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Ding Q, Zhang Y, Zhang Z, Huang P, Tian R, Zhou Z, Wang R, Xie Y. Revolutionizing oncology care: pioneering AI models to foresee pneumonia-related mortality. Front Oncol 2025; 15:1520512. [PMID: 40177245 PMCID: PMC11961870 DOI: 10.3389/fonc.2025.1520512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 02/26/2025] [Indexed: 04/05/2025] Open
Abstract
BACKGROUND Pneumonia is a leading cause of morbidity and mortality among patients with cancer, and survival time is a primary concern. Despite their importance, there is a dearth of accurate predictive models in clinical settings. This study aimed to determine the incidence of pneumonia as a cause of death in patients with cancer, analyze trends and risk factors associated with mortality, and develop corresponding predictive models. METHODS We included 26,938 cancer patients in the United States who died from pneumonia between 1973 and 2020, as identified through the Surveillance, Epidemiology, and End Results (SEER) program. Cox regression analysis was used to ascertain the prognostic factors for patients with cancer. The CatBoost model was constructed to predict survival rates via a cross-validation method. Additionally, our model was validated using a cohort of cancer patients from our institution and deployed via a free-access software interface. RESULTS The most common cancers resulting in pneumonia-related deaths were prostate (n=7300) and breast (n=5107) cancers, followed by lung and bronchus (n=2839) cancers. The top four cancer systems were digestive (n=5882), endocrine (n=5242), urologic (n=5198), and hematologic (n=3104) systems. The majority of patients were over 70 years old (57.7%), and 54.4% were male. Our CatBoost model demonstrated high precision and accuracy, outperforming other models in predicting the survival of cancer patients with pneumonia (6-month AUC=0.8384,1-year AUC=0.8255,2-year AUC=0.8039, and 3-year AUC=0.7939). The models also revealed robust performance in an external independent dataset (6-month AUC=0.689; 1-year AUC=0.838; 2-year AUC=0.834; and 3-year AUC=0.828). According to the SHAP explanation analysis, the top five factors affecting prognosis were surgery, stage, age, site, and sex; surgery was the most significant factor in both the short-term (6 months and 1 year) and long-term (2 years and 3 years) prognostic models; surgery improved patient prognosis for digestive and endocrine tumor sites with respect to both short- and long-term outcomes but decreased the prognosis of urological and hematologic tumors. CONCLUSION Pneumonia remains a major cause of illness and death in patients with cancer, particularly those with digestive system cancers. The early identification of risk factors and timely intervention may help mitigate the negative impact on patients' quality of life and prognosis, improve outcomes, and prevent early deaths caused by infections, which are often preventable.
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Affiliation(s)
- Qunzhe Ding
- School of Information Management, Wuhan University, Wuhan, Hubei, China
| | - Yi Zhang
- Department of Rheumatology and Immunology, Changzheng Hospital, Naval Military Medical University, Shanghai, China
| | - Zihao Zhang
- Georgetown University Medical Center Department of Oncology, Washington D.C., CO, United States
| | - Peijie Huang
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai, China
| | - Rui Tian
- Georgetown University Medical Center Department of Oncology, Washington D.C., CO, United States
| | - Zhigang Zhou
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai, China
| | - Ruilan Wang
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai, China
| | - Yun Xie
- Department of Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang, Shanghai, China
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Liu J, Li N, Wang B, Zhao W, Zhi J, Jia X, Jia Y, Tie Y. SARS-CoV-2 Infection Aggravates Physical and Mental Health in Cancer Patients Compared to Co-Living Individuals. Cancer Med 2025; 14:e70795. [PMID: 40129313 PMCID: PMC11933713 DOI: 10.1002/cam4.70795] [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: 10/09/2024] [Revised: 02/19/2025] [Accepted: 03/10/2025] [Indexed: 03/26/2025] Open
Abstract
INTRODUCTION Cancer patients are particularly vulnerable to the psychological sequels of COVID-19 due to their immunocompromised state and the disruptions to their regular oncological care. There is limited research comparing the effects of SARS-CoV-2 on cancer patients and their co-living individuals. This study aims to explore the similarities and differences in physical and psychological outcomes between these two groups, with a 1-year follow-up to assess long-term effects. METHODS This retrospective observational study was conducted between January and February 2023. A total of 107 participants were included: 72 cancer patients and 35 co-living individuals, all diagnosed with COVID-19. Clinical and laboratory data were collected. Depression, anxiety, and fatigue were assessed at two timepoints: shortly after COVID-19 diagnosis and 1 year later. RESULTS Cancer patients exhibited higher rates of gastrointestinal symptoms, such as diarrhea (20.83% vs. 5.71%, p = 0.045), which were associated with increased anxiety and depression (p < 0.05). Advanced-stage cancer (p < 0.01) and lack of vaccination (p < 0.01) correlated with worse psychological outcomes. Female cancer patients reported higher depression scores (p < 0.05). Laboratory findings indicated higher neutrophil percentages (p < 0.001), fibrinogen (p < 0.001), and D-dimer levels (p = 0.015) in cancer patients, signaling a higher risk of inflammation and thrombosis. Both groups showed improvements in depression and fatigue over the 1-year follow-up, but cancer patients continued to report greater psychological distress (p < 0.001) and fatigue (p = 0.024). CONCLUSION Cancer patients infected with COVID-19 experienced more severe physical and psychological symptoms compared to their co-living individuals, with persistent differences 1 year after infection. TRIAL REGISTRATION ChiCTR2300067577.
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Affiliation(s)
- Jiayao Liu
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
- Hebei Medical UniversityShijiazhuangChina
| | - Na Li
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
| | - Bin Wang
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
| | - Wujie Zhao
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
| | - Jie Zhi
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
| | - Xiaojing Jia
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
| | - Yitao Jia
- The Third Department of OncologyHebei General HospitalShijiazhuangChina
| | - Yanqing Tie
- Department of Clinical LaboratoryHebei General HospitalShijiazhuangChina
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Barghash RF, Gemmati D, Awad AM, Elbakry MMM, Tisato V, Awad K, Singh AV. Navigating the COVID-19 Therapeutic Landscape: Unveiling Novel Perspectives on FDA-Approved Medications, Vaccination Targets, and Emerging Novel Strategies. Molecules 2024; 29:5564. [PMID: 39683724 PMCID: PMC11643501 DOI: 10.3390/molecules29235564] [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: 09/26/2024] [Revised: 11/21/2024] [Accepted: 11/22/2024] [Indexed: 12/18/2024] Open
Abstract
Amidst the ongoing global challenge of the SARS-CoV-2 pandemic, the quest for effective antiviral medications remains paramount. This comprehensive review delves into the dynamic landscape of FDA-approved medications repurposed for COVID-19, categorized as antiviral and non-antiviral agents. Our focus extends beyond conventional narratives, encompassing vaccination targets, repurposing efficacy, clinical studies, innovative treatment modalities, and future outlooks. Unveiling the genomic intricacies of SARS-CoV-2 variants, including the WHO-designated Omicron variant, we explore diverse antiviral categories such as fusion inhibitors, protease inhibitors, transcription inhibitors, neuraminidase inhibitors, nucleoside reverse transcriptase, and non-antiviral interventions like importin α/β1-mediated nuclear import inhibitors, neutralizing antibodies, and convalescent plasma. Notably, Molnupiravir emerges as a pivotal player, now licensed in the UK. This review offers a fresh perspective on the historical evolution of COVID-19 therapeutics, from repurposing endeavors to the latest developments in oral anti-SARS-CoV-2 treatments, ushering in a new era of hope in the battle against the pandemic.
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Affiliation(s)
- Reham F. Barghash
- Institute of Chemical Industries Research, National Research Centre, Dokki, Cairo 12622, Egypt
- Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), Cairo 12451, Egypt
| | - Donato Gemmati
- Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
| | - Ahmed M. Awad
- Department of Chemistry, California State University Channel Islands, Camarillo, CA 93012, USA
| | - Mustafa M. M. Elbakry
- Faculty of Biotechnology, October University for Modern Sciences and Arts (MSA), Cairo 12451, Egypt
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo 11566, Egypt
| | - Veronica Tisato
- Centre Hemostasis & Thrombosis, University of Ferrara, 44121 Ferrara, Italy
| | - Kareem Awad
- Institute of Pharmaceutical and Drug Industries Research, National Research Center, Dokki, Cairo 12622, Egypt;
| | - Ajay Vikram Singh
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589 Berlin, Germany
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Andrianto, A, Hermawan, HO, Harsoyo, PM, Zaini BSI, Muhammad AR. Perindopril and losartan affect ACE-2 and IL- 6 expression in obese rat model. NARRA J 2024; 4:e681. [PMID: 39280311 PMCID: PMC11391957 DOI: 10.52225/narra.v4i2.681] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 06/19/2024] [Indexed: 09/18/2024]
Abstract
Obesity has emerged as a worldwide health concern due to its increasing prevalence. Adipocytes have the ability to express angiotensin-converting enzyme 2 receptors (ACE2) and several adipocytokines. These expressions could lead to the activation of a cytokine storm, which in turn promotes the development of cardiovascular diseases. The aim of this study was to investigate the impact of perindopril and losartan exposure on the ACE2 and interleukin 6 (IL-6) levels in adipocyte cells. This study used an in vivo true experimental design utilizing a post-test-only control group. A total of 24 adult male albino rats were divided into four groups, one group served as the non-obese (negative control), while the other three groups were obese: (1) the positive control (untreated obese rats); (2) perindopril group (2 mg/kg BW/day orally for 4 weeks); and (3) losartan group (20 mg/kg BW/day for 4 weeks). Afterwards, the rats were euthanized, and the visceral fat tissue were obtained during dissection. The levels of ACE2 and IL-6 were measured using the enzyme-linked immunosorbent assay (ELISA). Losartan administration in obese rats resulted in a notable elevation in ACE2 levels compared to both the perindopril group (losartan vs perindopril, p=0.011) and the positive control (p=0.004). In addition, the treatment of perindopril and losartan in obese rats resulted in a significant reduction in IL-6 levels when compared to the positive control (perindopril vs positive control, p=0.020; losartan vs positive control, p=0.002, respectively). This study provides insight into the administration of perindopril and losartan, which could suppress the pro-inflammatory (IL-6) but increase the ACE2 levels in adipose tissue.
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Affiliation(s)
- Andrianto Andrianto,
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Cardiology and Vascular Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Hanestya O. Hermawan,
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Cardiology and Vascular Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Primasitha M. Harsoyo,
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- Department of Cardiology and Vascular Medicine, Dr. Soetomo General Academic Hospital, Surabaya, Indonesia
| | - Bagas SI. Zaini
- Muhammadiyah Babat General Hospital, Lamongan, Indonesia
- Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia
| | - Akbar R. Muhammad
- Faculty of Medicine, Universitas Nahdlatul Ulama Surabaya, Surabaya, Indonesia
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Low M, Suresh H, Zhou X, Bhuyan DJ, Alsherbiny MA, Khoo C, Münch G, Li CG. The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: A promising therapeutic compound against the cytokine storm. PLoS One 2024; 19:e0299965. [PMID: 39018291 PMCID: PMC11253928 DOI: 10.1371/journal.pone.0299965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Accepted: 06/26/2024] [Indexed: 07/19/2024] Open
Abstract
The challenges of the COVID-19 pandemic have highlighted an increasing clinical demand for safe and effective treatment options against an overzealous immune defence response, also known as the "cytokine storm". Andrographolide is a naturally derived bioactive compound with promising anti-inflammatory activity in many clinical studies. However, its cytokine-inhibiting activity, in direct comparison to commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), has not been extensively investigated in existing literature. The anti-inflammatory activities of andrographolide and common NSAIDs, such as diclofenac, aspirin, paracetamol and ibuprofen were measured on lipopolysaccharide (LPS) and interferon-γ induced RAW264.7 cells. The levels of PGE2, nitric oxide (NO), TNF-α & LPS-induced release of pro-inflammatory cytokines on differentiated human macrophage THP-1 cells were measured against increasing concentrations of andrographolide and aforementioned NSAIDs. The associated mechanistic pathway was examined on NFκB using flow cytometry on the human endothelial-leukocyte adhesion molecule (ELAM9) (E-selectin) transfected RAW264.7 cells with green fluorescent protein (GFP). Andrographolide exhibited broad and potent anti-inflammatory and cytokine-inhibiting activity in both cell lines by inhibiting the release of IL-6, TNF-α and IFN-γ, which are known to play a key role in the etiology of cytokine storm and the pathogenesis of inflammation. In comparison, the tested NSAIDs demonstrated weak or no activity against proinflammatory mediators except for PGE2, where the activity of andrographolide (IC50 = 8.8 μM, 95% CI = 7.4 to 10.4 μM) was comparable to that of paracetamol (IC50 = 7.73 μM, 95% CI = 6.14 to 9.73 μM). The anti-inflammatory action of andrographolide was associated with its potent downregulation of NFκB. The wide-spectrum anti-inflammatory activity of andrographolide demonstrates its therapeutic potential against cytokine storms as an alternative to NSAIDs.
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Affiliation(s)
- Mitchell Low
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
| | - Harsha Suresh
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
- School of Medicine, Western Sydney University, Campbelltown, Australia
| | - Xian Zhou
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
| | - Deep Jyoti Bhuyan
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
| | | | - Cheang Khoo
- Wentworth Institute of Higher Education, Surry Hills, Sydney, Australia
| | - Gerald Münch
- School of Medicine, Western Sydney University, Campbelltown, Australia
| | - Chun Guang Li
- NICM Health Research Institute, Western Sydney University, Penrith, Australia
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Arab FL, Hoseinzadeh A, Mohammadi FS, Rajabian A, Faridzadeh A, Mahmoudi M. Immunoregulatory effects of nanocurcumin in inflammatory milieu: Focus on COVID-19. Biomed Pharmacother 2024; 171:116131. [PMID: 38198954 DOI: 10.1016/j.biopha.2024.116131] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 12/31/2023] [Accepted: 01/02/2024] [Indexed: 01/12/2024] Open
Abstract
The use of natural compounds, such as curcumin, to treat infections caused by bacteria, viruses, fungi, parasites, inflammatory diseases, and various types of cancer is an active and dynamic area of research. Curcumin has a long history of use in the food industry, and there is currently a growing interest in its therapeutic applications. Numerous clinical trials have consistently shown that curcumin, a polyphenolic compound, is safe and well-tolerated even at high doses. There is no toxicity limit. However, the clinical efficacy of curcumin has been limited by its constraints. However, scientific evidence indicates that the use of adjuvants and carriers, such as nanoparticles, exosomes, micelles, and liposomes, can help overcome this limitation. The properties, functions, and human benefits of using nanocurcumin are well-supported by scientific research. Recent evidence suggests that nanocurcumin may be a beneficial therapeutic modality due to its potential to decrease gene expression and secretion of specific inflammatory biomarkers involved in the cytokinestorm seen in severe COVID-19, as well as increase lymphocyte counts. Nanocurcumin has demonstrated the ability to improve clinical manifestations and modulate immune response and inflammation in various autoinflammatory diseases. Additionally, its efficacy, affordability, and safety make it a promising replacement for residual cancer cells after tumor removal. However, further studies are necessary to evaluate the safety and efficacy of nanocurcumin as a new therapeutic in clinical trials, including appropriate dosage, frequency, and duration.
