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Kitano M, Ohnishi H, Makino A, Miyamoto T, Hayashi Y, Mizuno K, Kaba S, Kawai Y, Kojima T, Kishimoto Y, Yamamoto N, Tomonaga K, Omori K. An Infection Model for SARS-CoV-2 Using Rat Transplanted with hiPSC-Airway Epithelial Cells. Tissue Eng Part A 2025; 31:361-372. [PMID: 38832872 DOI: 10.1089/ten.tea.2024.0016] [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: 06/06/2024] Open
Abstract
Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.
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Affiliation(s)
- Masayuki Kitano
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Hiroe Ohnishi
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Akiko Makino
- Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto City, Japan
| | - Tatsuo Miyamoto
- Department of Molecular and Cellular Physiology, Research Institute for Cell Design Medical Science, Graduate School of Medicine, Yamaguchi University, Ube City, Japan
| | - Yasuyuki Hayashi
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Keisuke Mizuno
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Shinji Kaba
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Yoshitaka Kawai
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Tsuyoshi Kojima
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Yo Kishimoto
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
| | - Norio Yamamoto
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
- Department of Otolaryngology, Kobe City Medical Center General Hospital, Kobe city, Japan
| | - Keizo Tomonaga
- Department of Virus Research, Institute for Life and Medical Sciences, Kyoto University, Kyoto City, Japan
| | - Koichi Omori
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of medicine, Kyoto University, Kyoto City, Japan
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Serrano-Gonzalo I, Menéndez-Jandula B, Franco-García E, Arévalo-Vargas I, Lahoz-Gil C, Latre P, Roca-Esteve S, Köhler R, López de Frutos L, Giraldo P. Neutrophil extracellular traps and macrophage activation contibute to thrombosis and post-covid syndrome in SARS-CoV-2 infection. Front Immunol 2025; 16:1507167. [PMID: 40066452 PMCID: PMC11891236 DOI: 10.3389/fimmu.2025.1507167] [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: 10/07/2024] [Accepted: 02/04/2025] [Indexed: 05/13/2025] Open
Abstract
Background SARS-CoV-2 infection activates macrophages and induces the release of neutrophil extracellular traps (NETs). Excess NETs is linked to inflammatory and thrombotic complications observed in COVID-19. Aim To explore the impact of NETs and macrophage activation on SARS-CoV-2-infected patients who developed complications. Methods We included 30 patients from the first (March 2020) and 30 from the second wave (July 2021), collecting two plasma samples at diagnosis and seven days later. Data on demographics, comorbidities, and basic analytical data were compiled. NETs markers (myeloperoxidase (MPO), neutrophil elastase (NE), p-selectin (P-SEL) and S100A8/S100A9 heterodimer (MRP)) and macrophage activation markers (Chitotriosidase activity (ChT), CCL18/PARC and YKL-40) were measured. Results The first wave had higher incidences of post-COVID syndrome, ICU admissions, and mortality. Patients of each wave showed elevated blood cells, liver enzymes, and coagulation markers at the time of diagnosis, with fibrinogen and D-Dimer differing between waves. NET and macrophage markers, NE, MPO, MRP, DNAse, ChT, and CCL18 were elevated, while P-SEL, cfDNA, and YKL-40 were decreased if compared to controls. A decrease in NE and DNAse is a link to lower levels of these two markers in complications versus without complications. Conclusions This study emonstrates alterations in NETs and macrophage activation markers in COVID-19 patients, indicating an imbalance in inflammatory response regulation.
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Affiliation(s)
- Irene Serrano-Gonzalo
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
- Grupo de Investigación Mecanismos de Enfermedad Crónica e Investigación Traslacional (MECIT), Zaragoza, Spain
- Grupo Estudio de Enfermedades de Depósito Lisosomal (GEEDL), Sociedad Española de Hematología y Hemoterapia (SEHH), Zaragoza, Spain
- Grupo de Investigación en Enfermedad de Gaucher (GIIS-012), Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | | | - Esther Franco-García
- Grupo de Investigación Mecanismos de Enfermedad Crónica e Investigación Traslacional (MECIT), Zaragoza, Spain
- Grupo Estudio de Enfermedades de Depósito Lisosomal (GEEDL), Sociedad Española de Hematología y Hemoterapia (SEHH), Zaragoza, Spain
- Servicio de Hematología, Hospital Ntra Sra de Gracia, Zaragoza, Spain
| | - Isidro Arévalo-Vargas
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
- Grupo de Investigación Mecanismos de Enfermedad Crónica e Investigación Traslacional (MECIT), Zaragoza, Spain
- Grupo de Investigación en Enfermedad de Gaucher (GIIS-012), Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
| | - Calos Lahoz-Gil
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
| | - Paz Latre
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
- Medicina de Familia, Servicio de Atención primaria., Zaragoza, Spain
| | - Sonia Roca-Esteve
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
| | - Ralf Köhler
- Grupo de Investigación Mecanismos de Enfermedad Crónica e Investigación Traslacional (MECIT), Zaragoza, Spain
- Grupo de Investigación en Enfermedad de Gaucher (GIIS-012), Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
- Fundación Aragonesa para la Investigación y el Desarrollo (ARAID), Zaragoza, Spain
| | - Laura López de Frutos
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
- Grupo Estudio de Enfermedades de Depósito Lisosomal (GEEDL), Sociedad Española de Hematología y Hemoterapia (SEHH), Zaragoza, Spain
| | - Pilar Giraldo
- Fundación Española para el Estudio y Terapéutica de la Enfermedad de Gaucher y otras lisosomales (FEETEG), Zaragoza, Spain
- Grupo de Investigación Mecanismos de Enfermedad Crónica e Investigación Traslacional (MECIT), Zaragoza, Spain
- Grupo Estudio de Enfermedades de Depósito Lisosomal (GEEDL), Sociedad Española de Hematología y Hemoterapia (SEHH), Zaragoza, Spain
- Grupo de Investigación en Enfermedad de Gaucher (GIIS-012), Instituto de Investigación Sanitaria Aragón, Zaragoza, Spain
- Servicio de Hematología, Hospital QuironSalud, Zaragoza, Spain
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van der Mescht MA, Steel HC, Anderson R, Rossouw TM. Vascular endothelial growth factor A: friend or foe in the pathogenesis of HIV and SARS-CoV-2 infections? Front Cell Infect Microbiol 2025; 14:1458195. [PMID: 40008234 PMCID: PMC11850333 DOI: 10.3389/fcimb.2024.1458195] [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: 07/02/2024] [Accepted: 10/28/2024] [Indexed: 02/27/2025] Open
Abstract
This review article discusses the role of vascular endothelial growth factor A (VEGF-A) in the pathogenesis of SARS-CoV-2 and HIV infection, both conditions being renowned for their impact on the vascular endothelium. The processes involved in vascular homeostasis and angiogenesis are reviewed briefly before exploring the interplay between hypoxia, VEGF-A, neuropilin-1 (NRP-1), and inflammatory pathways. We then focus on SARS-CoV-2 infection and show how the binding of the viral pathogen to the angiotensin-converting enzyme 2 receptor, as well as to NRP-1, leads to elevated levels of VEGF-A and consequences such as coagulation, vascular dysfunction, and inflammation. HIV infection augments angiogenesis via several mechanisms, most prominently, by the trans-activator of transcription (tat) protein mimicking VEGF-A by binding to its receptor, VEGFR-2, as well as upregulation of NRP-1, which enhances the interaction between VEGF-A and VEGFR-2. We propose that the elevated levels of VEGF-A observed during HIV/SARS-CoV-2 co-infection originate predominantly from activated immune cells due to the upregulation of HIF-1α by damaged endothelial cells. In this context, a few clinical trials have described a diminished requirement for oxygen therapy during anti-VEGF treatment of SARS-CoV-2 infection. The currently available anti-VEGF therapy strategies target the binding of VEGF-A to both VEGFR-1 and VEGFR-2. The blocking of both receptors could, however, lead to a negative outcome, inhibiting not only pathological, but also physiological angiogenesis. Based on the examination of published studies, this review suggests that treatment targeting selective inhibition of VEGFR-1 may be beneficial in the context of SARS-CoV-2 infection.
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Affiliation(s)
| | | | | | - Theresa M. Rossouw
- Department of Immunology, Faculty of Health Sciences, University of
Pretoria, Pretoria, South Africa
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4
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Bach ML, Laftih S, Andresen JK, Pedersen RM, Andersen TE, Madsen LW, Madsen K, Hinrichs GR, Zachar R, Svenningsen P, Lund L, Johansen IS, Hansen LF, Palarasah Y, Jensen BL. ACE2 and TMPRSS2 in human kidney tissue and urine extracellular vesicles with age, sex, and COVID-19. Pflugers Arch 2025; 477:83-98. [PMID: 39382598 PMCID: PMC11711140 DOI: 10.1007/s00424-024-03022-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 10/10/2024]
Abstract
SARS-CoV-2 virus infects cells by engaging with ACE2 requiring protease TMPRSS2. ACE2 is highly expressed in kidneys. Predictors for severe disease are high age and male sex. We hypothesized that ACE2 and TMPRSS2 proteins are more abundant (1) in males and with increasing age in kidney and (2) in urine and extracellular vesicles (EVs) from male patients with COVID-19 and (3) SARS-CoV-2 is present in urine and EVs during infection. Kidney cortex samples from patients subjected to cancer nephrectomy (male/female; < 50 years/˃75 years, n = 24; ˃80 years, n = 15) were analyzed for ACE2 and TMPRSS2 protein levels. Urine from patients hospitalized with SARS-CoV-2 infection was analyzed for ACE2 and TMPRSS2. uEVs were used for immunoblotting and SARS-CoV-2 mRNA and antigen detection. Tissue ACE2 and TMPRSS2 protein levels did not change with age. ACE2 was not more abundant in male kidneys in any age group. ACE2 protein was associated with proximal tubule apical membranes in cortex. TMPRSS2 was observed predominantly in the medulla. ACE2 was elevated significantly in uEVs and urine from patients with COVID-19 with no sex difference compared with urine from controls w/wo albuminuria. TMPRSS2 was elevated in uEVs from males compared to female. ACE2 and TMPRSS2 did not co-localize in uEVs/apical membranes. SARS-CoV-2 nucleoprotein and mRNA were not detected in urine. Higher kidney ACE2 protein abundance is unlikely to explain higher susceptibility to SARS-CoV-2 infection in males. Kidney tubular cells appear not highly susceptible to SARS-CoV-2 infection. Loss of ACE2 into urine in COVID could impact susceptibility and angiotensin metabolism.
