Search Results (2,551)

People with C3 Dense Deposit Disease (C3DDD), a rare autoimmune disease, often also have ocular complications. Due to the rarity of this disease, there is little known about ocular complications in populations across the world. This paper aimed to assess literature on retinal complications in people with C3 Dense Deposit Disease. A scoping review was conducted and three databases (Embase, Medline All, and Web of Science) were searched using agreed search terms and Boolean operators. All references were imported into Covidence for screening by two reviewers. Any conflicts were resolved by a third reviewer. Data were extracted into an Excel spreadsheet and analysis was conducted using SPSS Version 29. After full text screening, 38 studies were included in the review. These studies were from 1990–2023 and most (67%) being case reports. All studies were conducted in the United States (55%) or Europe (45%). Most studies reported drusen-like deposits in the retina (75%) and retinal pigment epithelial detachment (18%) and macular atrophy (11%). Choroidal Neovascularisation (CNV) was found in 16% of cases. People with C3 Dense Deposit Disease are at risk of ocular complications, primarily drusen-like deposits. Further population-based research and progression is needed. Full article

Background/Objectives: Saliva as a diagnostic medium for COVID-19 requires fewer resources to collect and is more readily adopted across a range of testers. Our study compared an Emergency Use Authorized direct saliva-to-RT-qPCR test against an FDA-authorized nasal swab RT-qPCR assay for participants who reported symptoms of respiratory infection. Methods: We analyzed 737 symptomatic participants who self-selected to test at either a community testing facility or a walk-in clinic due to respiratory symptoms and provided matched saliva and nasal swab samples. Samples were collected between March and September of 2023, both before and after the declared end of the public health emergency. Results: A total of 120 participants tested positive in at least one of the tests. For participants testing in the first 5 days of reported symptoms, the saliva test had a 94.0 positive percent agreement (PPA; 95% C.I. 88.9–99.1%) with the nasal test and a 99.0 negative percent agreement (NPA; 95% C.I. 98.1–99.9%). The viral load decreased beyond day 1 of reported symptoms for saliva testing. Viral load increased up to day 4 for nasal swabs and then decreased. The same number of discordant positive samples (five each) occurred for both tests within 5 days of symptoms onset. Conclusions: In the endemic phase of COVID-19 and for development of new tests, testing methods that are less invasive are more likely to be adopted. The results of saliva-based versus nasal swab PCR measurements relative to days of symptom onset are needed to optimize future testing strategies. Full article