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Affiliation(s)
- Fahimeh Lavi Arab
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Akram Hoseinzadeh
- Immunology Research Center, Bu‑Ali Research Institute, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Fatemeh Sadat Mohammadi
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arezoo Rajabian
- Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Arezoo Faridzadeh
- Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahmoud Mahmoudi
- Department of Immunology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Rasmi Y, Shokati A, Hatamkhani S, Farnamian Y, Naderi R, Jalali L. Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID-19 infection. Rev Med Virol 2024; 34:e2506. [PMID: 38282395 DOI: 10.1002/rmv.2506] [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: 07/23/2022] [Revised: 07/06/2023] [Accepted: 12/17/2023] [Indexed: 01/30/2024]
Abstract
Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. Dopamine receptors are widely distributed throughout the nervous system and in immune cells. Several viruses, including human immunodeficiency virus and Japanese encephalitis virus, can use dopaminergic receptors to replicate in the nervous system and are involved in viral neuropathogenesis. In addition, studies suggest that dopaminergic receptors may play a role in the progression and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds to angiotensin-converting enzyme 2 receptors on the surface of neuronal cells, the spike protein of the virus can bind to dopaminergic receptors on neighbouring cells to accelerate its life cycle and exacerbate neurological symptoms. In addition, recent research has shown that dopamine is an important regulator of the immune-neuroendocrine system. Most immune cells express dopamine receptors and other dopamine-related proteins, indicating the importance of dopaminergic immune regulation. The increase in dopamine concentration during SARS-CoV2 infection may reduce immunity (innate and adaptive) that promotes viral spread, which could lead to neuronal damage. In addition, dopaminergic signalling in the nervous system may be affected by SARS-CoV-2 infection. COVID -19 can cause various neurological symptoms as it interacts with the immune system. One possible treatment strategy for COVID -19 patients could be the use of dopamine antagonists. To fully understand how to protect the neurological system and immune cells from the virus, we need to study the pathophysiology of the dopamine system in SARS-CoV-2 infection.
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Affiliation(s)
- Yousef Rasmi
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ameneh Shokati
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
- Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences (TUMS), Tehran, Iran
| | - Shima Hatamkhani
- Experimental and Applied Pharmaceutical Sciences Research Center, Urmia University of Medical Sciences, Urmia, Iran
- Department of Clinical Pharmacy, School of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran
| | - Yeganeh Farnamian
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Roya Naderi
- Nephrology and Kidney Transplant Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Ladan Jalali
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
- Department of Biochemistry, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
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Maiti AK. Therapeutic Challenges in COVID-19. Curr Mol Med 2024; 24:14-25. [PMID: 36567277 DOI: 10.2174/1566524023666221222162641] [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: 09/02/2022] [Revised: 10/18/2022] [Accepted: 11/10/2022] [Indexed: 12/27/2022]
Abstract
SARS-CoV2 is a novel respiratory coronavirus and, understanding its molecular mechanism is a prerequisite to developing effective treatment for COVID-19. This RNA genome-carrying virus has a protein coat with spikes (S) that attaches to the ACE2 receptor at the cell surface of human cells. Several repurposed drugs are used to treat COVID-19 patients that are proven to be largely unsuccessful or have limited success in reducing mortalities. Several vaccines are in use to reduce the viral load to prevent developing symptoms. Major challenges to their efficacy include the inability of antibody molecules to enter cells but remain effective in the bloodstream to kill the virus. The efficacy of vaccines also depends on their neutralizing ability to constantly evolve new virus strains due to novel mutations and evolutionary survival dynamics. Taken together, SARS-CoV2 antibody vaccines may not be very effective and other approaches based on genetic, genomic, and protein interactome could be fruitful to identify therapeutic targets to reduce disease-related mortalities.
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Affiliation(s)
- Amit K Maiti
- Department of Genetics and Genomics, Mydnavar, 28475 Greenfield Rd, Southfield MI 48076, USA
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9
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Elsaghir A, El-Sabaa EMW, Zahran AM, Mandour SA, Salama EH, Aboulfotuh S, El-Morshedy RM, Tocci S, Mandour AM, Ali WE, Abdel-Wahid L, Sayed IM, El-Mokhtar MA. Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19. Int J Mol Sci 2023; 24:17614. [PMID: 38139439 PMCID: PMC10744088 DOI: 10.3390/ijms242417614] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 12/11/2023] [Accepted: 12/13/2023] [Indexed: 12/24/2023] Open
Abstract
Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression. Our study included 73 hospitalized COVID-19 patients, of which 33 were moderately affected and 40 suffered from severe infection. A flow cytometric analysis was used to analyze the frequency of T-regulatory cells (T-regs), CD39+ T-regs, and CD39+CD4+ T-cells. Plasma concentrations of adenosine, IL-10, and TGF-β were quantified via an ELISA. An RT-qPCR was used to analyze the gene expression of CD73 and adenosine receptors (A1, A2A, A2B, and A3). T-reg cells were higher in COVID-19 patients compared to healthy controls (7.4 ± 0.79 vs. 2.4 ± 0.28; p < 0.0001). Patients also had a higher frequency of the CD39+ T-reg subset. In addition, patients who suffered from a severe form of the disease had higher CD39+ T-regs compared with moderately infected patients. CD39+CD4+ T cells were increased in patients compared to the control group. An analysis of serum adenosine levels showed a marked decrease in their levels in patients, particularly those suffering from severe illness. However, this was paralleled with a marked decline in the expression levels of CD73. IL-10 and TGF-β levels were higher in COVID-19; in addition, their values were also higher in the severe group. In conclusion, there are distinct immunological alterations in CD39+ lymphocyte subsets and a dysregulation in the adenosine signaling pathway in COVID-19 patients which may contribute to immune dysfunction and disease progression. Understanding these immunological alterations in the different immune cell subsets and adenosine signaling provides valuable insights into the pathogenesis of the disease and may contribute to the development of novel therapeutic approaches targeting specific immune mechanisms.
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Affiliation(s)
- Alaa Elsaghir
- Department of Microbiology & Immunology, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt
| | - Ehsan M. W. El-Sabaa
- Department of Microbiology & Immunology, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt
| | - Asmaa M. Zahran
- Department of Clinical Pathology, South Egypt Cancer Institute, Assiut University, Assiut 71515, Egypt
| | - Sahar A. Mandour
- Department of Microbiology and Immunology, Faculty of Pharmacy, Deraya University, Minia 11566, Egypt
| | - Eman H. Salama
- Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag 82524, Egypt
| | - Sahar Aboulfotuh
- Department of Clinical Pathology, Faculty of Medicine, Sohag University, Sohag 82524, Egypt
| | - Reham M. El-Morshedy
- Department of Chest Diseases and Tuberculosis, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Stefania Tocci
- Department of Biomedical & Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA
| | - Ahmed Mohamed Mandour
- Department of Anesthesia and ICU, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Wael Esmat Ali
- Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt
| | - Lobna Abdel-Wahid
- Gastroenterology and Hepatology Unit, Internal Medicine Department, Assiut University, Assiut 71515, Egypt
| | - Ibrahim M. Sayed
- Department of Biomedical & Nutritional Sciences, Zuckerberg College of Health Sciences, University of Massachusetts Lowell, Lowell, MA 01854, USA
| | - Mohamed A. El-Mokhtar
- Gilbert & Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 36, Lebanon
- Department of Medical Microbiology & Immunology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
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Liu G, Chen T, Zhang X, Hu B, Shi H. Causal relationship between COVID-19 and myocarditis or pericarditis risk: a bidirectional Mendelian randomization study. Front Cardiovasc Med 2023; 10:1271959. [PMID: 38162133 PMCID: PMC10755931 DOI: 10.3389/fcvm.2023.1271959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Accepted: 11/28/2023] [Indexed: 01/03/2024] Open
Abstract
Background & aims Coronavirus disease 2019 (COVID-19) is strongly associated with myocarditis or pericarditis risk in observational studies, however, there are still studies that do not support the above conclusion. Whether the observed association reflects causation needs to be confirmed. We performed a bidirectional Mendelian randomization (MR) study to assess the causal relationship of COVID-19, which was divided into three groups, namely severe COVID-19, hospitalized COVID-19, and COVID-19 infection, measured by myocarditis or pericarditis. Methods We extracted summary genome-wide association statistics for the severe COVID-19 (case: 13,769, control: 1,072,442), hospitalized COVID-19 (case: 32,519, control: 2,062,805), COVID-19 infection (case: 122,616, control: 2,475,240), myocarditis (case 1,521, control 191,924), and pericarditis (case 979, control 286,109) among individuals of European ancestry. Independent genetic variants that exhibited a significant association with each phenotype at the genome-wide level of significance were utilized as instrumental variables. Estimation of the causal effect was mainly performed using the random effects inverse-variance weighted method (IVW). Additionally, other tests such as MR-Egger intercept, MR-PRESSO, Cochran's Q-test, "Leave-one-out", and funnel plots were conducted to assess the extent of pleiotropy and heterogeneity. Results Non-associations in the IVW and sensitivity analyses were observed for COVID-19 with myocarditis or pericarditis. Severe COVID-19 was not associated with myocarditis [odds ratio (OR), 1.00; 95% confidence interval (CI), 0.89-1.12; P = 0.99], pericarditis (OR = 0.90, 95% CI, 0.78-1.04, P = 0.17). Similar results can be observed in hospitalized COVID-19, and COVID-19 infection. At the same time, null associations were observed for myocarditis or pericarditis with COVID-19 traits in the reverse direction. The main results are kept stable in the sensitivity analysis. Conclusion There is no evidence that COVID-19 is independently and causally associated with myocarditis or pericarditis.
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Affiliation(s)
- Guihong Liu
- Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Tao Chen
- Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China
| | - Xin Zhang
- Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Binbin Hu
- Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Huashan Shi
- Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
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Zhang JL, Wang SH, Cui SN, Zhang J, Li SZ, Li L, Zuo YG. Severe acute respiratory syndrome coronavirus 2 infection in patients with autoimmune bullous diseases in China. J Dermatol 2023; 50:1433-1441. [PMID: 37501390 DOI: 10.1111/1346-8138.16900] [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: 04/11/2023] [Revised: 06/15/2023] [Accepted: 07/04/2023] [Indexed: 07/29/2023]
Abstract
Patients with autoimmune bullous diseases (AIBDs) are considered to be immunocompromised and, consequently, they may be more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and have poorer outcomes. However, the risk and repercussions of SARS-CoV-2 infection in patients with AIBDs have not been fully understood. Therefore, we aimed to investigate the risk factors of SARS-CoV-2 infection and the impact of SARS-CoV-2 on patients with AIBDs. From December 2022 to January 2023, all patients with AIBDs who visited our clinic were enrolled in this study. Meanwhile, web-based questionnaires and telesurveys were used as supplements. Information about patients' demographics, comorbidities, SARS-CoV-2 infection, and vaccination, as well as AIBD status and treatments were collected and analyzed. The diagnosis of SARS-CoV-2 infection was based on a positive polymerase chain reaction test, and/or an antigen test, or the presence of typical symptoms in conjunction with an epidemiological history. Finally, 95 patients with AIBDs were enrolled, including 47 cases of pemphigus and 48 cases of pemphigoid cases, and 73 had symptoms consistent with coronavirus disease 2019. Common symptoms after SARS-CoV-2 infection were fever (80.8%), fatigue (75.0%), cough (71.2%), muscle/joint pain (49.3%), and sore throat (45.2%). No significant differences were found between SARS-CoV-2-infected and asymptomatic patients. Patients who had hypertension (p = 0.034), hyperlipidemia (p = 0.017), or more than two comorbidities (p = 0.011) were more likely to develop pneumonia after infection. Patients with pemphigus who did not achieve disease control (p = 0.045) or had an oral corticosteroid dose ≥15 mg/day (p = 0.024) and patients with pemphigoid with a disease duration ≥2 years (p = 0.037) were more prone to AIBDs aggravation. In conclusion, patients with AIBDs are generally susceptible to SARS-CoV-2 infection. Individuals with newly diagnosed AIBDs, uncontrolled disease, and a higher corticosteroid dose are more susceptible to disease exacerbation.
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Affiliation(s)
- Jia-Ling Zhang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Si-Hang Wang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sheng-Nan Cui
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie Zhang
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Si-Zhe Li
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Li Li
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ya-Gang Zuo
- Department of Dermatology, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Hamed M, Alamoudi D. Recurrent COVID-19 Infection in a Refractory/Classical Hodgkin's Lymphoma Patient Undergoing Autologous Stem Cell Transplantation: A Case Report. Cureus 2023; 15:e46950. [PMID: 38022277 PMCID: PMC10640764 DOI: 10.7759/cureus.46950] [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] [Accepted: 10/13/2023] [Indexed: 12/01/2023] Open
Abstract
Patients with challenging hematological malignancies like classic Hodgkin lymphoma (cHL) can be further complicated when affected by a concurrent coronavirus disease-2019 (COVID-19) infection and often face unique and complex management and outcomes. In this case report, we describe a refractory or relapsed classic Hodgkin lymphoma patient with a recurrent infection of COVID-19 three times preceding chemotherapy. A 52-year-old female presented to our hospital with a second incidence of COVID-19 and a complaint of fever, anorexia, night sweats, and abdominal lymphadenopathy, for which she was diagnosed with mixed cellularity classic Hodgkin lymphoma. Three weeks later, in consideration of her manifestation of lung disease, which was due to her past medical history of airway hypersensitivity and abnormal pulmonary function test along with testing positive for COVID-19, she was started with the first-line chemotherapy of the brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine chemotherapy regimen, commonly referred to as Bv-AVD, without bleomycin. After six cycles of chemotherapy, at the end of treatment, positron emission tomography/computed tomography (PET/CT) revealed the progression of nodes in the abdomen and the development of new lymphadenopathy in the chest and right supraclavicular region. Hence, it was considered refractory Hodgkin's lymphoma, and the patient was referred for salvage therapy. She was started on salvage chemotherapy with brentuximab/bendamustine (BvB). Follow-up evaluations after two cycles of BvB continued to show newer lesions in the right sub-diaphragmatic area, internal mammary, and supraclavicular lymph nodes. Therefore, the patient was switched to pembrolizumab immunotherapy, a PD-1 inhibitor. After four cycles of pembrolizumab monotherapy, PET/CT showed significant improvement with a complete molecular response (CMR). Then, she was admitted for high-dose therapy/autologous stem cell transplantation (HDT/ASCT) after collecting stem cells. PET/CT: three months post-ASCT, she continued to be in a CMR with a Deauville score of 1. The patient was continued on pembrolizumab maintenance for six months afterward. Currently, the patient is healthy and doing well. COVID-19 patients with hematological malignancies may experience compromised viral elimination and a prolonged period of viral infection, which may also worsen the symptoms and outcomes and entitle them to comprehensive and extended care.
