Social isolation and loneliness have increasingly emerged as closely linked to onset and progression of non-communicable chronic diseases (NCDs). The aim of this review is to highlight the importance of addressing social isolation in the prevention and management of NCDs such as obesity, type 2 diabetes, and cardiovascular diseases in order to hinder their development and improve their outcomes.

Social isolation and loneliness affect a significant portion of the older adult population, due to decrease in social interactions, chronic illnesses and sensory impairments. However, many other vulnerable populations may experience social isolation because of psychiatric or disabling health conditions, substances abuse, low socioeconomic status, unemployment and belonging to ethnic or marginalized minorities. The unprecedented COVID-19-related social distancing can be taken as a proof-of-concept of the detrimental role of poor interactions in NCDs prevention and management not only at individual level but also in a public health perspective. Indeed, social isolation has been linked to unhealthy lifestyle choices, disrupted sleep quality, low utilization of healthcare, preventive services and adherence to treatments. Underlying mechanisms like inflammation and stress responses may also play a role in the association between social isolation and worse NCDs outcomes.

Social isolation negatively impacts on the development, progression and management of NCDs. Effective interventions for social isolation should address both societal factors and healthcare-related needs. To counteract the detrimental effects of social distancing during COVID-19 pandemic, the use of telemedicine was implemented. However, telemedicine is not always available, and legislative and age-related barriers persist.

The efficacy and safety of acalabrutinib, a Bruton tyrosine kinase (BTK) inhibitor, was evaluated in 2 phase 2 studies in hospitalized patients with coronavirus disease 2019 (COVID-19) who received acalabrutinib + best supportive care (BSC) versus BSC alone (Clinicaltrials.gov: NCT04380688 and NCT04346199). The primary endpoint was the percentage of patients alive and free of respiratory failure on day 14 (rest of the world [RoW] study) and day 28 (US study). In the RoW study, 177 patients were randomized (acalabrutinib + BSC: n = 89; BSC: n = 88); in the US study, 62 patients were randomized (acalabrutinib + BSC: n = 31; BSC: n = 31). The percentage of patients who met the primary endpoint was similar in both studies (RoW study: acalabrutinib + BSC: 83.1%, BSC: 90.9%; US study: acalabrutinib + BSC: 80.6%, BSC: 83.9%). No new safety concerns were reported. Overall, no significant clinical benefit of adding acalabrutinib to BSC in patients hospitalized with COVID-19 was observed.

The JAK family, particularly JAK3, plays a crucial role in immune signaling and inflammatory responses. Dysregulated JAK3 activation in SARS-CoV-2 infections has been associated with severe inflammation and respiratory complications, making JAK inhibitors a viable therapeutic option. However, their use raises concerns regarding immunosuppression, which could increase susceptibility to secondary infections. While long-term adverse effects are less of a concern in acute COVID-19 treatment, patient selection and monitoring remain critical. Furthermore, adverse effects associated with oral JAK3 inhibitors necessitate the exploration of alternative strategies to optimize therapeutic efficacy while minimizing risks. This review highlights the role of JAK3 in immune and epithelial cells, examines the adverse effects of oral JAK3 inhibitors in COVID-19 and other treatments, and discusses alternative therapeutic strategies for improving patient outcomes.

The aim of this study was to evaluate the incidence, severity, duration of oral manifestations in individuals with Coronavirus Disease 2019 (COVID-19) and the association of these manifestations with the severity of COVID-19 and the patient's oral hygiene.

This study included 820 patients with confirmed COVID-19. A questionnaire form including oral hygiene habits, the severity of Covid-19, the presence, severity and durations of oral manifestations was prepared, and a web-based survey was performed using Google-forms. Obtained data was analysed with Pearson chi-square and Fisher's exact tests with statistical significance set at P < 0.05.

The most commonly reported manifestations were taste dysfunction (63.4%), xerostomia (59.9%), halitosis (31.1%), dysphagia (27.8%), hypersensitive teeth (27.2%) and gingival bleeding (14.3%). The incidence of the oral manifestations was found significantly associated with severity of COVID-19 (P = 0.000 V = 0.151), presence of systemic diseases (P = 0.034, V = 0.074) and age (P = 0.023, V = 0.099). Tooth brushing decreased the incidence of aphthous like lesions of tongue during Covid-19 (p < 0.05).

Maintenance of oral hygiene was associated with a reduced incidence of aphthous-like lesions, underscoring the protective role of routine oral care. These findings highlight the need to integrate oral health assessment and hygiene education into COVID-19 management protocols, which may also be important for potential future pandemics.

COVID-19 is caused by SARS-CoV-2 and has a diverse spectrum of clinical presentations ranging from asymptomatic cases to severe and critical cases that result in the death of the patient. Alongside the viral factors host factors like Age, deregulation of the immune response and presence of comorbidity determine the patient's outcome. Here we sought to assess the impact of age on natural antibody response, CBC-based inflammatory markers, and outcome of COVID-19 patients. We divided the participants into three groups, young (≤ 35 years), middle-aged (40-60 years), and old (≥ 65 years) patients and collected and analyzed sociodemographic, clinical, and laboratory parameters. We found that elderly patients showed higher (P < 0.05) levels of inflammation like increased neutrophil percentages, NLR, lymphopenia, and low Hgb levels, compared to middle-aged and young patients. Interestingly these markers were also associated with mortality of COVID-19 patients. On the other hand, no significant difference was observed in ion concentration, lipid profile, and coagulation test between the three age groups. We also found that elderly patients showed significantly (P < 0.05) decreased levels of natural antibody response to SARS-CoV-2 infection compared with the two groups. Lastly, we assessed the effect of dexamethasone treatment, even if statistically not significant (P > 0.05) we observed a positive trend among patients under dexamethasone in the aspect of decreasing inflammatory markers. To conclude we showed that SARS-CoV-2 is characterized by an age-dependent deregulation of inflammatory markers that are associated with mortality among COVID-19 patients.

