tailored management strategies, particularly in those at highest risk of severe pathology and adverse clinical outcomes. Full article

Background Veno-venous extracorporeal membrane oxygenation (VV-ECMO) supports critically ill patients with respiratory failure. However, ECMO may induce systemic inflammation, hemolysis, and hemodilution, potentially resulting in endothelial activation and damage. Therefore, this study explored the longitudinal changes in circulating markers of inflammation, hemolysis, and endothelial activation and damage in patients with COVID-19 on VV-ECMO. Methods Plasma was obtained before, within 48 h as well as on day 4, week 1, and week 2 of ECMO support and after decannulation. Circulating markers were measured using Luminex, ELISA, and spectrophotometry. Human pulmonary endothelial cells were exposed to patient plasma, and in vitro endothelial permeability was assessed using electric cell-substrate impedance sensing. Results From April 2020 to January 2022, plasma was collected from 14 patients (71.4% male; age 54 (45–61) years). IL-6 levels decreased (1.238 vs. 0.614 ng/mL, p = 0.039) while ICAM-1 increased (667 vs. 884 ng/mL, p = 0.003) over time when compared to pre-ECMO. Angiopoietin-1 decreased after ECMO initiation (7.57 vs. 3.58 ng/mL, p = 0.030), whereas angiopoietin-2 increased (5.20 vs. 10.19 ng/mL, p = 0.017), particularly in non-survivors of ECMO. Cell-free hemoglobin decreased directly after VV-ECMO initiation but remained stable thereafter (55.29 vs. 9.19 mg/dL, p = 0.017). Moreover, the plasma obtained at several time points during the ECMO run induced in vitro pulmonary endothelial hyperpermeability. Conclusions This exploratory study shows that patients on VV-ECMO support due to COVID-ARDS exhibit progressive endothelial activation and damage but not inflammation and hemolysis. Larger prospective studies are necessary to elucidate pathophysiological pathways leading to endothelial activation and damage, thereby reducing organ failure in these critically ill patients. Full article

Background/Objectives: Acute Fibrinous and Organizing Pneumonia (AFOP) is a rare pulmonary condition histologically characterized by intra-alveolar fibrin deposition and organizing pneumonia without hyaline membranes. This study aims to describe the clinicopathologic and radiologic features of isolated AFOP nodules presenting as solitary pulmonary nodules (SPNs) mimicking malignancy in patients with recent COVID-19 infection. Methods: We retrospectively analyzed consecutive cases of histologically confirmed AFOP (n = 20) and organizing pneumonia (OP; n = 119) presenting radiologically as SPNs suspicious for malignancy from January 2021 to December 2023. Clinical data, COVID-19 status, radiologic features (including nodular characteristics, ground-glass opacity [GGO], and consolidation), and histopathological findings were collected and analyzed. Digital image analysis quantified the intra-alveolar fibrin content. Results: AFOP nodules showed a significant association with previous COVID-19 infection compared to OP (55% vs. 0.8%, p < 0.001). Radiologically, AFOP lesions were predominantly located in the upper lobes, frequently exhibiting a mixed pattern of GGO and consolidation within solitary nodules (8–28 mm diameter), distinctly differing from the predominantly lower-lobe homogeneous consolidations in OP. Histologically, AFOP was defined by prominent intra-alveolar fibrin “balls,” correlating significantly with radiological consolidation patterns (r = 0.991, p < 0.05). Regions of consolidation demonstrated higher fibrin contents compared to areas of predominant GGO. Conclusions: Isolated AFOP nodules presenting as SPNs post-COVID-19 infection strongly mimic malignancy radiologically, highlighting the necessity for multidisciplinary diagnostic approaches integrating radiological and histopathological data to avoid unnecessary interventions. Recognition of this rare but distinctive clinical entity is essential for appropriate patient management. Full article

Acute surgical abdomen is characterized by intense, sudden abdominal pain due to intra-abdominal conditions requiring prompt surgical intervention. The coronavirus disease 2019 (COVID-19) pandemic has led to various complications related to the disease’s complex pathophysiological mechanisms, hence the hypothesis of COVID-19-induced acute abdominal surgical pathologies. The connection between acute surgical abdomen and COVID-19 involves two primary mechanisms. First, there is the presence of angiotensin-converting enzyme 2 (ACE2) receptors in multiple abdominal organs. This facilitates the cytokine storm through direct viral injury and inflammation. Second, the hypercoagulable state induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increases the thrombotic risk within abdominal vessels, which can subsequently lead to ischemia. ACE2 receptors are notably expressed in the gastric, duodenal, and rectal epithelium, with SARS-CoV-2 viral RNA and nucleocapsid proteins detected in these tissues. The inflammatory response results in significant endothelial damage, activating coagulation pathways that cause monocellular infiltration, lymphocytic inflammation, and uncontrolled coagulation. These findings highlight the need for further research to clarify how COVID-19 leads to acute abdominal pathologies. Understanding these mechanisms is vital for improving clinical management and patient outcomes during future health crises and in the aftermath of the pandemic. Full article

