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Guglielmi V, Colangeli L, Parrotta ME, Ciammariconi A, Milani I, D'Adamo M, Sbraccia P, Capoccia D. Social isolation and loneliness in non-communicable chronic diseases: Impact of COVID-19 pandemic, population aging and technological progress. Nutr Metab Cardiovasc Dis 2025; 35:104015. [PMID: 40189996 DOI: 10.1016/j.numecd.2025.104015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/07/2025] [Accepted: 03/10/2025] [Indexed: 04/29/2025]
Abstract
AIMS 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. DATA SYNTHESIS 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. CONCLUSIONS 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.
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Affiliation(s)
- Valeria Guglielmi
- Department of Systems Medicine, University of Rome Tor Vergata, Obesity Medical Center, University Hospital Policlinico Tor Vergata, Rome, Italy.
| | - Luca Colangeli
- Department of Systems Medicine, University of Rome Tor Vergata, Obesity Medical Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Maria Eugenia Parrotta
- Department of Systems Medicine, University of Rome Tor Vergata, Obesity Medical Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Azzurra Ciammariconi
- Department of Systems Medicine, University of Rome Tor Vergata, Obesity Medical Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Ilaria Milani
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
| | - Monica D'Adamo
- Department of Systems Medicine, University of Rome Tor Vergata, Obesity Medical Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Paolo Sbraccia
- Department of Systems Medicine, University of Rome Tor Vergata, Obesity Medical Center, University Hospital Policlinico Tor Vergata, Rome, Italy
| | - Danila Capoccia
- Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
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Scheinberg P, Khoshnevis MR, Robinson PA, Guerreros A, Sato VAH, Fonseca BAL, Prozesky HW, Romero JOC, Fogliatto L, Meisenberg BR, Park DJ, Gupta A, Patel P, Townsley DM, Zheng L, Munugalavadla V. Efficacy and safety of acalabrutinib with best supportive care versus best supportive care in patients with COVID-19 requiring hospitalization. Immunohorizons 2025; 9:vlaf023. [PMID: 40461100 PMCID: PMC12133263 DOI: 10.1093/immhor/vlaf023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Accepted: 12/24/2024] [Indexed: 06/11/2025] Open
Abstract
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.
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Affiliation(s)
- Phillip Scheinberg
- Division of Hematology, Hospital A Beneficência Portuguesa, São Paulo, Brazil
| | - Matt R Khoshnevis
- Center for Critical Care, Houston Methodist Hospital, Houston, TX, United States
| | - Philip A Robinson
- Infection Prevention and Hospital Epidemiology, Hoag Memorial Hospital Presbyterian, Newport Beach, CA, United States
| | | | - Victor A H Sato
- International Research Center, Hospital Alemao Oswaldo Cruz, São Paulo, Brazil
| | - Benedito A L Fonseca
- Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (FMRP), São Paulo, Brazil
| | - Hans W Prozesky
- Division of Infectious Diseases, Department of Medicine, Stellenbosch University and TREAD Research, Tygerberg Hospital, Cape Town, South Africa
| | - José Omar Chacón Romero
- Hospital Sub-direction, IMSS HGR No. 1 Dr Carlos Mac Gregor Sanchez Navarro, Mexico City, Mexico
| | - Laura Fogliatto
- Hematology and Hemotherapy Department, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil
| | - Barry R Meisenberg
- Department of Medicine, Anne Arundel Medical Center, Annapolis, MD, United States
| | - David J Park
- Hematology and Oncology, Providence St Jude Medical Center/Providence Medical Foundation, Fullerton, CA, United States
| | - Ashok Gupta
- Oncology Research and Development, AstraZeneca, Gaithersburg, MD, United States
| | - Priti Patel
- Haematology Research and Development, AstraZeneca, South San Francisco, CA, United States
| | - Danielle M Townsley
- Oncology Research and Development, AstraZeneca, Gaithersburg, MD, United States
| | - Lianqing Zheng
- Oncology Biometrics, AstraZeneca, South San Francisco, CA, United States
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Kumar N, Segovia D, Kumar P, Atti HB, Kumar S, Mishra J. Mucosal implications of oral Jak3-targeted drugs in COVID patients. Mol Med 2025; 31:203. [PMID: 40410684 PMCID: PMC12100796 DOI: 10.1186/s10020-025-01260-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Accepted: 05/12/2025] [Indexed: 05/25/2025] Open
Abstract
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.
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Affiliation(s)
- Narendra Kumar
- ILR-College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX, USA.
| | - Daniel Segovia
- ILR-College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX, USA
| | - Priyam Kumar
- University of Pennsylvania, Philadelphia, PA, USA
| | - Hima Bindu Atti
- ILR-College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX, USA
| | - Soaham Kumar
- Veterans Memorial High School, Corpus Christi, TX, USA
| | - Jayshree Mishra
- ILR-College of Pharmacy, Texas A&M University Health Science Center, Kingsville, TX, USA.
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4
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Yılmaz Çınar B, Türkoğlu O, Becerik S. Oral hygiene influence on the incidence and severity of oral manifestations in Coronavirus Disease 2019. BMC Oral Health 2025; 25:755. [PMID: 40399926 PMCID: PMC12096546 DOI: 10.1186/s12903-025-06075-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 04/29/2025] [Indexed: 05/23/2025] Open
Abstract
INTRO 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. METHODS 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. RESULTS 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). CONCLUSION 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.
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Affiliation(s)
| | - Oya Türkoğlu
- Department of Periodontology, Ege University, School of Dentistry, Bornova, İzmi̇r, 35100, Turkey
| | - Sema Becerik
- Department of Periodontology, Ege University, School of Dentistry, Bornova, İzmi̇r, 35100, Turkey.
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5
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Tizazu AM, Gize A, Ali S. Age influences blood cell-based immune deregulation antibody response and unfavorable clinical outcomes in COVID-19 patients. Sci Rep 2025; 15:17431. [PMID: 40394243 PMCID: PMC12092784 DOI: 10.1038/s41598-025-95722-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Accepted: 03/24/2025] [Indexed: 05/22/2025] Open
Abstract
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.
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Affiliation(s)
- Anteneh Mehari Tizazu
- Department of Microbiology, Immunology and Parasitology, School of Medicine, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.
| | - Addisu Gize
- Department of Microbiology, Immunology and Parasitology, School of Medicine, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
- CIHLMU Center for International Health, LMU University Hospital, LMU Munich, Germany
| | - Solomon Ali
- Department of Microbiology, Immunology and Parasitology, School of Medicine, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
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Boscolo A, Bruni A, Giani M, Garofalo E, Sella N, Pettenuzzo T, Peralta A, Bombino M, Palcani M, Rezoagli E, Pozzi M, Falcioni E, Biamonte E, Murgolo F, Gottin L, Longhini F, Grasso S, Navalesi P, Foti G, FERS. Retrospective Analysis of Fungal Isolations in Patients on Veno-Venous Extracorporeal Membrane Oxygenation: The Multicenter RANGER STUDY 2.0. J Fungi (Basel) 2025; 11:377. [PMID: 40422711 DOI: 10.3390/jof11050377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2025] [Revised: 05/07/2025] [Accepted: 05/08/2025] [Indexed: 05/28/2025] Open
Abstract
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.
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Affiliation(s)
- Annalisa Boscolo
- Department of Medicine (DIMED), University of Padua, 35122 Padua, Italy
- Institute of Anesthesia and Critical Care, Padua University Hospital, 35128 Padua, Italy
| | - Andrea Bruni
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
| | - Marco Giani
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
- Department of Emergency and Intensive Care, Fondazione IRCSS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Eugenio Garofalo
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
| | - Nicolò Sella
- Institute of Anesthesia and Critical Care, Padua University Hospital, 35128 Padua, Italy
| | - Tommaso Pettenuzzo
- Institute of Anesthesia and Critical Care, Padua University Hospital, 35128 Padua, Italy
| | - Arianna Peralta
- Institute of Anesthesia and Critical Care, Padua University Hospital, 35128 Padua, Italy
| | - Michela Bombino
- Department of Emergency and Intensive Care, Fondazione IRCSS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Matteo Palcani
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
| | - Emanuele Rezoagli
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
- Department of Emergency and Intensive Care, Fondazione IRCSS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Matteo Pozzi
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
- Department of Emergency and Intensive Care, Fondazione IRCSS San Gerardo dei Tintori, 20900 Monza, Italy
| | - Elena Falcioni
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37129 Verona, Italy
- Cardiothoracic and Vascular Intensive Care Unit, Verona University Hospital, 37126 Verona, Italy
| | - Eugenio Biamonte
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
| | - Francesco Murgolo
- Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Leonardo Gottin
- Department of Surgery, Dentistry, Paediatrics and Gynaecology, University of Verona, 37129 Verona, Italy
- Cardiothoracic and Vascular Intensive Care Unit, Verona University Hospital, 37126 Verona, Italy
| | - Federico Longhini
- Department of Medical and Surgical Sciences, Magna Graecia University, 88100 Catanzaro, Italy
| | - Salvatore Grasso
- Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari "Aldo Moro", 70121 Bari, Italy
| | - Paolo Navalesi
- Department of Medicine (DIMED), University of Padua, 35122 Padua, Italy
- Institute of Anesthesia and Critical Care, Padua University Hospital, 35128 Padua, Italy
| | - Giuseppe Foti
- School of Medicine and Surgery, University of Milano Bicocca, 20900 Monza, Italy
- Department of Emergency and Intensive Care, Fondazione IRCSS San Gerardo dei Tintori, 20900 Monza, Italy
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Yildirim M, Halacli B, Kaya EK, Ulusoydan E, Ortac Ersoy E, Topeli A. Prognostic Accuracy of Nutritional Assessment Tools in Critically-Ill COVID-19 Patients. J Clin Med 2025; 14:3382. [PMID: 40429378 PMCID: PMC12112212 DOI: 10.3390/jcm14103382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2025] [Revised: 04/23/2025] [Accepted: 05/07/2025] [Indexed: 05/29/2025] Open
Abstract
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.
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Affiliation(s)
- Mehmet Yildirim
- Department of Internal Medicine, Division of Intensive Care, Faculty of Medicine, Hacettepe University, 06080 Ankara, Türkiye; (B.H.); (E.K.K.)
| | - Burcin Halacli
- Department of Internal Medicine, Division of Intensive Care, Faculty of Medicine, Hacettepe University, 06080 Ankara, Türkiye; (B.H.); (E.K.K.)
| | - Esat Kivanc Kaya
- Department of Internal Medicine, Division of Intensive Care, Faculty of Medicine, Hacettepe University, 06080 Ankara, Türkiye; (B.H.); (E.K.K.)
| | - Ege Ulusoydan
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, 06080 Ankara, Türkiye
| | - Ebru Ortac Ersoy
- Department of Internal Medicine, Division of Intensive Care, Faculty of Medicine, Hacettepe University, 06080 Ankara, Türkiye; (B.H.); (E.K.K.)
| | - Arzu Topeli
- Department of Internal Medicine, Division of Intensive Care, Faculty of Medicine, Hacettepe University, 06080 Ankara, Türkiye; (B.H.); (E.K.K.)
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Hermann M, Filipsky R, Bukowski N, Gerger G, Hermann A, Krenn K, Teufel A, Kimberger O, Laxar D, Maleczek M, Schaden E, Wiegele M, Willschke H, Tiboldi A. Long-Term Health-Related Quality of Life Following Survival of Acute Respiratory Distress Syndrome and Extracorporeal Membrane Oxygenation Due to COVID-19. J Clin Med 2025; 14:3358. [PMID: 40429356 PMCID: PMC12112094 DOI: 10.3390/jcm14103358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2025] [Revised: 05/06/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
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.