Background: Veno-venous extracorporeal membrane oxygenation (V-V ECMO) represents a progressively adopted life-sustaining intervention worldwide, particularly in the management of acute respiratory distress syndrome. Nevertheless, data concerning the prognostic significance of fungal isolation in this setting remain unclear. This study aims (i) to assess the incidence of fungal infection and colonization in a homogeneous cohort of V-V ECMO patients, and (ii) to evaluate the association between fungal infection or colonization and 1-year mortality, with a focus on the impact of specific fungal species. Methods: All consecutive adults admitted to the Intensive Care Units of five Italian university-affiliated hospitals and requiring V-V ECMO were screened. Exclusion criteria were age < 18 years, pregnancy, veno-arterial or mixed ECMO-configuration, incomplete records and survival < 24 h after V-V ECMO placement. A standard protocol of microbiological surveillance was applied and the distinction between different fungal species were made through in vivo and vitro tests. Cox-proportional hazards models, Kaplan-Meier curves and linear logistic regressions were applied for investigating mortality. Results: Two-hundred and seventy-nine V-V ECMO patients (72% male) were enrolled. The overall fungal isolation was 41% (n. 114): 23% infections and 18% colonizations. The overall 1-year mortality, among fungal isolations, was 40%, with no different risk in case of fungal infection (26 out of 63, 41%) (aHR 0.85, 95% CI [0.53-1.37], p-value 0.505) and colonization (20 out of 51, 39%) (aHR 0.86, 95%CI [0.51-1.43], p-value 0.556), as compared to patients never detecting fungi (68 out of 165, 41%, reference). According to the isolated mycotic species, as compared to Candida sp. group (reference), the risk of death was greater when different fungal species (e.g., Aspergillus sp. and Candida sp.) were concomitantly isolated in the same patient (OR 1.17, 95%CI [1.12-11.07], p-value 0.031. Conclusions: In the overall population, 23% V-V ECMO patients recorded 'late' fungal infections and 18% fungal colonizations, with a similar risk of death as compared to patients never experiencing fungi during the V-V ECMO course. The detection of concomitant different fungal species was an independent risk factor for 1-year mortality.

Objectives: Critically ill COVID-19 patients are at high risk of malnutrition; however, no study has directly compared the prognostic accuracy of different nutritional assessment tools. This study aimed to determine the optimal cutoff values for the Modified Nutrition Risk in the Critically Ill (mNUTRIC) score, Nutritional Risk Screening 2002 (NRS 2002), and Malnutrition Universal Screening Tool (MUST) and to evaluate their predictive value for ICU mortality. Method: A retrospective analysis was conducted on patients with laboratory-confirmed COVID-19 admitted to our ICU between 20 March 2020 and 15 June 2021. Clinical and laboratory data, as well as patient outcomes, were retrieved from electronic medical records and patient charts. The mNUTRIC, NRS 2002, and MUST scores were calculated at ICU admission. Results: The study included 397 patients, with 273 survivors and 124 non-survivors. The median age was 65 (55-76) years, and the median BMI was 26.1 (24.0-29.4). Non-survivors had significantly higher median scores in all three nutritional assessment tools compared to survivors (mNUTRIC: 5 vs. 3, NRS 2002: 4 vs. 3, MUST: 2 vs. 2; p < 0.01). At the optimal cutoff values, mNUTRIC ≥ 4 demonstrated the highest prognostic accuracy (sensitivity: 0.77, specificity: 0.74; AUC = 0.75, CI = 0.70-0.81), followed by NRS 2002 ≥ 4 (sensitivity: 0.63, specificity: 0.60; AUC = 0.62, CI = 0.56-0.67) and MUST ≥ 3 (sensitivity: 0.21, specificity: 0.91; AUC = 0.56, CI = 0.50-0.68). Higher scores were associated with increased disease severity, poorer patient performance, prolonged hospital stays, and elevated ICU, 28-day, and overall hospital mortality rates. Among the three assessment tools, only an mNUTRIC score of ≥ 4 was independently associated with ICU mortality (OR = 1.54, CI = 1.21-1.96, p < 0.01). Conclusions: At ICU admission, mNUTRIC ≥ 4, NRS 2002 ≥ 4, and MUST ≥ 3 were identified as the most accurate predictors of mortality in critically ill COVID-19 patients. However, only the mNUTRIC score was an independent predictor of ICU mortality.

Background: Patients suffering from severe COVID-19 often develop acute respiratory distress syndrome (ARDS), necessitating intensive care unit (ICU) and extracorporeal membrane oxygenation (ECMO). Survivors frequently experience negative impacts on their health-related quality of life. These individuals may experience a range of symptoms and may require extended hospitalization and rehabilitation. The objective of this prospective cohort study was to assess the long-term health-related quality of life in intensive care survivors of COVID-19-related ARDS who received ECMO therapy, >18 months after their ICU discharge. Methods: The health-related quality of life of COVID-19 survivors who had received extracorporeal membrane oxygenation was evaluated using an augmented version of the Short-Form Health Survey-36, >18 months after their ICU discharge. The outcomes were compared to preexisting data from a meta-analysis analyzing patients with non-COVID-19 ARDS and ECMO therapy. Results: Of the 43 eligible patients (mean age 52 ± 9.5 years), 18 patients (46.2%) responded to the written invitation and were included in this study. The four subscales of the Short-Form Health Survey-36 survey, performed via telephone interview, that showed the most severe limitations (points) were role limitation due to physical problems (37.5), emotional problems (47.9), social functioning (38.1), and general health (49.2). The general health, energy/fatigue (vitality), and physical functioning significantly correlated with higher age (p = 0.004, p = 0.003, and p = 0.05, respectively). A longer duration of extracorporeal membrane oxygenation was positively associated with an improved energy/fatigue ratio (vitality) and emotional well-being (p = 0.04 and p = 0.02, respectively). Compared to survivors of non-COVID-19 ARDS treated with ECMO, the survivors in our cohort scored significantly lower on social functioning, physical functioning, and general health (p < 0.01, p = 0.02, p < 0.01). Conclusions: Patients who have recovered from intensive care treatment for COVID-19-related ARDS and have received ECMO therapy continue to experience more severe impairments in their physical, mental, and cognitive health-related quality of life. A longer ECMO duration may improve outcomes in this selected patient population.