Background: COVID-19-associated coagulopathy (CAC) is a complex condition, with high rates of thrombosis, high levels of inflammation markers and hypercoagulation (increased levels of fibrinogen and D-Dimer), as well as extensive microthrombosis in the lungs and other organs of the deceased. It resembles, without being identical, other coagulation disorders such as sepsis-DIC (SIC/DIC), hemophagocyte syndrome (HPS) and thrombotic microangiopathy (TMA). Platelets (PLTs), key regulators of thrombosis, inflammation and immunity, are considered an important risk mediator in COVID-19 pathogenesis. Platelet index MPV/PLT ratio is reported in the literature as more specific in the prognosis of platelet-related systemic thrombogenicity. Studies of MPV/PLT ratio with regards to the severity of COVID-19 disease are limited, and there are no references regarding this ratio to the outcome of COVID-19 disease at specific time points of hospitalization. The aim of this study is to evaluate the relationship of COVID-19 mortality with the red cell distribution width–coefficient of variation (RDW-CV), platelets and MPV/PLT ratio parameters. Methods: Values of these parameters in 511 COVID-19 hospitalized patients were recorded (a) on admission, (b) as mean values of the 1st and 2nd week of hospitalization, (c) over the total duration of hospitalization, (d) as nadir and zenith values, and (e) at discharge. Results: As for mortality (survivors vs. deceased), statistical analysis with ROC curves showed that regarding the values of the parameters on admission, only the RDW-CV baseline was of prognostic value. Platelet parameters, absolute number and MPV/PLT ratio had predictive potential for the disease outcome only as 2nd week values. On the contrary, with regards to disease severity (mild/moderate versus severe/critical), only the MPV/PLT ratio on admission can be used for prognosis, and to a moderate degree. On multivariable logistic regression analysis, only the RDW-CV mean hospitalization value (RDW-CV mean) was an independent and prognostic variable for mortality. Regarding disease severity, the MPV/PLT ratio on admission and RDW-CV mean were independent and prognostic variables. Conclusions: RDW-CV, platelets and MPV/PLT ratio hematological parameters could be of predictive value for mortality and severity in COVID-19 disease, depending on the hospitalization timeline. 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: Heart rate variability (HRV) has been widely investigated as a predictor of disease and mortality across diverse patient populations; however, there remains no consensus on the optimal set or combination of time and frequency domain nor on nonlinear features for reliable prediction across clinical contexts. Given the relevance of the COVID-19 pandemic and the unique clinical profiles of these patients, this retrospective observational study explored the potential of HRV analysis for early prediction of in-hospital mortality using ECG signals recorded during the initial moments of ICU admission in COVID-19 patients. Methods: HRV indices were extracted from four ECG leads (I, II, III, and aVF) using sliding windows of 2, 5, and 7 min across observation intervals of 15, 30, and 60 min. The raw data posed significant challenges in terms of structure, synchronization, and signal quality; thus, from an original set of 381 records from 321 patients, after data pre-processing steps, a final dataset of 82 patients was selected for analysis. To manage data complexity and evaluate predictive performance, two feature selection methods, four feature reduction techniques, and five classification models were applied to identify the optimal approach. Results: Among the feature aggregation methods, compiling feature means across patient windows (Method D) yielded the best results, particularly for longer observation intervals (e.g., using LDA, the best AUC of $0.82\pm 0.13$ was obtained with Method D versus $0.63\pm 0.09$ with Method C using 5 min windows). Linear Discriminant Analysis (LDA) was the most consistent classification algorithm, demonstrating robust performance across various time windows and further improvement with dimensionality reduction. Although Gradient Boosting and Random Forest also achieved high AUCs and F1-scores, their performance outcomes varied across time intervals. Conclusions: These findings support the feasibility and clinical relevance of using short-term HRV as a noninvasive, data-driven tool for early risk stratification in critical care, potentially guiding timely therapeutic decisions in high-risk ICU patients and thereby reducing in-hospital mortality. Full article

This study included 221 patients with COVID-19 who were admitted to the emergency department of Avicenne Hospital in Rabat between August 2020 and August 2021. Patients were divided into three groups according to their D-dimer levels (<1, 1–2, and >2 µg/mL). Adjusted and unadjusted logistic regression analyses were performed to assess the association between elevated D-dimer levels and in-hospital mortality. Pearson’s correlation analysis was performed to explore the relationship between D-dimer levels and various biological and clinical parameters. The results revealed a statistically significant difference in the mean (SD) age among the three groups (p = 0.006). Analysis showed a statistically significant difference in the means (SD) of oxygen saturation, duration of hospital stay, and breathing rate among the three independent groups of COVID-19 patients. Patients with elevated D-dimer levels (greater than 2 µg/mL) experienced worse outcomes than those in the other groups, with severity, transfer to intensive care, and in-hospital mortality of 55 (40.7%), 35 (16%), and 24 (11%) patients, respectively, with p-values of 0.048, 0.002, and 0.002, respectively. Patients in the D-dimer > 2 µg/mL group had significantly higher C-reactive protein (CRP), lactate dehydrogenase, urea, cardiac troponin, B-type natriuretic peptide, and ferritin levels than those in the other two groups. The p-value was significant among the three groups (p = 0.044, p = 0.001, and p < 0.001). Age and elevated D-dimer levels (greater than 2 µg/mL) were associated with mortality in patients diagnosed with COVID-19. Correlation analysis indicated that D-dimer in COVID-19 patients is associated with worsening respiratory, hepatic, cardiac, and coagulation parameters, suggesting their utility as an integrative marker of disease severity. D-dimer levels > 2 µg/mL were identified as an independent risk factor for COVID-19 in-hospital mortality. Measuring and monitoring D-dimer levels can assist clinicians in taking timely actions and predicting the prognosis of patients with COVID-19. Full article