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Affiliation(s)
- Martina Hermann
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Rebecca Filipsky
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Nils Bukowski
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Gernot Gerger
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Alexander Hermann
- Intensive Care Unit 13i2, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria
| | - Katharina Krenn
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Anna Teufel
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Oliver Kimberger
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Daniel Laxar
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Mathias Maleczek
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Eva Schaden
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Marion Wiegele
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
| | - Harald Willschke
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
| | - Akos Tiboldi
- Department of Anaesthesia, Clinical Division of General Anaesthesia and Intensive Care Medicine, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, 1090 Vienna, Austria
- Ludwig Boltzmann Institute Digital Health and Patient Safety, 1180 Vienna, Austria
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Muñoz-Carrillo JL, Palomeque-Molina PI, Villacis-Valencia MS, Gutiérrez-Coronado O, Chávez-Ruvalcaba F, Vázquez-Alcaraz SJ, Villalobos-Gutiérrez PT, Palomeque-Molina J. Relationship between periodontitis, type 2 diabetes mellitus and COVID-19 disease: a narrative review. Front Cell Infect Microbiol 2025; 15:1527217. [PMID: 40406515 PMCID: PMC12095153 DOI: 10.3389/fcimb.2025.1527217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 04/16/2025] [Indexed: 05/26/2025] Open
Abstract
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.
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Affiliation(s)
- José Luis Muñoz-Carrillo
- Laboratorio de Inmunología, Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno, Jalisco, Mexico
- Escuela de Odontología, Global University, Aguascalientes, Aguascalientes, Mexico
| | | | | | - Oscar Gutiérrez-Coronado
- Laboratorio de Inmunología, Centro Universitario de los Lagos, Universidad de Guadalajara, Lagos de Moreno, Jalisco, Mexico
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10
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Dourliou V, Kakaletsis N, Stamou D, Champla A, Tsakiri K, Agapakis D, Didangelos T. Diabetes Mellitus and Multidrug-Resistant Gram-Negative Bacterial Infections in Critically Ill COVID-19 Patients: A Retrospective Observational Study. Diagnostics (Basel) 2025; 15:1190. [PMID: 40428183 PMCID: PMC12110607 DOI: 10.3390/diagnostics15101190] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2025] [Revised: 05/03/2025] [Accepted: 05/05/2025] [Indexed: 05/29/2025] Open
Abstract
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.
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Affiliation(s)
- Vasiliki Dourliou
- Department of Adult Intensive Care Unit, Ippokrateio General Hospital, 54642 Thessaloniki, Greece; (D.S.); (A.C.); (K.T.)
| | - Nikolaos Kakaletsis
- Internal Medicine Unit, Ippokrateio General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece;
| | - Dafni Stamou
- Department of Adult Intensive Care Unit, Ippokrateio General Hospital, 54642 Thessaloniki, Greece; (D.S.); (A.C.); (K.T.)
| | - Antigoni Champla
- Department of Adult Intensive Care Unit, Ippokrateio General Hospital, 54642 Thessaloniki, Greece; (D.S.); (A.C.); (K.T.)
| | - Kalliopi Tsakiri
- Department of Adult Intensive Care Unit, Ippokrateio General Hospital, 54642 Thessaloniki, Greece; (D.S.); (A.C.); (K.T.)
| | - Dimitrios Agapakis
- Department of Internal Medicine, Aghios Pavlos General Hospital, 55134 Thessaloniki, Greece;
| | - Triantafyllos Didangelos
- Diabetes Center, 1st Propaedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, 54636 Thessaloniki, Greece;
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11
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Bhargava A, Szpunar S, Saravolatz L. The prognostic nutritional index as a risk factor for severe COVID-19 infection among hospitalized patients: A multicenter historical cohort study. Am J Med Sci 2025:S0002-9629(25)01018-3. [PMID: 40320145 DOI: 10.1016/j.amjms.2025.04.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Revised: 04/12/2025] [Accepted: 04/28/2025] [Indexed: 05/19/2025]
Abstract
INTRODUCTION 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. OBJECTIVE To evaluate whether PNI was independently associated with the severity of COVID-19 infection among hospitalized patients in the United States. METHODS 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. RESULTS 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). CONCLUSIONS 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.
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Affiliation(s)
- Ashish Bhargava
- Department of Internal Medicine, Wayne State University, Detroit, MI, USA; Division of Infectious Disease, Department of Internal Medicine, Henry Ford Health - St John Hospital, Detroit, MI, USA; Thomas Mackey Center for Infectious Disease Research, Henry Ford Health - St John Hospital, Detroit, MI, USA.
| | - Susan Szpunar
- Department of Biomedical Investigations and Research, Henry Ford Health - St John Hospital, Detroit, MI, USA
| | - Louis Saravolatz
- Department of Internal Medicine, Wayne State University, Detroit, MI, USA; Division of Infectious Disease, Department of Internal Medicine, Henry Ford Health - St John Hospital, Detroit, MI, USA; Thomas Mackey Center for Infectious Disease Research, Henry Ford Health - St John Hospital, Detroit, MI, USA
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12
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Jiménez-Zarazúa O, Gil-Veloz M, Vélez-Ramírez LN, Lozada Hernández EE, Mondragón JD. Assessment of epicardial adipose tissue in patients with severe and critical COVID-19 pneumonia as a predictor of in-hospital mortality. Respir Med 2025; 241:108085. [PMID: 40185162 DOI: 10.1016/j.rmed.2025.108085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 04/01/2025] [Accepted: 04/02/2025] [Indexed: 04/07/2025]
Abstract
INTRODUCTION 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. METHODS 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. RESULTS 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. DISCUSSION 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.
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Affiliation(s)
- O Jiménez-Zarazúa
- Hospital General Zona 21 IMSS, Department of Internal Medicine, León, Guanajuato, Mexico; Universidad Nacional Autonóma de México, Escuela Nacional de Estudios Superiores-León, León, Guanajuato, Mexico.
| | - M Gil-Veloz
- Servicios de Salud del Instituto Mexicano del Seguro Social para el Bienestar (IMSS-BIENESTAR), Hospital Regional de Alta Especialidad del Bajío, Department of Pediatric Infectology, León, Guanajuato, Mexico
| | - L N Vélez-Ramírez
- Hospital General León, Department of Radiology, León, Guanajuato, Mexico; Universidad de Guanajuato, School of Medicine and Nutrition, León, Guanajuato, Mexico
| | - E E Lozada Hernández
- Servicio de Salud del Instituto Mexicano del Seguro Social para el Bienestar (IMSS-BIENESTAR), Hospital Regional de Alta Especialidad del Bajío, Department of Surgery, León, Guanajuato, Mexico
| | - J D Mondragón
- University of Groningen, University Medical Center Groningen, Department of Neurology, Groningen, the Netherlands; Universidad Nacional Autónoma de México, Instituto de Neurobiología, Departamento de Neurobiología Conductual y Cognitiva, Laboratorio de Psicofisiología, Querétaro, Mexico; San Diego State University, Department of Psychology, Life-Span Human Senses Lab, San Diego, CA, USA.
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13
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Nandula SR, Brichacek B, Sen S. Podocyte-Specific Protein Expression in Urine Exosome Acts as a Marker for Renal Injury in Post-COVID State. Metab Syndr Relat Disord 2025; 23:205-210. [PMID: 40100769 DOI: 10.1089/met.2024.0199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/20/2025] Open
Abstract
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.
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Affiliation(s)
- Seshagiri Rao Nandula
- Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Beda Brichacek
- Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
| | - Sabyasachi Sen
- Department of Medicine and Biochemistry, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA
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14
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Sasaki K, Garcia-Manero G, Nigo M, Jabbour E, Ravandi F, Wierda WG, Jain N, Takahashi K, Montalban-Bravo G, Daver NG, Thompson PA, Pemmaraju N, Kontoyiannis DP, Sato J, Karimaghaei S, Soltysiak KA, Raad II, Kantarjian HM, Carter BW. Artificial Intelligence Assessment of Chest Radiographs for COVID-19. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2025; 25:319-327. [PMID: 39710565 PMCID: PMC11993350 DOI: 10.1016/j.clml.2024.11.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 10/21/2024] [Accepted: 11/25/2024] [Indexed: 12/24/2024]
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
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Affiliation(s)
- Koji Sasaki
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Hematology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
| | | | - Masayuki Nigo
- Division of Infectious Diseases, Department of Internal Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
| | - Elias Jabbour
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Farhad Ravandi
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - William G Wierda
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Nitin Jain
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Koichi Takahashi
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | - Naval G Daver
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Philip A Thompson
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Naveen Pemmaraju
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Dimitrios P Kontoyiannis
- Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Junya Sato
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Sam Karimaghaei
- McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX
| | - Kelly A Soltysiak
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Issam I Raad
- Department of Infectious Disease, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Hagop M Kantarjian
- Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Brett W Carter
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX
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15
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He Y, Zheng Q, Zhifang Z, Xiaofeng N, Shenggen W, Xue M, Zheng C, Liu Z. When COVID-19 meets diabetes: A bibliometric analysis. Diabetes Res Clin Pract 2025; 223:112118. [PMID: 40132732 DOI: 10.1016/j.diabres.2025.112118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 03/13/2025] [Accepted: 03/19/2025] [Indexed: 03/27/2025]
Abstract
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.
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Affiliation(s)
- Yingli He
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, China
| | - Qingcong Zheng
- Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
| | - Zhang Zhifang
- Fujian Center for Disease Control and Prevention, Fuzhou 350012, China
| | | | - Wu Shenggen
- Fujian Center for Disease Control and Prevention, Fuzhou 350012, China
| | - Mengzhou Xue
- Department of Cerebrovascular Diseases, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
| | - Chunfu Zheng
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
| | - Zhijun Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xi'an Jiaotong University, China.
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16
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Hong P, Chen Y, Xia J, Surani S, Dai Y, Zhu J. The effects of different prone ventilation strategies on mechanical power and respiratory mechanics in acute respiratory distress syndrome patients: a prospective, single-center observational study. J Thorac Dis 2025; 17:2411-2422. [PMID: 40400920 PMCID: PMC12090122 DOI: 10.21037/jtd-2025-267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Accepted: 04/21/2025] [Indexed: 05/13/2025]
Abstract
Background 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. Methods 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. Results 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. Conclusions 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.
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Affiliation(s)
- Pei Hong
- Nursing Studies, Zhejiang University School of Medicine, Hangzhou, China
- Department of Intensive Care Unit, The Fifth Affiliated Hospital of Wenzhou Medical University (Lishui Central Hospital), Lishui, China
| | - Yuequn Chen
- Department of Intensive Care Unit, The Fifth Affiliated Hospital of Wenzhou Medical University (Lishui Central Hospital), Lishui, China
| | - Junli Xia
- Department of Intensive Care Unit, The Fifth Affiliated Hospital of Wenzhou Medical University (Lishui Central Hospital), Lishui, China
| | - Salim Surani
- Department of Medicine & Pharmacology, Texas A&M University, College Station, TX, USA
| | - Yexing Dai
- Department of Intensive Care Unit, The Fifth Affiliated Hospital of Wenzhou Medical University (Lishui Central Hospital), Lishui, China
| | - Junhong Zhu
- Nursing Studies, Zhejiang University School of Medicine, Hangzhou, China
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17
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Ghaffarpour S, Ghazanfari T, Ardestani SK, Naghizadeh MM, Vaez Mahdavi MR, Salehi M, Majd AMM, Rashidi A, Chenary MR, Mostafazadeh A, Rezaei A, Khodadadi A, Iranparast S, Khazaei HA. Cytokine profiles dynamics in COVID-19 patients: a longitudinal analysis of disease severity and outcomes. Sci Rep 2025; 15:14209. [PMID: 40269030 PMCID: PMC12019550 DOI: 10.1038/s41598-025-98505-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 04/11/2025] [Indexed: 04/25/2025] Open
Abstract
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.