Inflammation plays a fundamental role in the development and bidirectional association of di-verse diseases, such as periodontitis and type 2 diabetes mellitus (T2DM), which generates important clinical complications, where chronic exposure to high levels of blood glucose affects the repair process of periodontal tissues. Likewise, it has been observed that comorbidity, between these two diseases, influences the development of the COVID-19 disease towards a more severe course. However, there is currently very little scientific evidence on the relationship between periodontitis, T2DM and COVID-19 disease. This narrative review aims to provide an understanding of the current and most relevant aspects of the relationship between periodontitis, T2DM and COVID-19 disease. A narrative review was performed through a systematic search of published studies, without date restrictions, indexed in the electronic databases of PubMed, for the inclusion of articles in English, and LILACS for the inclusion of articles in Spanish. This review included different articles, which addressed the most important aspects to present a current perspective on the relationship and influence between periodontitis, T2DM and COVID-19 disease. Comorbidity between periodontitis and T2DM represents a greater risk of developing a more severe course of COVID-19 disease, because these three diseases share three important axes: a clinicopathological axis; an axis associated with glycemia, and an immunological axis associated with inflammation.

Background: Diabetes mellitus (DM) is an independent risk factor for severe SARS-CoV-2 infection and is linked to higher incidences of infections and adverse outcomes in patients with DM. This study examines the association between DM and multidrug-resistant Gram-negative bacteria (MDR-GNB) in critically ill, intubated COVID-19 patients in the intensive care unit (ICU) and evaluates mortality rates and clinical factors contributing to unfavorable outcomes. Methods: This retrospective observational study included intubated COVID-19 patients diagnosed with secondary infections due to MDR-GNB. Patients were treated for acute respiratory distress syndrome (ARDS) in a tertiary care university hospital ICU between October 2020 and February 2022. Collected data included demographics, comorbidities, medication, and laboratory parameters including blood tests and culture samples. Results: Among 416 COVID-19 patients, 112 (26.9%) had T2DM. Cultures from lower respiratory tract specimens revealed a significantly higher likelihood of isolating Acinetobacter baumannii in patients with DM (OR: 2.18, 95% CI: 1.40-3.40, p < 0.001), and DM is an independent predictor of isolation Acinetobacter baumannii in bronchial secretions of COVID-19 intubated patients (OR: 2.046, 95% CI: 1.256-3.333. p < 0.004). DM was not significantly associated with differences in length of stay (LOS) until discharge or death (HR: 0.76, 95% CI: 0.51-1.12, p = 0.16; HR: 0.91, 95% CI: 0.70-1.19, p = 0.50) or 28-day ICU mortality (OR: 1.12, 95% CI: 0.52-2.41, p = 0.77). Age was linked to an increased 28-day mortality risk in patients with DM (OR: 1.10, 95% CI: 1.02-1.18, p = 0.011). Conclusions: In critically ill intubated COVID-19 patients, DM emerged as a significant and independent predictor for the isolation of Acinetobacter baumannii from bronchial secretions, highlighting a key link between DM and specific multidrug-resistant pathogens, even though no broader association with MDR-GNB-related secondary infections was observed.

Malnutrition is a critical prognostic factor in COVID-19, affecting up to 50 % of hospitalized patients and increasing their mortality risk tenfold compared to well-nourished patients. The prognostic nutritional index (PNI) assesses nutritional and immune status and can help gauge the severity of COVID-19.

To evaluate whether PNI was independently associated with the severity of COVID-19 infection among hospitalized patients in the United States.

This study was a historical cohort study of adult patients with COVID-19 hospitalized in five hospitals in southeast Michigan. Data collected from the electronic medical record were analyzed using SPSS v. 29.0, and a p-value <0.05 was considered statistically significant.

Data were included on 286 patients, with a mean age of 58.7 ± 17.5 years, 53.5 % (153/286) female, and 48.3 % (138/286) black/African American. The most common comorbidities were hypertension (62.9 %), obesity (54.2 %) and type 2 diabetes mellitus (32.1 %). Of the 286 patients, 144 (50.3) had severe/ critical disease. Patients with severe COVID-19 had significantly lower mean PNI levels than those with mild to moderate disease (35.1 ± 5.2 vs 37.7 ± 6.4, p < 0.001). After controlling for smoking status, vaccination status, race, and home steroid use, PNI remained an independent predictor for severe/ critical COVID-19 (OR=0.92, p < 0.001).

This study demonstrated that PNI is an independent predictor of severe COVID-19. The PNI score can be easily calculated from routine blood tests for every patient and helps risk stratify hospitalized COVID-19 patients. Additional research is needed to confirm these results.

Given the impact of cardiovascular conditions on COVID-19 outcomes, there is increasing interest in assessing risk factors like epicardial adipose tissue (EAT). EAT contributes to metabolic syndrome, which worsens cardiovascular health through inflammation and insulin resistance, and triples mortality risk in COVID-19 patients. This study examined the relationship between EAT volume (EATV) and clinical outcomes in severe and critical SARS-CoV-2 pneumonia, hypothesizing that higher EATV would correlate with increased severity and mortality.

This multicenter retrospective cohort study of 750 COVID-19 patients with severe or critical pneumonia explored the relationships between EATV, the pulmonary severity index (PSI), the Kirby index, and 30-day in-hospital mortality. Outcomes included Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation IV, Charlson comorbidity index, Kirby index, PSI, and 30-day in-hospital mortality. This retrospective cohort study evaluates EATV as a prognostic factor for COVID-19 mortality.

EATV was significantly higher in patients with critical pneumonia and was also associated with increased mortality. EATV was the most robust predictor of in-hospital mortality, with a cut-off of 117 cm3 indicating a higher risk.

Epicardial adipose tissue volume was linked to increased mortality in patients with severe and critical pneumonia, especially in the third tertile. It was also associated with higher pulmonary severity indices and 30-day in-hospital mortality. Clinicians should consider EATV alongside inflammatory biomarkers to improve patient stratification and potentially enhance outcomes through earlier intervention.