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Affiliation(s)
- Marie Lykke Bach
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
| | - Sara Laftih
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Jesper K Andresen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Rune M Pedersen
- Department of Clinical Microbiology, Odense University Hospital, and Research Unit for Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | - Thomas Emil Andersen
- Department of Clinical Microbiology, Odense University Hospital, and Research Unit for Clinical Microbiology, University of Southern Denmark, Odense, Denmark
| | - Lone W Madsen
- Department of Infectious Diseases, Odense University Hospital, and Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
- Unit for Infectious Diseases, Department of Medicine, Sygehus Lillebælt, Kolding, Denmark
| | - Kirsten Madsen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
- Department of Pathology, Odense University Hospital, Odense, Denmark
| | - Gitte R Hinrichs
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
- Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Rikke Zachar
- Department of Nephrology, Odense University Hospital, Odense, Denmark
| | - Per Svenningsen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Lars Lund
- Department of Urology, Odense University Hospital, Odense, Denmark
| | - Isik S Johansen
- Department of Infectious Diseases, Odense University Hospital, and Research Unit for Infectious Diseases, University of Southern Denmark, Odense, Denmark
| | | | - Yaseelan Palarasah
- Unit of Inflammation and Cancer Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
| | - Boye L Jensen
- Unit of Cardiovascular and Renal Research, Department of Molecular Medicine, University of Southern Denmark, Odense, Denmark
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Zhang L, Yu H, Yang J, Su R, Zhang J, Zeng R, Liu Y, Zhang L, Xu J. Poor nutrition doubles post-COVID-19 syndrome risk in cancer patients: insights from a Chinese multicentre study. Front Nutr 2024; 11:1479918. [PMID: 39574527 PMCID: PMC11580423 DOI: 10.3389/fnut.2024.1479918] [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: 08/13/2024] [Accepted: 10/01/2024] [Indexed: 11/24/2024] Open
Abstract
Background Since 2019, approximately 760 million SARS-CoV-2 cases have been reported globally, with post-COVID-19 syndrome posing significant challenges for cancer patients due to their immunosuppressed status and poor nutritional conditions. The role of nutritional status in influencing their infection risk and post-COVID-19 outcomes remains unclear, underscoring the need for targeted research and strategies. Objective To investigate the impact of baseline nutritional status on SARS-CoV-2 infection and the risk of post-COVID-19 syndrome in cancer patients. Methods A multicenter cross-sectional study was conducted from December 2022 to June 2023 in four tertiary hospitals across China. Cancer inpatients aged 18 years and older were enrolled and classified into two groups based on their Nutritional Risk Screening (NRS) scores. The correlation between SARS-CoV-2 infection, post-COVID-19 syndrome and nutritional status were analyzed using multivariable logistic regression. Results Among 834 eligible cancer patients, 10.8% were in the high nutritional risk group (NRS ≥ 3). The prevalence of SARS-CoV-2 infection was 58.8% (95% confidence interval, CI: 56.8-60.8%), and post-COVID-19 syndrome was 21.0% (95% CI: 10.4-14.4%). After adjusting for confounding factors, the high nutritional risk group had a significantly higher prevalence of post-COVID-19 syndrome compared to the low nutritional risk group (32.7% vs. 19.5%, AOR: 2.37, 95% CI: 1.23-4.54, p = 0.010). However, no significant difference in SARS-CoV-2 infection rates was found between the two groups (61.1% vs. 58.5%, AOR: 1.12, 95% CI: 0.70-1.80; p = 0.634). Interpretation Poor baseline nutritional status in cancer patients is associated with a higher prevalence of post-COVID-19 syndrome, providing preliminary information on post-COVID-19 syndrome in this population. These findings underscore the importance of adequate nutritional management in cancer patients, particularly during pandemic recurrences.
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Affiliation(s)
- Liangyuan Zhang
- Clinical Research Academy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, China
| | - Haihang Yu
- Clinical Research Academy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, China
| | - Jianzhou Yang
- Department of Public Health and Preventive Medicine, Changzhi Medical College, Changzhi, Shanxi, China
| | - Rila Su
- Cancer Center of Inner Mongolia People’s Hospital, Hohhot, Inner Mongolia, China
- Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States
| | - Jiaqi Zhang
- Clinical Research Academy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, China
| | - Rongbiao Zeng
- Clinical Research Academy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Epidemiology, China Medical University, Shenyang, Liaoning, China
| | - Yajie Liu
- Department of Radiation Therapy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Lei Zhang
- Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
| | - Junjie Xu
- Clinical Research Academy, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China
- Department of Public Health and Preventive Medicine, Changzhi Medical College, Changzhi, Shanxi, China
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Dos Santos PR, Dos Santos UR, de Santana Silva ÍTS, Fehlberg HF, Ferreira FB, Albuquerque GR, Mariano APM, da Silva MF, Lemos LS, Piton KA, de Melo Silva M, Fontana R, Guimarães Rocha Aguiar ER, Marin LJ, Gadelha SR. Influence of SARS-CoV-2 variants on COVID-19 epidemiological and clinical profiles: a comparative analysis of two waves of cases. Virol J 2024; 21:260. [PMID: 39438927 PMCID: PMC11515746 DOI: 10.1186/s12985-024-02538-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/14/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND The COVID-19 pandemic has been the most significant health challenge of the last century. Multiple and successive waves of COVID-19 cases, driven particularly by the emergence of new SARS-CoV-2 variants, have kept the world in a constant state of alert. METHODS We present an observational, descriptive, cross-sectional study aimed at identifying SARS-CoV-2 variants circulating during two local waves of COVID-19 cases in southern Bahia, Brazil (late 2021 and late 2022), and analyzing the association between the detected variants and the epidemiological and clinical characteristics of the disease. For this purpose, data and nasopharyngeal samples from individuals in southern Bahia, Brazil, with suspected COVID-19 were included. Viral detection was performed by RT-qPCR, and SARS-CoV-2 variants were identified by next-generation viral sequencing. RESULTS A total of 368 nasopharyngeal samples were tested. Approximately 23% of the samples from late 2021 tested positive for SARS-CoV-2, while in 2022, the positivity rate was about 56%. All sequenced samples from 2021 were identified as the Delta variant, while in 2022, all samples were classified as the Omicron variant. Overall, individuals who tested positive for SARS-CoV-2 in 2022 were younger than those who tested positive in 2021. Moreover, we observed significant differences in the clinical spectrum of SARS-CoV-2 infection when comparing the two periods. Individuals who presented with anosmia/ageusia were more likely to test positive for SARS-CoV-2 infection in 2021 but not in 2022. Additionally, fever, dry cough, pharyngalgia, headache, and rhinorrhea were more frequent among individuals infected with the Omicron variant than among those infected with the Delta variant. CONCLUSIONS The profile of COVID-19 in southern Bahia differed when analyzing two distinct waves of the pandemic in the region. These differences are likely related to the variants, which may differ in transmissibility and virulence, thereby altering the dynamics of the pandemic. This underscores the importance of genomic surveillance in better understanding the behavior of viral infections.
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Affiliation(s)
- Pérola Rodrigues Dos Santos
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Pós-Graduação em Ciências da Saúde, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Uener Ribeiro Dos Santos
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Faculdade AGES de Medicina de Irecê, Colegiado de Ciências Biológicas e da Saúde, Irecê, Bahia, Brasil
| | - Íris Terezinha Santos de Santana Silva
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Programa de Pós-Graduação em Biologia e Biotecnologia de Microrganismos, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Hllytchaikra Ferraz Fehlberg
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Programa de Pós-Graduação em Ciência Animal, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Fabrício Barbosa Ferreira
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Programa de Pós-Graduação em Biologia e Biotecnologia de Microrganismos, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - George Rego Albuquerque
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Departamento de Ciências Agrárias e Ambientais, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Ana Paula Melo Mariano
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Murillo Ferreira da Silva
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Programa de Pós-Graduação em Biologia e Biotecnologia de Microrganismos, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Leonardo Santos Lemos
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Pós-Graduação em Ciências da Saúde, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Karoline Almeida Piton
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Mylene de Melo Silva
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Renato Fontana
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
- Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | | | - Lauro Juliano Marin
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil
| | - Sandra Rocha Gadelha
- Laboratório de Farmacogenômica e Epidemiologia Molecular, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil.
- Departamento de Ciências Biológicas, Universidade Estadual de Santa Cruz, Ilhéus, Bahia, Brasil.
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Alkhofash NF, Ali BR. The Evaluation of Drugs as Potential Modulators of the Trafficking and Maturation of ACE2, the SARS-CoV-2 Receptor. Biomolecules 2024; 14:764. [PMID: 39062478 PMCID: PMC11274373 DOI: 10.3390/biom14070764] [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: 05/18/2024] [Revised: 06/15/2024] [Accepted: 06/17/2024] [Indexed: 07/28/2024] Open
Abstract
ACE2, part of the angiotensin-converting enzyme family and the renin-angiotensin-aldosterone system (RAAS), plays vital roles in cardiovascular and renal functions. It is also the primary receptor for SARS-CoV-2, enabling its entry into cells. This project aimed to study ACE2's cellular trafficking and maturation to the cell surface and assess the impact of various drugs and compounds on these processes. We used cellular and biochemical analyses to evaluate these compounds as potential leads for COVID-19 therapeutics. Our screening assay focused on ACE2 maturation levels and subcellular localization with and without drug treatments. Results showed that ACE2 maturation is generally fast and robust, with certain drugs having a mild impact. Out of twenty-three tested compounds, eight significantly reduced ACE2 maturation levels, and three caused approximately 20% decreases. Screening trafficking inhibitors revealed significant effects from most molecular modulators of protein trafficking, mild effects from most proposed COVID-19 drugs, and no effects from statins. This study noted that manipulating ACE2 levels could be beneficial or harmful, depending on the context. Thus, using this approach to uncover leads for COVID-19 therapeutics requires a thorough understanding ACE2's biogenesis and biology.