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Affiliation(s)
- Sara Ghaffarpour
- Immunoregulation Research Center, Shahed University, Tehran, Iran
| | - Tooba Ghazanfari
- Immunoregulation Research Center, Shahed University, Tehran, Iran.
- Department of Immunology, Shahed University, Tehran, Iran.
| | - Sussan Kaboudanian Ardestani
- Immunoregulation Research Center, Shahed University, Tehran, Iran
- Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | | | | | - Mohammadreza Salehi
- Department of Infectious Diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Azadeh Rashidi
- Immunoregulation Research Center, Shahed University, Tehran, Iran
| | | | - Amrollah Mostafazadeh
- Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Abbas Rezaei
- Department of Immunology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ali Khodadadi
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Sara Iranparast
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hossein Ali Khazaei
- Department of Immunology and Internal Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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Ladetto MF, Gantner ME, Rodenak-Kladniew BE, Rodriguez S, Cuestas ML, Talevi A, Castro GR. Promising Prodiginins Biological Activities. Chem Biodivers 2025:e202402940. [PMID: 40244866 DOI: 10.1002/cbdv.202402940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 04/10/2025] [Accepted: 04/17/2025] [Indexed: 04/19/2025]
Abstract
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.
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Affiliation(s)
- María F Ladetto
- Laboratorio de Nanobiomateriales, CINDEFI-Departamento de Química, Facultad de Ciencias Exactas, CONICET-UNLP (CCT La Plata), La Plata, Buenos Aires, Argentina
- Institute for Research in Microbiology and Medical Parasitology (IMPaM), University of Buenos Aires, Buenos Aires, Argentina
| | - Melisa E Gantner
- Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Boris E Rodenak-Kladniew
- Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, CCT-La Plata, Facultad de Ciencias Médicas, La Plata, Argentina
| | - Santiago Rodriguez
- Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - María L Cuestas
- Institute for Research in Microbiology and Medical Parasitology (IMPaM), University of Buenos Aires, Buenos Aires, Argentina
| | - Alan Talevi
- Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB), Departamento de Ciencias Biológicas, Facultad de Ciencias Exactas, Universidad Nacional de La Plata (UNLP), La Plata, Buenos Aires, Argentina
| | - Guillermo R Castro
- Nanomedicine Research Unit (Nanomed), Center for Natural and Human Sciences, Federal University of ABC (UFABC), Santo Andre, Sao Paulo, Brazil
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Bachiller S, Vitallé J, Camprubí-Ferrer L, García M, Gallego I, López-García M, Galvá MI, Cañizares J, Rivas-Jeremías I, Díaz-Mateos M, Gasca-Capote C, Moral-Turón C, Galán-Villamor L, Fontillón M, Sobrino S, Cisneros JM, López-Cortés LF, Deierborg T, Ruiz-Mateos E. SARS-CoV-2 post-acute sequelae linked to inflammation via extracellular vesicles. Front Immunol 2025; 16:1501666. [PMID: 40330474 PMCID: PMC12052859 DOI: 10.3389/fimmu.2025.1501666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Accepted: 03/31/2025] [Indexed: 05/08/2025] Open
Abstract
Background 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. Methods 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. Results 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. Conclusions 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.
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Affiliation(s)
- Sara Bachiller
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
| | - Joana Vitallé
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | - Lluís Camprubí-Ferrer
- Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Lund University, Lund, Sweden
| | - Manuel García
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | - Isabel Gallego
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
- Department of Medical Biochemistry, Molecular Biology and Immunology, School of Medicine, University of Seville, Seville, Spain
| | | | | | | | - Inmaculada Rivas-Jeremías
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | | | - Carmen Gasca-Capote
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | - Cristina Moral-Turón
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | | | - María Fontillón
- Service of Pathological Anatomy, Virgen del Rocío University Hospital, Seville, Spain
| | - Salvador Sobrino
- Digestive Service, Virgen del Rocío University Hospital, Seville, Spain
| | - José Miguel Cisneros
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | - Luis Fernando López-Cortés
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
| | - Tomas Deierborg
- Experimental Neuroinflammation Laboratory, Department of Experimental Medical Sciences, Lund University, Lund, Sweden
| | - Ezequiel Ruiz-Mateos
- Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital, Spanish National Research Council (CSIC), University of Seville, Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Seville, Spain
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20
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Li X, Lin Q, Zhang D, Huang Z, Yu J, Zhao J, Li W, Liu W. Triglyceride-glucose index and prognosis in non-diabetic critically ill patients: data from the eICU database. Front Med (Lausanne) 2025; 12:1558968. [PMID: 40265186 PMCID: PMC12011771 DOI: 10.3389/fmed.2025.1558968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 03/26/2025] [Indexed: 04/24/2025] Open
Abstract
Background 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. Methods 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. 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. Conclusion 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.
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Affiliation(s)
- Xi Li
- Pharmacy Department, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China
| | - Qiujin Lin
- Department of Critical Care Medicine, Pengpai Memorial Hospital, Shanwei, China
| | - Dewen Zhang
- Department of Pharmacy, Pengpai Memorial Hospital, Shanwei, China
| | - Zhenhua Huang
- Department of Emergency Medicine, Health Science Center, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
| | - Jinshi Yu
- Pharmacy Department, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China
| | - Jiaqi Zhao
- Pharmacy Department, Shenzhen Qianhai Shekou Free Trade Zone Hospital, Shenzhen, China
| | - Wenzhou Li
- Shenzhen Baoan Women’s and Children’s Hospital, Shenzhen, China
| | - Wei Liu
- Department of Emergency Medicine, The Huangpu People’s Hospital, Zhongshan, China
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21
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Yang OO. The immunopathogenesis of SARS-CoV-2 infection: Overview of lessons learned in the first 5 years. JOURNAL OF IMMUNOLOGY (BALTIMORE, MD. : 1950) 2025:vkaf033. [PMID: 40180332 DOI: 10.1093/jimmun/vkaf033] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 02/11/2025] [Indexed: 04/05/2025]
Abstract
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.
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Affiliation(s)
- Otto O Yang
- Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
- Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
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22
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de la Cuesta-Torrado M, Vitale V, Velloso Alvarez A, Neira-Egea P, Diss C, Cuervo-Arango J. The Effect of Vaccination Status on Total Lymphocyte Count in Horses Affected by Equine Herpes Virus-1 Myeloencephalopathy. Animals (Basel) 2025; 15:1019. [PMID: 40218411 PMCID: PMC11987750 DOI: 10.3390/ani15071019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/26/2025] [Accepted: 03/30/2025] [Indexed: 04/14/2025] Open
Abstract
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.
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Affiliation(s)
- María de la Cuesta-Torrado
- Department of Animal Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain; (V.V.); (A.V.A.); (C.D.); (J.C.-A.)
- Veterinary Teaching Hospital, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain;
| | - Valentina Vitale
- Department of Animal Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain; (V.V.); (A.V.A.); (C.D.); (J.C.-A.)
- Veterinary Teaching Hospital, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain;
| | - Ana Velloso Alvarez
- Department of Animal Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain; (V.V.); (A.V.A.); (C.D.); (J.C.-A.)
- Veterinary Teaching Hospital, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain;
| | - Patricia Neira-Egea
- Veterinary Teaching Hospital, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain;
| | - Clairianne Diss
- Department of Animal Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain; (V.V.); (A.V.A.); (C.D.); (J.C.-A.)
- Clinique Equine de Provence, 13760 Saint-Cannat, France
| | - Juan Cuervo-Arango
- Department of Animal Medicine and Surgery, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain; (V.V.); (A.V.A.); (C.D.); (J.C.-A.)
- Veterinary Teaching Hospital, Universidad Cardenal Herrera-CEU, CEU Universities, 46115 Alfara del Patriarca, Valencia, Spain;
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23
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Eltobgy M, Klamer B, Farkas D, Londino JD, Englert JA, Horowitz JC, Mallampalli RK, Brock G, Bednash JS. Plasma proteomic profiles correlate with organ dysfunction in COVID-19 ARDS. Physiol Rep 2025; 13:e70300. [PMID: 40170544 PMCID: PMC11962209 DOI: 10.14814/phy2.70300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Accepted: 03/18/2025] [Indexed: 04/03/2025] Open
Abstract
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.
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Grants
- K08HL169725 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- R01HL142767 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- R01HL141195 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- P01HL114453 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- R01HL097376 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- R01HL081784 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- R01HL096376 HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- UM1TR004548 HHS | NIH | National Center for Advancing Translational Sciences (NCATS)
- OSU | College of Medicine Office of Research, Ohio State University (COMOR)
- HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)
- HHS | NIH | National Center for Advancing Translational Sciences (NCATS)
- OSU | College of Medicine Office of Research, Ohio State University (COMOR)
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Affiliation(s)
- Moemen Eltobgy
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
| | - Brett Klamer
- Department of Biomedical InformaticsThe Ohio State UniversityColumbusOhioUSA
| | - Daniela Farkas
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
| | - James D. Londino
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
- The Center for RNA BiologyCollege of Medicine, the Ohio State UniversityColumbusOhioUSA
| | - Joshua A. Englert
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
| | - Jeffrey C. Horowitz
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
| | - Rama K. Mallampalli
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
| | - Guy Brock
- Department of Biomedical InformaticsThe Ohio State UniversityColumbusOhioUSA
| | - Joseph S. Bednash
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep MedicineThe Ohio State UniversityColumbusOhioUSA
- Dorothy M. Davis Heart and Lung Research Institute (DHLRI), College of Medicine, The Ohio State UniversityColumbusOhioUSA
- The Center for RNA BiologyCollege of Medicine, the Ohio State UniversityColumbusOhioUSA
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24
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Zhenghua D, Ji Y, Wanjun Y, Gen L, Yabiao Z, Lingyun J. Analysis of respiratory RNA virus detection in the laboratory of a teaching hospital in Shanghai from 2017 to 2023. Diagn Microbiol Infect Dis 2025; 111:116729. [PMID: 39954394 DOI: 10.1016/j.diagmicrobio.2025.116729] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2024] [Revised: 11/16/2024] [Accepted: 02/03/2025] [Indexed: 02/17/2025]
Abstract
OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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.
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Affiliation(s)
- Dong Zhenghua
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China; Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Shanghai, China
| | - Yang Ji
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China; Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Shanghai, China
| | - Yu Wanjun
- Department of Clinical Laboratory, QingPu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai, 201799, China
| | - Li Gen
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China
| | - Zheng Yabiao
- Wuhan Beanno Biological Technology Co., Ltd, Wuhan, Hubei Province, China
| | - Ji Lingyun
- Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China; Key Laboratory of Pathogen-Host Interaction, Ministry of Education, Shanghai, China; School of Life Sciences, Fudan University, Shanghai, China.