Introduction: Severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) has been associated with the development of COVID-19. COVID-19 may cause endothelial cell dysfunction (ECD), which can lead to cardiometabolic diseases and podocytopathy. In this study, we explored whether presence of hyperglycemia predisposes to SARS-CoV-2 infection, in vitro, and whether COVID-19 can put an individual at a higher risk of persistent renal damage in the long-term following acute COVID infection. To estimate renal damage, we evaluated albuminuria and podocytopathy. Podocytopathy was estimated by measuring podocyte-specific protein levels in urine-derived exosomes from patients who were admitted with acute COVID-19 at 10 days, 6 months, and 12 months post-acute SARS-CoV-2 infection. Methods: Blood and urine samples from patients with SARS-CoV-2 post-infection were procured from the George Washington University COVID repository. Peripheral blood mononuclear cells and urine exosomes were isolated. Podocyte-specific proteins Podocalyxin (PODXL) and Nephrin (NEPH) were identified from urine exosomes. Results: Urine exosomal podocalyxin levels were significantly high at 10 week (n = 18; P = 0.001), 6 month (n = 25; P = 0.003) and 12 month (n = 14; P = 0.0001) time points. Nephrin levels were also noted to be high at 10 week (n = 18; P = 0.001) and 12 month (n = 14; P = 0.007) time points, compared with urine samples obtained from type 2 diabetes subjects who never had COVID-19. Though urinary podocyte-specific proteins were high, compared to control, there were no significant differences noted on urine albumin:creatinine ratios (UACR) between the groups. Conclusion: Persistent high levels of podocyte-specific proteins noted in urinary exosomes even at 12 months post-Covid may lead to the development of chronic kidney disease.

The sensitivity of reverse-transcription polymerase chain reaction (RT-PCR) is limited for diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chest computed tomography (CT) is reported to have high sensitivity; however, given the limited availability of chest CT during a pandemic, the assessment of more readily available imaging, such as chest radiographs, augmented by artificial intelligence may substitute for the detection of the features of coronavirus disease 2019 (COVID-19) pneumonia.

We trained a deep convolutional neural network to detect SARS-CoV-2 pneumonia using publicly available chest radiography imaging data including 8,851 normal, 6,045 pneumonia, and 200 COVID-19 pneumonia radiographs. The entire cohort was divided into training (n = 13,586) and test groups (n = 1510). We assessed the accuracy of prediction with independent external data.

The sensitivity and positive predictive values of the assessment by artificial intelligence were 96.8% and 90.9%, respectively. In the first external validation of 204 chest radiographs among 107 patients with confirmed COVID-19, the artificial intelligence algorithm correctly identified 174 (85%) chest radiographs as COVID-19 pneumonia among 97 (91%) patients. In the second external validation with 50 immunocompromised patients with leukemia, the higher probability of the artificial intelligence assessment for COVID-19 was correlated with suggestive features of COVID-19, while the normal chest radiographs were closely correlated with the likelihood of normal chest radiographs by the artificial intelligence prediction.

The assessment method by artificial intelligence identified suspicious lung lesions on chest radiographs. This novel approach can identify patients for confirmatory chest CT before the progression of COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19) survivors are concerned about the likelihood of developing further diseases. This study examines the global trends in scientific research on diabetes associated with COVID-19 from several perspectives. Bibliometric analyses are used to undertake a scientific review of the literature. The Web of Science Core Collection (WoSCC) database was used to acquire bibliographic information on diabetes related to COVID-19 from Jan 2020 to Dec. 2023. The visual map was built via advanced CiteSpace 6.2.R6. 7,348 papers were found. Khunti Kamlesh and Rizzo-Manfredi are the most well-known high-yield authors in this area, and the top ten authors collaborate extensively. Most of these papers came from universities. Harvard Medical School has the most publications, followed by Wuhan University and Huazhong University of Science and Technology. China and the United States are the countries with the most publications. Angiotensin-converting enzymes, chronic disease, intensive care unit, viral infection, and gestational diabetes mellitus were scored 0-11, 2, 3, and 4, respectively. Zhou et al.'s work on this topic, which appeared in the prominent medical journal The Lancet, was cited 1,366 times, highlighting its importance. "clinical characteristics," "diabetes mellitus," "metabolic syndrome," and "angiotensin-converting enzyme" were used as keywords for reference co-citation and clustering data identify. Over the last four years, related investigations have focused primarily on observing clinical aspects. This report is important for developing treatment strategies, directing future research, and guiding clinical practice.

Acute respiratory distress syndrome (ARDS) is a common pathological condition among critically ill patients that often requires mechanical ventilation support. However, mechanical ventilation increases the risk of ventilator-induced lung injury (VILI). Different prone ventilation strategies may have varying effects on mechanical power (MP) and respiratory mechanics. This study aimed to compare the effects of prone ventilation and lateral-prone ventilation on MP and respiratory mechanics in ARDS patients to assess the relative risks of VILI associated with these strategies.

This prospective, single-center observational study employed a randomized trial. One hundred and twenty-two patients with moderate-to-severe ARDS admitted to the Department of Critical Care Medicine at Lishui Central Hospital between December 2021 and April 2024 were enrolled in this study. Patients were randomly assigned to receive either prone or lateral-prone ventilation strategies. The primary outcomes included MP, driving pressure (DP), static lung compliance (Cstat), airway resistance (Raw), the oxygenation index [i.e., the oxygen saturation to fraction of inspired oxygen (SpO2/FiO2) ratio], the mortality rate, and the duration of the mechanical ventilation. Statistical analyses were performed to compare the effects of the two ventilation strategies on the respiratory mechanics and clinical outcomes.

The baseline characteristics of the patients, such as age, gender, and body mass index, were comparable between the two groups. No significant differences were found between the groups in terms of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. No significant differences were observed in the SpO2/FiO2 ratio, mean arterial pressure (MAP), or Raw at different time points. However, MP differed significantly between the prone and lateral-prone groups. No significant differences were found between the two groups regarding heart rate (HR), MAP, and Cstat.

Compared to prone ventilation, lateral-prone ventilation significantly reduced MP in ARDS patients. The early adoption of lateral-prone ventilation may help mitigate the risk of VILI. This strategy holds clinical promise and warrants further validation and optimization.

