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Ma YN, Ma SR, Yang L, Wu J, Wang YR, Bao LJ, Ma L, Wu QQ, Wang ZH. Diagnostic biomarkers and immune infiltration profiles common to COVID-19, acute myocardial infarction and acute ischaemic stroke using bioinformatics methods and machine learning. BMC Neurol 2025; 25:201. [PMID: 40340571 PMCID: PMC12060493 DOI: 10.1186/s12883-025-04212-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2024] [Accepted: 04/28/2025] [Indexed: 05/10/2025] Open
Abstract
BACKGROUND COVID-19 is a disease that affects people globally. Beyond affecting the respiratory system, COVID-19 patients are at an elevated risk for both venous and arterial thrombosis. This heightened risk contributes to an increased probability of acute complications, including acute myocardial infarction (AMI) and acute ischemic stroke (AIS). Given the unclear relationship between COVID-19, AMI, and AIS, it is crucial to gain a deeper understanding of their associations and potential molecular mechanisms. This study aims to utilize bioinformatics to analyze gene expression data, identify potential therapeutic targets and biomarkers, and explore the role of immune cells in the disease. METHODS This study employed three Gene Expression Omnibus (GEO) datasets for analysis, which included data on COVID-19, AMI and AIS. We performed enrichment analysis on the co-DEGs for these three diseases to clarify gene pathways and functions, and also examined the relationship between co-DEGs and immune infiltration. Machine learning techniques and protein-protein interaction networks (PPI) were used to identify hub genes within the co-DEGs. Finally, we employed a dual validation strategy integrating independent GEO datasets and in vitro experiments with human blood samples to comprehensively assess the reliability of our experimental findings. RESULTS We identified 88 co-DEGs associated with COVID-19, AMI and AIS. Enrichment analysis results indicated that co-DEGs were significantly enriched in immune inflammatory responses related to leukocytes and neutrophils. Immune infiltration analysis revealed significant differences in immune cell populations between the disease group and the normal group. Finally, genes selected through machine learning methods included: CLEC4E, S100A12, and IL1R2. Based on the PPI network, the top ten most influential DEGs were identified as MMP9, TLR2, TLR4, ITGAM, S100A12, FCGR1A, CD163, FCER1G, FPR2, and CLEC4D. The integration of the protein-protein interaction (PPI) network with machine learning techniques facilitated the identification of S100A12 as a potential common biomarker for early diagnosis and a therapeutic target for all three diseases. Ultimately, validation of S100A12 showed that it was consistent with our experimental results, confirming its reliability as a biomarker. Moreover, it demonstrated good diagnostic performance for the three diseases. CONCLUSION We employed bioinformatics methods and machine learning to investigate common diagnostic biomarkers and immune infiltration characteristics of COVID-19, AMI and AIS. Functional and pathway analyses indicated that the co-DEGs were primarily enriched in immune inflammatory responses related to leukocytes and neutrophils. Through two machine learning approaches and the PPI network, and subsequent validation and evaluation, we identified S100A12 as a potential common therapeutic target and biomarker related to immune response that may influence these three diseases.
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Affiliation(s)
- Ya-Nan Ma
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Si-Rong Ma
- School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Li Yang
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Juan Wu
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Ya-Rong Wang
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Li-Jia Bao
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Li Ma
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China
| | - Qing-Qiu Wu
- Department of Geriatrics and Specialty Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
| | - Zhen-Hai Wang
- Institute of Medical Sciences, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
- Diagnosis and Treatment Engineering Technology Research Center of Nervous System Diseases of Ningxia Hui Autonomous Region, Yinchuan, Ningxia, China.
- Neurology Center, Ningxia Medical University General Hospital, Yinchuan, Ningxia, China.