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25
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Li Z, Peng M, Cheng L, Wang Z, Wu Z, Feng F, Feng X, Wang S, Guo Y, Li Y. Identification of aberrant interferon-stimulated gene associated host responses potentially linked to poor prognosis in COVID-19 during the Omicron wave. Virol J 2025; 22:89. [PMID: 40155905 PMCID: PMC11954226 DOI: 10.1186/s12985-025-02696-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 03/06/2025] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS These findings define aberrant Interferon-stimulated gene associated host responses and reveal potential mechanisms and therapeutic targets for Omicron or other viral infection.
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Affiliation(s)
- Zhan Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Min Peng
- Division of Respiratory and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Linlin Cheng
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - ZiRan Wang
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ziyan Wu
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Futai Feng
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Xinxin Feng
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Siyu Wang
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Ye Guo
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
| | - Yongzhe Li
- Department of Clinical Laboratory, State Key Laboratory of Complex, Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
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Li L, Feng T, Shen Q, Shi X, Wei Z, Chen W, Yang F, Zhu Y, Zhang C, Zhang S, Zhang Q, Fu S, Wang N, Tian WX, Liu J, Si L. Natural Infection of Omicron BA.5.2 in Patients Provides Broad Immune Responses Against SARS-CoV-2. Microorganisms 2025; 13:746. [PMID: 40284583 PMCID: PMC12029644 DOI: 10.3390/microorganisms13040746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Revised: 03/22/2025] [Accepted: 03/23/2025] [Indexed: 04/29/2025] Open
Abstract
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.
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Affiliation(s)
- Le Li
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China
| | - Tang Feng
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Quan Shen
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xiaoshan Shi
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Zhigong Wei
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Wanze Chen
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Fan Yang
- University of Chinese Academy of Sciences, Beijing 100049, China
- Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Yueting Zhu
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Chengxin Zhang
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Shuang Zhang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Qisi Zhang
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Shengwei Fu
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Ning Wang
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
| | - Wen-xia Tian
- College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong 030801, China
| | - Jiyan Liu
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Longlong Si
- State Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
- University of Chinese Academy of Sciences, Beijing 100049, China
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Woo HJ, Heo ST, Yoo JR, Kim M, Oh J, Bae IG, Bae S, Yoon YR, Hwang JH, Hyun M, Kim HA, Jung SI, Kwon KT, Hwang S, Kim UJ, Kang G, Kim YJ, Yun JH, Kim TE, Kwon TK, Kim MG. Dynamic biomarkers and Cox regression with time-dependent covariate for mortality prediction in severe fever with thrombocytopenia syndrome. Sci Rep 2025; 15:9293. [PMID: 40102577 PMCID: PMC11920429 DOI: 10.1038/s41598-025-94416-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 03/13/2025] [Indexed: 03/20/2025] Open
Abstract
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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Affiliation(s)
- Hyun Ji Woo
- Department of Healthcare Engineering, Graduate School, Jeonbuk National University, Jeonju, Republic of Korea
- Nanum Space Co., Ltd, Jeonju, Jeonbuk, Republic of Korea
| | - Sang Taek Heo
- Division of Infectious Diseases, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Jeong Rae Yoo
- Division of Infectious Diseases, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Misun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - Jaeseong Oh
- Department of Pharmacology, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea
| | - In-Gyu Bae
- Division of Infectious Diseases, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, Republic of Korea
| | - Sohyun Bae
- Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Young-Ran Yoon
- Department of Clinical Pharmacology, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Jeong-Hwan Hwang
- Division of Infectious Diseases, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Republic of Korea
| | - Miri Hyun
- Division of Infectious Diseases, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Hyun Ah Kim
- Division of Infectious Diseases, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Sook In Jung
- Division of Infectious Diseases, Department of Internal Medicine, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Ki Tae Kwon
- Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Soyoon Hwang
- Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, Republic of Korea
| | - Uh Jin Kim
- Division of Infectious Diseases, Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Gaeun Kang
- Division of Clinical Pharmacology, Department of Pharmacology, Chonnam National University Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Young Jun Kim
- Division of Infectious Diseases, Department of Internal Medicine, Wonkwang University Hospital, Iksan, Republic of Korea
| | - Ji Hyun Yun
- Division of Infectious Diseases, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea
| | - Tae-Eun Kim
- Department of Clinical Pharmacology, Konkuk University Medical Center, Seoul, Republic of Korea
| | - Tae-Kyu Kwon
- Division of Biomedical Engineering, College of Engineering, Jeonbuk National University, Jeonju, Republic of Korea
| | - Min-Gul Kim
- Nanum Space Co., Ltd, Jeonju, Jeonbuk, Republic of Korea.
- Department of Pharmacology, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Republic of Korea.
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Ozgun Niksarlioglu EY, Uysal MA, Seyhan EC, Kıyık M, Çetinkaya E. Hypersensitivity pneumonitis in Covid-19: mortality, risk factors, and clinical outcomes from a 30-case observational study. SARCOIDOSIS, VASCULITIS, AND DIFFUSE LUNG DISEASES : OFFICIAL JOURNAL OF WASOG 2025; 42:16163. [PMID: 40100115 PMCID: PMC12013693 DOI: 10.36141/svdld.v42i1.16163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 09/13/2024] [Indexed: 03/20/2025]
Affiliation(s)
- Elif Yelda Ozgun Niksarlioglu
- Health Science University, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Chest Diseases, Istanbul, Turkey
| | - Mehmet Atilla Uysal
- Health Science University, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Chest Diseases, Istanbul, Turkey
| | - Ekrem Cengiz Seyhan
- Health Science University, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Chest Diseases, Istanbul, Turkey
| | - Murat Kıyık
- Health Science University, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Chest Diseases, Istanbul, Turkey
| | - Erdoğan Çetinkaya
- Health Science University, Yedikule Chest Diseases and Thoracic Surgery Training and Research Hospital, Department of Chest Diseases, Istanbul, Turkey
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Wang Z, Zhao L, Xie K. Development and validation of a nomogram to assess the occurrence of liver dysfunction in patients with COVID-19 pneumonia in the ICU. BMC Infect Dis 2025; 25:332. [PMID: 40065225 PMCID: PMC11892215 DOI: 10.1186/s12879-025-10684-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 02/18/2025] [Indexed: 03/14/2025] Open
Abstract
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.
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Affiliation(s)
- Zhiwei Wang
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Lina Zhao
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China
| | - Keliang Xie
- Department of Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.
- Laboratory of Anesthesia and Critical Care Medicine in Colleges and Universities of Shandong Province, School of Anesthesiology, Shandong Second Medical University, Weifangaq, Weifang, Shandong, 261053, China.
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Ma W, Tang S, Yao P, Zhou T, Niu Q, Liu P, Tang S, Chen Y, Gan L, Cao Y. Advances in acute respiratory distress syndrome: focusing on heterogeneity, pathophysiology, and therapeutic strategies. Signal Transduct Target Ther 2025; 10:75. [PMID: 40050633 PMCID: PMC11885678 DOI: 10.1038/s41392-025-02127-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Revised: 12/27/2024] [Accepted: 12/27/2024] [Indexed: 03/09/2025] Open
Abstract
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.
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Affiliation(s)
- Wen Ma
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
- Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China
| | - Songling Tang
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Peng Yao
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Tingyuan Zhou
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
- Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China
| | - Qingsheng Niu
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Peng Liu
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Shiyuan Tang
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yao Chen
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Lu Gan
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.
| | - Yu Cao
- Department of Emergency Medicine, Institute of Disaster Medicine and Institute of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, China.
- Institute for Disaster Management and Reconstruction, Sichuan University-The Hong Kong Polytechnic University, Chengdu, China.
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Gianfrate G, Gillie B, Renner C, Gruber B. Descriptive Analysis of COVID-19 Patients Who Required Endoscopic Evaluation for Gastrointestinal Bleeding. Cureus 2025; 17:e81241. [PMID: 40291252 PMCID: PMC12028926 DOI: 10.7759/cureus.81241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/26/2025] [Indexed: 04/30/2025] Open
Abstract
INTRODUCTION 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. MATERIALS AND METHODS 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.). RESULTS 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%). CONCLUSIONS 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.
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Affiliation(s)
| | - Breanna Gillie
- General Surgery, St Elizabeth Youngstown Hospital, Youngstown, USA
| | - Charles Renner
- Vascular Surgery, University of Kentucky College of Medicine, Lexington, USA
| | - Brian Gruber
- Trauma Surgery, St Elizabeth Youngstown Hospital, Youngstown, USA
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Cabrera JMÍ, Lagos-Villaseca A, Fuentes-L Pez E, Rosenbaum AS, Willson MÍ, Palma S, Kattan E, Vera M, Aquevedo AS, Napolitano C, Cabello P. Role of Prolonged Intubation in Vocal Fold Motion Impairment in Critically Ill Patients. J Voice 2025; 39:457-463. [PMID: 38806325 DOI: 10.1016/j.jvoice.2024.04.030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 04/26/2024] [Accepted: 04/26/2024] [Indexed: 05/30/2024]
Abstract
OBJECTIVE 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. STUDY DESIGN Retrospective cohort study. SETTING Multicenter. METHODS 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). RESULTS 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). CONCLUSIONS 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.
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Affiliation(s)
- Jos Mar Ía Cabrera
- Department of Otolaryngology, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Antonia Lagos-Villaseca
- Department of Otolaryngology, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Eduardo Fuentes-L Pez
- Departamento de Ciencias de la Salud, Carrera de Fonoaudiolog.ía, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Andr S Rosenbaum
- Department of Otolaryngology, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Mat Ías Willson
- Department of Otolaryngology, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile; Otolaryngology Service, Hospital Padre Hurtado, Santiago, Chile
| | - Soledad Palma
- Otolaryngology Service, Complejo Asistencial Dr. S..tero del R.ío, Santiago, Chile
| | - Eduardo Kattan
- Intensive Medicine Department, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Magdalena Vera
- Intensive Medicine Department, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Andr S Aquevedo
- Intensive Care Service, Complejo Asistencial Dr. S..tero del R.ío, Santiago, Chile
| | - Carla Napolitano
- Department of Otolaryngology, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile
| | - Pablo Cabello
- Department of Otolaryngology, Faculty of Medicine, Pontificia Universidad Cat..lica de Chile, Santiago, Chile; Otolaryngology Service, Complejo Asistencial Dr. S..tero del R.ío, Santiago, Chile.
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Oliveira ACO, Annoni R, Volpe MS, Guimaraes FS, Leite CF, Paro FM, Dias LMS, Accioly MF. Instruments used by physiotherapists to assess functional capacity in hospitalized patients with COVID-19: An online survey. Heart Lung 2025; 70:170-176. [PMID: 39700837 DOI: 10.1016/j.hrtlng.2024.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 12/01/2024] [Accepted: 12/02/2024] [Indexed: 12/21/2024]
Abstract
BACKGROUND 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. OBJECTIVES 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.
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Affiliation(s)
| | - Raquel Annoni
- Departamento de Fisioterapia, Escola de Educação Física, Fisioterapia e Terapia Ocupacional, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
| | - Marcia Souza Volpe
- Departamento de Ciências do Movimento Humano, Universidade Federal de São Paulo, Santos, SP, Brazil
| | - Fernando Silva Guimaraes
- Departamento de Fisioterapia Cardiorrespiratória e Musculoesquelética, Faculdade de Fisioterapia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | | | - Flavia Marini Paro
- Departamento de Educação Integrada em Saúde, Universidade Federal do Espírito Santo, Vitória, ES, Brazil
| | | | - Marilita Falangola Accioly
- Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil; Laboratório de Investigação Funcional dos Sistemas Cardiopulmonar e Metabólico, Departamento de Fisioterapia Aplicada, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.
