Search Results (913)

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

Background: 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

The COVID-19 pandemic, caused by SARS-CoV-2, has led to a wide range of acute and chronic disease manifestations. While most infections are mild, a significant number of patients develop severe illness marked by respiratory failure, thromboinflammation, and multi-organ dysfunction. In addition, post-acute sequelae—commonly known as long-COVID—can persist for months. Recent studies have identified the emergence of diverse autoantibodies in COVID-19, including those targeting nuclear antigens, phospholipids, type I interferons, cytokines, endothelial components, and G-protein-coupled receptors. These autoantibodies are more frequently detected in patients with moderate to severe disease and have been implicated in immune dysregulation, vascular injury, and persistent symptoms. This review examines the underlying immunological mechanisms driving autoantibody production during SARS-CoV-2 infection—including molecular mimicry, epitope spreading, and bystander activation—and discusses their functional roles in acute and post-acute disease. We further explore the relevance of autoantibodies in maternal–fetal immunity and comorbid conditions such as autoimmunity and cancer, and we summarize current and emerging therapeutic strategies. A comprehensive understanding of SARS-CoV-2-induced autoantibodies may improve risk stratification, inform clinical management, and guide the development of targeted immunomodulatory therapies. Full article

Background and Objectives: Euthyroid sick syndrome, or non-thyroidal illness syndrome, has been observed in severely ill patients and has been found to be an index of prognosis. It has been detected in patients with severe infectious diseases, e.g., those with severe COVID-19 infection. Prognostic indicators of the outcome of severe COVID-19 disease are important for the prognosis of individual as well as groups of patients. The aim of this study was to identify euthyroid sick syndrome in patients admitted for severe COVID-19 disease and its relationship to disease severity and outcome. Materials and Methods: In a cohort of patients admitted to hospital for severe COVID-19 disease, thyroid function in patients requiring hospitalization was evaluated by measuring TSH, FreeT₃ (FT₃), and FreeT₄ (FT₄) levels. Patients were classified into four groups: a group with uncompromised respiratory function (pO2 > 70 mmHg, without need of oxygen supplementation) (disease severity 1); a group with mild respiratory insufficiency (pO2 50–60 mmHg, in need of oxygen supplementation with nasal cannula) (disease severity 2); a group with severe respiratory insufficiency (pO2 < 50 mmHg, in need of oxygen supplementation with high flow oxygen) (disease severity 3); and a group with severe respiratory insufficiency requiring intubation (pO2 < 60 mmHg on high flow oxygen supplementation) (disease severity 4). Results: In this cohort, euthyroid sick syndrome was diagnosed in 57.1% of the patients. The presence of euthyroid sick syndrome was related to increased disease severity and adverse disease outcome, i.e., death. FT₃ levels were inversely related to CRP levels. Conclusions: Euthyroid sick syndrome may be observed in severe COVID-19 disease and is related to increased disease severity and adverse outcomes. Measurement of thyroid hormones in patients hospitalized for severe COVID-19 infection may aid in the prognosis of the disease. Full article

Interferon (IFN) signaling plays vital roles in host defense against viral infection. However, a variety of observations have been reported in the literature regarding the roles of IFN signaling in COVID-19. Thus, it would be important to reach a clearer picture regarding the activation or suppression of IFN signaling in COVID-19. In this work, regulation of marker genes for IFN signaling was examined in natural infection, viral challenge, and vaccination based on 13 public transcriptome datasets. Three subsets of interferon-stimulated genes (ISGs) were selected for detailed examination, including one set of marker genes for type I IFN signaling (ISGa) and two sets of marker genes for type II IFN signaling (IFN-γ signaling, GBPs for the GBP gene cluster, and HLAd for the HLA-D gene cluster). In natural infection, activation of ISGa and GBPs was accompanied by the suppression of HLAd in hospitalized patients. Suppression of GBPs was also observed in certain critical conditions. The scale of regulation was much greater for ISGa than that of GBPs and HLAd. In addition, the suppression of HLAd was correlated with disease severity, and it took much longer for HLAd to return to the level of healthy controls than that for ISGa and GBPs. Upon viral challenge, the activation of ISGa and GBPs was similar to that of natural infection, while the suppression of HLAd was not observed. Moreover, GBPs’ return to the pre-infection level was at a faster pace than that of ISGa. Upon COVID-19 vaccination, activation was observed for all of these three gene sets, and the scale of activation was comparable for ISGa and GBPs. Notably, it took a much shorter time for GBPs and ISGa to return to the level of healthy controls than that in COVID-19 infection. In addition, the baseline values and transient activation of these gene sets were also associated with subsequent vaccination response. The intricate balance of IFN signaling was demonstrated in mild breakthrough infection, where attenuated response was observed in people with prior vaccination compared to that in vaccine-naïve subjects. Overall, distinctive temporal profiles of IFN signaling were observed in natural infection, viral challenge, and vaccination. The features observed in this work may provide novel insights into the disease management and vaccine development. Full article