Puerto Rico has faced significant damage from natural disasters and the COVID-19 pandemic, disrupting clinical services and scientific research logistics. In response, the RCMI-CCRHD Program at the UPR-MSC organized a retreat with the objective of understanding the challenges faced by its research network during the pandemic and strategies to overcome them. The retreat featured presentations on COVID-19 supplemental projects and included a discussion group. Twenty attendees identified the challenges they encountered and the strategies developed through an open-ended question and a satisfaction survey, implementing a mixed-method approach. We performed a content analysis on the open-ended survey questions and used descriptive statistics for the satisfaction survey. Key challenges included remote work implementation, recruitment difficulties, and mental health concerns. Attendees shared actions taken to address these issues, such as modifying protocols for remote planning and using digital platforms for improving communication. They also recognized opportunities that arose from remote work, which allowed them to focus on publishing and adapting mental health support tools. The retreat received positive feedback, with 93.8% of attendees giving a five-star rating. By reflecting on these experiences, investigators can refine strategies and implement effective solutions. Recommendations include flexible IRB protocols, improved digital tools, community involvement, and robust emergency preparedness plans. Full article

In 2022, the World Health Organization reported that tuberculosis (TB) was the second leading cause of death globally from a single infectious agent following COVID-19. The development of new antitubercular agents with novel mechanisms of action for use in complex TB therapy is considered a key approach to combating TB. In this study, we examined the gene expression profile of M. smegmatis when exposed to a promising antituberculosis agent, quinoxaline 1,4-dioxide (QdNO) 7-chloro-2-(ethoxycarbonyl)-3-methyl-6-(piperazin-1-yl)quinoxaline-1,4-dioxide-1 (LCTA-3368). We investigated how the bacterial response changed with different minimum inhibitory concentrations (MIC) (1/4 × MIC, 1/2 × MIC, and 1 × MIC) and durations (30 min and 90 min) of treatment with the drug. Our analysis revealed significant upregulation in genes involved in DNA repair and replication processes, as well as changes in the expression of 95 genes encoding proteins with oxidoreductase activity. We additionally showed that the concentration of reactive oxygen species increases in a dose-dependent manner upon exposure of M. smegmatis to LCTA-3368. These findings support the proposed mechanism of antibacterial action of QdNOs, which is associated with the formation of free radicals leading to DNA damage. Full article

Supply chains, which have numerous participants, are exposed and vulnerable. In recent years, this has been evident in disruptions caused by circumstances that have changed the context, such as (1) the COVID-19 pandemic, (2) the Suez Canal blockade, and (3) the war in Ukraine. These circumstances caused disruptions in supply chains and surprised numerous participants in the international market, individual organizations, as well as states and entities around the world. This caused confusion and large financial losses for numerous global market participants and for people all around the world. The purpose of this paper is to design three original models, the implementation of which should significantly reduce the damage caused by disruptions in supply chains in future crises: (1) a model for individual organizations, (2) a national economy model, and (3) a global model. The authors applied methods of scientific cognition and analyzed three case studies from the recent past. The key finding is that by applying the models with four components (methods, measures, quality tools, and indicators), the resilience of supply chains increases the damage from disruptions in supply chains during future crises can be significantly reduced, and the quality of life of everyone on the planet will be less threatened. Full article

Background: The metabolome of COVID-19 patients has been studied sparsely, with most research focusing on a limited number of plasma metabolites or small cohorts. This is the first study to test saliva metabolites in COVID-19 patients in a comprehensive way, revealing patterns significantly linked to disease and severity, highlighting saliva’s potential as a non-invasive tool for pathogenesis or diagnostic studies. Methods: We included 30 asymptomatic subjects with no prior COVID-19 infection or vaccination, 102 patients with mild SARS-CoV-2 infection, and 61 hospitalized patients with confirmed SARS-CoV-2 status. Saliva samples were analyzed using hydrophilic interaction liquid chromatography–mass spectrometry (HILIC-MS/MS) in positive and negative ionization modes. Results: Significant differences in metabolites were identified in COVID-19 patients, with distinct patterns associated with disease severity. Dipeptides such as Val-Glu and Met-Gln were highly elevated in moderate cases, suggesting specific protease activity related to SARS-CoV-2. Acetylated amino acids like N-acetylserine and N-acetylhistidine increased in severe cases. Bacterial metabolites, including muramic acid and indole-3-carboxaldehyde, were higher in mild–moderate cases, indicating that oral microbiota differs according to disease severity. In severe cases, polyamines and organ-damage-related metabolites, such as N-acetylspermine and 3-methylcytidine, were significantly increased. Interestingly, most metabolites that were reduced in moderate cases were elevated in severe cases. Conclusions: Saliva metabolomics offers insightful information that is potentially useful in studying COVID-19 severity and for diagnosis. Full article