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Affiliation(s)
- Munerah Hamed
- Department of Pathology, Faculty of Medicine, Umm Al-Qura University, Makkah, SAU
| | - Doaa Alamoudi
- Department of Pathology and Laboratory Medicine, Division of Molecular Medicine, King Abdulaziz Medical City, National Guard Health Affairs, Jeddah, SAU
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Mwangi VI, Netto RLA, de Morais CEP, Silva AS, Silva BM, Lima AB, Neves JCF, Borba MGS, Val FFDAE, de Almeida ACG, Costa AG, Sampaio VDS, Gardinassi LG, de Lacerda MVG, Monteiro WM, de Melo GC. Temporal patterns of cytokine and injury biomarkers in hospitalized COVID-19 patients treated with methylprednisolone. Front Immunol 2023; 14:1229611. [PMID: 37662953 PMCID: PMC10468998 DOI: 10.3389/fimmu.2023.1229611] [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: 05/26/2023] [Accepted: 07/26/2023] [Indexed: 09/05/2023] Open
Abstract
Background The novel coronavirus disease 2019 (COVID-19) presents with complex pathophysiological effects in various organ systems. Following the COVID-19, there are shifts in biomarker and cytokine equilibrium associated with altered physiological processes arising from viral damage or aggressive immunological response. We hypothesized that high daily dose methylprednisolone improved the injury biomarkers and serum cytokine profiles in COVID-19 patients. Methods Injury biomarker and cytokine analysis was performed on 50 SARS-Cov-2 negative controls and 101 hospitalized severe COVID-19 patients: 49 methylprednisolone-treated (MP group) and 52 placebo-treated serum samples. Samples from the treated groups collected on days D1 (pre-treatment) all the groups, D7 (2 days after ending therapy) and D14 were analyzed. Luminex assay quantified the biomarkers HMGB1, FABP3, myoglobin, troponin I and NTproBNP. Immune mediators (CXCL8, CCL2, CXCL9, CXCL10, TNF, IFN-γ, IL-17A, IL-12p70, IL-10, IL-6, IL-4, IL-2, and IL-1β) were quantified using cytometric bead array. Results At pretreatment, the two treatment groups were comparable demographically. At pre-treatment (D1), injury biomarkers (HMGB1, TnI, myoglobin and FABP3) were distinctly elevated. At D7, HMGB1 was significantly higher in the MP group (p=0.0448) compared to the placebo group, while HMGB1 in the placebo group diminished significantly by D14 (p=0.0115). Compared to healthy control samples, several immune mediators (IL-17A, IL-6, IL-10, MIG, MCP-1, and IP-10) were considerably elevated at baseline (all p≤0.05). At D7, MIG and IP-10 of the MP-group were significantly lower than in the placebo-group (p=0.0431, p=0.0069, respectively). Longitudinally, IL-2 (MP-group) and IL-17A (placebo-group) had increased significantly by D14. In placebo group, IL-2 and IL-17A continuously increased, as IL-12p70, IL-10 and IP-10 steadily decreased during follow-up. The MP treated group had IL-2, IFN-γ, IL-17A and IL-12p70 progressively increase while IL-1β and IL-10 gradually decreased towards D14. Moderate to strong positive correlations between chemokines and cytokines were observed on D7 and D14. Conclusion These findings suggest MP treatment could ameliorate levels of myoglobin and FABP3, but appeared to have no impact on HMGB1, TnI and NTproBNP. In addition, methylprednisolone relieves the COVID-19 induced inflammatory response by diminishing MIG and IP-10 levels. Overall, corticosteroid (methylprednisolone) use in COVID-19 management influences the immunological molecule and injury biomarker profile in COVID-19 patients.
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Affiliation(s)
- Victor Irungu Mwangi
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | | | - Carlos Eduardo Padron de Morais
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Arineia Soares Silva
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Bernardo Maia Silva
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Amanda Barros Lima
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
| | | | - Mayla Gabriela Silva Borba
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Fernando Fonseca de Almeida e Val
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Anne Cristine Gomes de Almeida
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás (UFG), Goiânia, Brazil
| | - Allyson Guimarães Costa
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Programa de Pós-Graduação em Imunologia Básica e Aplicada, Instituto de Ciências Biológicas, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Diretoria de Ensino e Pesquisa, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM), Manaus, Brazil
- Escola de Enfermagem de Manaus, Universidade Federal do Amazonas (UFAM), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) Universidade do Estado do Amazonas (UEA), Manaus, Brazil
| | - Vanderson de Souza Sampaio
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Instituto Todos pela Saúde, São Paulo, São Paulo, Brazil
| | - Luiz Gustavo Gardinassi
- Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás (UFG), Goiânia, Brazil
| | - Marcus Vinicius Guimarães de Lacerda
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Instituto Leônidas & Maria Deane/Fundação Oswaldo Cruz (ILMD/Fiocruz Amazônia), Manaus, Brazil
| | - Wuelton Marcelo Monteiro
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
| | - Gisely Cardoso de Melo
- Programa de Pós-Graduação em Medicina Tropical, Universidade do Estado do Amazonas (UEA), Manaus, Brazil
- Fundação de Medicina Tropical Heitor Vieira Dourado (FMT-HVD), Manaus, Brazil
- Programa de Pós-Graduação em Ciências Aplicadas à Hematologia, Fundação Hospitalar de Hematologia e Hemoterapia do Amazonas (HEMOAM) Universidade do Estado do Amazonas (UEA), Manaus, Brazil
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Ünal Toprak F, Coşkun Palaz S, Çağlar S. The impact of health literacy levels on women's fear of contracting Covid-19 and their attitudes toward holistic complementary and alternative medicine: Mediation analysis results. Health Care Women Int 2023; 44:869-884. [PMID: 35616392 DOI: 10.1080/07399332.2022.2070623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 04/07/2022] [Accepted: 04/22/2022] [Indexed: 10/18/2022]
Abstract
Researchers aim to examine mediating variable role of health literacy in the relationship between fear of contracting Covid-19 in women and use of holistic complementary alternative medicine. The study was conducted as descriptive cross-sectional. The researchers collected study data by conducting an online questionnaire from 285 women between April 01 and June 30, 2021. In our study, a significant relationship was found between education level and health literacy, having a chronic illness, not being able to find a permanent job and fear of Covid-19 (p < 0.05). Positive correlation exists between fear of contracting Covid-19 and Holistic Complementary and Alternative Medicine Practice (correlation between HCAM Practice β=.21). When health literacy variable is included, the level of relationship decreases (β=.18). The researchers determined that as the level of health literacy increased, the women resorted to HCAM practices less despite their fear of contracting Covid-19.
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Affiliation(s)
- Filiz Ünal Toprak
- Department of Midwifery, Gulhane Faculty of Health Sciences, University of Health Sciences, Ankara, Turkey
| | - Simge Coşkun Palaz
- Department of Nursing, Faculty of Health Sciences, Bolu Abant İzzet Baysal University, Bolu, Turkey
| | - Songül Çağlar
- Department of Nursing, Faculty of Health Sciences, Bolu Abant İzzet Baysal University, Bolu, Turkey
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Nigro O, Oltolini C, Barzaghi F, Uberti Foppa C, Cicalese MP, Massimino M, Schiavello E. Pediatric cancer care management during the COVID-19 pandemic: a review of the literature and a single-centre real-life experience of an Italian pediatric oncology unit. Expert Rev Anticancer Ther 2023; 23:927-942. [PMID: 37712347 DOI: 10.1080/14737140.2023.2245148] [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: 01/31/2023] [Accepted: 08/02/2023] [Indexed: 09/16/2023]
Abstract
INTRODUCTION The severe acute respiratory syndrome coronavirus-2 pandemic significantly affected clinical practice, also in pediatric oncology units. Cancer patients needed to be treated with an adequate dose density despite the SARS-CoV-2 infection, balancing risks of developing severe COVID-19 disease. AREAS COVERED Although the pandemic spread worldwide, the prevalence of affected children was low. The percentage of children with severe illness was approximately 1-6%. Pediatric cancer patients represent a prototype of a previously healthy immune system that is hampered by the tumor itself and treatments, such as chemotherapy and steroids. Through a review of the literature, we reported the immunological basis of the response to SARS-CoV-2 infection, the existing antiviral treatments used in pediatric cancer patients, and the importance of vaccination. In conclusion, we reported the real-life experience of our pediatric oncology unit during the pandemic period. EXPERT OPINION Starting from the data available in literature, and our experience, showing the rarity of severe COVID-19 disease in pediatric patients with solid tumors, we recommend carefully tailoring all the oncological treatments (chemotherapy/targeted therapy/stem cell transplantation/radiotherapy). The aim is the preservation of the treatment's timing, balanced with an evaluation of possible severe COVID-19 disease.
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Affiliation(s)
- Olga Nigro
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Chiara Oltolini
- Unit of Infectious and Tropical Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Federica Barzaghi
- Pediatric Immunohematology and Bone Marrow Transplantation Unit and San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), San Raffaele Scientific Institute, Milan, Italy
| | - Caterina Uberti Foppa
- Unit of Infectious and Tropical Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Maria Pia Cicalese
- Pediatric Immunohematology and Bone Marrow Transplantation Unit and San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), San Raffaele Scientific Institute, Milan, Italy
- Vita-Salute San Raffaele University, Milan, Italy
| | - Maura Massimino
- Pediatric Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Lu H, Ma J, Li Y, Zhang J, An Y, Du W, Cai X. Bioinformatic and systems biology approach revealing the shared genes and molecular mechanisms between COVID-19 and non-alcoholic hepatitis. Front Mol Biosci 2023; 10:1164220. [PMID: 37405258 PMCID: PMC10315682 DOI: 10.3389/fmolb.2023.1164220] [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: 02/12/2023] [Accepted: 06/01/2023] [Indexed: 07/06/2023] Open
Abstract
Introduction: Coronavirus disease 2019 (COVID-19) has become a global pandemic and poses a serious threat to human health. Many studies have shown that pre-existing nonalcoholic steatohepatitis (NASH) can worsen the clinical symptoms in patients suffering from COVID-19. However, the potential molecular mechanisms between NASH and COVID-19 remain unclear. To this end, key molecules and pathways between COVID-19 and NASH were herein explored by bioinformatic analysis. Methods: The common differentially expressed genes (DEGs) between NASH and COVID-19 were obtained by differential gene analysis. Enrichment analysis and protein-protein interaction (PPI) network analysis were carried out using the obtained common DEGs. The key modules and hub genes in PPI network were obtained by using the plug-in of Cytoscape software. Subsequently, the hub genes were verified using datasets of NASH (GSE180882) and COVID-19 (GSE150316), and further evaluated by principal component analysis (PCA) and receiver operating characteristic (ROC). Finally, the verified hub genes were analyzed by single-sample gene set enrichment analysis (ssGSEA) and NetworkAnalyst was used for the analysis of transcription factor (TF)-gene interactions, TF-microRNAs (miRNA) coregulatory network, and Protein-chemical Interactions. Results: A total of 120 DEGs between NASH and COVID-19 datasets were obtained, and the PPI network was constructed. Two key modules were obtained via the PPI network, and enrichment analysis of the key modules revealed the common association between NASH and COVID-19. In total, 16 hub genes were obtained by five algorithms, and six of them, namely, Kruppel-like factor 6 (KLF6), early growth response 1 (EGR1), growth arrest and DNA-damage-inducible 45 beta (GADD45B), JUNB, FOS, and FOS-like antigen 1 (FOSL1) were confirmed to be closely related to NASH and COVID-19. Finally, the relationship between hub genes and related pathways was analyzed, and the interaction network of six hub genes was constructed with TFs, miRNAs, and compounds. Conclusion: This study identified six hub genes related to COVID-19 and NASH, providing a new perspective for disease diagnosis and drug development.
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Gupta A, Marzook H, Ahmad F. Comorbidities and clinical complications associated with SARS-CoV-2 infection: an overview. Clin Exp Med 2023; 23:313-331. [PMID: 35362771 PMCID: PMC8972750 DOI: 10.1007/s10238-022-00821-4] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Accepted: 03/12/2022] [Indexed: 01/08/2023]
Abstract
The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes major challenges to the healthcare system. SARS-CoV-2 infection leads to millions of deaths worldwide and the mortality rate is found to be greatly associated with pre-existing clinical conditions. The existing dataset strongly suggests that cardiometabolic diseases including hypertension, coronary artery disease, diabetes and obesity serve as strong comorbidities in coronavirus disease (COVID-19). Studies have also shown the poor outcome of COVID-19 in patients associated with angiotensin-converting enzyme-2 polymorphism, cancer chemotherapy, chronic kidney disease, thyroid disorder, or coagulation dysfunction. A severe complication of COVID-19 is mostly seen in people with compromised medical history. SARS-CoV-2 appears to attack the respiratory system causing pneumonia, acute respiratory distress syndrome, which lead to induction of severe systemic inflammation, multi-organ dysfunction, and death mostly in the patients who are associated with pre-existing comorbidity factors. In this article, we highlighted the key comorbidities and a variety of clinical complications associated with COVID-19 for a better understanding of the etiopathogenesis of COVID-19.
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Affiliation(s)
- Anamika Gupta
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, UAE
| | - Hezlin Marzook
- Cardiovascular Research Group, Sharjah Institute for Medical Research, University of Sharjah, Sharjah, 27272, UAE
| | - 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.