Background: Coronavirus disease 2019 (COVID-19) is frequently complicated by cardiovascular involvement. Soluble growth stimulation-expressed gene 2 (sST2) is a promising cardiovascular biomarker, but its prognostic value in COVID-19 remains unclear. Methods: This retrospective cohort study included 314 hospitalized COVID-19 patients classified into mild/moderate (n = 168) and severe/critical (n = 146). Plasma sST2 were measured using an enzyme-linked immunosorbent assay. Correlation analyses evaluated associations between sST2 and clinical parameters. Cox regression assessed the independent predictive value for cardiovascular events and all-cause mortality. Results: sST2 levels were significantly higher in severe/critical patients (16.877 ng/mL) than in mild/moderate cases (6.189 ng/mL) and healthy controls (4.003 ng/mL). sST2 positively correlated with cardiac injury markers (cTnI, CK-Mb, NT-proBNP), inflammatory indices (IL-1β, hsCRP), D-dimer, and inversely correlated with a left ventricular ejection fraction (r = −0.86). Elevated sST2 independently predicted cardiovascular events (HR = 2.972) and mortality (HR = 4.681). The Kaplan–Meier survival analysis demonstrated higher cardiovascular event rates and lower survival probabilities in patients with elevated sST2. The ROC curve indicated sST2 outperformed cTnI and NT-proBNP in predicting cardiovascular events (AUC = 0.898) and mortality (AUC = 0.871). Conclusion: Elevated sST2 is associated with myocardial injury, inflammation, and poor prognosis in COVID-19, supporting its value for risk stratification. Full article

Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration of AM is markedly increased in the novel coronavirus disease COVID-19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research. Full article

Background/Objectives: Neutralizing autoantibodies against type I interferons, particularly interferon-alpha (IFN-α), have been implicated in severe COVID-19 outcomes. This study investigated the prevalence and functional significance of anti-IFN-α autoantibodies (AAbs) in hospitalized unvaccinated COVID-19 patients and their association with COVID-19 disease severity. Methods: We retrospectively analyzed serum samples from 122 hospitalized COVID-19 patients (asymptomatic/mild: n = 69, moderate: n = 35, severe/critical: n = 18) and 32 healthy uninfected controls. Anti-IFN-α AAbs were quantified using a commercial enzyme-linked immunosorbent assay (ELISA) kit, with functional neutralization assessed via competitive ELISA and STAT1 phosphorylation inhibition. Statistical comparisons were performed using one-way ANOVA for parametric data and the Kruskal–Wallis test for non-parametric variables. Results: Anti-IFN-α AAbs were detected in 24.6% of COVID-19 patients, with all clinical subgroups showing significantly higher titers compared to healthy controls (p < 0.05). Although no significant differences in anti-IFN-α AAb levels were found between mild, moderate, and severe cases, patients with severe or critical COVID-19 had markedly higher mean titers (10,511.3 ng/mL) compared to non-severe (mild + moderate) cases (375.2 ng/mL, p < 0.001). Strongly neutralizing anti-IFN-α AAbs, with high titers (>20,000 ng/mL) and the ability to inhibit STAT1 phosphorylation, were identified in three severe COVID-19 cases. Anti-IFN-α AAb levels correlated positively with CRP (r = 0.80, p < 0.0001), LDH (r = 0.80, p = 0.001), and neutrophil count (r = 0.52, p = 0.003), and negatively with lymphocyte count (r = −0.59, p = 0.0006). Conclusions: Elevated and functionally neutralizing anti-IFN-α AAbs were associated with severe COVID-19. These findings support their role as a risk factor for poor outcomes and emphasize the importance of early COVID-19 vaccination. Screening may help identify high-risk individuals, particularly those unvaccinated or with immune vulnerabilities. Full article