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Affiliation(s)
- Nesreen F. Alkhofash
- Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates;
| | - Bassam R. Ali
- Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates;
- ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al-Ain P.O. Box 15551, United Arab Emirates
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Ma J, Tian Z, Shi Q, Dong X, Sun Y. Affinity chromatography for virus-like particle manufacturing: Challenges, solutions, and perspectives. J Chromatogr A 2024; 1721:464851. [PMID: 38574547 DOI: 10.1016/j.chroma.2024.464851] [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: 01/20/2024] [Revised: 03/25/2024] [Accepted: 03/26/2024] [Indexed: 04/06/2024]
Abstract
The increasing medical application of virus-like particles (VLPs), notably vaccines and viral vectors, has increased the demand for commercial VLP production. However, VLP manufacturing has not yet reached the efficiency level achieved for recombinant protein therapeutics, especially in downstream processing. This review provides a comprehensive analysis of the challenges associated with affinity chromatography for VLP purification with respect to the diversity and complexity of VLPs and the associated upstream and downstream processes. The use of engineered affinity ligands and matrices for affinity chromatography is first discussed. Although several representative affinity ligands are currently available for VLP purification, most of them have difficulty in balancing ligand universality, ligand selectivity and mild operation conditions. Then, phage display technology and computer-assisted design are discussed as efficient methods for the rapid discovery of high-affinity peptide ligands. Finally, the VLP purification by affinity chromatography is analyzed. The process is significantly influenced by virus size and variation, ligand type and chromatographic mode. To address the updated regulatory requirements and epidemic outbreaks, technical innovations in affinity chromatography and process intensification and standardization in VLP purification should be promoted to achieve rapid process development and highly efficient VLP manufacturing, and emphasis is given to the discovery of universal ligands, applications of gigaporous matrices and platform technology. It is expected that the information in this review can provide a better understanding of the affinity chromatography methods available for VLP purification and offer useful guidance for the development of affinity chromatography for VLP manufacturing in the decades to come.
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Affiliation(s)
- Jing Ma
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Zengquan Tian
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Qinghong Shi
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
| | - Xiaoyan Dong
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China
| | - Yan Sun
- Department of Biochemical Engineering, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering and Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin 300350, China.
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Camelo ALM, Zamora Obando HR, Rocha I, Dias AC, Mesquita ADS, Simionato AVC. COVID-19 and Comorbidities: What Has Been Unveiled by Metabolomics? Metabolites 2024; 14:195. [PMID: 38668323 PMCID: PMC11051775 DOI: 10.3390/metabo14040195] [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: 01/18/2024] [Revised: 03/14/2024] [Accepted: 03/26/2024] [Indexed: 04/28/2024] Open
Abstract
The COVID-19 pandemic has brought about diverse impacts on the global population. Individuals with comorbidities were more susceptible to the severe symptoms caused by the virus. Within the crisis scenario, metabolomics represents a potential area of science capable of providing relevant information for understanding the metabolic pathways associated with the intricate interaction between the viral disease and previous comorbidities. This work aims to provide a comprehensive description of the scientific production pertaining to metabolomics within the specific context of COVID-19 and comorbidities, while highlighting promising areas for exploration by those interested in the subject. In this review, we highlighted the studies of metabolomics that indicated a variety of metabolites associated with comorbidities and COVID-19. Furthermore, we observed that the understanding of the metabolic processes involved between comorbidities and COVID-19 is limited due to the urgent need to report disease outcomes in individuals with comorbidities. The overlap of two or more comorbidities associated with the severity of COVID-19 hinders the comprehension of the significance of each condition. Most identified studies are observational, with a restricted number of patients, due to challenges in sample collection amidst the emergent situation.
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Affiliation(s)
- André Luiz Melo Camelo
- Laboratory of Analysis of Biomolecules Tiselius, Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil; (A.L.M.C.); (H.R.Z.O.); (I.R.); (A.C.D.); (A.d.S.M.)
| | - Hans Rolando Zamora Obando
- Laboratory of Analysis of Biomolecules Tiselius, Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil; (A.L.M.C.); (H.R.Z.O.); (I.R.); (A.C.D.); (A.d.S.M.)
| | - Isabela Rocha
- Laboratory of Analysis of Biomolecules Tiselius, Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil; (A.L.M.C.); (H.R.Z.O.); (I.R.); (A.C.D.); (A.d.S.M.)
| | - Aline Cristina Dias
- Laboratory of Analysis of Biomolecules Tiselius, Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil; (A.L.M.C.); (H.R.Z.O.); (I.R.); (A.C.D.); (A.d.S.M.)
| | - Alessandra de Sousa Mesquita
- Laboratory of Analysis of Biomolecules Tiselius, Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil; (A.L.M.C.); (H.R.Z.O.); (I.R.); (A.C.D.); (A.d.S.M.)
| | - Ana Valéria Colnaghi Simionato
- Laboratory of Analysis of Biomolecules Tiselius, Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (UNICAMP), Campinas 13083-970, São Paulo, Brazil; (A.L.M.C.); (H.R.Z.O.); (I.R.); (A.C.D.); (A.d.S.M.)
- National Institute of Science and Technology for Bioanalytics—INCTBio, Institute of Chemistry, Universidade Estadual de (UNICAMP), Campinas 13083-970, São Paulo, Brazil
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10
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Dimnjaković J, Buble T, Ivanko P, Poljičanin T, Karanović Štambuk S, Brborović H, Brborović O. Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis. PLoS One 2024; 19:e0301056. [PMID: 38536830 PMCID: PMC10971752 DOI: 10.1371/journal.pone.0301056] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2023] [Accepted: 03/08/2024] [Indexed: 01/03/2025] Open
Abstract
INTRODUCTION Patients with diabetes mellitus type 2 and chronic kidney disease (T2DM-CKD) have a 5 times higher risk of developing severe SARS-CoV-2 infection than those without these 2 diseases. The goal of this study is to provide information on T2DM-CKD and COVID-19 outcomes, with an emphasis on the association with anti-diabetic medications. METHODOLOGY Study is designed as a retrospective cohort analysis covering the years 2020 and 2021. Data from the National Diabetes Registry (CroDiab) were linked to hospital data, primary healthcare data, Causes of Death Registry data, the SARS-CoV-2 vaccination database, and the SARS-CoV-2 test results database. Study outcomes were cumulative incidence of SARS-CoV-2 positivity, COVID-19 hospitalizations, and COVID-19 deaths. For outcome predictors, logistic regression models were developed. RESULTS Of 231 796 patients with diabetes mellitus type 2 in the database, 7 539 were T2DM-CKD (3.25%). The 2-year cumulative incidences of all three studies' outcomes were higher in T2DM-CKD than in diabetes patients without CKD (positivity 18.1% vs. 14.4%; hospitalization 9.7% vs. 4.2%; death 3.3% vs. 1.1%, all p<0.001). For COVID-19 hospitalization, protective factors were SGLT-2 inhibitors use (OR 0.430; 95%CI 0.257-0.719) and metformin use (OR 0.769; 95% CI 0.643-0.920), risk factors were insulin use (1.411; 95%CI 1.167-1.706) and sulfonylureas use (OR 1.226; 95% CI 1.027-1.464). For SARS-CoV-2 positivity protective factors were SGLT-2 inhibitors (0.607; 95% CI 0.448-0.823), repaglinide use (OR 0.765; 95% CI 0.593-0.986) and metformin use (OR 0.857; 95% CI 0.770-0.994). DPP-4 inhibitors showed a non-significant decrease in risk for COVID-19 death (OR 0.761; 95% CI 0.568-1.019). CONCLUSION T2DM-CKD are heavily burdened by COVID-19 disease. Our results suggest no association between antidiabetic drugs and COVID-19 death outcome while SGLT-2 and metformin show to be protective against COVID-19 hospitalization and infection, repaglinide against infection, and insulin and sulfonylureas show to be risk factors for COVID-19 hospitalization and infection. Further research in T2DM-CKD is needed.
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Affiliation(s)
- Jelena Dimnjaković
- Division for Health Informatics and Biostatistics, Department for Biostatistics, Croatian Institute of Public Health, Zagreb, Croatia
| | - Tamara Buble
- Division for Health Informatics and Biostatistics, Department for Biostatistics, Croatian Institute of Public Health, Zagreb, Croatia
| | - Pero Ivanko
- Division for Health Informatics and Biostatistics, Department for Biostatistics, Croatian Institute of Public Health, Zagreb, Croatia
| | | | - Sandra Karanović Štambuk
- Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Centre Zagreb, Zagreb, Croatia
- Department of Internal Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Hana Brborović
- Department of Environmental and Occupational Health and Sports Medicine, School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Ognjen Brborović
- Department of Social Medicine and Organization of Health Care, School of Medicine, University of Zagreb, Zagreb, Croatia
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Correa RA, Arancibia F, De Ávila Kfouri R, Chebabo A, García G, Gutiérrez Robledo LM, Lopardo G, Nemerovsky J, Pérez CM, Rendon A, Ruiz-Palacios GM, Aggarwal B, Berzanskis A, Cintra O. Understanding the Burden of Respiratory Syncytial Virus in Older Adults in Latin America: An Expert Perspective on Knowledge Gaps. Pulm Ther 2024; 10:1-20. [PMID: 38358618 PMCID: PMC10881952 DOI: 10.1007/s41030-024-00253-3] [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: 12/19/2023] [Accepted: 01/12/2024] [Indexed: 02/16/2024] Open
Abstract
Respiratory syncytial virus (RSV) is a significant global health concern and major cause of hospitalization, particularly among infants and older adults. The clinical impact of RSV is well characterized in infants; however, in many countries, the burden and risk of RSV in older populations are overlooked. In Latin America, there are limited data on RSV epidemiology and disease management in older adults. Therefore, the impact of RSV in this region needs to be addressed. Here, current insights on RSV infections in older populations in Latin America, including those with underlying health conditions, are discussed. We also outline the key challenges limiting our understanding of the burden of RSV in Latin America in a worldwide context and propose an expert consensus to improve our understanding of the burden of RSV in the region. By so doing, we aim to ultimately improve disease management and outcomes of those at risk and to alleviate the impact on healthcare systems.A graphical plain language summary is available with this article.