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Song L, Ye H, Lv Z, Liu Y, Lu Z, Chen J, Pan H, Cai L, Chen Y, Huang S, Zan X, Huang X, Yu C. Hexahistidine-metal assembly encapsulated fibroblast growth factor 21 for lipopolysaccharide-induced acute lung injury. Eur J Pharm Biopharm 2025; 208:114650. [PMID: 39870250 DOI: 10.1016/j.ejpb.2025.114650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 01/29/2025]
Abstract
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.
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Affiliation(s)
- Lanlan Song
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Huihui Ye
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Zhanghang Lv
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Yichen Liu
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Ziyi Lu
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Jun Chen
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Haofeng Pan
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Luqiong Cai
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China
| | - Yuxin Chen
- Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Shiqing Huang
- Wenzhou Medical University, Wenzhou, Zhejiang 325000, China
| | - Xingjie Zan
- Joint Centre of Translational Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325001, China.
| | - Xiaoying Huang
- Division of Pulmonary Medicine, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou Key Laboratory of Interdiscipline and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, China.
| | - Chang Yu
- Intervention Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
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Alzahrani S, Ennaceur S, Arbaein T. Outcomes of patients in intensive care units according to COVID-19 status: analysis of 114 854 cases in Saudi Arabia. Ann Saudi Med 2025; 45:86-94. [PMID: 40189854 PMCID: PMC11973436 DOI: 10.5144/0256-4947.2025.86] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2025] [Accepted: 02/22/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND 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. OBJECTIVES Examine ICU health outcomes, including mortality, length of stay (LOS), and discharge rates, among COVID-19 and non-COVID-19 patients. DESIGN Retrospective, cross-sectional study. SETTING A national cross-sectional dataset provided by the Ministry of Health in Saudi Arabia. PATIENTS AND METHODS 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. MAIN OUTCOME MEASURES ICU outcomes including mortality, LOS and discharge rate. SAMPLE SIZE 114 854 ICU patients. RESULTS 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). CONCLUSION 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. LIMITATIONS The data used in this study has missing critical information such as laboratory results, socioeconomic variables, and hospitalization characteristics.
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Affiliation(s)
- Sahal Alzahrani
- From the Department of Public Health, Saudi Electronic University, Jeddah, Saudi Arabia
| | - Soukaina Ennaceur
- From the Department of Public Health, Saudi Electronic University, Jeddah, Saudi Arabia
| | - Turky Arbaein
- From the Department of Health Management and Hospital, Umm Al-Qura University, Makkah, Saudi Arabia
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Fratta Pasini AM, Stranieri C, Di Leo EG, Bertolone L, Aparo A, Busti F, Castagna A, Vianello A, Chesini F, Friso S, Girelli D, Cominacini L. Identification of Early Biomarkers of Mortality in COVID-19 Hospitalized Patients: A LASSO-Based Cox and Logistic Approach. Viruses 2025; 17:359. [PMID: 40143288 PMCID: PMC11946718 DOI: 10.3390/v17030359] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 02/06/2025] [Accepted: 02/20/2025] [Indexed: 03/28/2025] Open
Abstract
This study aimed to identify possible early biomarkers of mortality among clinical and biochemical parameters, iron metabolism parameters, and cytokines detected within 24 h from admission in hospitalized COVID-19 patients. We enrolled 80 hospitalized patients (40 survivors and 40 non-survivors) with COVID-19 pneumonia and acute respiratory failure. The median time from the onset of COVID-19 symptoms to hospital admission was lower in non-survivors than survivors (p < 0.05). Respiratory failure, expressed as the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen (P/F), was more severe in non-survivors than survivors (p < 0.0001). Comorbidities were similar in both groups. Among biochemical parameters and cytokines, eGFR and interleukin (IL)-1β were found to be significantly lower (p < 0.05), while LDH, IL-10, and IL-8 were significantly higher in non-survivors than in survivors (p < 0.0005, p < 0.05 and p < 0.005, respectively). Among other parameters, LDH values distribution showed the most significant difference between study groups (p < 0.0001). LASSO feature selection combined with Cox proportional hazards and logistic regression models was applied to identify features distinguishing between survivors and non-survivors. Both approaches highlighted LDH as the strongest predictor, with IL-22 and creatinine emerging in the Cox model, while IL-10, eGFR, and creatinine were influential in the logistic model (AUC = 0.744 for Cox, 0.723 for logistic regression). In a similar manner, we applied linear regression for predicting LDH levels, identifying the P/F ratio as the top predictor, followed by IL-10 and eGFR (NRMSE = 0.128). Collectively, these findings underscore LDH's critical role in mortality prediction, with P/F and IL-10 as key determinants of LDH increases in this Italian COVID-19 cohort.
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Affiliation(s)
- Anna Maria Fratta Pasini
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Chiara Stranieri
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Edoardo Giuseppe Di Leo
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Lorenzo Bertolone
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Antonino Aparo
- Interdepartmental Laboratory of Medical Research, Research Center LURM, University of Verona, 37134 Verona, Italy;
| | - Fabiana Busti
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Annalisa Castagna
- Department of Medicine, Section of Internal Medicine B, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy (S.F.)
| | - Alice Vianello
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Fabio Chesini
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Simonetta Friso
- Department of Medicine, Section of Internal Medicine B, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy (S.F.)
| | - Domenico Girelli
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
| | - Luciano Cominacini
- Department of Medicine, Section of Internal Medicine D, University of Verona, Policlinico G.B. Rossi, Piazzale L.A. Scuro 10, 37134 Verona, Italy; (C.S.); (E.G.D.L.); (L.B.); (F.B.); (A.V.); (F.C.); (D.G.); (L.C.)
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Ji X, Guo Y, Tang L, Gao C. Identifying and Validating Prognostic Hyper-Inflammatory and Hypo-Inflammatory COVID-19 Clinical Phenotypes Using Machine Learning Methods. J Inflamm Res 2025; 18:3009-3024. [PMID: 40034687 PMCID: PMC11874972 DOI: 10.2147/jir.s504028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 02/18/2025] [Indexed: 03/05/2025] Open
Abstract
Background COVID-19 exhibits complex pathophysiological manifestations, characterized by significant clinical and biological heterogeneity. Identifying phenotypes may enhance our understanding of the disease's diverse trajectories, benefiting clinical practice and trials. Methods This study included adult patients with COVID-19 from Xinhua Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, between December 15, 2022, and February 15, 2023. The k-prototypes clustering method was employed using 50 clinical variables to identify phenotypes. Machine learning algorithms were then applied to select key classifier variables for phenotype recognition. Results A total of 1376 patients met the inclusion criteria. K-prototypes clustering revealed two distinct subphenotypes: Hypo-inflammatory subphenotype (824 [59.9%]) and Hyper-inflammatory subphenotype (552 [40.1%]). Patients in Hypo-inflammatory subphenotype were younger, predominantly female, with low mortality and shorter hospital stays. In contrast, Hyper-inflammatory subphenotype patients were older, predominantly male, exhibiting a hyperinflammatory state with higher mortality and rates of organ dysfunction. The AdaBoost model performed best for subphenotype prediction (Accuracy: 0.975, Precision: 0.968, Recall: 0.976, F1: 0.972, AUROC: 0.975). "CRP", "IL-2R", "D-dimer", "ST2", "BUN", "NT-proBNP", "neutrophil percentage", and "lymphocyte count" were identified as the top-ranked variables in the AdaBoost model. Conclusion This analysis identified two phenotypes based on COVID-19 symptoms and comorbidities. These phenotypes can be accurately recognized using machine learning models, with the AdaBoost model being optimal for predicting in-hospital mortality. The variables "CRP", "IL-2R", "D-dimer", "ST2", "BUN", "NT-proBNP", "neutrophil percentage", and "lymphocyte count" play a significant role in the prediction of subphenotypes. Use the identified subphenotypes for risk stratification in clinical practice. Hyper-inflammatory subphenotypes can be closely monitored, and preventive measures such as early admission to the intensive care unit or prophylactic anticoagulation can be taken.
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Affiliation(s)
- Xiaojing Ji
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China
| | - Yiran Guo
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China
| | - Lujia Tang
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China
| | - Chengjin Gao
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, People’s Republic of China
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Yuan MQ, Song L, Wang ZR, Zhang ZY, Shi M, He J, Mo Q, Zheng N, Yao WQ, Zhang Y, Dong T, Li Y, Zhang C, Song J, Huang L, Xu Z, Yuan X, Fu JL, Zhen C, Cai J, Dong J, Zhang J, Xie WF, Li Y, Zhang B, Shi L, Wang FS. Long-term outcomes of mesenchymal stem cell therapy in severe COVID-19 patients: 3-year follow-up of a randomized, double-blind, placebo-controlled trial. Stem Cell Res Ther 2025; 16:94. [PMID: 40001244 PMCID: PMC11863646 DOI: 10.1186/s13287-025-04148-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Accepted: 01/14/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND The long-term effects and outcomes of human mesenchymal stem cell (MSC) therapy in patients with severe coronavirus disease 2019 (COVID-19) remain poorly understood. This study aimed to evaluate the extended safety and efficacy of MSC treatment in severe patients with COVID-19 who participated in our earlier randomized, double-blind, placebo-controlled clinical trial, with follow-up conducted over 3 years. METHODS One hundred patients with severe COVID-19 were randomized to receive either an MSC infusion (n = 65, 4 × 107 cells/dose, on days 0, 3, and 6) or a placebo, with both groups receiving the standard of care. At 36 months post-MSC therapy, patients were followed up to long-term safety and efficacy, particularly the effects of MSC therapy on persistent COVID-19 symptoms. Evaluated outcomes included lung imaging results, 6-min walking distance (6-MWD), pulmonary function test results, quality of life scores based on the Short Form-36 (SF-36) health survey, Long COVID symptoms, new-onset comorbidities, tumor marker levels, and rates of COVID-19 reinfection. RESULTS Three years post-treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) in the placebo group showed normal findings on computed tomography (CT) images (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 0.65-4.34). The general health (GH) score from the SF-36 was higher in the MSC group (67.0) compared to the placebo group (50.0), with a difference of 12.86 (95% CI: 1.44-24.28). Both groups showed similar results for total lung severity scores (TSS), 6-MWD, pulmonary function tests, and Long COVID symptoms. No significant differences between groups were observed in new-onset complications (including tumorigenesis) or tumor marker levels. After adjusting for China's dynamic zero-COVID-19 strategy, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reinfection rates were 53.06% (26/49) in the MSC group and 67.86% (19/28) in the placebo group (OR = 0.54, 95% CI: 0.20-1.41). CONCLUSIONS These findings support the long-term safety of MSC therapy in patients with severe COVID-19 over 3 years. MSC treatment may offer potential benefits for lung recovery and improved quality of life in patients experiencing Long COVID symptoms. TRIAL REGISTRATION ClinicalTrials.gov, NCT04288102. Registered 28 February 2020, https://clinicaltrials.gov/study/NCT04288102 .