Background: Patients with mild coronavirus disease 2019 (COVID-19) are usually managed in an outpatient setting. Pulmonary functions in this setting have not been explored. This study aimed to determine abnormal lung functions in COVID-19 patients under a home isolation program. Methods: A prospective study was conducted in asymptomatic or mild COVID-19 patients with normal chest radiographs at two medical centers in Thailand. Spirometry data, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), forced expiratory flow at 25–75% of FVC (FEF25–75), and bronchodilator responsiveness (BDR), were collected. Spirometry was performed after disease resolution at baseline and 3-month follow-up. Abnormal lung functions were classified into airway obstruction, restrictive defect, mixed defect, small airway disease, and BDR. Results: A total of 250 patients (58% female) were included. The mean age was 37.4 ± 15.2 years. Asymptomatic patients accounted for 7.6%. Common symptoms included fever (55.6%) and cough (60.0%). Abnormal lung functions were observed in 28.4% of patients, with a restrictive lung pattern (14.4%), airway obstruction (4.8%), mixed defect (0.4%), small airway disease (8.4%), and BDR (2.8%). Significant changes from baseline were noted in FVC (1.21%), FEV₁/FVC (−1.51%predicted), PEF (0.06%), and FEF_25–75 (−2.76%). Logistic regression analysis indicated that a higher body mass index was associated with a lower risk of abnormal lung function. Conclusions: Ventilatory defects were observed in one-third of patients with mild COVID-19 who did not require hospitalization, mainly presenting as restrictive patterns and small airway disease. Even mild cases may have residual pulmonary impairment, warranting further long-term studies. Full article

Background/Objectives: Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and for innate immune defense. We aimed to evaluate whether surfactant protein gene expression varies with the severity of COVID-19. Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (requiring hospitalization), or severe (requiring ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) in blood cells using RT-qPCR. Relative expression was normalized to GAPDH and compared among the groups using the 2^−ΔΔCt method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. Results: Distinct surfactant gene expression patterns were markedly associated with disease severity. Transcripts of SFTPB and SFTPC decreased with increasing severity of the disease. Notably, SFTPC expression was ~49-fold higher in mild cases compared to asymptomatic COVID-19-positive patients (p < 0.0001), but then decreased by ~54-fold in severe cases relative to mild (p < 0.0001), returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe cases. SFTPA2 was ~50-fold higher in severe versus mild cases (p < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases (p < 0.0001; ~9.6-fold higher than in mild). SFTPA1 showed only a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences remained statistically significant after outlier exclusion. Conclusions: COVID-19 severity is correlated with profound changes in surfactant gene expression in blood. Critically ill patients exhibit loss of key surfactant components (SP-B and SP-C transcripts) alongside an excessive SP-D response. These preliminary findings suggest an imbalance that may contribute to lung injury in severe disease. However, further validation is needed to establish surfactant proteins, such as SP-D, as biomarkers of COVID-19 severity. Full article

Background: Vaccines are crucial for preventing infectious diseases, as both humoral and cellular immune responses play a vital role in combating viral infections. The cellular immune response is crucial against SARS-CoV-2, particularly with the emergence of new variants that evade antibody neutralization. This study focuses on the immune memory response in individuals who have been vaccinated with the Sinopharm BBIBP-CorV vaccine. Methods: A cross-sectional study evaluated lymphocyte subpopulations using flow cytometry in 52 vaccinated adults (30 females, 22 males) who had been exposed to SARS-CoV-2 or diagnosed with COVID-19. Conducted from February to June 2023 during the Omicron variant’s circulation, this study assessed antigens—CD154 in CD4+ T cells, CD107 and CD314 in CD8+ T cells, CD314 in NK cells, and CD86 in CD19 B cells—after stimulation with viral peptides and an inactivated virus. Granzyme B and IFN-γ were quantified using ELISA. Results: The memory response, regardless of gender, age, or Body Mass Index (BMI), was mild but significant upon exposure to a viral antigen or inactivated virus. An increase in the secretion of IFN-γ and granzyme B was also observed. Conclusions: It is suggested that the vaccine was able to generate a mild long-term memory against the SARS-CoV-2 virus in vaccinated adult individuals, independent of gender and BMI. Full article

Background: During the COVID-19 pandemic, a high-volume field clinic was rapidly established in Taichung, Taiwan, to manage patients with mild symptoms and reduce hospital burden. To streamline workflow and support timely care, a tailored medical informatics system was developed and implemented midway through clinic operations. Methods: We conducted a retrospective observational study analyzing data from 8287 patients who visited the clinic between 20 May and 4 June 2022. Patients were divided into two groups based on whether they received care before or after the informatics system was introduced (28 May). The primary outcomes included consultation volume, physician workload distribution, and operational efficiency during peak hours. A secondary analysis examined the subgroup receiving antiviral prescriptions. Results: After system implementation, the total number of consultations during peak hours increased significantly (from 138.6 to 199.0, a 43.5% increase; p = 0.001), along with the average number of consultations per physician (from 12.3 to 22.5, an 83% increase; p = 0.003). Similar trends were observed in the subgroup receiving antiviral therapy, despite the complexity of prescribing decisions. These prescribing trends suggest improved identification of high-risk patients and more timely antiviral initiation, which are critical for reducing disease progression and preventing hospitalization. Conclusions: The integration of a targeted medical informatics system significantly improved consultation efficiency and workload equity in a field clinic setting. This experience highlights a scalable model for digitally enhanced, rapid-response outpatient care during public health emergencies. Full article