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Affiliation(s)
- Ricardo Amorim Correa
- Medical School, Pulmonology and Thoracic Surgery Department, Federal University of Minas Gerais, Belo Horizonte, Brazil
| | - Francisco Arancibia
- Pulmonary Department, Instituto Nacional del Tórax and Clínica Santa María, Santiago de Chile, Chile
| | - Renato De Ávila Kfouri
- Pediatric Infectious Disease Specialist, Brazilian Pediatric Society and Brazilian Immunization, São Paulo, Brazil
| | - Alberto Chebabo
- University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | | | - Luis Miguel Gutiérrez Robledo
- National Institute of Medical Sciences and Nutrition "S Zubiran" and National Institute of Geriatric Medicine, Mexico City, Mexico
| | - Gustavo Lopardo
- Infectious Diseases Department, Hospital Bernardo Houssay, Buenos Aires, Argentina
| | - Julio Nemerovsky
- Geriatrician Physician, Argentine Society of Gerontology and Geriatrics, Buenos Aires, Argentina
| | - Carlos M Pérez
- Faculty of Medicine and Science, Universidad San Sebastian, Santiago, Chile
| | - Adrian Rendon
- Universidad Autonoma de Nuevo León, Hospital Universitario "Dr. Jose Eleuterio Gonzalez", Centro de Investigación, Prevención y Tratamiento de Infecciones Respiratorias (CIPTIR), Monterrey, Mexico
| | - Guillermo M Ruiz-Palacios
- Department of Infectious Diseases, National Institute of Medical Sciences and Nutrition, Mexico City, Mexico
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Halinouskaya NV, Smychok VB, Nikalaeva NV, Zvenigorodskaya NO, Tabanjkova YV, Kabylka LA, Korsak ES. [Functional status of patients after myocardial revascularization combined with chronic low back pain at the sanatorium-resort stage of medical rehabilitation]. VOPROSY KURORTOLOGII, FIZIOTERAPII, I LECHEBNOI FIZICHESKOI KULTURY 2024; 101:30-41. [PMID: 38372735 DOI: 10.17116/kurort202410101130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2024]
Abstract
Chronic ischemic heart disease (CIHD) is the leading cause of morbidity and mortality, increasing in proportion to the growth of the older population. Rehabilitative measures in patients who have undergone the myocardial revascularization, with back pain currently have insufficient evidence base. The differentiated program of medical rehabilitation (MR) at the stage of sanatorium-resort treatment is not regulated. A description of the comorbid patients' functional status will create a differentiated system of individual rehabilitation program set up. OBJECTIVE To develop an algorithm for assessing the functional status of patients after myocardial revascularization with chronic low back pain. MATERIAL AND METHODS The single-center cross-sectional cohort study (September 2021 - May 2022 yrs) included 50 patients after a myocardial revascularization with chronic low back pain (36 women, 14 men; median age 63.5 [55.5; 67.5] years), who were the study group and 10 patients with CIHD (5 women, 5 men; median age 65.0 [62.0; 68.0] years) who joined the control group. All patients underwent clinical (neurological and therapeutic examination), functional (clinical tests, echocardiography) and laboratory (general and biochemical blood analysis, blood cytokine levels) investigations, the functional class of impairment was defined. RESULTS There are 4 groups with combined pain syndrome (cardiogenic and vertebrogenic) in different ratios due to different functional and laboratory status among patients after the myocardial revascularization with chronic back pain. The presence of cardiogenic pain syndrome was associated with an increase in leukocyte and peripheral blood glucose levels, interleukin-6, myocardial mass enlargement, while vertebrogenic pain syndrome correlated with personal anxiety. CONCLUSION The evaluation of the functional status of patients according to the degree of severity of cardiogenic and vertebrogenic pain syndrome has revealed a simple method of pathogenetically based differentiation selection for individual rehabilitation program of patient development.
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Affiliation(s)
| | - V B Smychok
- National Science and Practice Centre of Medical Assessment and Rehabilitation, Minsk, Belarus
| | | | | | | | - L A Kabylka
- Gomel State Medical University, Gomel, Belarus
| | - E S Korsak
- Gomel State Medical University, Gomel, Belarus
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Melinte OE, Robu Popa D, Dobrin ME, Cernomaz AT, Grigorescu C, Nemes AF, Gradinaru AC, Vicol C, Todea DA, Vulturar DM, Cioroiu IB, Trofor AC. Assessment of Some Risk Factors and Biological Predictors in the Post COVID-19 Syndrome in Asthmatic Patients. J Pers Med 2023; 14:21. [PMID: 38248722 PMCID: PMC10820086 DOI: 10.3390/jpm14010021] [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: 11/17/2023] [Revised: 12/15/2023] [Accepted: 12/17/2023] [Indexed: 01/23/2024] Open
Abstract
Long COVID-19 or post-COVID infection (PCI) refers to the prolongation of symptoms in people who have been infected with the SARS-CoV-2 virus. Some meta-analysis studies have shown that patients with comorbidities, such as diabetes, obesity or hypertension, have severe complications after infection with the SARS-CoV-2 virus. The presence of chronic respiratory diseases such as bronchial asthma, COPD, pulmonary hypertension or cystic fibrosis increases the risk of developing severe forms of the COVID-19 disease. The risk of developing the severe form of COVID-19 was observed in patients with bronchial asthma being treated with corticosteroids, but also in those hospitalized with severe asthma. The biological variables determined in patients with PCI infection showed changes, especially in the hematological parameters, but also in some inflammatory markers. The aim of this study was to investigate some biological predictors in post-COVID-19 infection in patients with asthma and various comorbidities. In the case of patients diagnosed with moderate and severe forms of COVID-19, the variation in biological tests has shown high concentrations for serum glucose, lactate dehydrogenase and C-reactive protein. Additionally, the calculation of the relative risk (RR) based on the associated comorbidities in patients with PCI points to higher values for patients with asthma, hypertension, diabetes and obesity (RR moderate/severe form = 0.98/1.52), compared to patients with PCI and asthma (RR moderate/severe form = 0.36/0.63). Based on the statistical results, it can be concluded that the alanine aminotransferase (ALT) activity (p = 0.006) and the age of patients (p = 0.001) are the variables that contribute the most to the separation of the four classes of comorbidities considered.
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Affiliation(s)
- Oana Elena Melinte
- Discipline of Pneumology, III-rd Medical Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (O.E.M.); (A.T.C.); (C.V.); (A.C.T.)
| | - Daniela Robu Popa
- Discipline of Pneumology, III-rd Medical Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (O.E.M.); (A.T.C.); (C.V.); (A.C.T.)
| | | | - Andrei Tudor Cernomaz
- Discipline of Pneumology, III-rd Medical Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (O.E.M.); (A.T.C.); (C.V.); (A.C.T.)
| | - Cristina Grigorescu
- Discipline of the Thoracic Surgery, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | | | - Adina Catinca Gradinaru
- Discipline of Pharmaceutical Botany, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Cristina Vicol
- Discipline of Pneumology, III-rd Medical Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (O.E.M.); (A.T.C.); (C.V.); (A.C.T.)
| | - Doina Adina Todea
- Discipline of Pneumology, Department of Medical Sciences, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj, Romania; (D.A.T.); (D.M.V.)
| | - Damiana Maria Vulturar
- Discipline of Pneumology, Department of Medical Sciences, Faculty of Medicine, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400012 Cluj, Romania; (D.A.T.); (D.M.V.)
| | - Ionel Bogdan Cioroiu
- Romanian Academy-Iasi Branch, Research Center for Oenology, 700490 Iasi, Romania;
| | - Antigona Carmen Trofor
- Discipline of Pneumology, III-rd Medical Department, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (O.E.M.); (A.T.C.); (C.V.); (A.C.T.)
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Rezaeian S, Razmjooei F, Pourmokhtari M, Abdoli A, Mofazzal Jahromi MA, Bagheri K. Hematological, inflammatory, and novel biomarkers assessment as an eminent strategy for clinical management of COVID-19. Heliyon 2023; 9:e22896. [PMID: 38076059 PMCID: PMC10703635 DOI: 10.1016/j.heliyon.2023.e22896] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 10/23/2023] [Accepted: 11/22/2023] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND Different biomarkers have been suggested as novel biomarkers of coronavirus disease 2019 (COVID-19) theragnosis. With the aim of having a better clinical management of COVID-19, we decided to determine the relationship between hematological, inflammatory, and novel biomarkers with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) immunoglobulin (Ig)M and IgG antibodies. METHODS Blood samples from 127 confirmed COVID-19 patients aged 11-84 years old were collected and tested for SARS-CoV-2 IgM and IgG antibodies alongside with hematological, inflammatory, and novel biomarkers. The Spearman correlation test was utilized to analyze the correlation between these biomarkers with SARS-CoV-2 IgM and IgG antibodies. RESULTS The SARS-CoV-2 IgM antibody significantly correlated with erythrocyte sedimentation rate (ESR) (r = 0.329, p = 0.000), C-reactive protein (CRP) (r = 0.459, p = 0.000), interleukin (IL)-6 (r = 0.345, p = 0.000), IL-8 (r = 0.263, p = 0.003), neutrophil to lymphocyte ratio (NLR) (r = 0.182, p = 0.040), derived NLR (dNLR) (r = 0.197, p = 0.026), neutrophil to monocyte ratio (NMR) (r = 0.184, p = 0.038), and CRP to lymphocyte ratio (CLR) (r = 0.495, p = 0.000). Also, we find significant correlation between SARS-CoV-2 IgG antibody with hemoglobin (Hb) (r = -0.257, p = 0.004), hematocrit (Hct) (r = -0.227, p = 0.010), mean corpuscular Hb concentration (MCHC) (r = -0.212, p = 0.017), lymphocyte count (r = -0.211, p = 0.017), platelet count (r = 0.179, p = 0.044), ESR (r = 0.461, p = 0.000), CRP (r = 0.344, p = 0.000), IL-6 (r = 0.178, p = 0.046), IL-8 (r = 0.237, p = 0.007), platelet to lymphocyte ratio (PLR) (r = 0.295, p = 0.001), and CLR (r = 0.376, p = 0.000). CONCLUSION Hematological biomarkers (Hb, Hct, MCHC, lymphocyte count, and platelet count), inflammatory biomarkers (ESR, CRP, IL-6, and IL-8), and novel biomarkers (dNLR, NLR, NMR, PLR, and CLR) are valuable indicators for clinical management of COVID-19.