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Iaconis D, Caccuri F, Manelfi C, Talarico C, Bugatti A, Filippini F, Zani A, Novelli R, Kuzikov M, Ellinger B, Gribbon P, Riecken K, Esposito F, Corona A, Tramontano E, Beccari AR, Caruso A, Allegretti M. DHFR Inhibitors Display a Pleiotropic Anti-Viral Activity against SARS-CoV-2: Insights into the Mechanisms of Action. Viruses 2023; 15:v15051128. [PMID: 37243214 DOI: 10.3390/v15051128] [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: 04/05/2023] [Revised: 05/04/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
During the COVID-19 pandemic, drug repurposing represented an effective strategy to obtain quick answers to medical emergencies. Based on previous data on methotrexate (MTX), we evaluated the anti-viral activity of several DHFR inhibitors in two cell lines. We observed that this class of compounds showed a significant influence on the virus-induced cytopathic effect (CPE) partly attributed to the intrinsic anti-metabolic activity of these drugs, but also to a specific anti-viral function. To elucidate the molecular mechanisms, we took advantage of our EXSCALATE platform for in-silico molecular modelling and further validated the influence of these inhibitors on nsp13 and viral entry. Interestingly, pralatrexate and trimetrexate showed superior effects in counteracting the viral infection compared to other DHFR inhibitors. Our results indicate that their higher activity is due to their polypharmacological and pleiotropic profile. These compounds can thus potentially give a clinical advantage in the management of SARS-CoV-2 infection in patients already treated with this class of drugs.
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Affiliation(s)
- Daniela Iaconis
- EXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy
| | - Francesca Caccuri
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Candida Manelfi
- EXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy
| | - Carmine Talarico
- EXSCALATE, Dompé Farmaceutici SpA, Via Tommaso De Amicis, 95, 80131 Napoli, Italy
| | - Antonella Bugatti
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Federica Filippini
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Alberto Zani
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
| | - Rubina Novelli
- Dompè Famaceutici SpA, Via Campo di Pile snc, 67100 L'Aquila, Italy
| | - Maria Kuzikov
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany
- Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
| | - Bernhard Ellinger
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany
- Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
| | - Philip Gribbon
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Schnackenburgallee 114, 22525 Hamburg, Germany
- Fraunhofer Cluster of Excellence for Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
| | - Kristoffer Riecken
- Research Department Cell and Gene Therapy, Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
| | - Francesca Esposito
- Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria SS554, 09042 Monserrato (CA), Italy
| | - Angela Corona
- Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria SS554, 09042 Monserrato (CA), Italy
| | - Enzo Tramontano
- Department of Life and Environmental Sciences, University of Cagliari, Cittadella Universitaria SS554, 09042 Monserrato (CA), Italy
| | | | - Arnaldo Caruso
- Section of Microbiology Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy
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19
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Maynard N, Armstrong AW. The Impact of Immune-Modulating Treatments for Dermatological Diseases on the Risk of Infection with SARS-CoV-2 and Outcomes Associated with COVID-19 Illness. CURRENT DERMATOLOGY REPORTS 2023; 12:45-55. [PMID: 37304177 PMCID: PMC10068706 DOI: 10.1007/s13671-023-00385-w] [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] [Accepted: 02/13/2023] [Indexed: 04/05/2023]
Abstract
Purpose of Review Immune-modulating treatments are used in dermatology for a variety of conditions. The authors aim to review the data regarding the safety of these treatments during the COVID-19 pandemic, namely the risk of infection with SARS-CoV-2 and the outcomes associated with COVID-19-related illness. Recent Findings Several large-scale studies found no increased risk of COVID-19 infection for patients on TNF-α inhibitors, IL-17 inhibitors, IL-12/23 inhibitors, IL-23 inhibitors, dupilumab, and methotrexate. They also found that these patients did not have worse outcomes when infected with COVID-19. The data regarding JAK inhibitors, rituximab, prednisone, cyclosporine, mycophenolate mofetil, and azathioprine are more mixed. Summary Based on current research and guidelines from the American Academy of Dermatology and the National Psoriasis Foundation, dermatology patients on immune-modulating therapies can continue treatment during the COVID-19 pandemic when they are not infected with SARS-CoV-2. For patients who have COVID-19, guidelines encourage individualized assessment of the benefits and risks of continuing or temporarily withholding treatment.
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Affiliation(s)
- Nicole Maynard
- Keck School of Medicine of USC, 1975 Zonal Avenue, KAM 510, MC 9034, Los Angeles, CA 90089 USA
| | - April W. Armstrong
- Keck School of Medicine of USC, 1975 Zonal Avenue, KAM 510, MC 9034, Los Angeles, CA 90089 USA
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20
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Schulz S, Sletta H, Fløgstad Degnes K, Krysenko S, Williams A, Olsen SM, Vernstad K, Mitulski A, Wohlleben W. Optimization of FK-506 production in Streptomyces tsukubaensis by modulation of Crp-mediated regulation. Appl Microbiol Biotechnol 2023; 107:2871-2886. [PMID: 36949330 PMCID: PMC10033298 DOI: 10.1007/s00253-023-12473-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 03/24/2023]
Abstract
FK-506 is a potent immunosuppressive macrocyclic polyketide with growing pharmaceutical interest, produced by Streptomyces tsukubaensis. However, due to low levels synthesized by the wild-type strain, biotechnological production of FK-506 is rather limited. Optimization strategies to enhance the productivity of S. tsukubaensis by means of genetic engineering have been established. In this work primarily global regulatory aspects with respect to the FK-506 biosynthesis have been investigated with the focus on the global Crp (cAMP receptor protein) regulator. In expression analyses and protein-DNA interaction studies, the role of Crp during FK-506 biosynthesis was elucidated. Overexpression of Crp resulted in two-fold enhancement of FK-506 production in S. tsukubaensis under laboratory conditions. Further optimizations using fermentors proved that the strategy described in this study can be transferred to industrial scale, presenting a new approach for biotechnological FK-506 production. KEY POINTS: • The role of the global Crp (cAMP receptor protein) regulator for FK-506 biosynthesis in S. tsukubaensis was demonstrated • Crp overexpression in S. tsukubaensis was applied as an optimization strategy to enhance FK-506 and FK-520 production resulting in two-fold yield increase.
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Affiliation(s)
- Susann Schulz
- Department of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany
- Novartis AG, Stein, Switzerland
| | - Håvard Sletta
- Department of Biotechnology and Nanomedicine, SINTEF Industry, Richard Birkelands vei 3, Trondheim, Norway.
| | - Kristin Fløgstad Degnes
- Department of Biotechnology and Nanomedicine, SINTEF Industry, Richard Birkelands vei 3, Trondheim, Norway
| | - Sergii Krysenko
- Department of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany
- Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany
- Valent BioSciences, 1910 Innovation Wy Suite 100, Libertyville, IL, 60048, USA
| | - Alicia Williams
- Department of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany
| | - Silje Malene Olsen
- Department of Biotechnology and Nanomedicine, SINTEF Industry, Richard Birkelands vei 3, Trondheim, Norway
| | - Kai Vernstad
- Department of Biotechnology and Nanomedicine, SINTEF Industry, Sem Sælands veg 2a, Trondheim, Norway
| | - Agnieszka Mitulski
- Department of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany
- Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany
| | - Wolfgang Wohlleben
- Department of Microbiology and Biotechnology, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
- Cluster of Excellence 'Controlling Microbes to Fight Infections', University of Tübingen, Auf der Morgenstelle 28, 72076, Tübingen, Germany.
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21
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Sendagire H, Kiwuwa S, Dhamani A, Akugizibwe R, Lwasa Y, Bukenya A, Mukasa HK, Kakeeto P, Nankinga Z, Bbosa G, Babirye J, Nankabirwa H, Nabadda S. Staging of COVID-19 disease; using selected laboratory profiles for prediction, prevention and management of severe SARS-CoV-2 infection in Africa-review. Afr Health Sci 2023; 23:1-15. [PMID: 37545952 PMCID: PMC10398495 DOI: 10.4314/ahs.v23i1.2] [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] [Indexed: 08/08/2023] Open
Abstract
There are many uncertainties on the future management of the coronavirus disease 19 (COVID-19) in Africa. By July 2021, Africa had lagged behind the rest of the world in Covid-19 vaccines uptake, accounting for just 1.6% of doses administered globally. During that time COVID 19 was causing an average death rate of 2.6% in Africa, surpassing the then global average of 2.2%. There were no clear therapeutic guidelines, yet inappropriate and unnecessary treatments may have led to unwanted adverse events such as worsening of hyperglycemia and precipitating of ketoacidosis in administration of steroid therapy. in order to provide evidence-based policy guidelines, we examined peer-reviewed published articles in PubMed on COVID 19, or up-to date data, we focused our search on publications from 1st May 2020 to 15th July, 2021. For each of the studies, we extracted data on pathophysiology, selected clinical chemistry and immunological tests, clinical staging and treatment. Our review reports a gross unmet need for vaccination, inadequate laboratory capacity for immunological tests and the assessment of individual immune status, clinical staging and prediction of disease severity. We recommend selected laboratory tools in the assessment of individual immune status, prediction of disease severity and determination of the exact timing for suitable therapy, especially in individuals with co-morbidities.
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Affiliation(s)
- Hakim Sendagire
- College of Health Sciences, Makerere University, Kampala, Uganda
- Faculty of Health Sciences, Islamic University in Uganda
- National Health Laboratory and Diagnostics Services, Ministry of Health, Uganda
| | - Steven Kiwuwa
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Ali Dhamani
- College of Health Sciences, Makerere University, Kampala, Uganda
| | | | - Yasin Lwasa
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Andrew Bukenya
- College of Health Sciences, Makerere University, Kampala, Uganda
| | | | | | | | - Godfrey Bbosa
- College of Health Sciences, Makerere University, Kampala, Uganda
| | - Juliet Babirye
- College of Health Sciences, Makerere University, Kampala, Uganda
| | | | - Susan Nabadda
- National Health Laboratory and Diagnostics Services, Ministry of Health, Uganda
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22
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Ahadiat SAA, Hosseinian Z. SARS‑CoV‑2 and Seizure: An Insight Into the Pathophysiology. Anesth Pain Med 2023; 13:e134129. [PMID: 37404265 PMCID: PMC10317025 DOI: 10.5812/aapm-134129] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2022] [Revised: 12/18/2022] [Accepted: 12/20/2022] [Indexed: 07/20/2023] Open
Affiliation(s)
| | - Zeinab Hosseinian
- Department of Bimolecular and Biomedicine, University of Girona, Girona, Spain
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23
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Li K, Yu XH, Maskey AR, Musa I, Wang ZZ, Garcia V, Guo A, Yang N, Srivastava K, Dunkin D, Li JX, Guo L, Cheng YC, Yuan H, Tiwari R, Li XM. Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid. Front Pharmacol 2023; 13:1042756. [PMID: 36793921 PMCID: PMC9922998 DOI: 10.3389/fphar.2022.1042756] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 12/23/2022] [Indexed: 01/31/2023] Open
Abstract
Introduction: Cytochrome P450 (CYP) 3A4 is a major drug metabolizing enzyme for corticosteroids (CS). Epimedium has been used for asthma and variety of inflammatory conditions with or without CS. It is unknown whether epimedium has an effect on CYP 3A4 and how it interacts with CS. We sought to determine the effects of epimedium on CYP3A4 and whether it affects the anti-inflammatory function of CS and identify the active compound responsible for this effect. Methods: The effect of epimedium on CYP3A4 activity was evaluated using the Vivid CYP high-throughput screening kit. CYP3A4 mRNA expression was determined in human hepatocyte carcinoma (HepG2) cells with or without epimedium, dexamethasone, rifampin, and ketoconazole. TNF-α levels were determined following co-culture of epimedium with dexamethasone in a murine macrophage cell line (Raw 264.7). Active compound (s) derived from epimedium were tested on IL-8 and TNF-α production with or without corticosteroid, on CYP3A4 function and binding affinity. Results: Epimedium inhibited CYP3A4 activity in a dose-dependent manner. Dexamethasone enhanced the expression of CYP3A4 mRNA, while epimedium inhibited the expression of CYP3A4 mRNA and further suppressed dexamethasone enhancement of CYP3A4 mRNA expression in HepG2 cells (p < 0.05). Epimedium and dexamethasone synergistically suppressed TNF-α production by RAW cells (p < 0.001). Eleven epimedium compounds were screened by TCMSP. Among the compounds identified and tested only kaempferol significantly inhibited IL-8 production in a dose dependent manner without any cell cytotoxicity (p < 0.01). Kaempferol in combination with dexamethasone showed complete elimination of TNF-α production (p < 0.001). Furthermore, kaempferol showed a dose dependent inhibition of CYP3A4 activity. Computer docking analysis showed that kaempferol significantly inhibited the catalytic activity of CYP3A4 with a binding affinity of -44.73kJ/mol. Discussion: Inhibition of CYP3A4 function by epimedium and its active compound kaempferol leads to enhancement of CS anti-inflammatory effect.