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Affiliation(s)
- Meng-Qi Yuan
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Le Song
- Department of Infectious Diseases, Chinese PLA General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China
| | - Ze-Rui Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
- Senior Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, China
| | - Zi-Ying Zhang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Ming Shi
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
- Medical School of Chinese PLA, Beijing, 100853, China
| | - Junli He
- Department of Infectious Diseases, Chinese PLA General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China
| | - Qiong Mo
- Department of Infectious Diseases, Chinese PLA General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China
| | - Ning Zheng
- Department of Infectious Diseases, Chinese PLA General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China
| | - Wei-Qi Yao
- Wuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd, Hubei, 430030, China
- VCANBIO Cell & Gene Engineering Corp., Ltd, Tianjin, 300000, China
- Department of Biology and Medicine, Hubei University of Technology, Wuhan, 430030, Hubei, China
| | - Yu Zhang
- Wuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd, Hubei, 430030, China
- VCANBIO Cell & Gene Engineering Corp., Ltd, Tianjin, 300000, China
| | - Tengyun Dong
- Wuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd, Hubei, 430030, China
| | - Yuanyuan Li
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Chao Zhang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Jinwen Song
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Lei Huang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Zhe Xu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Xin Yuan
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Jun-Liang Fu
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Cheng Zhen
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Jianming Cai
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Jinghui Dong
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Jianzeng Zhang
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, China
| | - Wei-Fen Xie
- Department of Gastroenterology, Changzheng Hospital, Naval Medical University, 415 Fengyang Road, Shanghai, 200003, China
| | - Yonggang Li
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China
| | - Bo Zhang
- Department of Infectious Diseases, Chinese PLA General Hospital of Central Theater Command, Wuhan, 430070, Hubei, China.
| | - Lei Shi
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China.
- Medical School of Chinese PLA, Beijing, 100853, China.
| | - Fu-Sheng Wang
- Senior Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, No. 100 Western 4Th Ring Road, Beijing, 100039, China.
- Medical School of Chinese PLA, Beijing, 100853, China.
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Suresh V, Shamim MA, Ghosh V, Dave T, Jayan M, Verma A, Sanker V, Roy P, Bardhan M. SGLT2 Inhibitors in COVID-19: Umbrella Review, Meta-Analysis, and Bayesian Sensitivity Assessment. Diseases 2025; 13:67. [PMID: 40136608 PMCID: PMC11941288 DOI: 10.3390/diseases13030067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 01/27/2025] [Accepted: 02/01/2025] [Indexed: 03/27/2025] Open
Abstract
BACKGROUND Several studies have reported a reduced risk of COVID-19-related mortality in patients taking antidiabetic medications. This is an umbrella review, meta-analysis, and Bayesian sensitivity assessment of SGLT2 inhibitors (SGLT2is) in COVID-19 patients with type 2 diabetes mellitus (T2DM). METHODS A search was conducted on the MEDLINE (PubMed), EMBASE, Cochrane, and ClinicalTrials.gov databases on 5/12/2023. We performed an umbrella review of systematic reviews and meta-analyses on the effects of SGLT2is in T2DM patients with COVID-19 and critically appraised them using AMSTAR 2.0. Trials investigating SGLT2i use in COVID-19 patients post-hospitalisation and observational studies on prior SGLT2i use among COVID-19 patients were included in the meta-analysis, adhering to the PRISMA guidelines. RESULTS SGLT2is exhibited significantly lower odds of mortality (OR 0.67, 95% CI 0.53-0.84) and hospitalisation (OR 0.84, 0.75-0.94) in COVID-19 patients with T2DM. Bayesian sensitivity analyses corroborated most of the findings, with differences observed in hospitalisation and mortality outcomes. SGLT-2 inhibitors showed an OR of 1.20 (95% CI 0.64-2.27) for diabetic ketoacidosis. Publication bias was observed for hospitalisation, but not for mortality. The GRADE assessment indicated a low to very low quality of evidence because of the observational studies included. CONCLUSIONS The prophylactic use of SGLT2is reduces mortality and hospitalisation among COVID-19 patients, particularly in patients with diabetes. The utility of SGLT2is after hospitalisation is uncertain and warrants further investigation. A limited efficacy has been observed under critical conditions. Individualised assessment is crucial before integration into COVID-19 management.
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Affiliation(s)
- Vinay Suresh
- King George’s Medical University, Lucknow 226003, India
| | - Muhammad Aaqib Shamim
- Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur 342005, India
| | - Victor Ghosh
- Andhra Medical College, Visakhapatnam 530002, India
| | - Tirth Dave
- Bukovinian State Medical University, 58002 Chernivtsi, Ukraine
| | - Malavika Jayan
- Department of Internal Medicine, Bangalore Medical College and Research Institute, Bangalore 560002, India
| | - Amogh Verma
- Department of Internal Medicine, Rama Medical College Hospital and Research Centre, Hapur 245304, India
| | - Vivek Sanker
- Department of Neurosurgery, Trivandrum Medical College Hospital, Trivandrum 695011, India
| | - Priyanka Roy
- Department of Labour, Government of West Bengal, Kolkata 700001, India
| | - Mainak Bardhan
- The Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA
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Dedeoğlu Demir B, Enç N, Börekçi Ş. The effect of prone positioning on ventilator parameters, blood gas levels, and ventilator-associated pneumonia in intensive care unit patients: a randomized controlled trial. BMC Nurs 2025; 24:203. [PMID: 39984994 PMCID: PMC11846282 DOI: 10.1186/s12912-025-02817-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2024] [Accepted: 02/10/2025] [Indexed: 02/23/2025] Open
Abstract
OBJECTIVES This study was planned to compare the prone position and non-prone position groups and to evaluate arterial blood gas results, mechanical ventilator values and ventilator-associated pneumonia (VAP) status before, during, and after patients were brought back to the non-prone position. DESIGN This study is a randomized controlled trial with a parallel-group design and a 1:1 allocation ratio. A block randomisation method was used to ensure balanced allocation between two groups. SETTING The research was conducted in the 14-bed and 26-bed general ICUs of two private hospitals on the European side of Istanbul. PARTICIPANTS The 94 eligible participants were randomly divided into two groups. 52 participants were assigned to the prone position group, while 42 participants were assigned to the non-prone position group, which served as the control group. In the end, 40 participants were in each group. INTERVENTION The intervention involved placing patients in the prone position and monitoring their arterial blood gas results, mechanical ventilator values, and VAP status at multiple stages: before, during, and after returning them to the non-prone position. Each patient was followed for a minimum of 5 days. RESULTS The majority of the participants were male (51.2%) and aged 45-64 (48.8%). The comparison of experimental and control groups indicated statistically significant difference in saturation, FiO₂, inspiratory-expiratory tidal volume, and blood gas levels of the patients in the treatment group (p = 0.001; p < 0.01). CONCLUSIONS The change in the experimental group was greater than in the control group. In conclusion, the mechanical ventilator parameters and blood gas levels of the patients in the treatment group were better than those of the patients in the control group. It is recommended as an effective practice in patients receiving prone position mechanical ventilation (MV). CLINICAL TRIAL REGISTRATION NUMBER AND REGISTRATION DATE NCT05760716/ March 6, 2023 (This trial was registered retrospectively at ClinicalTrials.gov (Registration Number: NCT05760716) after its completion due to demanded revisions. The integrity of the data and adherence to the study protocol were ensured throughout. The trial adhered to ethical standards (ethics committee approval, informed consent) even if it was not registered prospectively).
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Affiliation(s)
- Burcu Dedeoğlu Demir
- Faculty of Health Sciences Department of Nursing, Istanbul Arel University, Cevizlibag Campus, Merkez Efendi Mah. Eski Londra Asfaltı Cd. No:1/3, Cevizlibağ- Zeytinburnu, Istanbul, 34010, Turkey.
| | - Nuray Enç
- Florence Nightingale Faculty Of Nursing, Istanbul University-Cerrahpasa, Abide-i Hürriyet Cd, 34381, Şişli/İstanbul, Istanbul, Turkey
| | - Şermin Börekçi
- Cerrahpasa Faculty of Medicine, Department of Internal Medicine, Department of Thoracic Diseases, Istanbul, Turkey
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Cárdenas-Marín PA, Cordoba-Melo BD, Carrillo-Gómez DC, León-Giraldo H, Mendoza I, Flórez N, Larrea Gómez RE, Mercedes JM, Herrera CJ, Lugo-Peña J, Cárdenas-Aldaz LP, Rossel V, Ramírez Ramírez R, Fernández HF, Retana AU, Sierra-Lara Martinez JD, Figueiredo EL, Yabar Galindo WG, Quintana Da Silva MA, Romero A, Silva P, Alvarado A, Valencia A, Gomez-Mesa JE. Impact of myocardial injury on cardiovascular complications in hospitalized patients with COVID-19: insights from Latin America. Front Cardiovasc Med 2025; 12:1545142. [PMID: 40034989 PMCID: PMC11872895 DOI: 10.3389/fcvm.2025.1545142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2024] [Accepted: 01/26/2025] [Indexed: 03/05/2025] Open
Abstract
Introduction Viral infection by SARS-CoV2 is a pandemic affecting over 600 million people worldwide. One of five hospitalized patients may present myocardial injury, strongly associated with disease severity and mortality. Methodology Retrospective cross-sectional study of hospitalized COVID-19 patients diagnosed between May 01, 2020, and June 30, 2021, from the database of the Registro Latinoamericano de Enfermedad Cardiovascular y COVID-19 (CARDIO COVID 19-20) with a troponin value recorded during hospitalization. A descriptive analysis of sociodemographic and clinical characteristics was performed. Bivariate analysis was conducted according to the presence or absence of myocardial injury. Survival analysis was made using Kaplan-Meier curves, by the presence of myocardial injury. A multivariate Poisson regression model was performed to determine factors associated with mortality. Statistical analyses were performed using the RStudio V.1.4.1717 package. Results A total of 2,134 patients were included, 64.2% were male, and 911 patients had myocardial injury. The median age of the total population was 61 years. Individuals with myocardial injury had a higher prevalence of hypertension, diabetes, and dyslipidemia. Survival probability was lower in this subgroup. Patients with myocardial injury had a 1.95 times higher risk of death. Age, male sex, chronic kidney disease, arrhythmias, decompensated heart failure, requirement of inotropic/vasopressor, and invasive mechanical ventilation were related to higher mortality risk in patients with myocardial injury. Conclusion Patients with COVID-19 and myocardial injury exhibit a broad spectrum of cardiac abnormalities. Myocardial injury is associated with a higher disease severity and risk of in-hospital mortality. This multicenter study uniquely represents data from 13 Latin American countries, offering regional insights into the impact of myocardial injury during the COVID-19 pandemic.