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Zeller SL, Kim MG, Al-Mufti F, Hanft SJ, Kim M, Pisapia JM. Safety of emergency endoscopic endonasal surgery in COVID-positive patients with hemorrhagic complications of pituitary region tumors: A case report and review of the literature. Surg Neurol Int 2024; 15:460. [PMID: 39777193 PMCID: PMC11704428 DOI: 10.25259/sni_663_2024] [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: 08/06/2024] [Accepted: 11/02/2024] [Indexed: 01/11/2025] Open
Abstract
Background Pituitary apoplexy (PA) is a rare, life-threatening clinical syndrome that occurs in response to acute ischemic infarction or hemorrhage of a pituitary adenoma. We report two cases of sudden neurologic and visual decline in patients with pituitary region masses in coronavirus disease (COVID)-positive patients with a focus on potential pathophysiological mechanisms and a safe approach to treatment. Case Description Case one is a 58-year-old male presenting with sudden-onset headache and visual disturbance. He was febrile and tested positive for COVID-19. Magnetic resonance imaging (MRI) revealed a large sellarsuprasellar mass with intratumoral hemorrhagic components. He underwent endoscopic endonasal resection with subsequent improvement in vision and oculomotor function. Pathology was consistent with hemorrhagic pituitary adenoma. Case two is a 15-year-old male presenting with sudden-onset severe headache and acute visual loss. He also tested positive for COVID-19. MRI revealed a sellar-suprasellar mass with a regional mass effect. He underwent endoscopic endonasal resection with improvement in vision over time. Pathology was consistent with craniopharyngioma. There was no evidence of intraoperative COVID-19 transmission among members of the surgical team, who were monitored for 2 weeks after surgery. Conclusion PA in the setting of severe acute respiratory syndrome coronavirus 2 infection should be considered in the differential diagnosis of a COVID-positive patient presenting with acute severe headache, visual loss, and/or ophthalmoplegia; we discuss proposed mechanisms related to inflammation, coagulability, and hypoxia. The absence of intraoperative COVID-19 transmission during transsphenoidal resection performed in an emergency setting suggests that the risk of exposure may be attenuated with safety precautions.
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Affiliation(s)
- Sabrina L Zeller
- Department of Neurosurgery Westchester Medical Center, Valhalla, New York, United States
| | - Michael G. Kim
- Department of Neurosurgery Westchester Medical Center, Valhalla, New York, United States
| | - Fawaz Al-Mufti
- Department of Neurosurgery Westchester Medical Center, Valhalla, New York, United States
| | - Simon J. Hanft
- Department of Neurosurgery Westchester Medical Center, Valhalla, New York, United States
| | - Matthew Kim
- Department of Otolaryngology-Head and Neck Surgery, Westchester Medical Center, Valhalla, New York, United States
| | - Jared M. Pisapia
- Department of Neurosurgery Westchester Medical Center, Valhalla, New York, United States
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Webster TK, Lowe LS, Kim DK, Rohde CH. COVID-19 and postoperative complications after plastic surgery procedures: More than just hypercoagulability. J Plast Reconstr Aesthet Surg 2024; 98:287-297. [PMID: 39321531 DOI: 10.1016/j.bjps.2024.09.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 08/04/2024] [Accepted: 09/01/2024] [Indexed: 09/27/2024]
Abstract
BACKGROUND Although plastic surgery procedures generally demonstrate less than 2% incidence of venous thromboembolism (VTE) outcomes, the post-COVID era data remain elusive. This study sought to elucidate the relationship between COVID-19 infection and the risk of VTE outcomes across plastic surgery procedures. METHODS Plastic surgery procedures were identified in the 2012-2022 National Surgical Quality Improvement Program databases. The outcomes of interest were the postoperative occurrence of VTE, defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), and postoperative complication. Propensity score matching was used to 1) compare overall rates of VTE between the pre-pandemic era and pandemic era cohorts and 2) compare rates of VTE and overall postoperative complications in cases with and without COVID-19 diagnosis in the years 2021-2022 (p < 0.05). RESULTS Overall, 269,006 plastic surgery cases were identified, comprising general breast (76%) and trunk (9.4%) procedures. Non-breast free tissue transfer cases were associated with the highest rates of DVT (1.3%) and trunk procedures with the highest rates of PE (0.7%). After propensity score matching, the overall rate of VTE after the onset of the COVID-19 pandemic was not significantly different from the pre-pandemic era (p = 0.40). In a separately matched cohort, COVID-19 diagnosis did not significantly predict the risk for VTE (p = 0.48) but did significantly predict the risk for overall postoperative complications (p < 0.001). CONCLUSIONS Although COVID-19 diagnosis itself did not predict the risk of VTE in matched analysis, it significantly predicted the overall postoperative complications. Future studies may further investigate the effects of COVID-19 infection over longer periods of follow-up.
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Affiliation(s)
- Theresa K Webster
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Lauren S Lowe
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Dylan K Kim
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Christine H Rohde
- Division of Plastic and Reconstructive Surgery, Department of Surgery, New York-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY 10032, USA.