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Affiliation(s)
- Sanaz Rezaeian
- Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran
- Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Fatemeh Razmjooei
- Student Research Committee, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Masoome Pourmokhtari
- Department of Orthopedics, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Amir Abdoli
- Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran
- Department of Parasitology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Mirza Ali Mofazzal Jahromi
- Zoonoses Research Center, Jahrom University of Medical Sciences, Jahrom, Iran
- Department of Immunology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
- Department of Advanced Medical Sciences & Technologies, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran
| | - Kambiz Bagheri
- Department of Immunology, Faculty of Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Iran
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15
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Olajuyin AM, Olajuyin AK, Zhang X, Hu Q. Immunomodulatory macrophages and Treg in pulmonary hypertension. COMPARATIVE CLINICAL PATHOLOGY 2023; 33:163-173. [DOI: 10.1007/s00580-023-03540-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 11/20/2023] [Indexed: 01/03/2025]
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16
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Violán C, Carrasco-Ribelles LA, Collatuzzo G, Ditano G, Abedini M, Janke C, Reinkemeyer C, Giang LTT, Liviero F, Scapellato ML, Mauro M, Rui F, Porru S, Spiteri G, Monaco MGL, Carta A, Otelea M, Rascu A, Fabiánová E, Klöslová Z, Boffetta P, Torán-Monserrat P. Multimorbidity and Serological Response to SARS-CoV-2 Nine Months after 1st Vaccine Dose: European Cohort of Healthcare Workers-Orchestra Project. Vaccines (Basel) 2023; 11:1340. [PMID: 37631908 PMCID: PMC10459685 DOI: 10.3390/vaccines11081340] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 07/25/2023] [Accepted: 08/03/2023] [Indexed: 08/29/2023] Open
Abstract
Understanding antibody persistence concerning multimorbidity is crucial for vaccination policies. Our goal is to assess the link between multimorbidity and serological response to SARS-CoV-2 nine months post-first vaccine. We analyzed Healthcare Workers (HCWs) from three cohorts from Italy, and one each from Germany, Romania, Slovakia, and Spain. Seven groups of chronic diseases were analyzed. We included 2941 HCWs (78.5% female, 73.4% ≥ 40 years old). Multimorbidity was present in 6.9% of HCWs. The prevalence of each chronic condition ranged between 1.9% (cancer) to 10.3% (allergies). Two regression models were fitted, one considering the chronic conditions groups and the other considering whether HCWs had diseases from ≥2 groups. Multimorbidity was present in 6.9% of HCWs, and higher 9-months post-vaccine anti-S levels were significantly associated with having received three doses of the vaccine (RR = 2.45, CI = 1.92-3.13) and with having a prior COVID-19 infection (RR = 2.30, CI = 2.15-2.46). Conversely, lower levels were associated with higher age (RR = 0.94, CI = 0.91-0.96), more time since the last vaccine dose (RR = 0.95, CI = 0.94-0.96), and multimorbidity (RR = 0.89, CI = 0.80-1.00). Hypertension is significantly associated with lower anti-S levels (RR = 0.87, CI = 0.80-0.95). The serological response to vaccines is more inadequate in individuals with multimorbidity.
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Affiliation(s)
- Concepción Violán
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe, 08303 Mataró, Spain; (L.A.C.-R.); (P.T.-M.)
- Germans Trias i Pujol Research Institute (IGTP), Camí de les Escoles, s/n, 08916 Badalona, Spain
- Grup de REcerca en Impacte de les Malalties Cròniques i les Seves Trajectòries (GRIMTra) (2021 SGR 01537), Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe, 08303 Barcelona, Spain
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS) (RD21/0016/0029), Insitituto de Salud Carlos III, Av. de Monforte de Lemos, 5, 28029 Madrid, Spain
- Direcció d’Atenció Primària Metropolitana Nord Institut Català de Salut, Ctra. de Barcelona, 473, Sabadell, 08204 Barcelona, Spain
- Universitat Autónoma de Barcelona, Plaça Cívica, 08193 Bellaterra, Spain
| | - Lucía A. Carrasco-Ribelles
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe, 08303 Mataró, Spain; (L.A.C.-R.); (P.T.-M.)
- Grup de REcerca en Impacte de les Malalties Cròniques i les Seves Trajectòries (GRIMTra) (2021 SGR 01537), Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe, 08303 Barcelona, Spain
- Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS) (RD21/0016/0029), Insitituto de Salud Carlos III, Av. de Monforte de Lemos, 5, 28029 Madrid, Spain
| | - Giulia Collatuzzo
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.C.); (G.D.); (M.A.); (P.B.)
| | - Giorgia Ditano
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.C.); (G.D.); (M.A.); (P.B.)
| | - Mahsa Abedini
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.C.); (G.D.); (M.A.); (P.B.)
| | - Christian Janke
- Division of Infectious Diseases and Tropical Medicine, LMU Klinikum, Leopoldstraße 5, 80802 Munich, Germany; (C.J.); (C.R.)
| | - Christina Reinkemeyer
- Division of Infectious Diseases and Tropical Medicine, LMU Klinikum, Leopoldstraße 5, 80802 Munich, Germany; (C.J.); (C.R.)
| | - Le Thi Thu Giang
- Department of Pediatrics, Dr. von Hauner Children’s Hospital, University Hospital, LMU Munich, Lindwurmstrasse 4, 80337 Munich, Germany;
| | - Filippo Liviero
- Department of Cardiac Thoracic Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy;
| | | | - Marcella Mauro
- Unit of Occupational Medicine, Department of Medical Sciences, University of Trieste, 34129 Trieste, Italy; (M.M.); (F.R.)
| | - Francesca Rui
- Unit of Occupational Medicine, Department of Medical Sciences, University of Trieste, 34129 Trieste, Italy; (M.M.); (F.R.)
| | - Stefano Porru
- Occupational Medicine Unit, University Hospital of Verona, 37134 Verona, Italy; (S.P.); (G.S.); (M.G.L.M.); (A.C.)
- Section of Occupational Health, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Gianluca Spiteri
- Occupational Medicine Unit, University Hospital of Verona, 37134 Verona, Italy; (S.P.); (G.S.); (M.G.L.M.); (A.C.)
| | - Maria Grazia Lourdes Monaco
- Occupational Medicine Unit, University Hospital of Verona, 37134 Verona, Italy; (S.P.); (G.S.); (M.G.L.M.); (A.C.)
| | - Angela Carta
- Occupational Medicine Unit, University Hospital of Verona, 37134 Verona, Italy; (S.P.); (G.S.); (M.G.L.M.); (A.C.)
- Section of Occupational Health, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
| | - Marina Otelea
- University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania; (M.O.); (A.R.)
| | - Agripina Rascu
- University of Medicine and Pharmacy “Carol Davila”, 020022 Bucharest, Romania; (M.O.); (A.R.)
| | - Eleonóra Fabiánová
- Occupational Health Department, Regional Authority of Public Health, 97556 Banská Bystrica, Slovakia; (E.F.); (Z.K.)
- Public Health Department, Faculty of Health, Catholic University, 03401 Ružomberok, Slovakia
| | - Zuzana Klöslová
- Occupational Health Department, Regional Authority of Public Health, 97556 Banská Bystrica, Slovakia; (E.F.); (Z.K.)
- Public Health Department, Faculty of Health, Catholic University, 03401 Ružomberok, Slovakia
| | - Paolo Boffetta
- Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy; (G.C.); (G.D.); (M.A.); (P.B.)
| | - Pere Torán-Monserrat
- Unitat de Suport a la Recerca Metropolitana Nord, Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe, 08303 Mataró, Spain; (L.A.C.-R.); (P.T.-M.)
- Germans Trias i Pujol Research Institute (IGTP), Camí de les Escoles, s/n, 08916 Badalona, Spain
- Direcció d’Atenció Primària Metropolitana Nord Institut Català de Salut, Ctra. de Barcelona, 473, Sabadell, 08204 Barcelona, Spain
- Department of Medicine, Faculty of Medicine, Universitat de Girona, 17001 Girona, Spain
- Multidisciplinary Research Group in Health and Society (GREMSAS) (2021 SGR 01484), Institut Universitari d’Investigació en Atenció Primària Jordi Gol (IDIAP Jordi Gol), Mare de Déu de Guadalupe, 08303 Barcelona, Spain
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Mediavilla JR, Lozy T, Lee A, Kim J, Kan VW, Titova E, Amin A, Zody MC, Corvelo A, Oschwald DM, Baldwin A, Fennessey S, Zuckerman JM, Kirn T, Chen L, Zhao Y, Chow KF, Maniatis T, Perlin DS, Kreiswirth BN. Molecular and Clinical Epidemiology of SARS-CoV-2 Infection among Vaccinated and Unvaccinated Individuals in a Large Healthcare Organization from New Jersey. Viruses 2023; 15:1699. [PMID: 37632041 PMCID: PMC10457875 DOI: 10.3390/v15081699] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/01/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations, from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOCs) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOCs, including Alpha (n = 714), Delta (n = 1877), and Omicron (n = 1802). Omicron isolates were further sub-typed as BA.1 (n = 899), BA.2 (n = 853), or BA.4/BA.5 (n = 50); the remaining 614 isolates were classified as "Other". Approximately 31.5% (1577/5007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p < 0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p < 0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p < 0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.