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Affiliation(s)
- Ke Li
- Guangdong Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Foshan, China
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
| | - Xiu-Hua Yu
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
- Central Laboratory, Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China
| | - Anish R. Maskey
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
| | - Ibrahim Musa
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
| | - Zhen-Zheng Wang
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
- Academy of Chinese Medical Science, Henan University of Chinese Medicine, Zhengzhou, China
| | - Victor Garcia
- Department of Pharmacology, New York Medical College, Valhalla, NY, United States
| | - Austin Guo
- Department of Pharmacology, New York Medical College, Valhalla, NY, United States
| | - Nan Yang
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
- General Nutraceutical Technology, Elmsford, NY, United States
| | - Kamal Srivastava
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
- General Nutraceutical Technology, Elmsford, NY, United States
| | - David Dunkin
- Department of Pediatrics, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
| | - Jun-Xiong Li
- Guangdong Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou University of Chinese Medicine, Foshan, China
| | - Longgang Guo
- Guangzhou ImVin Pharmaceutical Co., Ltd., Guangzhou, China
| | - Yung-Chi Cheng
- Department of Pharmacology, School of Medicine, Yale University, New Haven, China
| | - Haoliang Yuan
- Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China
| | - Raj Tiwari
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
| | - Xiu-Min Li
- Department of Pathology, Microbiology and Immunology, New York Medical College, Valhalla, NY, United States
- Department of Otolaryngology, Westchester Medical Center New York Medical College, Valhalla, NY, United States
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24
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Jain NK, Tailang M, Jain HK, Chandrasekaran B, Sahoo BM, Subramanian A, Thangavel N, Aldahish A, Chidambaram K, Alagusundaram M, Kumar S, Selvam P. Therapeutic implications of current Janus kinase inhibitors as anti-COVID agents: A review. Front Pharmacol 2023; 14:1135145. [PMID: 37021053 PMCID: PMC10067607 DOI: 10.3389/fphar.2023.1135145] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 03/09/2023] [Indexed: 04/07/2023] Open
Abstract
Severe cases of COVID-19 are characterized by hyperinflammation induced by cytokine storm, ARDS leading to multiorgan failure and death. JAK-STAT signaling has been implicated in immunopathogenesis of COVID-19 infection under different stages such as viral entry, escaping innate immunity, replication, and subsequent inflammatory processes. Prompted by this fact and prior utilization as an immunomodulatory agent for several autoimmune, allergic, and inflammatory conditions, Jakinibs have been recognized as validated small molecules targeting the rapid release of proinflammatory cytokines, primarily IL-6, and GM-CSF. Various clinical trials are under investigation to evaluate Jakinibs as potential candidates for treating COVID-19. Till date, there is only one small molecule Jakinib known as baricitinib has received FDA-approval as a standalone immunomodulatory agent in treating critical COVID-19 patients. Though various meta-analyses have confirmed and validated the safety and efficacy of Jakinibs, further studies are required to understand the elaborated pathogenesis of COVID-19, duration of Jakinib treatment, and assess the combination therapeutic strategies. In this review, we highlighted JAK-STAT signalling in the pathogenesis of COVID-19 and clinically approved Jakinibs. Moreover, this review described substantially the promising use of Jakinibs and discussed their limitations in the context of COVID-19 therapy. Hence, this review article provides a concise, yet significant insight into the therapeutic implications of Jakinibs as potential anti-COVID agents which opens up a new horizon in the treatment of COVID-19, effectively.
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Affiliation(s)
- Nem Kumar Jain
- School of Pharmacy, ITM University, Gwalior, Madhya Pradesh, India
- School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh, India
| | - Mukul Tailang
- School of Studies in Pharmaceutical Sciences, Jiwaji University, Gwalior, Madhya Pradesh, India
| | - Hemant Kumar Jain
- Department of General Medicine, Government Medical College, Datia, Madhya Pradesh, India
| | - Balakumar Chandrasekaran
- Faculty of Pharmacy, Philadelphia University, Amman, Jordan
- *Correspondence: Balakumar Chandrasekaran, ; Palani Selvam,
| | - Biswa Mohan Sahoo
- Roland Institute of Pharmaceutical Sciences, Berhampur, Odisha, India
| | - Anandhalakshmi Subramanian
- Department of Microbiology and Clinical Parasitology, College of Medicine, King Khalid University, Abha, Saudi Arabia
| | - Neelaveni Thangavel
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia
| | - Afaf Aldahish
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - Kumarappan Chidambaram
- Department of Pharmacology, College of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - M. Alagusundaram
- School of Pharmacy, ITM University, Gwalior, Madhya Pradesh, India
| | - Santosh Kumar
- School of Sciences, ITM University, Gwalior, Madhya Pradesh, India
| | - Palani Selvam
- School of Medicine, College of Medicine and Health Sciences, Jijiga University, Jijiga, Ethiopia
- *Correspondence: Balakumar Chandrasekaran, ; Palani Selvam,
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25
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Perico N, Cortinovis M, Suter F, Remuzzi G. Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents. THE LANCET. INFECTIOUS DISEASES 2023. [PMID: 36030796 DOI: 10.1016/s1473-3099(22)00433] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
Abstract
COVID-19, caused by SARS-CoV-2, is characterised by a broad spectrum of symptom severity that requires varying amounts of care according to the different stages of the disease. Intervening at the onset of mild to moderate COVID-19 symptoms in the outpatient setting would provide the opportunity to prevent progression to a more severe illness and long-term complications. As early disease symptoms variably reflect an underlying excessive inflammatory response to the viral infection, the use of anti-inflammatory drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), in the initial outpatient stage of COVID-19 seems to be a valuable therapeutic strategy. A few observational studies have tested NSAIDs (especially relatively selective COX-2 inhibitors), often as part of multipharmacological protocols, for early outpatient treatment of COVID-19. The findings from these studies are promising and point to a crucial role of NSAIDs for the at-home management of people with initial COVID-19 symptoms.
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Affiliation(s)
- Norberto Perico
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy
| | - Monica Cortinovis
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy
| | - Fredy Suter
- Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy; Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.
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26
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Perico N, Cortinovis M, Suter F, Remuzzi G. Home as the new frontier for the treatment of COVID-19: the case for anti-inflammatory agents. THE LANCET. INFECTIOUS DISEASES 2023; 23:e22-e33. [PMID: 36030796 PMCID: PMC9411261 DOI: 10.1016/s1473-3099(22)00433-9] [Citation(s) in RCA: 48] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/20/2022] [Accepted: 06/20/2022] [Indexed: 02/09/2023]
Abstract
COVID-19, caused by SARS-CoV-2, is characterised by a broad spectrum of symptom severity that requires varying amounts of care according to the different stages of the disease. Intervening at the onset of mild to moderate COVID-19 symptoms in the outpatient setting would provide the opportunity to prevent progression to a more severe illness and long-term complications. As early disease symptoms variably reflect an underlying excessive inflammatory response to the viral infection, the use of anti-inflammatory drugs, especially non-steroidal anti-inflammatory drugs (NSAIDs), in the initial outpatient stage of COVID-19 seems to be a valuable therapeutic strategy. A few observational studies have tested NSAIDs (especially relatively selective COX-2 inhibitors), often as part of multipharmacological protocols, for early outpatient treatment of COVID-19. The findings from these studies are promising and point to a crucial role of NSAIDs for the at-home management of people with initial COVID-19 symptoms.
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Affiliation(s)
- Norberto Perico
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy
| | - Monica Cortinovis
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy
| | - Fredy Suter
- Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy
| | - Giuseppe Remuzzi
- Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Bergamo, Italy; Azienda Socio-Sanitaria Territoriale (ASST) Papa Giovanni XXIII, Bergamo, Italy.
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27
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Oronsky B, Larson C, Hammond TC, Oronsky A, Kesari S, Lybeck M, Reid TR. A Review of Persistent Post-COVID Syndrome (PPCS). Clin Rev Allergy Immunol 2023; 64:66-74. [PMID: 33609255 PMCID: PMC7896544 DOI: 10.1007/s12016-021-08848-3] [Citation(s) in RCA: 190] [Impact Index Per Article: 95.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/28/2021] [Indexed: 02/07/2023]
Abstract
Persistent post-COVID syndrome, also referred to as long COVID, is a pathologic entity, which involves persistent physical, medical, and cognitive sequelae following COVID-19, including persistent immunosuppression as well as pulmonary, cardiac, and vascular fibrosis. Pathologic fibrosis of organs and vasculature leads to increased mortality and severely worsened quality of life. Inhibiting transforming growth factor beta (TGF-β), an immuno- and a fibrosis modulator, may attenuate these post-COVID sequelae. Current preclinical and clinical efforts are centered on the mechanisms and manifestations of COVID-19 and its presymptomatic and prodromal periods; by comparison, the postdrome, which occurs in the aftermath of COVID-19, which we refer to as persistent post-COVID-syndrome, has received little attention. Potential long-term effects from post-COVID syndrome will assume increasing importance as a surge of treated patients are discharged from the hospital, placing a burden on healthcare systems, patients' families, and society in general to care for these medically devastated COVID-19 survivors. This review explores underlying mechanisms and possible manifestations of persistent post-COVID syndrome, and presents a framework of strategies for the diagnosis and management of patients with suspected or confirmed persistent post-COVID syndrome.
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Affiliation(s)
- Bryan Oronsky
- EpicentRx Inc, La Jolla, 11099 North Torrey Pines Road, Suite 160, La Jolla, CA 92037 USA
| | - Christopher Larson
- EpicentRx Inc, La Jolla, 11099 North Torrey Pines Road, Suite 160, La Jolla, CA 92037 USA
| | | | | | - Santosh Kesari
- Providence St. John’s Health Center, Santa Monica, CA USA
| | - Michelle Lybeck
- EpicentRx Inc, La Jolla, 11099 North Torrey Pines Road, Suite 160, La Jolla, CA 92037 USA
| | - Tony R. Reid
- EpicentRx Inc, La Jolla, 11099 North Torrey Pines Road, Suite 160, La Jolla, CA 92037 USA
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28
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Taşlı PN. Usage of celery root exosome as an immune suppressant; Lipidomic characterization of apium graveolens originated exosomes and its suppressive effect on PMA/ionomycin mediated CD4 + T lymphocyte activation. J Food Biochem 2022; 46:e14393. [PMID: 36181394 DOI: 10.1111/jfbc.14393] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 06/27/2022] [Accepted: 08/18/2022] [Indexed: 01/13/2023]
Abstract
Diseases such as autoimmune, cancer, neurodegenerative diseases or obesity have a serious impact on the lives of patients all rise from a common point; the immune system. Various in vitro and in vivo studies on regulating the immune system have been made to correct these diseases. As one of the key effector cells of the immune system, T lymphocytes are the focus of many of these studies. In this study, exosomes isolated from a known anti-inflammatory plant, celery, were used to suppress the inflammatory response of T lymphocytes. Celery-derived exosomes (C-Exo) were isolated using an aqueous two-phase isolation method. The size distribution, morphology, particle concentration, and GC-FAME-based lipidomic analysis were determined for the isolated C-Exo. T lymphocytes were stimulated using Phorbol 12-myristate 13-acetate (PMA)/ionomycin, and treated with various doses of C-Exo. T lymphocyte responses were measured using qPCR and capillary Western blots. According to the results, C-Exo suppressed T lymphocytes in a dose-dependent manner in in vitro conditions. These findings show the potential of C-Exo as a therapeutic agent for immune disorders. PRACTICAL APPLICATION: Excessive immune response in the body adversely affects the treatment mechanism and process of many diseases such as autoimmune disorders, neurodegenerative diseases and GDHV. In this preliminary study, the role of extracellular vesicles obtained from celery roots in suppressing this high immune response was investigated. The suppressive effect of celery exosome was observed by creating an immune response in T cells and PBMC cells, which play a leading role in the immune response. The role of these vesicles in immune suppression, obtained from the root part of the celery plant and characterized, was determined by measuring both mRNA, intracellular protein and extracellular cytokine levels. Celery exosome suppressed activated T lymphocyte cells and PBMC cells in a dose-dependent manner. These vesicles, which can be used as an edible, can be used in many areas as immunosuppressants.
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Affiliation(s)
- Pakize Neslihan Taşlı
- Department of Genetics and Bioengineering, Faculty of Engineering and Architecture, Yeditepe University, Istanbul, Turkey
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Karabulut Uzunçakmak S. SARS-CoV-2 Infection and Candidate Biomarkers. Eurasian J Med 2022; 54:16-22. [PMID: 36655440 PMCID: PMC11163343 DOI: 10.5152/eurasianjmed.2022.22305] [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: 10/15/2022] [Accepted: 11/27/2022] [Indexed: 01/19/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 is a virus that can still infect individuals and whose deadly effects continue despite the current vaccines and drugs. Since 2019, many studies on the pathogenesis of the disease have been completed and continue to be done. In addition to the diagnosis and treatment of the disease, many molecules that can be markers of the disease have been investigated. In the early stages of the pandemic, many nonspecific and infection-related laboratory findings and chest computed tomography were used to obtain information about the diagnosis of the disease. The more individual molecules became associated with the disease yet. The purpose of this review is to summarize the impact and role of many molecules associated with coronavirus disease-2019 infection that have been previously used and newly revealed. Numerous studies are summarized in this review. The obtained data show that previously used laboratory findings and new potential biomarkers are not specific to the disease. New potential biomarkers have been associated with the severity of the disease itself, as can be seen with lung imaging and even with routine laboratory findings. One of the important points that are seen frequently in studies is that the effectiveness of these molecules has been shown not only in coronavirus disease-2019 infection but also in many other diseases. This removes the pathogenesis of the disease from being a unique mechanism created by the Severe acute respiratory syndrome coronavirus 2 and provides a general perspective formed by viral or bacterial infections. However, there are still many molecular changes that need to be investigated. Future studies will continue to update themselves with the mutations of the virus.
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Wimalawansa S. Overcoming Infections Including COVID-19, by Maintaining Circulating 25(OH)D Concentrations Above 50 ng/mL. PATHOLOGY AND LABORATORY MEDICINE INTERNATIONAL 2022. [DOI: 10.2147/plmi.s373617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
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Cruciani M, Pati I, Masiello F, Pupella S, De Angelis V. Corticosteroids use for COVID-19: an overview of systematic reviews. LE INFEZIONI IN MEDICINA 2022; 30:469-479. [PMID: 36482954 PMCID: PMC9714993 DOI: 10.53854/liim-3004-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Accepted: 10/26/2022] [Indexed: 12/12/2022]
Abstract
PURPOSE A reappraisal of the validity of the conclusions of systematic reviews (SRs) and meta-analyses related to corticosteroids use for the treatment of COVID-19. MATERIAL AND METHODS An overview of SRs (umbrella review). The methodological quality of the SRs was assessed using tha AMSTAR-2 checklist; quality of the evidence was appraised following the GRADE approach. RESULTS 35 SRs were included in this overview. Data were from 307 overlapping reports, based on 121 individual primary studies (25 randomized clinical trials (RCTs), 96 non-RCTs. In critically ill patients the use of steroids significantly reduced mortality compared to standard of care in 80% of the SRs, more often with moderate/high level of certainty; however, in patients not requiring oxygen supplementation the use of steroids increased the overall mortality in 2/3 of the comparisons. Clinical progression of diseases (need for mechanical ventilation, or for intensive care admission) was more commonly observed among controls compared to steroids recipients (in 9 out of 14 comparisons; certainty of evidence from very-low to moderate). The occurrence of adverse events was similar among steroids recipients and controls. Other outcomes (i.e., viral clearance, length of hospital stay) or issue related to optimal dose and type of steroids were addressed in a minority of SRs, with a high level of uncertainty, so that no definitive conclusions can be drawn. CONCLUSIONS There is moderate certainty of evidence that corticosteroids reduce mortality and progression of disease in critically ill COVID-19 patients compared to standard of care, without increasing the occurrence of adverse events.