Background/Objectives: To assess quantitatively the correlation between the lung ultrasound severity scores (LUSSs) and chest CT severity scores (CTSSs) derived from low-dose computed tomography (LDCT) for evaluating pulmonary inflammation in COVID-19 patients. Methods: In this prospective observational study, from an initial cohort of 1000 patients, 555 adults (≥18 years) with confirmed COVID-19 were enrolled based on inclusion criteria. All underwent LDCT imaging, scored by the CTSS (0–25 points), quantifying involvement across five lung lobes. Lung ultrasound examinations using standardized semi-quantitative scales for the B-line (LUSS B) and consolidation (LUSS C) were performed in a subgroup of 170 patients; 110 had follow-up imaging after one week. Correlation analyses included Spearman’s and Pearson’s coefficients. Results: Significant positive correlations were found between the CTSS and both the LUSS B (r = 0.32; p < 0.001) and LUSS C (r = 0.24; p = 0.006), with the LUSS B showing a slightly stronger relationship. Each incremental increase in the LUSS B corresponded to an average increase of 0.18 CTSS points, whereas a one-point increase in the LUSS C corresponded to a 0.27-point CTSS increase. The mean influence of the LUSS on CTSS was 8.0%. Neither ultrasound score significantly predicted ICU admission or mortality (p > 0.05). Conclusion: Standardized lung ultrasound severity scores show a significant correlation with low-dose CT in assessing pulmonary involvement in COVID-19, particularly for the B-line artifacts. Lung ultrasound represents a valuable bedside tool, complementing—but not substituting—CT in predicting clinical severity. Integrating both imaging modalities may enable the acquisition of complementary bedside information and facilitate dynamic monitoring of disease progression. Full article

Background: As a disease with a still largely unknown course, post-COVID requires a comprehensive multidimensional perspective and structured monitoring, as offered by the C19-YRSm. There has not yet been a German version of the scale. Methods: After the translation of the COVID-19 Yorkshire Rehabilitation Scale (modified version, C19-YRSm) into German, we conducted an online survey with it between 23 May 2023 and 10 May 2024 for patients with post-COVID condition. Participation took place twice; people received either only the German version or both the German and the original English versions of the scale at one-week intervals. Based on the results, reliability and validity of the German version of the C19-YRSm were extensively tested. Results: Data of 414 participants were analysed, 156 of whom took part twice at least seven days apart. Cronbach’s alpha coefficients of the subscales of the German version ranged from 0.75 to 0.93. In the English version, it ranged from 0.82 to 0.93. All the subscales correlate with each other with p < 0.001. For the overall scale and for three of the four subscales, the intraclass coefficients, as a measure of the agreement between measurement results at two points in time, showed good consistency. Conclusions: This study confirmed the reliability, applicability, and clinical utility of the C19-YRSm, aligning with previous studies. With its multidimensional structure and excellent quality criteria, the C19-YRS is a valuable asset for clinical practice and research. The validated German C19-YRSm holds significant potential to facilitate tailored interventions, destigmatise post-COVID conditions, and enhance patient care in medical contexts. Full article

Infectious diseases poses a growing public health challenge. The COVID-19 pandemic has further emphasized the urgent need for rapid, accessible diagnostics. This study presents the development of an integrated, flexible point-of-care (POC) diagnostic system for the rapid detection of Corynebacterium diphtheriae, the pathogen responsible for diphtheria. The system comprises a microfluidic polymerase chain reaction (micro-PCR) device and an electrochemical DNA biosensor, both fabricated on flexible substrates. The micro-PCR platform offers rapid DNA amplification overcoming the time limitations of conventional thermocyclers. The biosensor utilizes specific molecular recognition and an electrochemical transducer to detect the amplified DNA fragment, providing a clear and direct indication of the pathogen’s presence. The combined system demonstrates the effective amplification and detection of a gene fragment from a toxic strain of C. diphtheriae, chosen due to its increasing incidence. The design leverages lab-on-a-chip (LOC) and microfluidic technologies to minimize reagent use, reduce cost, and support portability. Key challenges in microsystem design—such as flow control, material selection, and reagent compatibility—were addressed through optimized fabrication techniques and system integration. This work highlights the feasibility of using flexible, integrated microfluidic and biosensor platforms for the rapid, on-site detection of infectious agents. The modular and scalable nature of the system suggests potential for adaptation to a wide range of pathogens, supporting broader applications in global health diagnostics. The approach provides a promising foundation for next-generation POC diagnostic tools. Full article