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Affiliation(s)
- José R. Mediavilla
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
| | - Tara Lozy
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
- Department of Pediatrics, Hackensack University Medical Center, Hackensack, NJ 07601, USA
| | - Annie Lee
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
| | - Justine Kim
- Hackensack Meridian Health Biorepository, Hackensack, NJ 07601, USA
| | - Veronica W. Kan
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
| | - Elizabeth Titova
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
| | - Ashish Amin
- Hackensack Meridian Health Biorepository, Hackensack, NJ 07601, USA
| | - Michael C. Zody
- New York Genome Center, New York, NY 10013, USA (S.F.); (T.M.)
| | - André Corvelo
- New York Genome Center, New York, NY 10013, USA (S.F.); (T.M.)
| | | | - Amy Baldwin
- New York Genome Center, New York, NY 10013, USA (S.F.); (T.M.)
| | | | - Jerry M. Zuckerman
- Department of Patient Safety and Quality, Hackensack Meridian Health, Edison, NJ 08837, USA
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Thomas Kirn
- Public Health and Environmental Laboratories, New Jersey Department of Health, Ewing, NJ 08628, USA
| | - Liang Chen
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Yanan Zhao
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Kar Fai Chow
- Hackensack Meridian Health Biorepository, Hackensack, NJ 07601, USA
- Department of Pathology, Hackensack University Medical Center, Hackensack, NJ 07601, USA
| | - Tom Maniatis
- New York Genome Center, New York, NY 10013, USA (S.F.); (T.M.)
| | - David S. Perlin
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
| | - Barry N. Kreiswirth
- Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
- Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA
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Banerjee A, Somasundaram I, Das D, Jain Manoj S, Banu H, Mitta Suresh P, Paul S, Bisgin A, Zhang H, Sun XF, Duttaroy AK, Pathak S. Functional Foods: A Promising Strategy for Restoring Gut Microbiota Diversity Impacted by SARS-CoV-2 Variants. Nutrients 2023; 15:nu15112631. [PMID: 37299594 DOI: 10.3390/nu15112631] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/24/2023] [Accepted: 05/31/2023] [Indexed: 06/12/2023] Open
Abstract
Natural herbs and functional foods contain bioactive molecules capable of augmenting the immune system and mediating anti-viral functions. Functional foods, such as prebiotics, probiotics, and dietary fibers, have been shown to have positive effects on gut microbiota diversity and immune function. The use of functional foods has been linked to enhanced immunity, regeneration, improved cognitive function, maintenance of gut microbiota, and significant improvement in overall health. The gut microbiota plays a critical role in maintaining overall health and immune function, and disruptions to its balance have been linked to various health problems. SARS-CoV-2 infection has been shown to affect gut microbiota diversity, and the emergence of variants poses new challenges to combat the virus. SARS-CoV-2 recognizes and infects human cells through ACE2 receptors prevalent in lung and gut epithelial cells. Humans are prone to SARS-CoV-2 infection because their respiratory and gastrointestinal tracts are rich in microbial diversity and contain high levels of ACE2 and TMPRSS2. This review article explores the potential use of functional foods in mitigating the impact of SARS-CoV-2 variants on gut microbiota diversity, and the potential use of functional foods as a strategy to combat these effects.
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Affiliation(s)
- Antara Banerjee
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Indumathi Somasundaram
- Department of Biotechnology Engineering, Kolhapur Institute of Technology's College of Engineering, Kolhapur 416012, Maharashtra, India
| | - Diptimayee Das
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Samatha Jain Manoj
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Husaina Banu
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Pavane Mitta Suresh
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India
| | - Sujay Paul
- School of Engineering and Sciences, Tecnologico de Monterrey, Campus Queretaro, San Pablo 76130, Mexico
| | - Atil Bisgin
- Department of Medical Genetics, Medical Faculty, Cukurova University, Adana 01250, Turkey
| | - Hong Zhang
- Department of Medical Sciences, School of Medicine, Orebro University, SE-701 82 Orebro, Sweden
| | - Xiao-Feng Sun
- Division of Ocology, Department of Biomedical and Clinical Sciences, Linkoping University, SE-581 83 Linkoping, Sweden
| | - Asim K Duttaroy
- Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, 0313 Oslo, Norway
| | - Surajit Pathak
- Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai 603103, Tamil Nadu, India
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Smail SW, Babaei E, Amin K, Abdulahad WH. Serum IL-23, IL-10, and TNF-α predict in-hospital mortality in COVID-19 patients. Front Immunol 2023; 14:1145840. [PMID: 37283736 PMCID: PMC10239952 DOI: 10.3389/fimmu.2023.1145840] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 05/05/2023] [Indexed: 06/08/2023] Open
Abstract
Objective The hyperinflammatory response, caused by severe acute respiratory syndrome-2 (SARS-CoV-2), is the most common cause of death in patients with coronavirus disease 2019 (COVID-19). The etiopathogenesis of this illness is not fully understood. Macrophages appear to play a key part in COVID-19's pathogenic effects. Therefore, this study aims to examine serum inflammatory cytokines associated with the activation state of macrophages in COVID-19 patients and attempt to find accurate predictive markers for disease severity and mortality risk in hospital. Methods 180 patients with COVID-19 and 90 healthy controls (HCs) participated in this study. Patients were divided into three different subgroups, mild (n=81), severe (n=60), and critical groups (n=39). Serum samples were collected and IL (Interleukin)-10, IL-23, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), IL-17, monocyte chemoattractant protein-1 (MCP-1) and chemokine ligand 3 (CCL3) were determined by ELISA. In parallel, myeloperoxidase (MPO) and C-reactive protein (CRP) were measured using colorimetric and electrochemiluminescence methods, respectively. Data were collected, and their associations with disease progression and mortality were assessed using regression models and receiver operating characteristic (ROC) curves. Results Compared to HCs, a significant increase in IL-23, IL-10, TNF-α, IFN-γ and MCP-1, were observed in COVID-19 patients. Serum levels of IL-23, IL-10, and TNF-α were significantly higher in COVID-19 patients with critical cases compared to mild and severe cases, and correlated positively with CRP level. However, non-significant changes were found in serum MPO and CCL3 among the studied groups. Moreover, significant positive association has been observed among increased IL-10, IL-23 and TNF-α in serum of COVID-19 patients. Furthermore, a binary logistic regression model was applied to predict death's independent factors. Results showed that IL-10 alone or in combination with IL23 and TNF-α are strongly linked with non-survivors in COVID-19 patients. Finally, ROC curve results uncovered that IL-10, IL-23 and TNF-α were excellent predictors for prognosing COVID-19. Conclusion The elevations of IL-10, IL-23, and TNF-α levels were seen in severe and critical cases of COVID-19 patients and their elevations were linked to the in-hospital mortality of the disease. A prediction model shows that the determination of these cytokines upon admission is important and should be done on COVID-19 patients as a way of evaluating the prognosis of the disease. COVID-19 Patients with high IL-10, IL-23, and TNF-α on admission are more likely to experience a severe form of the disease; therefore, those patients should be cautionary monitored and treated.
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Affiliation(s)
- Shukur Wasman Smail
- Department of Biology, College of Science, Salahaddin University, Erbil, Iraq
| | - Esmaeil Babaei
- Department of Biology, School of Natural Sciences, University of Tabriz, Tabriz, Iran
- Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Kawa Amin
- College of Medicine, University of Sulaimani, Sulaymaniyah, Iraq
- Department of Medical Science, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden
| | - Wayel H. Abdulahad
- Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
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Pereira LRG, da Silva MVG, Germano CMR, Estevao IF, Melo DG. Impact of the SARS-CoV-2 infection in individuals with sickle cell disease: an integrative review. Front Med (Lausanne) 2023; 10:1144226. [PMID: 37200963 PMCID: PMC10187638 DOI: 10.3389/fmed.2023.1144226] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2023] [Accepted: 04/04/2023] [Indexed: 05/20/2023] Open
Abstract
Sickle cell disease is the most common hemoglobinopathy among humans. As the condition promotes susceptibility to infections, chronic inflammation, and hypercoagulability disorders, several international agencies have included individuals with this disease in the COVID-19 risk group for severe outcomes. However, available information about the subject is not properly systematized yet. This review aimed to understand and summarize the scientific knowledge about the impact of SARS-CoV-2 infection in patients with sickle cell disease. Searches were performed in the Medline, PubMed, and Virtual Health Library databases based on descriptors chosen according to the Medical Subject Headings. We analyzed studies published between 2020 and October 2022, developed with qualitative, quantitative, or mixed methodology, and written in English, Spanish, or Portuguese. The search resulted in 90 articles organized into six categories. There is disagreement in the literature about how different aspects related to sickle cell disease, such as chronic inflammation status, hypercoagulability, hemolytic anemia, use of hydroxyurea, and access to medical care interference with the clinical course of COVID-19. These topics deserve further investigation. It is evident, however, that the infection may manifest in an atypical way and act as a trigger for the development of sickle cell-specific complications, such as acute chest syndrome and vaso-occlusive crises, conditions that are associated with great morbidity and mortality. Therefore, healthcare professionals must be aware of the different forms of presentation of COVID-19 among these individuals. Specific guidelines and therapeutic protocols, as well as public policies for sickle cell individuals, must be considered. Systematic review registration This review (https://doi.org/10.17605/OSF.IO/NH4AS) and the review protocol (https://osf.io/3y649/) are registered in the Open Science Framework platform.