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Affiliation(s)
- Mario Cruciani
- National Blood Centre, Italian National Institute of Health, Rome, Italy
| | - Ilaria Pati
- National Blood Centre, Italian National Institute of Health, Rome, Italy
| | - Francesca Masiello
- National Blood Centre, Italian National Institute of Health, Rome, Italy
| | - Simonetta Pupella
- National Blood Centre, Italian National Institute of Health, Rome, Italy
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Tanaka S, Inoue M, Yamaji T, Iwasaki M, Minami T, Tsugane S, Sawada N. Increased risk of death from pneumonia among cancer survivors: A propensity score‐matched cohort analysis. Cancer Med 2022; 12:6689-6699. [PMID: 36408891 PMCID: PMC10067036 DOI: 10.1002/cam4.5456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2022] [Revised: 10/29/2022] [Accepted: 11/09/2022] [Indexed: 11/22/2022] Open
Abstract
BACKGROUND The repeated global pandemic of the new virus has led to interest in the possibility of severe pneumonia among cancer patients and survivors. Here, we aimed to assess the association between incident cancer and risk of death from pneumonia in Japanese in a large population-based cohort study. METHODS We used the data from The Japan Public Health Center-based Prospective Study (JPHC Study), which enrolled subjects aged 40 to 69 between 1990 and 1994 and followed their cancer incidence and mortality until 2013. After identifying 103,757 eligible subjects for analysis and imputing missing data on covariates by the chained equations approach, we conducted propensity score-matched analysis for 1:4 matching, leaving 14,520 cases diagnosed with cancer and 48,947 controls without cancer during the study period for final analysis. A Cox proportional hazards regression model was used to estimate the hazard ratio (HR) and corresponding confidence interval (CI) for the risk of death from pneumonia with comparison of cancer cases and cancer-free controls. RESULTS Compared to cancer-free individuals, risk of death from pneumonia was significantly higher among those who had any diagnosed cancer (HR, 1.41; 95%CI, 1.08-1.84); those within 1 year of diagnosis (HR, 23.0; 95% CI, 2.98-177.3); within 1 to <2 years (HR, 3.66; 95% CI, 1.04-12.9); and those with regional spread or distant metastatic cancer at initial diagnosis (HR, 2.01; 95% CI, 1.26-3.21). A history of lung, oesophageal, and head and neck cancer conferred the higher risk among site-specific cancers. CONCLUSION We found a positive association between incident cancer and risk of death from pneumonia in this study. These results imply the possibility that the immunocompromised status and respiratory failure due to antitumor treatment may have resulted in a more severe outcome from pneumonia among cancer survivors than the general population.
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Affiliation(s)
- Shiori Tanaka
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
| | - Manami Inoue
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
| | - Taiki Yamaji
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
| | - Motoki Iwasaki
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
| | - Tetsuji Minami
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
| | - Shoichiro Tsugane
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
- National Insitute of Health and Nutrition National Institutes of Biomedical Innovation, Health and Nutrition Tokyo Japan
| | - Norie Sawada
- Epidemiology and Prevention Group Institute for Cancer Control, National Cancer Center Tokyo Japan
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Nazerian Y, Ghasemi M, Yassaghi Y, Nazerian A, Mahmoud Hashemi S. Role of SARS-CoV-2-induced Cytokine Storm in Multi-Organ Failure: Molecular Pathways and Potential Therapeutic Options. Int Immunopharmacol 2022; 113:109428. [PMID: 36379152 PMCID: PMC9637536 DOI: 10.1016/j.intimp.2022.109428] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2022] [Revised: 10/19/2022] [Accepted: 11/01/2022] [Indexed: 11/09/2022]
Abstract
Coronavirus disease 2019 (COVID-19) outbreak has become a global public health emergency and has led to devastating results. Mounting evidence proposes that the disease causes severe pulmonary involvement and influences different organs, leading to a critical situation named multi-organ failure. It is yet to be fully clarified how the disease becomes so deadly in some patients. However, it is proven that a condition called “cytokine storm” is involved in the deterioration of COVID-19. Although beneficial, sustained production of cytokines and overabundance of inflammatory mediators causing cytokine storm can lead to collateral vital organ damages. Furthermore, cytokine storm can cause post-COVID-19 syndrome (PCS), an important cause of morbidity after the acute phase of COVID-19. Herein, we aim to explain the possible pathophysiology mechanisms involved in COVID-19-related cytokine storm and its association with multi-organ failure and PCS. We also discuss the latest advances in finding the potential therapeutic targets to control cytokine storm wishing to answer unmet clinical demands for treatment of COVID-19.
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Affiliation(s)
- Yasaman Nazerian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mobina Ghasemi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Younes Yassaghi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | | | - Seyed Mahmoud Hashemi
- Medical nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran,Corresponding author at: Medical nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran / Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Rezaei Tolzali MM, Noori M, Shokri P, Rahmani S, Khanzadeh S, Nejadghaderi SA, Fazlollahi A, Sullman MJM, Singh K, Kolahi A, Arshi S, Safiri S. Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review. Rev Med Virol 2022; 32:e2388. [PMID: 36029180 PMCID: PMC9539231 DOI: 10.1002/rmv.2388] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/02/2022] [Accepted: 08/09/2022] [Indexed: 01/09/2023]
Abstract
Tocilizumab is an interleukin (IL)-6 receptor inhibitor that has been proposed as a therapeutic agent for treating coronavirus disease 2019 (COVID-19). The aim of this umbrella review was to determine the efficacy of tocilizumab in treating COVID-19, and to provide an overview of all systematic reviews on this topic. We systematically searched PubMed, Scopus, the Web of Science collection, the Cochrane library, Epistemonikos, and Google Scholar, as well as the medRxiv preprint server. These databases were searched up to 30 September 2021, using the following keywords: 'SARS-CoV-2', 'COVID-19', 'tocilizumab', 'RHPM-1', 'systematic review', and 'meta-analysis'. Studies were included if they were systematic reviews (with or without meta-analysis) investigating the efficacy or safety of tocilizumab in confirmed COVID-19 patients. The AMSTAR 2 checklist was used to assess quality of the included articles, while publication bias was examined using Egger's test. A total of 50 eligible systematic reviews were included. The pooled estimates showed significant reductions in clinical failure (risk ratio (RR) 0.75; 95% confidence interval (CI), 0.61-0.93), deaths (RR 0.78; 95%CI, 0.71-0.85) and the need for mechanical ventilation (RR 0.77; 95%CI, 0.64-0.92) for those receiving tocilizumab compared with the control group. Also, an emerging survival benefit was demonstrated for those who received tocilizumab, over those in the control group (adjusted hazard ratio (aHR) 0.52; 95%CI, 0.43-0.63). In addition, tocilizumab substantially increased the number of ventilator-free days, compared with the control treatments (weighted mean difference (WMD) 3.38; 95%CI, 0.51-6.25). Furthermore, lymphocyte count (WMD 0.26 × 109 /L; 95%CI, 0.14-0.37), IL-6 (WMD 176.99 pg/mL; 95%CI, 76.34-277.64) and D-dimer (WMD 741.08 ng/mL; 95%CI, 109.42-1372.75) were all significantly elevated in those receiving tocilizumab. However, the level of lactate dehydrogenase (LDH) (WMD -30.88 U/L; 95%CI, -51.52, -10.24) and C-reactive protein (CRP) (WMD -104.83 mg/L; 95%CI, -133.21, -76.46) were both significantly lower after treatment with tocilizumab. Tocilizumab treatment reduced the risk of intubation, mortality and the length of hospital stay, without increasing the risk of superimposed infections in COVID-19 patients. Therefore, tocilizumab can be considered an effective therapeutic agent for treating patients with COVID-19.
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Affiliation(s)
| | - Maryam Noori
- Student Research CommitteeSchool of MedicineIran University of Medical SciencesTehranIran
- Urology Research CenterTehran University of Medical SciencesTehranIran
| | - Pourya Shokri
- School of MedicineShahid Beheshti University of Medical SciencesTehranIran
| | - Shayan Rahmani
- Student Research CommitteeSchool of MedicineShahid Beheshti University of Medical SciencesTehranIran
- Network of Immunity in InfectionMalignancy and Autoimmunity (NIIMA)Universal Scientific Education and Research Network (USERN)TehranIran
| | | | - Seyed Aria Nejadghaderi
- School of MedicineShahid Beheshti University of Medical SciencesTehranIran
- Systematic Review and Meta‐Analysis Expert Group (SRMEG)Universal Scientific Education and Research Network (USERN)TehranIran
| | - Asra Fazlollahi
- Student Research CommitteeTabriz University of Medical SciencesTabrizIran
| | - Mark J. M. Sullman
- Department of Life and Health SciencesUniversity of NicosiaNicosiaCyprus
- Department of Social SciencesUniversity of NicosiaNicosiaCyprus
| | - Kuljit Singh
- Department of MedicineGriffith UniversitySouthportQueenslandAustralia
| | - Ali‐Asghar Kolahi
- Social Determinants of Health Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Shahnam Arshi
- Social Determinants of Health Research CenterShahid Beheshti University of Medical SciencesTehranIran
| | - Saeid Safiri
- Research Center for Integrative Medicine in AgingAging Research InstituteTabriz University of Medical SciencesTabrizIran
- Department of Community MedicineFaculty of MedicineTabriz University of Medical SciencesTabrizIran
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Jin Q, Li W, Yu W, Zeng M, Liu J, Xu P. Analysis and identification of potential type II helper T cell (Th2)-Related key genes and therapeutic agents for COVID-19. Comput Biol Med 2022; 150:106134. [PMID: 36201886 PMCID: PMC9528635 DOI: 10.1016/j.compbiomed.2022.106134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 08/30/2022] [Accepted: 09/18/2022] [Indexed: 11/19/2022]
Abstract
COVID-19 pandemic poses a severe threat to public health. However, so far, there are no effective drugs for COVID-19. Transcriptomic changes and key genes related to Th2 cells in COVID-19 have not been reported. These genes play an important role in host interactions with SARS-COV-2 and may be used as promising target. We analyzed five COVID-19-associated GEO datasets (GSE157103, GSE152641, GSE171110, GSE152418, and GSE179627) using the xCell algorithm and weighted gene co-expression network analysis (WGCNA). Results showed that 5 closely correlated modular genes to COVID-19 and Th2 cell enrichment levels, including purple, blue, pink, tan and turquoise, were intersected with differentially expressed genes (DEGs) and 648 shared genes were obtained. GO and KEGG pathway enrichment analyses revealed that they were enriched in cell proliferation, differentiation, and immune responses after virus infection. The most significantly enriched pathway involved the regulation of viral life cycle. Three key genes, namely CCNB1, BUB1, and UBE2C, may clarify the pathogenesis of COVID-19 associated with Th2 cells. 11 drug candidates were identified that could down-regulate three key genes using the cMAP database and demonstrated strong drugs binding energies aganist the three keygenes using molecular docking methods. BUB1, CCNB1 and UBE2C were identified key genes for COVID-19 and could be promising therapeutic targets.
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Affiliation(s)
- Qiying Jin
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Wanxi Li
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Wendi Yu
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Maosen Zeng
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Jinyuan Liu
- Basic Medical College, Guangzhou University of Chinese Medicine, Guangzhou, PR China
| | - Peiping Xu
- Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou, PR China.
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Abstract
Knowledge on SARS-CoV-2 infection and its resultant COVID-19 in liver diseases has rapidly increased during the pandemic. Hereby, we review COVID-19 liver manifestations and pathophysiological aspects related to SARS-CoV-2 infection in patients without liver disease as well as the impact of COVID-19 in patients with chronic liver disease (CLD), particularly cirrhosis and liver transplantation (LT). SARS-CoV-2 infection has been associated with overt proinflammatory cytokine profile, which probably contributes substantially to the observed early and late liver abnormalities. CLD, particularly decompensated cirrhosis, should be regarded as a risk factor for severe COVID-19 and death. LT was impacted during the pandemic, mainly due to concerns regarding donation and infection in recipients. However, LT did not represent a risk factor per se of worse outcome. Even though scarce, data regarding COVID-19 specific therapy in special populations such as LT recipients seem promising. COVID-19 vaccine-induced immunity seems impaired in CLD and LT recipients, advocating for a revised schedule of vaccine administration in this population.
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Affiliation(s)
- Jean-François Dufour
- Hepatology, Department of Biomedical Research, University of Bern, Bern, Switzerland
| | - Thomas Marjot
- Oxford Liver Unit, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, UK
- Nuffield Department of Medicine, Translational Gastroenterology Unit, University of Oxford, Oxford, UK
| | - Chiara Becchetti
- Department of Hepatology and Gastroenterology, ASST Grande Ospedale Metropolitano Niguarda, Bern, Italy
- Department of Visceral Surgery and Medicine, Inselspital, University Hospital of Bern, Bern, Switzerland
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology and Metabolism, Medical University Innsbruck, Innsbruck, Austria
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Axelerad A, Stuparu AZ, Muja LF, Docu Axelerad S, Petrov SG, Gogu AE, Jianu DC. Narrative Review of New Insight into the Influence of the COVID-19 Pandemic on Cardiovascular Care. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1554. [PMID: 36363511 PMCID: PMC9694465 DOI: 10.3390/medicina58111554] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Revised: 10/21/2022] [Accepted: 10/26/2022] [Indexed: 09/10/2024]
Abstract
Background and Objectives: The purpose of this paper was to perform a literature review on the effects of the COVID-19 pandemic on cardiothoracic and vascular surgery care and departments. Materials and Methods: To conduct this evaluation, an electronic search of many databases was conducted, and the resulting papers were chosen and evaluated. Results: Firstly, we have addressed the impact of COVID-19 infection on the cardiovascular system from the pathophysiological and treatment points of view. Afterwards, we analyzed every cardiovascular disease that seemed to appear after a COVID-19 infection, emphasizing the treatment. In addition, we have analyzed the impact of the pandemic on the cardiothoracic and vascular departments in different countries and the transitions that appeared. Finally, we discussed the implications of the cardiothoracic and vascular specialists' and residents' work and studies on the pandemic. Conclusions: The global pandemic caused by SARS-CoV-2 compelled the vascular profession to review the treatment of certain vascular illnesses and find solutions to address the vascular consequences of COVID-19 infection. The collaboration between vascular surgeons, public health specialists, and epidemiologists must continue to investigate the impact of the pandemic and the response to the public health issue.