The recent COVID-19 pandemic has made the public aware of the importance of combating pathogenic microorganisms before they enter the human body. This growing threat from microorganisms prompted us to conduct research into a new type of coating that would be an alternative to the continuous disinfection of touch surfaces. Our goal was to design, synthesise and thoroughly characterise such a coating. In this work, we present a nanocomposite material composed of a thin-layer mesoporous SBA-15 silica matrix containing copper phosphonate groups, which act as catalytic centres responsible for the generation of reactive oxygen species (ROS). In order to verify the structure of the material, including its molecular structure, microscopic observations and Raman spectroscopy were performed. The generation of ROS was confirmed by fluorescence microscopy analysis using a fluorogenic probe. The antimicrobial activity was tested against a wide spectrum of Gram-positive and Gram-negative bacteria, while cytotoxicity was tested on BALB/c3T3 mouse fibroblast cells and HeLa cells. The studies fully confirmed the expected structure of the obtained material, its antimicrobial activity, and the absence of cytotoxicity towards fibroblast cells. The results obtained confirmed the high application potential of the tested nanocomposite coating. 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: Chronic cytomegalovirus (CMV) infection may favor the development of immunosenescence and inflammation that impair vaccine responses, including COVID-19. In addition, the polymorphism of the interferon-lambda gene (IFNλ) affects COVID-19 immune responses in older adults. Objective: We aimed to investigate the impact of IFNλ polymorphism (IL28B gene-rs12979860) on the immune/inflammatory response to vaccination with CoronaVac for COVID-19 in older adults who were CMV-seropositive. Methods: Blood samples from 42 CMV-seropositive older adults (73.7 ± 4.5 years) were collected before and 30 days after immunization with a second dose of the CoronaVac vaccine to evaluate the immune/inflammatory response. Results: At genotyping, 20 subjects were homozygous for the C/C alleles (Allele-1 group), 5 were homozygous for the T/T Alleles (Allele-2 group), and 17 were heterozygous (C/T, Alleles-1/2 group). The Allele-1 group showed higher IgG levels for COVID-19 (p = 0.0269) and intermediate monocyte percentage (p = 0.017), in contrast to a lower non-classical monocyte percentage (p = 0.0141) post-vaccination than pre-vaccination. Also, this group showed that IgG levels for CMV were positively associated with a systemic pro-inflammatory state and senescent T cells (CD4+ and CD8+). The Allele-2 group presented higher IFN-β levels at pre- (p = 0.0248) and post-vaccination (p = 0.0206) than the values in the Allele-1 and Alleles-1/2 groups, respectively. In addition, the Allele-2 and Alleles-1/2 groups showed that IgG levels for COVID-19 were positively associated with a balanced systemic inflammatory state. Conclusion: CMV-seropositivity in older adults who had Allele-1 could lead to an unbalanced systemic inflammatory state, which may impair their antibody response to COVID-19 vaccination compared to other volunteer groups. Full article

Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1/TMEM173 polymorphisms (rs78233829 C>G/p.Gly230Ala and rs1131769C>T/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29–3.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01–2.55). We also studied the LTZFL1 rs67959919 G/A polymorphism that was significantly associated with severe COVID-19 (p < 0.001; OR = 1.83; 95%CI = 1.28–2.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients. Full article

Prognostic scores that help allocate resources and time to the most critical patients could have potentially improved the response to the SARS-CoV-2 pandemic. We assessed the performance of five risk scores in predicting death or transfer to the intensive care unit (ICU) or sub-intensive care unit (SICU) in hospitalised patients with SARS-CoV-2 infection, with the three aims of retrospectively analysing the effectiveness of these tools, identifying frail patients at risk of death or complications due to infection, and applying these tools in the event of future pandemics. A retrospective observational study was conducted by evaluating data from patients hospitalised with SARS-CoV-2 infection. Among 134 patients considered, 119 were enrolled. All patients were adults, with a mean age of 64 years, and were hospitalised in the Infectious Diseases Division. We compared the five scores using receiver operating characteristic curves and calculation of the areas under the curve (AUCs) to determine their predictive performance. Four of the five scores demonstrated a high accuracy in predicting mortality among COVID-19-positive patients, with AUCs between 0.749 and 0.885. However, only two of the five scores showed good performance in predicting transfer to the ICU or SICU, with AUCs ranging from 0.740 to 0.802. The 4C Mortality Score and COVID-GRAM presented the highest performance for both outcomes. These two scores are easy to apply and low cost. They could still be used in clinical practice as predictive tools for frail and elderly patients with SARS-CoV-2 infection, as well as in the event of future pandemics. Full article