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Affiliation(s)
| | | | | | | | - Débora Gusmão Melo
- Department of Medicine, Federal University of São Carlos (UFSCar), São Carlos, Brazil
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21
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Aquiles-Barzola F, Verástegui-Sandoval A, Machco-Pasmiño H, Córdova-Limaylla N, Ladera-Castañeda M, Cervantes-Ganoza L, Cayo-Rojas C. Factors Associated with Epidemiological, Preventive and Health Care Knowledge of Dentists from North of the Peruvian Capital about COVID-19: A Cross-Sectional Study under a Predictive Model. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:1020. [PMID: 36673776 PMCID: PMC9858654 DOI: 10.3390/ijerph20021020] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 12/30/2022] [Accepted: 01/04/2023] [Indexed: 06/12/2023]
Abstract
Aim: In dental practice there is a high risk of contact with fluids that may contain SARS-CoV-2. Salivary secretions in the form of droplets are the main route of infection. The present study aimed to evaluate factors associated with epidemiological, preventive and health care knowledge of dentists from the north of the Peruvian capital about COVID-19. Materials and Methods: This analytical, observational, cross-sectional and prospective study evaluated 142 dental professionals from the Directorate of Integrated Health Networks (DIRIS) in the north of the Peruvian capital during June to August 2022. A validated questionnaire of 20 closed multiple-choice questions was used to measure the level of epidemiological, preventive and health care knowledge about COVID-19. A logit model was used to evaluate the influence of the following variables: age, sex, marital status, children, origin, university of origin, academic degree, work modality, work status and number of training courses. In addition, a predictive model was constructed with the causal variables considering a significance level of p < 0.05. Results: Epidemiological, preventive and health care knowledge about COVID-19 was fair in 17.6%, 34.5% and 57.7%, respectively. Likewise, all the variables analyzed were influential factors. It was observed that being single (OR = 0.05, CI: 0.01−0.26), having studied at a private university (OR = 0.09, CI: 0.023−0.38) and having received four to six trainings on COVID-19 related topics (OR = 0.02, CI: 0.002−0.238) were protective factors against fair knowledge. Conclusions: More than half of the dentists surveyed had fair knowledge about COVID-19. The factors that favored a good level of overall knowledge were: being single, having studied at a private university and having received 4 to 6 training courses on COVID-19-related topics. It is advisable that the competent authorities continue to educate dental professionals with training programs about infection control practices in accordance with the health care work they perform in their specialty. It will also be of utmost importance for the professional to be updated with reliable information accredited by the Centers for Disease Control and Prevention as well as the WHO.
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Affiliation(s)
- Flor Aquiles-Barzola
- Grupo de Investigación Salud y Bienestar Global, Faculty of Dentistry and Postgraduate School, Universidad Nacional Federico Villarreal, Lima 15001, Peru
- Faculty of Health Sciences, Professional Academic School of Dentistry, Universidad Privada Norbert Wiener, Lima 15046, Peru
| | - Arturo Verástegui-Sandoval
- Faculty of Health Sciences, Professional Academic School of Dentistry, Universidad Privada Norbert Wiener, Lima 15046, Peru
| | - Heriberto Machco-Pasmiño
- Faculty of Health Sciences, Professional Academic School of Dentistry, Universidad Privada Norbert Wiener, Lima 15046, Peru
| | - Nancy Córdova-Limaylla
- School of Stomatology, Universidad Privada San Juan Bautista, Lima 15067, Peru
- Academic Program of Dentistry, Universidad Peruana de Ciencias Aplicadas, Lima 15023, Peru
| | - Marysela Ladera-Castañeda
- Grupo de Investigación Salud y Bienestar Global, Faculty of Dentistry and Postgraduate School, Universidad Nacional Federico Villarreal, Lima 15001, Peru
| | | | - César Cayo-Rojas
- Grupo de Investigación Salud y Bienestar Global, Faculty of Dentistry and Postgraduate School, Universidad Nacional Federico Villarreal, Lima 15001, Peru
- School of Stomatology, Universidad Privada San Juan Bautista, Lima 15067, Peru
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Abd El-Ghani SES, Hamed RMR, Eid RA, Ibrahim AYM, Abdel-Hamid HM, Abdelrahman W, Ibrahim RE, Abdel-Aziz MM, Mohamed MS. Serum interleukin 1β and sP-selectin as biomarkers of inflammation and thrombosis, could they be predictors of disease severity in COVID 19 Egyptian patients? (a cross-sectional study). Thromb J 2022; 20:77. [PMID: 36522776 PMCID: PMC9754776 DOI: 10.1186/s12959-022-00428-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 09/20/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Thromboembolism was a chief cause of mortality in 70% of patients with COVID-19. Our objective was to see if serum interleukins 1 beta (IL-1β) and soluble platelets selectin (sP-selectin) could serve as novel markers of thromboembolism in COVID-19 patients. METHODS This cross sectional study involved 89 COVID-19 patients who were recruited from 1st of February to 1st of May 2021. Clinical and laboratory data were collected, and chest imaging was performed. The levels of IL-1β and sP-selectin were assessed in all cases through ELISA kits. Comparisons between groups were done using an unpaired t-test in normally distributed quantitative variables. In contrast, a non-parametric Mann-Whitney test was used for non-normally distributed quantitative variables. RESULTS Severe COVID-19 infection was associated with higher serum levels of CRP, Ferritin, LDH, D dimer, IL-1β and sP-selectin (P < 0.001) with significant correlation between levels of IL-1β and sP-selectin (r 0.37, P < 0.001), D-dimer (r 0.29, P 0.006) and Ferritin (r 0.5, p < 0.001). Likewise, a positive correlation was also found between levels of sP-selectin, D-dimer and Ferritin (r 0.52, P < 0.001) (r 0.59, P < 0.001). Imaging studies revealed that 9 (10.1%) patients developed venous and 14 (15.7%) developed arterial thrombosis despite receiving anticoagulant therapy. Patients with thrombotic events had significantly higher levels of IL-1β, sP-selectin and LDH serum levels. Meanwhile, there was no statistical significance between CRP, D-dimer or Ferritin levels and the development of thrombotic events. CONCLUSION IL-1β and sP-selectin levels can be promising predictors for severe COVID-19 infection and predictable thrombosis.
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Affiliation(s)
| | | | - Ragaey Ahmad Eid
- Department of Tropical Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | | | - Hoda M. Abdel-Hamid
- Department of Chest Diseases, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Walaa Abdelrahman
- Department of Rheumatology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Raghda Ebaid Ibrahim
- Department of Clinical & Chemical Pathology, Faculty of Medicine, Beni Suef University, Beni-Suef, Egypt
| | - Manar Mahmoud Abdel-Aziz
- Department of Clinical & Chemical Pathology, Faculty of Medicine, Beni Suef University, Beni-Suef, Egypt
| | - Marwa Salah Mohamed
- Department of Internal Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt
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Gül F, Gonen ZB, Jones OY, Taşlı NP, Zararsız G, Ünal E, Özdarendeli A, Şahin F, Eken A, Yılmaz S, Karakukçu M, Kırbaş OK, Gökdemir NS, Bozkurt BT, Özkul Y, Oktay BD, Uygut MA, Cinel I, Çetin M. A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™). Front Immunol 2022; 13:963309. [PMID: 36439138 PMCID: PMC9682905 DOI: 10.3389/fimmu.2022.963309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/20/2022] [Indexed: 07/22/2023] Open
Abstract
This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
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Affiliation(s)
- Fethi Gül
- Department of Anesthesiology and Reanimation, Division of Critical Care Medicine, School of Medicine, Marmara University, Istanbul, Türkiye
| | | | - Olcay Y. Jones
- Division of Rheumatology, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, United States
| | - Neslihan Pakize Taşlı
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye
| | - Gökmen Zararsız
- Department of Biostatistics, Faculty of Medicine, Erciyes University, Kayseri, Türkiye
| | - Ekrem Ünal
- Department of Pediatrics, Division of Pediatric Hematology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye
| | - Aykut Özdarendeli
- Faculty of Medicine, Vaccine Research and Development Application and Research Center, Erciyes University, Kayseri, Türkiye
| | - Fikrettin Şahin
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye
| | - Ahmet Eken
- Department of Biology, Faculty of Science, Erciyes University, Kayseri, Türkiye
| | - Semih Yılmaz
- Institute of Health Sciences, Department of Medical Biochemistry, Erciyes University, Kayseri, Türkiye
| | - Musa Karakukçu
- Department of Pediatrics, Division of Pediatric Hematology, Faculty of Medicine, Erciyes University, Kayseri, Türkiye
| | - Oğuz Kaan Kırbaş
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye
| | - Nur Seda Gökdemir
- Betül-Ziya Eren Genome and Stem Cell Center (GENKOK), Kayseri, Türkiye
| | - Batuhan Turhan Bozkurt
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, İstanbul, Türkiye
| | - Yusuf Özkul
- Faculty of Medicine, Erciyes University, Kayseri, Türkiye
| | - Burçin Doruk Oktay
- Department of Anesthesiology and Reanimation, Division of Critical Care Medicine, School of Medicine, Marmara University, İstanbul, Türkiye
| | - Muhammet Ali Uygut
- Vaccine Research and Development Application and Research Center, Erciyes University, Kayseri, Türkiye
| | - Ismail Cinel
- Department of Anesthesiology and Reanimation, Division of Critical Care Medicine, School of Medicine, Marmara University, İstanbul, Türkiye
| | - Mustafa Çetin
- Faculty of Medicine, Erciyes University, Kayseri, Türkiye
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Gül F, Gonen ZB, Jones OY, Taşlı NP, Zararsız G, Ünal E, Özdarendeli A, Şahin F, Eken A, Yılmaz S, Karakukçu M, Kırbaş OK, Gökdemir NS, Bozkurt BT, Özkul Y, Oktay BD, Uygut MA, Cinel I, Çetin M. A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™). Front Immunol 2022. [DOI: https://doi.org/10.3389/fimmu.2022.963309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
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Gül F, Gonen ZB, Jones OY, Taşlı NP, Zararsız G, Ünal E, Özdarendeli A, Şahin F, Eken A, Yılmaz S, Karakukçu M, Kırbaş OK, Gökdemir NS, Bozkurt BT, Özkul Y, Oktay BD, Uygut MA, Cinel I, Çetin M. A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™). Front Immunol 2022. [DOI: https:/doi.org/10.3389/fimmu.2022.963309] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia.