The outcome of the immune response depends on the content and magnitude of inflammatory mediators, the right time to start, and the duration of inflammatory responses. Patients with coronavirus disease 2019 (COVID-19) represent diverse disease severity. Understanding differences in immune responses in individuals with different disease severity levels can help elucidate disease mechanisms. Here, we serially analyzed the cytokine profiles of 809 patients with mild to critical COVID-19. The cytokine profile revealed an overall increase in IL-1β, IL-1Ra, TNF-α, IL-6, IL-2, IL-8, and IL-18 and impaired production of IFN-α and -β. Only an early rise in IL-1Ra, IL-6, and IL-2 levels was linked to worse disease outcomes. On the other hand, long-term rises in IL-1β, IL-1Ra, TNF-α, IL-6, IL-2, IL-8, and IL-18 levels were linked to worse disease outcomes. Principal component analysis identified a component, including IL-1β, TNF-α, IFN-α, and IL-12, that was associated with disease severity. Spearman analysis revealed that the correlation of IL-1β and IFN-α was entirely different between mild and critical patients. Therefore, the ratio of IL-1β to IFN-α seemed to be a suitable criterion for distinguishing critical patients from mild ones. The higher levels of the IL-1β to IFN-α ratio correlated with improved outcomes. These data point to an imbalance of IL-1β/IFNα, contributing to hyperinflammation in COVID-19.

Prodiginins are a large family of at least 34 pyrrolic compounds, including the well-studied red pigment prodigiosin. Prodiginins are produced by several microorganisms displaying broad biological activities, including antimicrobial, antiviral, antiparasitic, antiproliferative, and immunosuppressive activities. The present review aims to compile and analyze the main physicochemical and biological properties and mechanisms of action of prodiginins for microbial disease treatment, particularly SARS-CoV-2 disease and opportunistic infections related to COVID-19. The interaction of prodigiosin, as a model molecule, with cellular membranes, potential drug delivery devices, and toxicological studies, and in silico studies using molecular dynamics showed that the prodigiosin motif, which interacts with lipids, opens a new door for the potential therapeutic use of prodiginins.

Despite the efficacy of SARS-CoV-2 vaccines in reducing mortality and severe cases of COVID-19, a proportion of survivors experience long-term symptoms, known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study investigates the long-term immunological and neurodegenerative effects associated with extracellular vesicles (EVs) in COVID-19 survivors, 15 months after SARS-CoV-2 infection.

13 Controls and 20 COVID-19 survivors, 15 months after SARS-CoV-2 infection, were recruited. Pro-inflammatory cytokines were analyzed in both plasma and EVs. A deep-immunophenotyping of monocytes, T-cells and dendritic cells (DCs) was performed, along with immunostainings of SARS-CoV-2 in the colon.

Higher concentrations of pro-inflammatory cytokines and neurofilaments were found in EVs but not in plasma from COVID-19 survivors. Additionally, COVID-19 participants exhibited altered monocyte activation markers and elevated cytokine production upon lipopolysaccharide stimulation. Increased activation markers in CD4+ T-cells and decreased indoleamine 2,3-dioxygenase expression in DCs were observed in COVID-19 participants. Furthermore, the amount of plasmacytoid DCs expressing β7-integrin were higher in COVID-19, potentially associated with the viral persistence observed in the colon.

COVID-19 survivors exhibit long-term immune dysregulation and neurodegeneration, emphasizing the need for ongoing monitoring of PASC. The cargo of EVs can be a promising tool for early detection of virus-induced neurological disorders.

The triglyceride-glucose (TyG) index is a marker for insulin resistance (IR) linked to diabetes complications and poor outcomes. Its connection to all-cause mortality in non-diabetic critically ill patients is unknown. This study aims to investigate the TyG index's impact on mortality in this population, evaluating how IR affects their prognosis.

This study is retrospective observational research utilizing data from the eICU Collaborative Research Database. A total of 14,089 non-diabetic critically ill patients were included and categorized into three groups based on the TyG index measured on the first day of admission (T1, T2, and T3). Kaplan-Meier survival analysis was performed to compare the 28-day mortality rates among the different groups. Cox proportional hazards models were used to assess the relationship between the TyG index and 28-day mortality. Additionally, we conducted sensitivity analyses, subgroup analyses, and interaction analyses to assess the robustness of the results.

During the observation period, 730 patients (5.18%) died in the ICU, while 1,178 patients (8.36%) died in the hospital. The 28-day ICU mortality rate and hospital mortality rate significantly increased with higher TyG index values (P < 0.001). Cox proportional hazards models were used to assess the relationship between the TyG index and 28-day mortality. Specifically, Cox proportional hazards models were used to assess the relationship between the TyG index and 28-day mortality. Furthermore, the analysis showed a nonlinear effect of the TyG index on mortality in non-diabetic critically ill patients, with a critical point at 9.94. While Below 9.94, ICU and hospital mortality rates rose with higher TyG index values. But above 9.94, mortality didn't significantly increase despite further rises in the TyG index. Sensitivity and subgroup analyses confirmed the robustness of these results, and E-value analysis indicated strong resistance to unmeasured confounding factors.

The TyG index demonstrates a significant positive correlation with all-cause mortality in non-diabetic critically ill patients, exhibiting a nonlinear relationship. Consequently, the TyG index serves as a crucial tool for identifying high-risk patients, thereby assisting clinicians in formulating more effective monitoring and intervention strategies.

This review provides a broad overview of lessons learned in the five years since COVID-19 was identified. It is a bimodal disease, starting with an initially virus-driven phase, followed by resolution or ensuing inappropriate immune activation causing severe inflammation that is no longer strictly virus dependent. Humoral immunity is beneficial for preventing or attenuating the early stage, without benefit once the later stage begins. Neutralizing antibodies elicited by natural infection or vaccination are short-lived and highly vulnerable to viral sequence variation. By contrast, cellular immunity, particularly the CD8+ T cell arm, has a role in preventing or attenuating severe disease, is far less susceptible to viral variation, and is longer-lived than antibodies. Finally, an ill-defined phenomenon of prolonged symptoms after acute infection, termed "long COVID," is poorly understood but may involve various immunologic defects that are hyperactivating or immunosuppressive. Remaining issues include needing to better understand the immune dysregulation of severe disease to allow more tailored therapeutic interventions, developing antibody strategies that cope with the viral spike sequence variability, prolonging vaccine efficacy, and unraveling the mechanisms of long COVID to design therapeutic approaches.