This review explores the crucial role of established and emerging biomarkers in the diagnosis, management, and understanding of post-COVID-19 conditions. With COVID-19 affecting multiple organ systems, biomarkers have been instrumental in identifying ongoing inflammation and tissue damage, facilitating early diagnosis and prognostication. Specifically, markers like C-reactive protein (CRP), interleukin-6 (IL-6), and novel entities such as soluble urokinase plasminogen activator receptor (suPAR) and neutrophil extracellular traps (NETs) provide insights into the pathophysiological mechanisms and predict long-term outcomes. This review highlights the integration of these biomarkers into clinical workflows and their implications for personalized medicine, emphasizing their potential in guiding therapeutic interventions and monitoring recovery. Future directions suggest a focus on longitudinal studies to explore biomarker trajectories and their interaction with therapeutic outcomes, aiming to enhance the management of post-COVID-19 conditions and refine public health strategies. Full article

Background/Objectives: The rapid viral spread observed in coronavirus disease 2019 (COVID-19) is capable of inducing the secretion of excessive inflammatory cytokines. The resulting multi-organ damage is a severe complication that can be attenuated through adequate nutrition. Formulae enhanced with either glutamine or arginine are conditionally essential amino acids that have been proven to improve the condition of hospitalized patients. This retrospective study aimed to investigate the effects of administering an immune-enhancing enteral formula enhanced with arginine and glutamine on the clinical signs and biomarkers of patients with severe COVID-19. Methods: After checking the data of 232 patients enrolled in the biobank for completeness and eligibility, 31 patients with severe COVID-19 in the intensive care unit at Taipei Tzu Chi Hospital were grouped based on the type of enteral formula used: 16 patients received the control formula, and 15 patients received the immune-enhancing formula. Baseline characteristics, clinical signs, and inflammatory markers were analyzed for differences. Results: An increase in IL-10 levels in the intervention group was observed (p = 0.048). Changes in other inflammatory cytokine levels were insignificant. Conclusions: Providing an enteral formula enriched with glutamine and arginine to severe COVID-19 patients may help improve their anti-inflammatory marker levels. Further interventional study utilizing enteral formula enriched with glutamine and arginine is needed to confirm the findings of this study. Full article

The SARS-CoV-2 outbreak has resulted in a considerable number of deaths worldwide. The virus damages the pulmonary artery endothelium, leading to a condition known as microvascular pulmonary inflammatory thrombotic syndrome (MPITS), which can be fatal and cause multiple organ failure. The presence of preexisting comorbidities has been shown to significantly impact the severity and prognosis of patients with SARS-CoV-2 infection. The objective of this study was to compare the age groups of patients with coronavirus disease 2019 (COVID-19) and to identify the prevalence of comorbidities associated with death and survival in an area of southern Italy. The data set consisted of 1985 patients with confirmed cases of SARS-CoV-2 infection who were admitted to the A.O.U. San Giovanni di Dio e Ruggi d’Aragona Hospital in Salerno between January 2021 and December 2022. The results were presented for the overall population and stratified by outcome and age group. All analyses were performed using the XLSTAT (Lumivero, 2024, Paris, France) and STATA software (release 16.1, StataCorp LLG, College Station, TX, USA, 2019) packages. In the study, population, 636 cases (32%) resulted in death, with a higher prevalence in the 60–79 age group, followed by the ≥80 and 30–59 age groups. The most prevalent diseases among deceased and surviving patients with confirmed cases of SARS-CoV-2 infection were those affecting the circulatory system (61.5% vs. 55.5%), the respiratory system (55.8% vs. 26.2%), and the metabolic system (25.9% vs. 25.4%). In patients aged 30–79, respiratory diseases were the primary cause of mortality, whereas in those aged ≥80, circulatory system diseases were more prevalent. Among survivors, cardiovascular diseases were the most common comorbidities across all age groups, followed by respiratory diseases and endocrine, metabolic, and immune disorders. Moreover, these comorbidities were associated with an elevated risk of mortality. The study emphasizes the substantial influence of age and comorbidities on the mortality associated with SARS-CoV-2 infection. These findings highlight the necessity for targeted interventions to manage comorbid conditions in patients with SARS-CoV-2 infection, particularly in older adults. Full article