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Affiliation(s)
- Any Axelerad
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Alina Zorina Stuparu
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Lavinia Florenta Muja
- Department of Neurology, General Medicine Faculty, ‘Ovidius’ University, 900470 Constanta, Romania
- Department of Neurology, ‘Sf. Ap. Andrei’ County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | | | - Silvia Georgeta Petrov
- Doctoral School of the Faculty of Psychology and Educational Sciences within the University of Bucharest, 050663 Bucharest, Romania
| | - Anca Elena Gogu
- Department of Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
| | - Dragos Catalin Jianu
- Department of Neurology, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
- Centre for Cognitive Research in Neuropsychiatric Pathology (Neuropsy-Cog), Faculty of Medicine, “Victor Babeș” University of Medicine and Pharmacy, 300041 Timișoara, Romania
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Batiha GES, Al-kuraishy HM, Al-Gareeb AI, Welson NN. Pathophysiology of Post-COVID syndromes: a new perspective. Virol J 2022; 19:158. [PMID: 36210445 PMCID: PMC9548310 DOI: 10.1186/s12985-022-01891-2] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2022] [Accepted: 09/26/2022] [Indexed: 11/26/2022] Open
Abstract
Most COVID-19 patients recovered with low mortality; however, some patients experienced long-term symptoms described as "long-COVID" or "Post-COVID syndrome" (PCS). Patients may have persisting symptoms for weeks after acute SARS-CoV-2 infection, including dyspnea, fatigue, myalgia, insomnia, cognitive and olfactory disorders. These symptoms may last for months in some patients. PCS may progress in association with the development of mast cell activation syndrome (MCAS), which is a distinct kind of mast cell activation disorder, characterized by hyper-activation of mast cells with inappropriate and excessive release of chemical mediators. COVID-19 survivors, mainly women, and patients with persistent severe fatigue for 10 weeks after recovery with a history of neuropsychiatric disorders are more prone to develop PCS. High D-dimer levels and blood urea nitrogen were observed to be risk factors associated with pulmonary dysfunction in COVID-19 survivors 3 months post-hospital discharge with the development of PCS. PCS has systemic manifestations that resolve with time with no further complications. However, the final outcomes of PCS are chiefly unknown. Persistence of inflammatory reactions, autoimmune mimicry, and reactivation of pathogens together with host microbiome alterations may contribute to the development of PCS. The deregulated release of inflammatory mediators in MCAS produces extraordinary symptoms in patients with PCS. The development of MCAS during the course of SARS-CoV-2 infection is correlated to COVID-19 severity and the development of PCS. Therefore, MCAS is treated by antihistamines, inhibition of synthesis of mediators, inhibition of mediator release, and inhibition of degranulation of mast cells.
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Affiliation(s)
- Gaber El-Saber Batiha
- Department of Pharmacology and Therapeutics, Faculty of Veterinary Medicine, Damanhour University, Damanhour, Al Beheira, 22511 Egypt
| | - Hayder M. Al-kuraishy
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Ali I. Al-Gareeb
- Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, Baghdad, Iraq
| | - Nermeen N. Welson
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Beni-Suef University, Beni Suef, 62511 Egypt
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Pandit L, Sudhir A, Malli C, D'Cunha A. COVID-19 infection and vaccination against COVID-19: Impact on managing demyelinating CNS disorders in Southern India- experience from a demyelinating disease registry. Mult Scler Relat Disord 2022; 66:104033. [PMID: 35849990 PMCID: PMC9252866 DOI: 10.1016/j.msard.2022.104033] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 06/23/2022] [Accepted: 07/03/2022] [Indexed: 12/03/2022]
Abstract
BACKGROUND AND OBJECTIVE The impact of COVID-19 infection and the effect of COVID-19 vaccinations on patients with demyelinating central nervous system disease in low middle income countries (LMIC's) have not been reported in detail earlier. We sought to identify risk factors associated with COVID-19 infection and the role of vaccination in order to develop management guidelines relevant to our patients. METHODS A total of 621 patients from our registry that included 297 MS and 324 non MS disorders (Aquaporin- 4 antibody positive [50], Myelin oligodendrocyte glycoprotein antibody positive [81], seronegative [162] and clinically isolated syndrome [31]) were contacted. COVID-19 infection and vaccination status were queried. Patients who self reported COVID-19 infection based on a positive RT PCR report were compared with non infected patients to identify factors associated with susceptibility for COVID-19 infection. Univariate and multivariate analysis of potential risk factors included demographic and clinical features, body mass index (BMI), presence of comorbidities, absolute lymphocyte count, treatment types and vaccination status. RESULTS Sixty seven patients with MS and 27 with non MS disorders developed COVID-19 infection. Among them 81 patients had mild infection and remained quarantined at home. All 13 patients who needed hospitalization recovered. Vaccination status was known in 582 patients among whom 69.8% had completed or taken one dose of vaccine at the time of inquiry. Majority of treated patients (61.3%) were on nonspecific immunosuppressants. In univariate analysis, presence of ≥1 comorbidity was significantly associated with COVID-19 infection in both MS (p value 0.01, OR-2.28, 95%CI- 1.18-4.4) and non MS patients (p- 0.001, OR-4.4, 95% CI-1.88-10.24). In the latter, BMI ≥ 30 (p-0.04, OR-3.27, 95% CI- 0.98-10.87) and EDSS score ≥ 3 (p-0.02, OR- 2.59,95% CI- 1.08-6.23) were other significant associations. History of prior COVID-19 vaccination was associated with reduced frequency of COVID-19 infection among MS (p- 0.001,OR- 0.24,95% CI- 0.13-0.43) and non MS patients (p- 0.0001,OR-0.14, 95% CI- 0.058-0.35). In multivariate analysis presence of comorbidities significantly increased and prior vaccination significantly reduced frequency of COVID-19 infection for both MS and related disorders. Concurrent disease modifying treatments showed a trend for association with infection. In the unvaccinated group, patients on disease modifying treatment were significantly at risk of infection, 81.5% unvaccinated and treated versus 18.5% who were unvaccinated and untreated (p- 0.0001, OR-10.1, 95% CI-0.56-2.11). CONCLUSION Frequency and severity of COVID-19 infection was low among our patient cohort. Higher rate of infection in the treated group was significantly seen among unvaccinated patients. Our preliminary results suggests that in LMIC's, where "off label therapies" with inexpensive immunosuppressives are the main disease modifying drugs, mRNA vaccinations appear safe and effective against severe COVID-19 infection.
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Affiliation(s)
- L Pandit
- Center for Advanced Neurological Research, KS Hegde Medical Academy, Nitte University, Mangalore, India.
| | - A Sudhir
- Center for Advanced Neurological Research, KS Hegde Medical Academy, Nitte University, Mangalore, India
| | - C Malli
- Center for Advanced Neurological Research, KS Hegde Medical Academy, Nitte University, Mangalore, India
| | - A D'Cunha
- Center for Advanced Neurological Research, KS Hegde Medical Academy, Nitte University, Mangalore, India
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Zhu Y, Liu Y, Jiang H. Geriatric Health Care During the COVID-19 Pandemic: Managing the Health Crisis. Clin Interv Aging 2022; 17:1365-1378. [PMID: 36158515 PMCID: PMC9491878 DOI: 10.2147/cia.s376519] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2022] [Accepted: 08/20/2022] [Indexed: 01/08/2023] Open
Abstract
COVID-19 pandemic significantly threatens the health and well-being of older adults. Aging-related changes, including multimorbidity, weakened immunity and frailty, may make older people more susceptible to severe infection and place them at higher risk of morbidity and mortality from COVID-19. Various quarantine measures have been implemented to control the spread of COVID-19. Nevertheless, such social distancing has disrupted routine health care practices, such as accessibility of medical services and long-term continuous care services. The medical management of older adults with multimorbidity is significantly afflicted by COVID-19. Older persons with frailty or multiple chronic disease may poorly adapt to the altered health care system, having detrimental consequences on their physical and mental health. COVID-19 pandemic has posed great challenges to the health of older adults. We highlighted the difficulties and obstacles of older adults during this unprecedented time. Also, we provided potential strategies and recommendations for actions to mitigate the COVID-19 pandemic threats. Certain strategies like community primary health care, medication delivery and home care support are adopted by many health facilities and caregivers, whereas other services such as internet hospital and virtual medical care are promoted to be accessible in many regions. However, guidelines and policies based on high-quality data are still needed for better health promotion of older groups with increasing resilience during the COVID-19 pandemic.
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Affiliation(s)
- Yingqian Zhu
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.,Department of General Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
| | - Yue Liu
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.,Department of General Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
| | - Hua Jiang
- Department of Geriatrics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China.,Department of General Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, People's Republic of China
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SARS-CoV-2 Variants, Current Vaccines and Therapeutic Implications for COVID-19. Vaccines (Basel) 2022; 10:vaccines10091538. [PMID: 36146616 PMCID: PMC9504858 DOI: 10.3390/vaccines10091538] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/08/2022] [Accepted: 09/13/2022] [Indexed: 11/17/2022] Open
Abstract
Over the past two years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections, resulting in an unprecedented pandemic of coronavirus disease 2019 (COVID-19). As the virus spreads through the population, ongoing mutations and adaptations are being discovered. There is now substantial clinical evidence that demonstrates the SARS-CoV-2 variants have stronger transmissibility and higher virulence compared to the wild-type strain of SARS-CoV-2. Hence, development of vaccines against SARS-CoV-2 variants to boost individual immunity has become essential. However, current treatment options are limited for COVID-19 caused by the SARS-CoV-2 variants. In this review, we describe current distribution, variation, biology, and clinical features of COVID-19 caused by SARS-CoV-2 variants (including Alpha (B.1.1.7 Lineage) variant, Beta (B.1.351 Lineage) variant, Gamma (P.1 Lineage) variant, Delta (B.1.617.2 Lineage) variant, and Omicron (B.1.1.529 Lineage) variant and others. In addition, we review currently employed vaccines in clinical or preclinical phases as well as potential targeted therapies in an attempt to provide better preventive and treatment strategies for COVID-19 caused by different SARS-CoV-2 variants.
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Graceffa D, Sperati F, Bonifati C, Spoletini G, Lora V, Pimpinelli F, Pontone M, Pellini R, Di Bella O, Morrone A, Cristaudo A. Immunogenicity of three doses of anti-SARS-CoV-2 BNT162b2 vaccine in psoriasis patients treated with biologics. Front Med (Lausanne) 2022; 9:961904. [PMID: 36148445 PMCID: PMC9485492 DOI: 10.3389/fmed.2022.961904] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 08/15/2022] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION Psoriasis has not been directly linked to a poor prognosis for COVID-19, yet immunomodulatory agents used for its management may lead to increased vulnerability to the dangerous complications of SARS-CoV-2 infection, as well as impair the effectiveness of the recently introduced vaccines. The three-dose antibody response trend and the safety of BNT162b2 mRNA vaccine in psoriasis patients treated with biologic drugs have remained under-researched. MATERIALS AND METHODS Forty-five psoriatic patients on biologic treatment were enrolled to evaluate their humoral response to three doses of BNT162b2. IgG titers anti-SARS-CoV-2 spike protein were evaluated at baseline (day 0, first dose), after 3 weeks (second dose), four weeks post-second dose, at the time of the third dose administration and 4 weeks post-third dose. Seropositivity was defined as IgG ≥15 antibody-binding units (BAU)/mL. Data on vaccine safety were also collected by interview at each visit. RESULTS A statistically significant increase in antibody titers was observed after each dose of vaccine compared with baseline, with no significant differences between patients and controls. Methotrexate used in combination with biologics has been shown to negatively influence the antibody response to the vaccine. On the contrary, increasing body mass index (BMI) positively influenced the antibody response. No adverse effects were reported, and no relapses of psoriasis were observed in the weeks following vaccine administration in our study population. CONCLUSIONS Our data are largely consistent with the recent literature on this topic confirming the substantial efficacy and safety of BNT162b2 mRNA vaccine on psoriatic patients treated with biologics of different types and support the recommendation to perform additional doses in this specific subgroup of patients.
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Affiliation(s)
- Dario Graceffa
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Francesca Sperati
- Biostatistics Unit, San Gallicano Dermatological Institute IRCCS, Rome, Italy
| | - Claudio Bonifati
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Gabriele Spoletini
- General Surgery and Liver Transplantation, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Viviana Lora
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Fulvia Pimpinelli
- Microbiology and Virology Unit, Dermatological Clinical and Research Department, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Martina Pontone
- Microbiology and Virology Unit, Dermatological Clinical and Research Department, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Raul Pellini
- Department Otolaryngology Head and Neck Surgery, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Ornella Di Bella
- Medical Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Aldo Morrone
- Scientific Direction, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
| | - Antonio Cristaudo
- Department of Clinical Dermatology, San Gallicano Dermatological Institute, IRCCS, Rome, Italy
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Moslehi N, Jahromy MH, Ashrafi P, Vatani K, Nemati MAH, Moghadam PA, Rostamian F, Jahromi MH. Multi-organ system involvement in coronavirus disease 2019 (COVID-19): A mega review. J Family Med Prim Care 2022; 11:5014-5023. [PMID: 36505634 PMCID: PMC9731028 DOI: 10.4103/jfmpc.jfmpc_1570_21] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Revised: 12/16/2021] [Accepted: 05/17/2022] [Indexed: 12/15/2022] Open
Abstract
Since the pandemic of the coronavirus disease 2019 (COVID-19) infection, many people have been affected in different ways. The majority of infected people experience mild to moderate symptoms and recover without the need for hospitalization. However, in some affected people, it may lead to catastrophic disease. The severity of COVID-19 infection is widely influenced by co-morbidities, immune system functions, and extra-pulmonary organ injuries. Since the emergence of COVID-19, multi-organ involvement has been documented. In order to implement preventative and protective measures, full attention to potential organ injuries is required. Most existing articles and review papers are focused on a specific organ system, and their numbers are growing. In this review paper, attempts were made to collect review papers and articles published on seven organ system involvements in COVID-19 infection published till 15 July and highlight conclusions and managements of all affected organs. We tried to add to the medical knowledge on COVID-19, pointing out its multi-organ system impact. Finally, we tried to facilitate access to organized information and optimum conclusion by representing review tables for each organ system. Besides, this review article can clarify and magnify the empty research space easily for future investigations.