Equine herpesvirus 1-induced myeloencephalopathy has a significant impact on the equine industry. Nevertheless, the clinical variables that may affect the severity of the disease are still under investigation. The objective of this research is studying the relationship between the level of lymphopenia and vaccination status with the severity of the disease in horses at an event, considering whether they had been correctly vaccinated or not prior to exposure to EHV-1. Ten horses were admitted to a veterinary teaching hospital following an equine herpesvirus myeloencephalopathy outbreak during an international show jumping competition in Spain. Data were collected from passport vaccination records, daily analyses, and the clinical histories of the affected horses. Correctly vaccinated horses had a significantly longer hospitalization duration (6/10, 15.5 ± 1.2 days) compared to incorrectly vaccinated horses (4/10, 12.5 ± 1.2 days; p = 0.01). Lymphopenia (<1.6 × 103 lymphocytes/µL) was the most common leukogram abnormality. Correctly vaccinated horses demonstrated a higher lymphocyte count compared to incorrectly vaccinated horses within 24 h of admission (p < 0.01). This difference remained significant from days 1 to 4 and on day 6 post-admission (p =0.03). This study found that lymphopenia is a common leukogram alteration in equine herpesvirus 1-infected horses, and horses correctly vaccinated prior to an equine herpesvirus myeloencephalopathy outbreak tend to have a longer hospitalization time. Correctly vaccinated horses exhibited higher lymphocyte counts during the first 24 h and throughout hospitalization compared to incorrectly vaccinated horses. The immune system could play a relevant role in influencing the severity of equine herpesvirus myeloencephalopathy outbreaks, highlighting the need for further studies in this area.

Severe COVID-19 is often complicated by hypoxemic respiratory failure and acute respiratory distress syndrome (ARDS). Mechanisms governing lung injury and repair in ARDS remain poorly understood. We hypothesized that plasma proteomics may uncover protein biomarkers correlated with COVID-19 ARDS severity. We analyzed the plasma proteome from 32 patients with ARDS and COVID-19 using an aptamer-based platform of 7289 proteins, and correlated protein measurements with sequential organ failure assessment (SOFA) scores at days 1 and 7 of ICU admission. We identified 184 differentially abundant proteins correlated with SOFA at day 1 and 46 proteins at day 7. In a longitudinal analysis, we correlated dynamic changes in protein abundance and SOFA between days 1 and 7 and identified 40 significant proteins. Pathway analysis of significant proteins identified increased ephrin signaling and acute phase response signaling correlated with increased SOFA scores between days 1 and 7, while pathways related to pulmonary fibrosis signaling and wound healing had a negative correlation. These findings suggest that persistent inflammation may drive disease severity, while repair processes correlate with improvements in organ dysfunction. This approach is generalizable to future ARDS cohorts for identification of biomarkers and disease mechanisms as we strive towards targeted therapies in ARDS.

The aim of this study was to analyze the detection and epidemiological characteristics of common influenza viruses (IVA/IVB) and respiratory syncytial virus (RSV) in a teaching hospital in Shanghai from 2017 to 2023, and to investigate the impact of the COVID-19 epidemic on the transmission and detection rates of these viruses.

Retrospective analysis of IVA/IVB and RSV cases detected in hospitals from 2017 to 2023. Data was categorized into pre, during and post outbreaks based on the timing of the COVID-19 outbreak and further subdivided by season and age group. PCR and colloidal gold methods were used for virus detection and statistical analyses were performed accordingly.

Positive detection rates of pathogens were statistically different by age, period, season and detection method employed. Before the epidemic, the pathogen infections showed obvious seasonality but disappeared after 2019. Positive detection rates of influenza were higher in adolescents and young and middle-aged people while RSV detection was highest in adolescents. Detection by Gene Xpert real-time fluorescent PCR was superior in terms of timeliness and efficiency.

The COVID-19 pandemic and the massive public health intervention campaign have led to widespread changes in human behavior, significantly affecting the spread and activity of other seasonal respiratory viruses. Further, advances in detection methods have contributed to increased pathogen detection rates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron has demonstrated decreased pathogenicity, yet a few individuals suffer severe pneumonia from coronavirus disease 2019 (COVID-19) infection; the underlying mechanisms are unknown.

The present work investigated the role of Interferon-stimulated genes (ISGs) in the occurrence and progression of severe Omicron infection. The expression and dynamic changes of ISGs were assessed using quantitative real-time polymerase chain reaction (qRT-PCR), and the anti-ISG15 autoantibody in infected patients was detected by ELISA. Moreover, we evaluated the correlation of ISGs with disease severity and outcomes by comparing expression of ISGs among each group.

Decreased expression of several ISGs such as IFI6 are potentially linked to increased severity or poor outcomes of Omicron infection. Longitudinal data also demonstrates that the dynamic variation of IFI6 in the Omicron infection phase may be linked to the prognosis of the disease. The increase of anti-ISG15 autoantibody potentially links to the disease progression and poor outcome of patients with high level of ISG15 expression.

These findings define aberrant Interferon-stimulated gene associated host responses and reveal potential mechanisms and therapeutic targets for Omicron or other viral infection.

The implementation of COVID-19 policy and the rapid development of SARS-CoV-2 vaccines in the early pandemic significantly contained numerous outbreaks and reduced the severity and mortality of COVID-19. However, the population immunity induced by existing vaccines was insufficient to prevent SARS-CoV-2 outbreaks. The host immunity induced by the wide spread of Omicron variants and its influence on emerging SARS-CoV-2 variants are attracting broad attention. In this study, a clinical data analysis of the patients indicated that pre-vaccination reduced inflammatory responses and mitigated the severity of COVID-19 cases caused by natural infection with Omicron BA.5.2. The analysis of adaptive immune responses indicated that natural infection with BA.5.2 induced robust and broad immune responses, including both humoral and T cell-mediated immune responses (IFN-γ) against highly conserved viral antigens, and provided cross-reactive neutralization against various viral variants. Collectively, we report that the natural infection with Omicron BA.5.2 induced broad cross-reactive immunity against SARS-CoV-2 variants, which suggests that the development of a live attenuated SARS-CoV-2 vaccine with desired safety, high efficacy, broad spectrum, and long-term immune persistence is feasible. Therefore, we suggest that herd immunity, achieved through vaccination with attenuated vaccines, combined with booster doses of existing vaccines and antiviral therapy for people with high viral loads, may contribute to the eradication of this virus.