Discovered in late 2019, the SARS-CoV-2 coronavirus has caused the largest pandemic of the 21st century, claiming more than seven million lives. In most cases, the COVID-19 disease caused by the SARS-CoV-2 virus is relatively mild and affects only the upper respiratory tract; it most often manifests itself with fever, chills, cough, and sore throat, but also has less-common mild symptoms. In most cases, patients do not require hospitalization, and fully recover. However, in some cases, infection with the SARS-CoV-2 virus leads to the development of a severe form of COVID-19, which is characterized by the development of life-threatening complications affecting not only the lungs, but also other organs and systems. In particular, various forms of thrombotic complications are common among patients with a severe form of COVID-19. The mechanisms for the development of thrombotic complications in COVID-19 remain unclear. Accumulated data indicate that the pathogenesis of severe COVID-19 is based on disruptions in the functioning of various innate immune systems. The key role in the primary response to a viral infection is assigned to two systems. These are the pattern recognition receptors, primarily members of the toll-like receptor (TLR) family, and the complement system. Both systems are the first to engage in the fight against the virus and launch a whole range of mechanisms aimed at its rapid elimination. Normally, their joint activity leads to the destruction of the pathogen and recovery. However, disruptions in the functioning of these innate immune systems in COVID-19 can cause the development of an excessive inflammatory response that is dangerous for the body. In turn, excessive inflammation entails activation of and damage to the vascular endothelium, as well as the development of the hypercoagulable state observed in patients seriously ill with COVID-19. Activation of the endothelium and hypercoagulation lead to the development of thrombosis and, as a result, damage to organs and tissues. Immune-mediated thrombotic complications are termed “immunothrombosis”. In this review, we discuss in detail the features of immunothrombosis associated with SARS-CoV-2 infection and its potential underlying mechanisms. Full article

Objectives: Currently available research data points to COVID-19-related multi-organ system damage. This study aims to evaluate the impact of SARS-CoV-2 on the reproductive health, that is, plasma levels of FSH, LH, estradiol, AMH, and antral follicular count, of women undergoing level II ART techniques. Methods: This is a multicenter, prospective, and observational study by the reproductive medicine centers of Palermo’s Ospedali Riuniti Villa Sofia-Cervello Hospital and Vanvitelli University. From September 2022 to March 2024, 203 patients aged 24–43 were enrolled, all with diagnosed infertility and a history of SARS-CoV-2 infection. Symptomatic women, patients testing positive for HIV or other liver viruses, and patients with a history of ovarian cancer or who had taken gonadotoxic drugs were excluded. Plasma measurements of FSH, LH, estradiol, AMH, and antral follicular count were performed before and after infection. Results: The analysis accounting for the concentration of anti-Müllerian hormone (AMH) before and after COVID-19 infection shows an average concentration decrease from 1.33 ng/mL before SARS-CoV-2 infection to 0.97 ng/mL after infection. Average decrease after infection was −27.4%; average reduction of 1 follicle (95% CI: from −0.74 to −1.33) was reported following SARS-CoV-2 infection. Levels of E2 before and after SARS-CoV-2 infection did not vary significantly. Average FSH and LH levels before and after SARS-CoV-2 infection pointed to an increase. Conclusions: SARS-CoV-2 infection damages female reproductive health, causing significant reductions in AMH (−27.4%) and AFC (−1 antral follicle) values and an increase in FSH (+13.6%) and LH (+13.4%) values. No effect on E2 levels was reported. The pandemic has also affected the ability of infertile patients to access ART procedures, and that calls for a novel, updated blueprint designed to enhance our preparedness in the event that similar circumstances should occur again. Full article

Physiotherapy plays a crucial role in the rehabilitation of damaged or defective organs due to injuries or illnesses, often requiring long-term supervision by a physiotherapist in clinical settings or at home. AI-based support systems have been developed to enhance the precision and effectiveness of physiotherapy, particularly during the COVID-19 pandemic. These systems, which include game-based or tele-rehabilitation monitoring using camera-based optical systems like Vicon and Microsoft Kinect, face challenges such as privacy concerns, occlusion, and sensitivity to environmental light. Non-optical sensor alternatives, such as Inertial Movement Units (IMUs), Wi-Fi, ultrasound sensors, and ultrawide band (UWB) radar, have emerged to address these issues. Although IMUs are portable and cost-effective, they suffer from disadvantages like drift over time, limited range, and susceptibility to magnetic interference. In this study, a single UWB radar was utilized to recognize five therapeutic exercises related to the upper limb, performed by 34 male volunteers in a real environment. A novel feature fusion approach was developed to extract distinguishing features for these exercises. Various machine learning methods were applied, with the EnsembleRRGraBoost ensemble method achieving the highest recognition accuracy of 99.45%. The performance of the EnsembleRRGraBoost model was further validated using five-fold cross-validation, maintaining its high accuracy. Full article