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de Mello V, Pereira VDP, Rodrigues JPV, Penteado STDS, Pereira LRL, Varallo FR. [Central nervous system adverse events potentially associated with drugs used for COVID-19: scoping reviewEventos adversos en el sistema nervioso central potencialmente relacionados con los medicamentos para tratar la COVID-19: revisión exploratoria]. Rev Panam Salud Publica 2022; 46:e166. [PMID: 36320207 PMCID: PMC9595226 DOI: 10.26633/rpsp.2022.166] [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: 12/23/2021] [Accepted: 05/23/2022] [Indexed: 12/15/2022] Open
Abstract
Objective To identify central nervous system (CNS) adverse events potentially associated with prophylaxis or drug treatment for COVID-19, and to describe the characteristic of the individuals affected. Methods A scoping review was performed using a search strategy to retrieve articles from PubMed, EMBASE, SciELO, Scopus, CINAHL and BVS databases. Studies reporting on individuals receiving prophylactic or curative drugs for COVID-19 with at least one CNS adverse event were included. Articles reporting on CNS adverse events associated with medication for other health conditions were excluded. Results The search retrieved 1 547 articles, eight of which met the inclusion criteria. Seven studies had an observational design. A total of 3 035 individuals were assessed, of whom 1 701 were health care professionals and 1 978 were women. Curative treatment with hydroxychloroquine, chloroquine, lopinavir/ritonavir, and azithromycin was the most frequent (n = 5). The most common adverse events were headache, dizziness, mood disturbances, and drowsiness. Suicide was the most frequent severe event. Six adverse events were unexpected for hydroxychloroquine, chloroquine, and doxycycline. Conclusion Potential CNS adverse events were unspecific and in general potentially associated with the use of hydroxychloroquine (monotherapy or associated with antibiotics). The data confirm the unfavorable risk/benefit profile of these drugs for the prevention and management of signs and symptoms of SARS-CoV-2 infection.
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Affiliation(s)
- Vinícius de Mello
- Universidade de São Paulo (USP)Faculdade de Ciências Farmacêuticas de Ribeirão PretoRibeirão Preto (SP)BrasilUniversidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto (SP), Brasil.
| | - Vinícius de Paula Pereira
- Universidade de São Paulo (USP)Faculdade de Ciências Farmacêuticas de Ribeirão PretoRibeirão Preto (SP)BrasilUniversidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto (SP), Brasil.
| | - João Paulo Vilela Rodrigues
- Universidade de São Paulo (USP)Faculdade de Ciências Farmacêuticas de Ribeirão PretoRibeirão Preto (SP)BrasilUniversidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto (SP), Brasil.
| | - Suelem Tavares da Silva Penteado
- Universidade de São Paulo (USP)Faculdade de Ciências Farmacêuticas de Ribeirão PretoRibeirão Preto (SP)BrasilUniversidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto (SP), Brasil.
| | - Leonardo Régis Leira Pereira
- Universidade de São Paulo (USP)Faculdade de Ciências Farmacêuticas de Ribeirão PretoRibeirão Preto (SP)BrasilUniversidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto (SP), Brasil.
| | - Fabiana Rossi Varallo
- Universidade de São Paulo (USP)Faculdade de Ciências Farmacêuticas de Ribeirão PretoRibeirão Preto (SP)BrasilUniversidade de São Paulo (USP), Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Ribeirão Preto (SP), Brasil.
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Gupta A, Qaisar R, Halwani R, Kannan M, Ahmad F. TFPI and FXIII negatively and S100A8/A9 and Cystatin C positively correlate with D-dimer in COVID-19. Exp Biol Med (Maywood) 2022; 247:1570-1576. [PMID: 35723053 PMCID: PMC9554165 DOI: 10.1177/15353702221102117] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
D-dimer is an established biomarker of thromboembolism and severity in COVID-19. We and others have recently reported the dysregulation of tissue factor pathway inhibitor (TFPI), FXIII, fibrinolytic pathway, inflammatory markers, and tissue injury markers, particularly in severe COVID-19. However, association of these markers with thromboembolism in COVID-19 remains elusive. The correlation analyses between these markers in patients with moderate (non-ICU) and severe COVID-19 (ICU) were performed to delineate the potential pathomechanisms and impact of thromboembolism. We observe a negative correlation of plasma TFPI (r2 = 0.148, P = 0.035), FXIII (r2 = 0.242, P = 0.006), and plasminogen (r2 = 0.27, P = 0.003) with D-dimer, a biomarker of thromboembolism, levels in these patients. Further analysis revealed a strong positive correlation between fibrinolytic markers tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) (r2 = 0.584, P < 0.0001). Interestingly, a significant positive correlation of PAI-1, but not tPA, was observed with platelets and endothelial cells dysfunction markers P-selectin (r2 = 0.184, P = 0.01) and soluble CD40 ligand (sCD40 L) (r2 = 0.163, P = 0.02). Moreover, calprotectin (S100A8/A9) and cystatin C (CST3), previously linked with thromboembolism, exhibited positive correlations with each other (r2 = 0.339, P = 0.0007) and with the level of D-dimer independently in COVID-19. Finally, the tissue injury marker myoglobin demonstrated a strong positive correlation with D-dimer (r2 = 0.408, P = 0.0001). Taken together, inverse correlations of TFPI and FXIII with D-dimer suggest the TF pathway activation and aberrant fibrin polymerization in COVID-19 patients. The elevated level of PAI-1 is potentially contributed by activated platelets and endothelial cells. S100A8/A9 may also play roles in impaired fibrinolysis and thromboembolism, in part, through regulating the CST3. These findings strengthen the understanding of thromboembolism and tissue injury and may help in better management of thromboembolic complications in COVID-19 patients.
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Affiliation(s)
- Anamika Gupta
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE
| | - Rizwan Qaisar
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE
| | - Rabih Halwani
- Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE
| | - Meganathan Kannan
- Blood and Vascular Biology Research Lab, Department of Life Sciences, Central University of Tamil Nadu, Thiruvarur 610005, Tamil Nadu, India
| | - Firdos Ahmad
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, UAE,Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, UAE,Firdos Ahmad.
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SARS-CoV-2 infection- induced growth factors play differential roles in COVID-19 pathogenesis. Life Sci 2022; 304:120703. [PMID: 35700841 PMCID: PMC9188443 DOI: 10.1016/j.lfs.2022.120703] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 06/05/2022] [Accepted: 06/06/2022] [Indexed: 12/12/2022]
Abstract
Aims Biologically active molecules cytokines and growth factors (GFs) are critical regulators of tissue injury/repair and emerge as key players in COVID-19 pathophysiology. However, specific disease stage of GFs dysregulation and, whether these GFs have associations with thromboembolism and tissue injury/repair in COVID-19 remain vague. Main methods GF profiling in hospitalized moderate (non-ICU) and critically ill (ICU) COVID-19 patients was performed through legendPlex assay. Key findings Investigation revealed profound elevation of VEGF, PDGFs, EGF, TGF-α, FGF-basic, and erythropoietin (EPO) in moderate cases and decline or trend of decline with disease advancement. We found strong positive correlations of plasma VEGF, PDGFs, and EPO with endothelial dysfunction markers P-selectin and sCD40L. Interestingly, the HGF and G-CSF were upregulated at the moderate stage and remained elevated at the severe stage of COVID-19. Moreover, strong negative correlations of PDGFs (r2 = 0.238, P = 0.006), EPO (r2 = 0.18, P = 0.01) and EGF (r2 = 0.172, P = 0.02) and positive correlation of angiopoietin-2 (r2 = 0.267, P = 0.003) with D-dimer, a marker of thromboembolism, was observed. Further, plasma PDGFs (r2 = 0.199, P = 0.01), EPO (r2 = 0.115, P = 0.02), and EGF (r2 = 0.108, P = 0.07) exhibited negative correlations with tissue injury marker, myoglobin. Significance Taken together, unlike cytokines, most of the assessed GFs were upregulated at the moderate stage of COVID-19. The induction of GFs likely occurs due to endothelial dysfunction and may counter the adverse effects of cytokine storms which is reflected by inverse correlations of PDGFs, EPO, and EGF with thromboembolism and tissue injury markers. The findings suggest that the assessed GFs play differential roles in the pathogenesis of COVID-19.
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Ahmad R, Haque M. Surviving the Storm: Cytokine Biosignature in SARS-CoV-2 Severity Prediction. Vaccines (Basel) 2022; 10:vaccines10040614. [PMID: 35455363 PMCID: PMC9026643 DOI: 10.3390/vaccines10040614] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Revised: 04/08/2022] [Accepted: 04/12/2022] [Indexed: 02/04/2023] Open
Abstract
Simple Summary The world has been stricken mentally, physically, and economically by the COVID-19 virus. However, while SARS-CoV-2 viral infection results in mild flu-like symptoms in most patients, a number of those infected develop severe illness. These patients require hospitalization and intensive care. The severe disease can spiral downwards with eventual severe damage to the lungs and failure of multiple organs, leading to the individual’s demise. It is necessary to identify those who are developing a severe form of illness to provide early management. Therefore, it is crucial to learn about the mechanisms and chemical mediators that lead to critical conditions in SARS-CoV-2 infection. This paper reviews studies regarding the individual chemical mediators, pathways, and means that contribute to worsening health conditions in SARS-CoV-2 infection. Abstract A significant part of the world population has been affected by the devastating SARS-CoV-2 infection. It has deleterious effects on mental and physical health and global economic conditions. Evidence suggests that the pathogenesis of SARS-CoV-2 infection may result in immunopathology such as neutrophilia, lymphopenia, decreased response of type I interferon, monocyte, and macrophage dysregulation. Even though most individuals infected with the SARS-CoV-2 virus suffer mild symptoms similar to flu, severe illness develops in some cases, including dysfunction of multiple organs. Excessive production of different inflammatory cytokines leads to a cytokine storm in COVID-19 infection. The large quantities of inflammatory cytokines trigger several inflammation pathways through tissue cell and immune cell receptors. Such mechanisms eventually lead to complications such as acute respiratory distress syndrome, intravascular coagulation, capillary leak syndrome, failure of multiple organs, and, in severe cases, death. Thus, to devise an effective management plan for SARS-CoV-2 infection, it is necessary to comprehend the start and pathways of signaling for the SARS-CoV-2 infection-induced cytokine storm. This article discusses the current findings of SARS-CoV-2 related to immunopathology, the different paths of signaling and other cytokines that result in a cytokine storm, and biomarkers that can act as early signs of warning for severe illness. A detailed understanding of the cytokine storm may aid in the development of effective means for controlling the disease’s immunopathology. In addition, noting the biomarkers and pathophysiology of severe SARS-CoV-2 infection as early warning signs can help prevent severe complications.
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Affiliation(s)
- Rahnuma Ahmad
- Department of Physiology, Medical College for Women and Hospital, Plot No 4 Road 8/9, Sector-1, Dhaka 1230, Bangladesh;
| | - Mainul Haque
- Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Perdana Sungai Besi, Kuala Lumpur 57000, Malaysia
- Correspondence: or
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