Severe fever with thrombocytopenia syndrome (SFTS) is a fatal tick-borne infectious disease that lacks effective treatments. Dynamic analysis that reflects changes in the SFTS patient's condition is needed. This study aimed to evaluate the time-dependent predictive performance of key biomarkers using a time-dependent Cox regression model. A retrospective multicenter cohort study was conducted on 440 SFTS patients hospitalized in South Korea between 2013 and 2024. Time-dependent Cox regression and time-dependent receiver operating characteristic (ROC) analyses were applied to assess the prognostic value of Blood Urea Nitrogen (BUN), Prothrombin Time (PT), and Activated Partial Thromboplastin Time (aPTT). Missing data were handled using multiple imputation. aPTT consistently demonstrated high predictive accuracy (AUC > 0.90) throughout the disease course, indicating its sustained role in coagulopathy. PT exhibited strong early-stage predictive power (AUC = 0.86 on day 2) but declined over time, reflecting its utility for early monitoring. BUN showed a progressive increase in predictive performance (AUC = 0.70 on day 2 to AUC = 0.78 on day 8), supporting its relevance in later stages of disease progression. Non-survivors exhibited significantly higher levels of BUN, PT, and aPTT compared to survivors. This study demonstrates the utility of time-dependent analysis for evaluating dynamic biomarker changes in SFTS patients. aPTT is a robust predictor throughout the disease course, while PT is valuable for early-stage assessment and BUN for later-stage management. These findings suggest the importance of integrating dynamic biomarker monitoring into clinical decision-making to improve prognosis in SFTS patients.

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The global pandemic of novel coronavirus pneumonia (COVID-19) has resulted in millions of deaths over the past three years. As one of the most commonly affected extra-pulmonary organs, numerous studies have reported varying degrees of liver injury in a significant proportion of patients with COVID-19, particularly in severe and critically ill patients. Early prediction of liver dysfunction in hospitalized patients would facilitate the clinical management of COVID-19 and improve clinical prognosis, but reliable and valid predictive models are still lacking.MethodsWe collected data from 286 patients with RT-PCR confirmed COVID-19 admitted to various ICUs from the case system. These patients were randomly divided into a training cohort (50%) and a validation cohort (50%). In the training cohort, we first used ROC curves to measure the predictive efficiency of each of the variables for the development of liver damage during hospitalization in patients with COVID-19, followed by LASSO regression analysis to screen the variables for predictive models and logistic regression analysis to identify relevant risk factors. A nomogram based on these variables was created following the above model. Finally, the efficiency of the prediction models in the training and validation cohorts was assessed using AUC, consistency index (C index), calibration curves and Decision Curve Analysis.ResultsOut of a total of 80 parameters for COVID-19 patients admitted to the ICUs, 10 were determined to be significantly associated with the occurrence of liver dysfunction during hospitalization. Based on these predictors, further prediction models were used to construct and develop a nomogram that was offered for practical clinical application. The C-index of the column line graphs for the training and validation cohorts was 0.956 and 0.844 respectively. in addition, the calibration curves for the model showed a high degree of agreement between the predicted and actual incidence of liver dysfunction in patients with COVID-19.ConclusionBy developing a predictive model and associated nomogram, we predicted the incidence of liver dysfunction during hospitalization in patients with COVID-19 in the ICU. The model's predictive performance was determined in both the training and validation cohorts, contributing to the clinical management of COVID-19.

In recent years, the incidence of acute respiratory distress syndrome (ARDS) has been gradually increasing. Despite advances in supportive care, ARDS remains a significant cause of morbidity and mortality in critically ill patients. ARDS is characterized by acute hypoxaemic respiratory failure with diffuse pulmonary inflammation and bilateral edema due to excessive alveolocapillary permeability in patients with non-cardiogenic pulmonary diseases. Over the past seven decades, our understanding of the pathology and clinical characteristics of ARDS has evolved significantly, yet it remains an area of active research and discovery. ARDS is highly heterogeneous, including diverse pathological causes, clinical presentations, and treatment responses, presenting a significant challenge for clinicians and researchers. In this review, we comprehensively discuss the latest advancements in ARDS research, focusing on its heterogeneity, pathophysiological mechanisms, and emerging therapeutic approaches, such as cellular therapy, immunotherapy, and targeted therapy. Moreover, we also examine the pathological characteristics of COVID-19-related ARDS and discuss the corresponding therapeutic approaches. In the face of challenges posed by ARDS heterogeneity, recent advancements offer hope for improved patient outcomes. Further research is essential to translate these findings into effective clinical interventions and personalized treatment approaches for ARDS, ultimately leading to better outcomes for patients suffering from ARDS.

Gastrointestinal (GI) hemorrhage has been reported in patients with SARS-CoV-2. Although there is consensus that the infection is associated with GI sequelae, controversy remains regarding its clinical significance. Endoscopic intervention was limited during the pandemic due to safety concerns and resource constraints, which may have hindered a full assessment of the impact of GI hemorrhage on patient outcomes. This paper aims to evaluate the outcomes of patients diagnosed with SARS-CoV-2 and concurrent clinically significant GI hemorrhage.

A total of 125 patients (69 male, 56 female) over the age of 18, with signed procedural consent, were included. All met the criteria for a SARS-CoV-2 diagnosis and underwent diagnostic endoscopic intervention. Data were analyzed using the Mann-Whitney U test with Excel (Microsoft Corporation, Redmond, WA, USA) and SPSS Statistics version 25 (IBM Corp., Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp.).

The overall hospital length of stay was 8 ± 6 days. A subset analysis compared patients requiring ICU admission with those who did not. The average ICU length of stay was 13 ± 6 days, compared to 5 ± 3 days for non-ICU patients. Among patients who underwent esophagogastroduodenoscopy, 65% (70/108) required intervention, while 16% (3/19) of colonoscopies required intervention. There was no significant difference in underlying comorbidities or rates of non-invasive mechanical ventilation between groups. Overall mortality was 50% (62/125), with no significant difference between ICU (26/50) and non-ICU (36/75) patients (52% vs. 48%).