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Affiliation(s)
- Paula Andrea Cárdenas-Marín
- Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia
- Servicio de Cardiología, Departamento de Medicina Interna, Fundación Valle del Lili, Cali, Colombia
- Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia
| | - Brayan Daniel Cordoba-Melo
- Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia
- Servicio de Cardiología, Departamento de Medicina Interna, Fundación Valle del Lili, Cali, Colombia
- Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia
| | | | - Hoover León-Giraldo
- Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia
- Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia
| | - Iván Mendoza
- Instituto de Medicina Tropical, Universidad Central de Venezuela, Caracas, Venezuela
| | - Noel Flórez
- Servicio de Cardiología, Departamento de Medicina Interna, Fundación Valle del Lili, Cali, Colombia
| | | | | | - Cesar J. Herrera
- Departamento de Cardiología, Centro de Diagnóstico y Medicina Avanzada y de Conferencias Médicas y Telemedicina (CEDIMAT), Santo Domingo, Dominican Republic
| | - Julián Lugo-Peña
- Departamento de Cardiología, Clínica del Occidente, Bogotá, Colombia
| | | | - Victor Rossel
- Sección de Cardiología, Hospital del Salvador, Facultad de Medicina Universidad de Chile, Santiago, Chile
| | | | | | | | - J. Daniel Sierra-Lara Martinez
- Unidad de Cuidados Críticos Cardiovasculares, Instituto Nacional de Cardiología “Ignacio Chávez”, Ciudad de Mexico, Mexico
| | | | | | | | - Alexander Romero
- Departamento de Cardiología, Hospital Santo Tomas, Ciudad de Panamá, Panama
| | - Paula Silva
- Departamento de Cardiología, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina
| | - Armando Alvarado
- Servicio de Terapia Intensiva, Hospital Especializado de Villa Nueva, Villa Nueva, Guatemala
| | - Andrea Valencia
- Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia
| | - Juan Esteban Gomez-Mesa
- Centro de Investigaciones Clínicas, Fundación Valle del Lili, Cali, Colombia
- Servicio de Cardiología, Departamento de Medicina Interna, Fundación Valle del Lili, Cali, Colombia
- Facultad de Ciencias de la Salud, Universidad Icesi, Cali, Colombia
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Hosny S, Elshobary ME, El-Sheekh MM. Unleashing the power of microalgae: a pioneering path to sustainability and achieving the sustainable development goals. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2025:10.1007/s11356-025-35885-8. [PMID: 39920498 DOI: 10.1007/s11356-025-35885-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 12/30/2024] [Indexed: 02/09/2025]
Abstract
This study explores the remarkable potential of algae in addressing global sustainability challenges. Microalgae, in particular, emerge as sustainability champions. Their applications span an impressive array of industries and processes, including food and feed production, biofuels, cosmetics, pharmaceuticals, and environmental remediation. This versatility positions algae as key players in achieving over 50% of UN Sustainable Development Goals (SDGs) simultaneously, addressing issues such as climate action, clean water and sanitation, affordable and clean energy, and zero hunger. From sequestering carbon, purifying wastewater, and producing clean energy to combating malnutrition, algae demonstrates unparalleled potential. Their ability to flourish in extreme conditions and their rapid growth rates further enhance their appeal for large-scale cultivation. As research advances, innovative applications continue to emerge, such as algae-based bioplastics and dye-sensitized solar cells, promising novel solutions to pressing global issues. This study illuminates how harnessing the power of algae can drive us towards a more resilient, sustainable world. By leveraging algae's multifaceted capabilities, we can tackle climate change, resource scarcity, and economic development concurrently. The research highlights the critical role of algae in promoting circular economy principles and achieving a harmonious balance between human needs and environmental preservation, paving the way for a greener, more sustainable future.
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Affiliation(s)
- Shimaa Hosny
- National Institute of Oceanography and Fisheries (NIOF), Alexandria, Egypt
| | - Mostafa E Elshobary
- Botany and Microbiology Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt.
- Aquaculture Research, Alfred Wegener Institute (AWI) - Helmholtz Centre for Polar and Marine Research, Am Handelshafen, Bremerhaven, 27570, Germany.
| | - Mostafa M El-Sheekh
- Botany and Microbiology Department, Faculty of Science, Tanta University, Tanta, 31527, Egypt
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Pérez-Gisbert L, Morales-García C, Sánchez-Martínez JA, González-Gutiérrez MV, Valenza MC, Torres-Sánchez I. Severity Matters: How COVID-19 Severity Impacts Long-Term Effects on Symptoms, Physical Activity and Functionality-An Observational Study. Healthcare (Basel) 2025; 13:333. [PMID: 39942522 PMCID: PMC11817242 DOI: 10.3390/healthcare13030333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/28/2025] [Accepted: 02/03/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES The existing literature has described the common symptoms and long-term effects of coronavirus disease (COVID-19). However, there is a lack of detailed information on how different degrees of disease severity affect survivors differently. This study aims to fill that gap by evaluating the symptoms, physical activity, and functionality of COVID-19 survivors across a spectrum of severity levels, comparing them with those of healthy individuals. METHODS An observational study was carried out following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria and checklist. Participants were divided into 5 groups based on COVID-19 severity according to the World Health Organization classification: healthy (COVID-19-negative), mild (symptomatic without pneumonia or dyspnoea), moderate (pneumonia and dyspnoea without hospitalisation), severe (severe pneumonia requiring hospitalisation), and critical (severe pneumonia with admission to the intensive care unit). Descriptive variables, symptoms (Fatigue Borg Scale, Fatigue Impact Scale, Fatigue Severity Scale, Dyspnoea Borg Scale, Visual Analogue Scale, Hospital Anxiety and Depression Scale, and European Quality of Life-5 Dimensions), physical activity (the International Physical Activity Questionnaire) and functionality (Patient-Specific Functional Scale, Short Physical Performance Battery, Arm Curl test, and 2 min step test) were measured. RESULTS A total of 304 participants were included: healthy (n = 42), mild (n = 143), moderate (n = 49), severe (n = 52), and critical (n = 18) COVID-19 patients. The impact of COVID-19 on surviving patients varies significantly with the severity of the disease. The results show that the hospitalisation time, age, and comorbidities of the patients are greater in those with a greater severity of the disease. Patients with more severe COVID-19 also experience greater frailty, dysphagia, fatigue, dyspnoea, and pain. Additionally, those with severe cases have poorer overall health, reduced physical activity, and diminished functionality. No evidence of post-COVID-19 anxiety or depression is found in the sample, even considering the timeframe between the negative test and the assessment. CONCLUSIONS Patients with higher COVID-19 severity (severe or critical) experience more symptoms than those with lower COVID-19 severity (mild or moderate). Additionally, those with severe cases have poorer overall health, reduced physical activity and diminished functionality. Register: Clinicaltrials.gov: NCT05731817.
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Affiliation(s)
- Laura Pérez-Gisbert
- Physical Therapy Department, Faculty of Health Sciences, University of Granada, Avenida de la Ilustración nº 60, 18016 Granada, Spain; (L.P.-G.); (M.C.V.)
| | - Concepción Morales-García
- Pneumology Service, Virgen de las Nieves University Hospital, Avenida de las Fuerzas Armadas nº 2, 18014 Granada, Spain; (C.M.-G.); (J.A.S.-M.); (M.V.G.-G.)
| | - José Antonio Sánchez-Martínez
- Pneumology Service, Virgen de las Nieves University Hospital, Avenida de las Fuerzas Armadas nº 2, 18014 Granada, Spain; (C.M.-G.); (J.A.S.-M.); (M.V.G.-G.)
| | - María Victoria González-Gutiérrez
- Pneumology Service, Virgen de las Nieves University Hospital, Avenida de las Fuerzas Armadas nº 2, 18014 Granada, Spain; (C.M.-G.); (J.A.S.-M.); (M.V.G.-G.)
| | - Marie Carmen Valenza
- Physical Therapy Department, Faculty of Health Sciences, University of Granada, Avenida de la Ilustración nº 60, 18016 Granada, Spain; (L.P.-G.); (M.C.V.)
| | - Irene Torres-Sánchez
- Physical Therapy Department, Faculty of Health Sciences, University of Granada, Avenida de la Ilustración nº 60, 18016 Granada, Spain; (L.P.-G.); (M.C.V.)
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Subramaniam S, Jose A, Kenney D, O’Connell AK, Bosmann M, Douam F, Crossland N. Challenging the notion of endothelial infection by SARS-CoV-2: insights from the current scientific evidence. Front Immunol 2025; 16:1443932. [PMID: 39967675 PMCID: PMC11832389 DOI: 10.3389/fimmu.2025.1443932] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 01/14/2025] [Indexed: 02/20/2025] Open
Affiliation(s)
- Saravanan Subramaniam
- Department of Pharmacology and Toxicology, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, United States
- Renal Section, Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, United States
| | - Asha Jose
- Renal Section, Department of Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, United States
| | - Devin Kenney
- Department of Virology, Immunology and Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
- National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA, United States
| | - Aoife K. O’Connell
- National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA, United States
| | - Markus Bosmann
- Department of Medicine, Pulmonary Center, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, United States
- Department of Pathology and Laboratory Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, United States
| | - Florian Douam
- Department of Virology, Immunology and Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
- National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA, United States
| | - Nicholas Crossland
- Department of Virology, Immunology and Microbiology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, United States
- National Emerging Infectious Diseases Laboratories (NEIDL), Boston University, Boston, MA, United States
- Department of Pathology and Laboratory Medicine, Chobanian & Avedisian School of Medicine, Boston University, Boston, MA, United States
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Zhao Y, Tang Y, Wang QY, Li J. Ocular neuroinflammatory response secondary to SARS-CoV-2 infection-a review. Front Immunol 2025; 16:1515768. [PMID: 39967658 PMCID: PMC11832381 DOI: 10.3389/fimmu.2025.1515768] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 01/13/2025] [Indexed: 02/20/2025] Open
Abstract
With the consistent occurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the prevalence of various ocular complications has increased over time. SARS-CoV-2 infection has been shown to have neurotropism and therefore to lead to not only peripheral inflammatory responses but also neuroinflammation. Because the receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), can be found in many intraocular tissues, coronavirus disease 2019 (COVID-19) may also contribute to persistent intraocular neuroinflammation, microcirculation dysfunction and ocular symptoms. Increased awareness of neuroinflammation and future research on interventional strategies for SARS-CoV-2 infection are important for improving long-term outcomes, reducing disease burden, and improving quality of life. Therefore, the aim of this review is to focus on SARS-CoV-2 infection and intraocular neuroinflammation and to discuss current evidence and future perspectives, especially possible connections between conditions and potential treatment strategies.
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Affiliation(s)
| | | | | | - Jia Li
- Department of Glaucoma, The Second Hospital of Jilin University, Changchun, China
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Ran E, Zou Y, Zhao C, Liu K, Yuan J, Yang W, Zhao L, Yang Q, Yang J, Ju X, Cai L, Lang Y, Li X, Liu K, Liu F. COVID-19 in discharged patients with diabetes and chronic kidney disease: one-year follow-up and evaluation. Front Endocrinol (Lausanne) 2025; 16:1519993. [PMID: 39968301 PMCID: PMC11832373 DOI: 10.3389/fendo.2025.1519993] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Accepted: 01/15/2025] [Indexed: 02/20/2025] Open
Abstract
Purpose To evaluate the all-cause mortality rate and renal outcomes in patients with diabetes and chronic kidney disease (CKD) following hospital discharge for COVID-19. Methods This single-center prospective observational study included 187 discharged COVID-19 patients with diabetes and CKD, admitted between December 2022 and January 2023 at West China Hospital, Sichuan University. Cox regression analysis was used to assess mortality risk, and logistic regression was applied to identify risk factors for rapid CKD progression after discharge. Results During the one-year follow-up, the all-cause mortality rate was 26.7%, with a COVID-19-related acute kidney injury (AKI) incidence of 35.3%, and 35.8% of patients experienced rapid CKD progression after discharge. Cox proportional hazards regression indicated that sepsis and mechanical ventilation were major risk factors for post-discharge all-cause mortality. Logistic regression identified baseline eGFR < 60 mL/min/1.73 m² as an independent risk factor for rapid CKD progression. Conclusions During the one-year follow-up period, we observed that patients with diabetes and CKD exhibited higher all-cause mortality and experienced rapid deterioration of kidney function after acute infection with COVID-19. This underscores the importance of ongoing longitudinal follow-up to more accurately track the long-term health effects of COVID-19 on patients with diabetes and CKD.