Background: Greece is among the fastest-aging countries globally, with one of the highest proportions of elderly individuals. As a result, the prevalence of mild cognitive impairment (MCI) and dementia is among the highest in Europe. The distribution of affected individuals varies considerably across different regions of the country. Method: We estimated the number of people living with MCI or dementia in Greece and visualized these estimates using heatmaps by regions for four census years: 1991, 2001, 2011, and 2023 (the 2023 census was delayed due to the COVID-19 pandemic). Age- and sex-specific prevalence rates of MCI and dementia were obtained from the Hellenic Longitudinal Investigation of Aging and Diet. These prevalence rates were then applied to population data from each census to estimate the number of affected individuals per region. Results: There was a consistent increase in the number of people living with MCI, rising from 177,898 in 1991 to 311,189 in 2023. Dementia cases increased from 103,535 in 1991 to 206,939 in 2023. Projections based on future census data for 2035 and 2050 suggest that the number of people with MCI will reach 375,000 and 440,000, respectively, while dementia cases will increase to 250,000 in 2035 and 310,000 in 2050. Conclusion: Given that each person with dementia typically requires care from at least two caregivers over time, these projections highlight the profound impact the dementia epidemic will have on Greece. The heatmaps developed in this study can serve as valuable tools for policymakers in designing and implementing clinical care programs tailored to the needs of each region based on the projected burden of disease. Full article

Recent evidence suggests that SARS-CoV-2 may induce subtle anatomical changes in the retina, detectable through advanced imaging techniques. This retrospective case–control study utilized optical coherence tomography (OCT) to assess medium-term retinal alterations in 55 healthcare workers, including 25 individuals with PCR-confirmed COVID-19 and 30 non-COVID-19 controls, all of whom had worked in COVID-19 clinical settings. Comprehensive ophthalmological examinations, including OCT imaging, were conducted six months after infection. The analysis considered demographic variables, comorbidities, COVID-19 severity, risk factors, and treatments received. Central macular thickness (CMT) was significantly increased in the post-COVID-19 group (p < 0.05), with a weak but statistically significant positive correlation between CMT and disease severity (r = 0.245, p < 0.05), suggesting potential post-inflammatory retinal responses. No significant differences were observed in retinal nerve fiber layer (RNFL) or ganglion cell complex (GCL + IPL) thickness. However, mild negative trends in inferior RNFL and average GCL+IPL thickness may indicate early neurodegenerative changes. Notably, patients with comorbidities exhibited a significant reduction in superior and inferior RNFL thickness, pointing to possible long-term neurovascular impairment. These findings underscore the value of OCT imaging in identifying subclinical retinal alterations following COVID-19 and highlight the need for continued surveillance in recovered patients, particularly those with pre-existing systemic conditions. Full article

Background and Objectives: Chronic respiratory diseases, such as COPD, cystic fibrosis, and post-COVID-19, are frequently accompanied by psychological distress and physical impairment. As a non-pharmacological intervention, progressive muscle relaxation (PMR) may benefit these patients psychologically and physiologically. This systematic review aimed to evaluate the effects of PMR on anxiety, depression, fatigue, sleep quality, dyspnea, and pulmonary function in patients with COPD, CF, and COVID-19. Materials and Methods: Following PRISMA guidelines, a comprehensive search was conducted across PubMed, Scopus, Web of Science, MEDLINE, Cochrane, SpringerLink, and ClinicalTrials.gov. Eligible studies assessed PMR in adult patients with COPD, CF, or COVID-19. Psychological and physical outcomes were extracted, and methodological quality and risk of bias were evaluated using standardized tools. Results: A total of 32 studies were included in the analysis. PMR was consistently associated with reductions in anxiety, depression, fatigue, and sleep-related distress, particularly in patients with COPD and COVID-19. Some also reported improvements in dyspnea and mild pulmonary function tests, but these were more variable. Only one study evaluated PMR in patients with cystic fibrosis, providing the first clinical data for this group. Interventions were predominantly short-term, with significant variation in design, duration, and methodology, and the risk of bias was often moderate or high. Conclusions: PMR is a helpful strategy in treating chronic respiratory diseases, particularly for reducing psychological distress and improving sleep. However, the evidence is limited by methodological variations and lack of long-term follow-up. Rigorous research is needed to support clinical application, particularly in cystic fibrosis. Full article