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Affiliation(s)
- Naghmeh Moslehi
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mahsa Hadipour Jahromy
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
- Herbal Pharmacology Research Center, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Pegah Ashrafi
- School of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Kimia Vatani
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | | | - Parnian A. Moghadam
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Fatemeh Rostamian
- Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
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Laloglu E, Alay H. Role of transforming growth factor-beta 1 and connective tissue growth factor levels in coronavirus disease-2019-related lung Injury: a prospective, observational, cohort study. Rev Soc Bras Med Trop 2022; 55:e06152021. [PMID: 35894403 PMCID: PMC9359341 DOI: 10.1590/0037-8682-0615-2021] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Accepted: 04/20/2022] [Indexed: 11/22/2022] Open
Abstract
Background: Coronavirus disease-2019 (COVID-19) results in acute lung injury. This study examined the usefulness of serum transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF) levels in predicting disease severity in COVID-19 patients with pulmonary involvement. Methods: Fifty patients with confirmed COVID-19 and pulmonary involvement between September 2020, and February 2021 (Group 1) and 45 healthy controls (Group 2) were classified into three subgroups based on clinical severity: moderate, severe, and critical pneumonia. Serum TGF-β1 and CTGF concentrations were measured on days 1 and 7 of admission in Group 1 using an enzyme-linked immunosorbent assay. These concentrations were also measured in control cases. The mean serum TGF-β1 and CTGF levels were then compared among COVID-19 patients, based on clinical severity. Results: Significantly higher mean serum TGF-β1 and CTGF levels were observed on both days in Group 1 than in the control group. The mean serum TGF-β1 and CTGF levels on day 7 were also significantly higher than those on day 1 in Group 1. The critical patient group had the highest serum TGF-β1 and CTGF levels on both days, and the difference between this group and the moderate and severe pneumonia groups was significant. Cutoff values of 5.36 ng/mL for TGF-β1 and 626.2 pg/mL for CTGF emerged as predictors of COVID-19 with pulmonary involvement in receiver-operating characteristic curve analysis. Conclusions: TGF-β1 and CTGF are potential markers that can distinguish COVID-19 patients with pulmonary involvement and indicate disease severity. These findings may be useful for initiating treatment for early-stage COVID-19.
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Affiliation(s)
- Esra Laloglu
- Ataturk University, Faculty of Medicine, Department of Medical Biochemistry, Erzurum, Turkey
| | - Handan Alay
- Ataturk University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Erzurum, Turkey
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Narazaki M, Kishimoto T. Current status and prospects of IL-6–targeting therapy. Expert Rev Clin Pharmacol 2022; 15:575-592. [DOI: 10.1080/17512433.2022.2097905] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Affiliation(s)
- Masashi Narazaki
- Department of Advanced Clinical and Translational Immunology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
- Department of Respiratory Medicine, Clinical Immunology, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan
- Department of Immunopathology, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
| | - Tadamitsu Kishimoto
- Laboratory of Immune Regulation, World Premier International Immunology Frontier Research Center, Osaka University, Osaka, Japan
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Cazzaniga M, Testa S, Brambilla M, Vergori A, Viganoni M, Montini G. Incidence and outcome of SARS-CoV-2 infection in a pediatric kidney transplant recipient cohort from a single center in Northern Italy. Pediatr Transplant 2022; 26:e14335. [PMID: 35726833 PMCID: PMC9350330 DOI: 10.1111/petr.14335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 04/08/2022] [Accepted: 05/24/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Concern about SARS-CoV-2 infection has increased over the possible effects on immunocompromised patients. Among them, recipients of solid organ transplantation deserve special attention. Data from the adult population suggest they may be at high risk for developing severe COVID-19, but little data are available for pediatric solid organ transplantation recipients. METHODS From March 2020 to April 2021, KT recipients aged <21 years, routinely managed at our center, who underwent RT-PCR testing with nasopharyngeal swabs to detect SARS-CoV-2 infection, were studied. Tests were performed according to clinical and/or epidemiological criteria. RESULTS One hundred one transplanted patients were managed at our center during the observation period. Among this population, 57 patients were tested for SARS-CoV-2 infection with a RT-PCR test and were subsequently enrolled. A total of 111 swabs were performed. Twelve out of the 57 patients tested (21.1%) had a positive RT-PCR test result. Among the positive patients, eight were symptomatic (66.7%). Median duration of symptoms and RT-PCR positivity was two days (IQR 1-2.25) and 17 days (IQR 11-27.25), respectively. No patients required specific treatment or IS therapy reduction; no one was admitted to hospital. CONCLUSIONS Our data show that pediatric renal transplant recipients are at low risk of clinically relevant COVID-19, as is the healthy age-related population. On the contrary, our results differed substantially from those seen in adult SOT recipient populations that have a high incidence and an even earlier and higher mortality rate.
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Affiliation(s)
| | - Sara Testa
- Pediatric Nephrology, Dialysis and Transplant UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | - Marta Brambilla
- Pediatric Nephrology, Dialysis and Transplant UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly
| | | | | | - Giovanni Montini
- Pediatric Nephrology, Dialysis and Transplant UnitFondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMilanItaly,Department of Clinical Sciences and Community HealthUniversity of MilanMilanItaly
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Vachtenheim J, Novysedlak R, Svorcova M, Lischke R, Strizova Z. How COVID-19 Affects Lung Transplantation: A Comprehensive Review. J Clin Med 2022; 11:jcm11123513. [PMID: 35743583 PMCID: PMC9225085 DOI: 10.3390/jcm11123513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2022] [Revised: 06/08/2022] [Accepted: 06/15/2022] [Indexed: 02/04/2023] Open
Abstract
Lung transplant (LuTx) recipients are at a higher risk of developing serious illnesses from COVID-19, and thus, we have closely reviewed the consequences of the COVID-19 pandemic on lung transplantation. In most transplant centers, the overall LuTx activity significantly declined and led to a specific period of restricting lung transplantation to urgent cases. Moreover, several transplant centers reported difficulties due to the shortage of ICU capacities. The fear of donor-derived transmission generated extensive screening programs. Nevertheless, reasonable concerns about the unnecessary losses of viable organs were also raised. The overall donor shortage resulted in increased waiting-list mortality, and COVID-19-associated ARDS became an indication of lung transplantation. The impact of specific immunosuppressive agents on the severity of COVID-19 varied. Corticosteroid discontinuation was not found to be beneficial for LuTx patients. Tacrolimus concentrations were reported to increase during the SARS-CoV-2 infection, and in combination with remdesivir, tacrolimus may clinically impact renal functions. Monoclonal antibodies were shown to reduce the risk of hospitalization in SOT recipients. However, understanding the pharmacological interactions between the anti-COVID-19 drugs and the immunosuppressive drugs requires further research.
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Affiliation(s)
- Jiri Vachtenheim
- Prague Lung Transplant Program, 3rd Department of Surgery, First Faculty of Medicine, Charles University, University Hospital Motol, 150 06 Prague, Czech Republic; (J.V.J.); (R.N.); (M.S.); (R.L.)
| | - Rene Novysedlak
- Prague Lung Transplant Program, 3rd Department of Surgery, First Faculty of Medicine, Charles University, University Hospital Motol, 150 06 Prague, Czech Republic; (J.V.J.); (R.N.); (M.S.); (R.L.)
| | - Monika Svorcova
- Prague Lung Transplant Program, 3rd Department of Surgery, First Faculty of Medicine, Charles University, University Hospital Motol, 150 06 Prague, Czech Republic; (J.V.J.); (R.N.); (M.S.); (R.L.)
| | - Robert Lischke
- Prague Lung Transplant Program, 3rd Department of Surgery, First Faculty of Medicine, Charles University, University Hospital Motol, 150 06 Prague, Czech Republic; (J.V.J.); (R.N.); (M.S.); (R.L.)
| | - Zuzana Strizova
- Department of Immunology, Second Faculty of Medicine, Charles University, University Hospital Motol, 150 06 Prague, Czech Republic
- Correspondence: ; Tel.: +420-604712471
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Siddiqui MA, Bakirci O, Dönger U, Warasnhe K, Özçay F, Haberal M. Clinical Features and Outcomes Following SARS-CoV-2 Infection in Pediatric Liver Transplant Patients. EXP CLIN TRANSPLANT 2022; 20:66-71. [PMID: 35570604 DOI: 10.6002/ect.pediatricsymp2022.o22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Several studies suggest that chronic immunosuppression in pediatric liver transplant patients may affect the severity and mortality rates of SARS-CoV-2 infection. MATERIALS AND METHODS We assessed a total of 118 pediatric liver transplant recipients for SARS-CoV-2 infection, aged 1 to 18 years, followed between March 2019 and January 2022. We compared the clinical characteristics and outcomes of SARS-CoV-2 infection in pediatric liver transplant patients to 187 non-liver transplant pediatric patients with SARSCoV-2 infection who had been diagnosed at our institution between March 15, 2020, and December 31, 2020. Demographic data, clinical features, and laboratory findings from the patients were retrospectively collected from hospital reports and telephone inquiries. RESULTS A total of 20 liver transplant patients with SARS-CoV-2 infection were identified. Median age of liver transplant recipients with SARS-CoV-2 infection was higher than non-liver transplant pediatric patients with SARS-CoV-2 (14.8 [range, 7-16] vs 6.8 [range, 2-14] years; P = .016). There were no significant differences in mild and moderate disease courses of SARS-CoV-2 infection between liver transplant recipients and non-liver transplant pediatric patients (18 [90.0%] vs 133 [71.1%] patients [P = .188] and 2 [10%] vs 49 [26.2%] patients [P = .118], respectively). Fever was less frequently observed in liver transplant patients with SARS-CoV-2 infection compared with non-liver transplant patients (55.0% vs 80.2%; P = .015). We found no intergroup differences in sex (P = .342), hospitalization rate (P = .161), and overall clinical presentation. CONCLUSIONS Despite the immunosuppression regimens, liver transplant patients in our series survived SARS-CoV-2 infection without serious sequelae and without graft rejection. Overall, liver transplant and non-liver transplant pediatric patients with SARSCoV-2 infection experienced a mild disease course.
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Affiliation(s)
- Meraj Alam Siddiqui
- From the Department of Pediatrics, Baskent University Faculty of Medicine, Ankara, Turkey
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Kim Y, Li X, Huang Y, Kim M, Shaibani A, Sheikh K, Zhang GQ, Nguyen TP. COVID-19 Outcomes in Myasthenia Gravis Patients: Analysis From Electronic Health Records in the United States. Front Neurol 2022; 13:802559. [PMID: 35418937 PMCID: PMC8996116 DOI: 10.3389/fneur.2022.802559] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 02/28/2022] [Indexed: 02/03/2023] Open
Abstract
Background Myasthenia gravis (MG) is an autoimmune, neuromuscular condition and patients with MG are vulnerable due to immunosuppressant use and disease manifestations of dyspnea and dysphagia during the coronavirus disease 2019 (COVID-19) pandemic. Methods We conducted a retrospective cohort study using the Optum® de-identified COVID-19 Electronic Health Record (EHR) dataset. Primary outcomes, such as hospitalization, ventilator use, intensive care unit (ICU) admission, and death in COVID-19 patients with MG, were compared with those of COVID-19 patients without MG: the subgroups of non-MG included those with rheumatoid arthritis (RA), systemic lupus (SLE), and multiple sclerosis (MS). We further analyzed factors affecting mortality, such as age, race/ethnicity, comorbidities, and MG treatments. Results Among 421,086 individuals with COVID-19, there were 377 patients with MG, 7,362 patients with RA, 1,323 patients with SLE, 1,518 patients with MS, and 410,506 patients without MG. Patients with MG were older and had more comorbidities compared with non-MG patients and had the highest rates of hospitalization (38.5%), ICU admission (12.7%), ventilator use (3.7%), and mortality (10.6%) compared with all other groups. After adjusting for risk factors, patients with MG had increased risks for hospitalization and ICU compared with patients with non-MG and with RA but had risks similar to patients with SLE and with MS. The adjusted risk for ventilator use was similar across all groups, but the risk for mortality in patients with MG was lower compared with the SLE and MS groups. Among patients with MG, age over 75 years and dysphagia were predictors for increased COVID-19 mortality, but the recent MG treatment was not associated with COVID-19 mortality. Conclusions COVID-19 patients with MG are more likely to be admitted to the hospital and require ICU care. Older age and patients with dysphagia had an increased risk of mortality.
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Affiliation(s)
- Youngran Kim
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Xiaojin Li
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Yan Huang
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Minseon Kim
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Aziz Shaibani
- Nerve and Muscle Center of Texas, Houston, TX, United States
| | - Kazim Sheikh
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Guo-Qiang Zhang
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
| | - Thy Phuong Nguyen
- Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, United States
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Elahi R, Karami P, Heidary AH, Esmaeilzadeh A. An updated overview of recent advances, challenges, and clinical considerations of IL-6 signaling blockade in severe coronavirus disease 2019 (COVID-19). Int Immunopharmacol 2022; 105:108536. [PMID: 35074571 PMCID: PMC8747952 DOI: 10.1016/j.intimp.2022.108536] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 01/01/2022] [Accepted: 01/07/2022] [Indexed: 02/07/2023]
Abstract
Since 2019, COVID-19 has become the most important health dilemma around the world. The dysregulated immune response which results in ARDS and cytokine storm has an outstanding role in the progression of pulmonary damage in COVID-19. IL-6, through induction of pro-inflammatory chemokines and cytokines, is the pioneer of the hyperinflammatory condition and cytokine storm in severe COVID-19. Therefore, IL-6 pathway blockade is considered an emerging approach with high efficacy to reduce lung damage in COVID-19. This article aims to review the pleiotropic roles of the IL-6 pathway in lung damage and ARDS in severe COVID-19, and the rationale for IL-6 signaling blockade at different levels, including IL-6 soluble and membrane receptor pathways, IL-6 downstream signaling (such as JAK-STAT) inhibition, and non-specific anti-inflammatory therapeutic approaches. Recent clinical data of each method, with specific concentration on tocilizumab, along with other new drugs, such as sarilumab and siltuximab, have been discussed. Challenges of IL-6 signaling inhibition, such as the risk of superinfection and hepatic injury, and possible solutions have also been explained. Moreover, to achieve the highest efficacy, ongoing clinical trials and special clinical considerations of using different IL-6 inhibitors have been discussed in detail. Special considerations, including the appropriate timing and dosage, monotherapy or combination therapy, and proper side effect managment must be noticed regarding the clinical administration of these drugs. Future studies are still necessary to improve the productivity and unknown aspects of IL-6 signaling blockade for personalized treatment of severe COVID-19.
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Affiliation(s)
- Reza Elahi
- Zanjan University of Medical Sciences, Zanjan, Iran
| | - Parsa Karami
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Abdolreza Esmaeilzadeh
- Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran; Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran.
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