While studies have indicated an increased risk of GI complications in SARS-CoV-2 patients, many have not differentiated between hemorrhagic and non-hemorrhagic sequelae or accounted for the level of care. We conclude that there was higher mortality among patients requiring endoscopic intervention, regardless of their level of care or patient-specific factors.

COVID-19 upsurge in orotracheal intubation (OTI) has opened a new opportunity for studying associated complications. Vocal fold motion impairment (VFMI) is a known complication of OTI. The present study sought to determine the impact of OTI and prolonged OTI on the risk of developing VFMI; to identify both risk and protective factors associated with it.

Retrospective cohort study.

Multicenter.

Medical charts were reviewed for all patients that received invasive mechanical ventilation with a subsequent flexible laryngoscopic assessment between March 2020 and March 2022. The main outcomes were the presence of VFMI, including immobility (VFI) and hypomobility (VFH).

A total of 155 patients were included, 119 (76.8%) COVID-19 and 36 (23.2%) non-COVID-19 patients; overall 82 (52.9%) were diagnosed with VFMI. Eighty (52.3%) patients underwent a tracheostomy. The median (IQR) intubation duration was 18 (11...24.25) days, while the median (IQR) time to tracheostomy was 22 (16...29). In the adjusted model, we observed there was a 68% increased risk for VFMI from day 21 of intubation (RR: 1.68; 95% CI 1.07...2.65; P.ß=.ß0.025).

VFMI is a frequent complication in severely ill patients that undergo intubation. A prolonged OTI was associated with an increased risk of VFMI, highlighting the importance of timely tracheostomy. Further research is needed to confirm these findings in other subsets of critically ill patients.

Assessing functional capacity in hospitalized patients with COVID-19 may have been neglected due to a great demand for resources at the height of pandemic and the lack of specific assessment instruments for this population.

To identify the instruments used to evaluate functional capacity in COVID-19 patients hospitalized in COVID-19 wards and ICUs and the associations between use of assessment instruments and physiotherapist characteristics METHODS: The survey was conducted using REDCap web-based application, following the Consensus-Based Checklist for Reporting of Survey Studies guidelines. A non-probability recruitment approach aimed at physiotherapists who had treated hospitalized patients with COVID-19 in Brazil. The instruments were classified into four domains: muscle strength, mobility, activities of daily living, and physical performance, as for the International Classification of Functioning, Disability, and Health RESULTS: Overall, 485 physiotherapists responded to the survey, 81.9% of whom used one or more instruments to assess functional capacity. The Medical Research Council (59.6%) and the Six-Minute Walk Test (21.7%) were the most commonly used instruments in COVID-19 wards; the MRC (63.9%) and the Intensive Care Mobility Scale (33.1%), in ICUs. In COVID-19 wards, higher probability of using assessment instruments was associated with being male, having training on COVID-19 management, and working > 50 h/week. In ICUs, having training on COVID-19 management and working in university hospitals were associated with higher probability of using these instruments CONCLUSIONS: Most physiotherapists used one or more instruments to assess functional capacity, assessed more than one physical domain, and used the obtained results to plan interventions.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) represents a spectrum of potentially fatal conditions that currently lack effective drug treatment. Recent researches suggest that Fibroblast Growth Factor 21 (FGF21) may protect against ALI/ARDS. However, the clinical use of FGF21 is limited by its rapid degradation, restricted targeting capabilities, and numerous adverse effects. Addressing this challenge, the study employs a pH-responsive nanoparticle delivery system known as Hexahistidine-metal Assembly (HmA) for administering FGF21. The entrapment efficiency (EE%) and loading capacity (LCwt%) of HmA exceed 90 % and 35 %, respectively, while the HmA@FGF21 nanoparticles exhibit an average size of 130 nm, a PDI value of approximately 0.28, and a zeta potential of 24 mV. In animal experiments, HmA@FGF21 administered in lipopolysaccharide (LPS)-induced lung injury significantly exceed those of standalone FGF21, including mitigating the pathological manifestations and reducing the wet/dry ratio, total protein concentration, and overall cell count in BALF of ALI, whether administered via the airway or intravenously. This therapeutic approach therefore shows promise for precise delivery of FGF21 to the lungs to treat ALI, and may offer a novel, and efficient method for delivery of potential pharmacological agents to address other lung diseases.

The COVID-19 pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has profoundly affected global health systems. Healthcare systems across the globe have been pushed to their limits, with intensive care units (ICUs) witnessing a sharp rise in admissions, putting a strain on resources and personnel.

Examine ICU health outcomes, including mortality, length of stay (LOS), and discharge rates, among COVID-19 and non-COVID-19 patients.

Retrospective, cross-sectional study.

A national cross-sectional dataset provided by the Ministry of Health in Saudi Arabia.

All patients admitted to ICUs across Saudi Arabia between January 1, 2022, and December 31, 2022. Patients were classified as confirmed COVID-19 cases and non-COVID-19 cases. To evaluate the ICU outcomes, the study used multivariate regression models, adjusting for covariates including age, gender, region, citizenship, and comorbidity score.

ICU outcomes including mortality, LOS and discharge rate.

114 854 ICU patients.

The study population consisted of 114 854 ICU patients across various demographic and clinical categories. Mortality was found to be higher in COVID-19 patients than non-COVID-19 patients, with COVID-19 patients showing a 7% increase in mortality (OR=1.07, 95% CI: 1.02-1.12). Also, COVID-19 patients had 78% higher odds of being discharged home than the non-COVID-19 group (OR=1.78, 95% CI: 1.71-1.84). Moreover, the average LOS in the ICU was significantly shorter for COVID-19 patients than non-COVID-19 patients by 6% on average (Coefficient=-0.06, 95% CI: -0.07 to -0.03).

Significant differences were seen in ICU outcomes between patients with and without COVID-19, including mortality rates, discharge rates, and LOS. COVID-19 patients exhibited higher mortality rate and discharge rate, and shorter ICU LOS than those without COVID-19.

The data used in this study has missing critical information such as laboratory results, socioeconomic variables, and hospitalization characteristics.