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Affiliation(s)
- Enrong Ran
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Nephrology, Suining Central Hospital, Suining, China
| | - Yutong Zou
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Chuanyi Zhao
- Department of Clinical Research Management, West China Hospital of Sichuan University, Chengdu, China
| | - Kai Liu
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jiamin Yuan
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Wenjie Yang
- Division of Project Design and Statistics, West China Hospital of Sichuan University, Chengdu, China
| | - Lijun Zhao
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qing Yang
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jia Yang
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xuegui Ju
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Linli Cai
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Yanlin Lang
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Xingyuan Li
- Department of Clinical Research Management, West China Hospital of Sichuan University, Chengdu, China
| | - Ke Liu
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Fang Liu
- Department of Nephrology, West China Hospital, Sichuan University; Laboratory of Diabetic Kidney Disease, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, China
- Department of Clinical Research Management, West China Hospital of Sichuan University, Chengdu, China
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Suades R, Greco MF, Padró T, de Santisteban V, Domingo P, Benincasa G, Napoli C, Greco S, Madè A, Ranucci M, Devaux Y, Martelli F, Badimon L. Blood CD45 +/CD3 + lymphocyte-released extracellular vesicles and mortality in hospitalized patients with coronavirus disease 2019. Eur J Clin Invest 2025; 55:e14354. [PMID: 39548690 DOI: 10.1111/eci.14354] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 11/05/2024] [Indexed: 11/18/2024]
Abstract
BACKGROUND The global pandemic of coronavirus disease 2019 (COVID-19) represented a major public health concern. Growing evidence shows that plasma of COVID-19 patients contains large numbers of circulating extracellular vesicles (cEVs) that correlate with disease severity and recovery. In this study, we sought to characterize the longitudinal cEV signature in critically ill COVID-19 patients during hospitalization and its relation to mortality risk. METHODS cEVs were quantitatively and phenotypically analysed in hospitalized non-surviving COVID-19 patients at baseline (n = 42) and before exitus (n = 40) and in 40 healthy volunteers as a reference group by high sensitivity nano flow cytometry using specific markers for parental cell sources and activation. RESULTS Levels of cEV subtypes differed between patients with severe COVID-19 and healthy subjects, specifically those from platelets and endothelial, inflammatory and viral infected cells, which associate to high mortality risk. In the longitudinal analysis from baseline to the time point immediately preceding death, no changes were found for platelet, pan-leukocyte, and lung epithelial cell-shed cEVs, while endothelial cell releases of EVs (eEVs) significantly differed. Vascular endothelial growth factor receptor 2-positive eEVs were significantly increased before death compared to admission whereas endoglin and E-selectin-containing eEVs did not change. Conversely, lymphocyte (ℓEV), monocyte, macrophage, pericyte and progenitor cell-derived cEVs displayed significant reductions before exitus. Noteworthy, levels of CD45+/CD3+-ℓEVs were significantly associated to the patient's survival time. CONCLUSIONS An evolving cEV profile able to discriminate prompt risk of death during hospitalization has been defined suggesting a role for circulating and vascular cell-derived EVs in COVID-19 pathogenesis.
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Affiliation(s)
- Rosa Suades
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III (ISCIII), Madrid, Spain
| | - Maria F Greco
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- Department of Clinical Sciences and Community Health, Università Degli Studi di Milano, Milan, Italy
| | - Teresa Padró
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III (ISCIII), Madrid, Spain
| | | | - Pere Domingo
- Infectious Diseases Unit, Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau-IR SANT PAU, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain
| | - Giuditta Benincasa
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Claudio Napoli
- Department of Advanced Medical and Surgical Sciences (DAMSS), University of Campania "Luigi Vanvitelli", Naples, Italy
- Department of Internal Medicine and Specialistics, Division of Clinical Immunology, Immunohematology, Transfusion Medicine and Transplant Immunology (SIMT), Azienda Universitaria Policlinico (AOU), Naples, Italy
| | - Simona Greco
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Milan, Italy
| | - Alisia Madè
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Milan, Italy
| | - Marco Ranucci
- Department of Cardiovascular Anesthesia and Intensive Care, IRCCS Policlinico San Donato, Milan, Italy
| | - Yvan Devaux
- Cardiovascular Research Unit, Department of Precision Health, Luxembourg Institute of Health, Strassen, Luxembourg
| | - Fabio Martelli
- Molecular Cardiology Laboratory, IRCCS Policlinico San Donato, Milan, Italy
| | - Lina Badimon
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- Centro de Investigación Biomédica en Red Enfermedades Cardiovasculares (CIBERCV), Institute of Health Carlos III (ISCIII), Madrid, Spain
- Cardiovascular Research Chair, UAB, Barcelona, Spain
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Ashique S, Mishra N, Garg A, Garg S, Farid A, Rai S, Gupta G, Dua K, Paudel KR, Taghizadeh-Hesary F. A Critical Review on the Long-Term COVID-19 Impacts on Patients With Diabetes. Am J Med 2025; 138:308-329. [PMID: 38485111 DOI: 10.1016/j.amjmed.2024.02.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 02/20/2024] [Accepted: 02/23/2024] [Indexed: 04/30/2024]
Abstract
BACKGROUND The world is currently grappling with the potentially life-threatening coronavirus disease 2019 (COVID-19), marking it as the most severe health crisis in the modern era. COVID-19 has led to a pandemic, with the World Health Organization (WHO) predicting that individuals with diabetes are at a higher risk of contracting the virus compared to the general population. This review aims to provide a practical summary of the long-term impacts of COVID-19 on patients with diabetes. Specifically, it focuses on the effects of SARS-CoV-2 on different types of diabetic patients, the associated mortality rate, the underlying mechanisms, related complications, and the role of vitamin D and zinc in therapeutic and preventive approaches. METHODS Relevant literature was identified through searches on PubMed, Web of Science, and Science Direct in English, up to April 2023. RESULTS COVID-19 can lead to distressing symptoms and pose a significant challenge for individuals living with diabetes. Older individuals and those with pre-existing conditions such as diabetes, coronary illness, and asthma are more susceptible to COVID-19 infection. Managing COVID-19 in individuals with diabetes presents challenges, as it not only complicates the fight against the infection but also potentially prolongs the recovery time. Moreover, the virus may thrive in individuals with high blood glucose levels. Various therapeutic approaches, including antidiabetic drugs, are available to help prevent COVID-19 in diabetic patients. CONCLUSIONS Diabetes increases the morbidity and mortality risk for patients with COVID-19. Efforts are globally underway to explore therapeutic interventions aimed at reducing the impact of diabetes on COVID-19.
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Affiliation(s)
- Sumel Ashique
- Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences & Research, Durgapur, West Bengal, India
| | - Neeraj Mishra
- Amity Institute of Pharmacy, Amity University Madhya Pradesh (AUMP), Gwalior, Madhya Pradesh, India
| | - Ashish Garg
- Drug Delivery and Nanotechnology Laboratories, Department of Pharmaceutics, Guru Ramdas Khalsa Institute of Science and Technology (Pharmacy), Kukrikheda, Barela, Jabalpur, Madhya Pradesh, India
| | - Sweta Garg
- Guru Ramdas Khalsa Institute of Science and Technology, Pharmacy, Jabalpur, Madhya Pradesh, India
| | - Arshad Farid
- Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan, Pakistan
| | - Shweta Rai
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India
| | - Gaurav Gupta
- School of Pharmacy, Suresh Gyan Vihar University, Gyan Vihar Marg, Jagatpura, Jaipur, Rajasthan 302017, India
| | - Kamal Dua
- Faculty of Health, Australian Research Centre in Complementary and Integrative Medicine, University of Technology Sydney, Ultimo, NSW, Australia; Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW, Australia
| | - Keshav Raj Paudel
- Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, NSW, Australia
| | - Farzad Taghizadeh-Hesary
- ENT and Head and Neck Research Center, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Mancini M, Palazzi F, Iacono F. Restorative and endodontic clinical strategies during COVID-19 (SARS-CoV-2) pandemic: a revision of the literature. Minerva Dent Oral Sci 2025; 74:66-75. [PMID: 39387857 DOI: 10.23736/s2724-6329.24.05012-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
The aim of this study was to analyze clinical strategies supported by validated references during two of the most frequent dental emergencies (i.e. restorative and endodontic treatment) in the COVID-19 pandemic. Coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of an emergency in the health system worldwide and a potentially fatal disease. Person-to-person transmission of SARS-CoV-2 through aerosol and droplets led to extensive preventive measures to contain COVID-19 outbreak. Dental care providers have been exposed to a high risk of SARS-CoV-2 infection, due to the face-to-face communication and the exposure to saliva, blood, and other body fluids during routine interventions; this can also contribute to a high risk for cross-infection, even though dentist usually cope with those situations in everyday practice. Restorative and endodontic emergencies represented a high proportion of dental emergencies, with prolonged exposure time for dentists/endodontists in contact with suspected or confirmed infected patients. Lack of knowledge and undefined progression controlled the decision-making in clinical dentistry. The dynamicity of the situation determined change of views and recommendations in dental setting. The implementation of strict restorative and endodontics protocols are aimed at preventing circumstances similar to those observed with COVID-19.
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Affiliation(s)
- Manuele Mancini
- Department of Health Sciences, UniCamillus-Saint Camillus International Medical University, Rome, Italy -
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50
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Navarro-Romero F, Olalla-Sierra J, Martín-Escalante MD. Potential role of lung ultrasonography in outpatient follow-up of patients with COVID-19. A systematic review. Rev Clin Esp 2025; 225:101-110. [PMID: 39613099 DOI: 10.1016/j.rceng.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 10/19/2024] [Indexed: 12/01/2024]
Abstract
INTRODUCTION AND AIM Currently, the usefulness of lung ultrasound in the follow-up of patients after hospital discharge for SARS-CoV-2 pneumonia is not well known. The main objective of this systematic review is to investigate the persistence of alterations in lung ultrasound of patients who have had COVID-19 pneumonia. METHODS A systematic review has been carried out following the PRISMA regulations in the PubMed, EMBASE, Web of Science and Google Scholar database from January 2020 to May 2023 using the combination of MeSH terms: "lung ultrasound", "ultrasonography", "lung alterations", "persistence", "follow-up", "consequences", "hospital discharge", "COVID", "COVID-19", "SARS-CoV-2". Studies were selected that described alterations in the lung ultrasound of patients after having suffered from COVID-19 pneumonia. The JBI Critical Appraisal Tools were used to assess the risk of bias of the studies. No meta-analysis techniques were performed, the results being compared narratively. RESULTS From two to six months after COVID-19 pneumonia, pulmonary ultrasound abnormalities appear frequently and are proportional to the intensity of the initial episode. The most frequent anomalies are irregularities in the pleural line, the presence of B lines and/or subpleural consolidations, predominantly in the basal regions of the thorax. These findings seem to correlate with those of the chest CT. CONCLUSIONS Lung ultrasound offers technical and economic advantages that should be considered for the study of patients after hospital discharge for COVID-19.
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Affiliation(s)
- F Navarro-Romero
- Servicio de Medicina Interna, Hospital Costa del Sol, 29603 Málaga, Spain; Facultad de Medicina, Universidad de Málaga, 29010 Málaga, Spain.
| | - J Olalla-Sierra
- Servicio de Medicina Interna, Hospital Costa del Sol, 29603 Málaga, Spain
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