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Kryńska K, Kuliś K, Mazurek W, Gudowska-Sawczuk M, Zajkowska M, Mroczko B. The Influence of SARS-CoV-2 Infection on the Development of Selected Neurological Diseases. Int J Mol Sci 2024; 25:8715. [PMID: 39201402 PMCID: PMC11354773 DOI: 10.3390/ijms25168715] [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: 07/24/2024] [Revised: 08/07/2024] [Accepted: 08/08/2024] [Indexed: 09/02/2024] Open
Abstract
In 2024, over 775 million cases of COVID-19 were recorded, including approximately 7 million deaths, indicating its widespread and dangerous nature. The disease is caused by the SARS-CoV-2 virus, which can manifest a wide spectrum of symptoms, from mild infection to respiratory failure and even death. Neurological symptoms, such as headaches, confusion, and impaired consciousness, have also been reported in some COVID-19 patients. These observations suggest the potential of SARS-CoV-2 to invade the central nervous system and induce neuroinflammation during infection. This review specifically explores the relationship between SARS-CoV-2 infection and selected neurological diseases such as multiple sclerosis (MS), ischemic stroke (IS), and Alzheimer's disease (AD). It has been observed that the SARS-CoV-2 virus increases the production of cytokines whose action can cause the destruction of the myelin sheaths of nerve cells. Subsequently, the body may synthesize autoantibodies that attack nerve cells, resulting in damage to the brain's anatomical elements, potentially contributing to the onset of multiple sclerosis. Additionally, SARS-CoV-2 exacerbates inflammation, worsening the clinical condition in individuals already suffering from MS. Moreover, the secretion of pro-inflammatory cytokines may lead to an escalation in blood clot formation, which can result in thrombosis, obstructing blood flow to the brain and precipitating an ischemic stroke. AD is characterized by intense inflammation and heightened oxidative stress, both of which are exacerbated during SARS-CoV-2 infection. It has been observed that the SARS-CoV-2 demonstrates enhanced cell entry in the presence of both the ACE2 receptor, which is already elevated in AD and the ApoE ε4 allele. Consequently, the condition worsens and progresses more rapidly, increasing the mortality rate among AD patients. The above information underscores the numerous connections between SARS-CoV-2 infection and neurological diseases.
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Affiliation(s)
- Klaudia Kryńska
- Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland (B.M.)
| | - Katarzyna Kuliś
- Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland (B.M.)
| | - Wiktoria Mazurek
- Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland (B.M.)
| | - Monika Gudowska-Sawczuk
- Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland (B.M.)
| | - Monika Zajkowska
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland;
| | - Barbara Mroczko
- Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland (B.M.)
- Department of Neurodegeneration Diagnostics, Medical University of Bialystok, Waszyngtona 15A St., 15-269 Bialystok, Poland;
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Baig AM, Rosko S, Jaeger B, Gerlach J, Rausch H. Unraveling the enigma of long COVID: novel aspects in pathogenesis, diagnosis, and treatment protocols. Inflammopharmacology 2024; 32:2075-2090. [PMID: 38771409 DOI: 10.1007/s10787-024-01483-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Accepted: 04/17/2024] [Indexed: 05/22/2024]
Abstract
Long COVID, now unmistakably identified as a syndromic entity encompassing a complex spectrum of symptoms, demands immediate resolution of its elusive pathogenic underpinnings. The intricate interplay of diverse factors presents a complex puzzle, difficult to resolve, and thus poses a substantial challenge. As instances of long COVID manifest by repeated infections of SARS-CoV-2 and genetic predisposition, a detailed understanding in this regard is needed. This endeavor is a comprehensive exploration and analysis of the cascading pathogenetic events driven by viral persistence and replication. Beyond its morbidity, long COVID, more disabling than fatal, exacts one of the most substantial tolls on public health in contemporary times, with the potential to cripple national economies. The paper introduces a unified theory of long COVID, detailing a novel pathophysiological framework that interlinks persistent SARS-CoV-2 infection, autoimmunity, and systemic vascular pathology. We posit a model where viral reservoirs, immune dysregulation, and genetic predispositions converge to perpetuate disease. It challenges prevailing hypotheses with new evidence, suggesting innovative diagnostic and therapeutic approaches. The paper aims to shift the paradigm in long COVID research by providing an integrative perspective that encapsulates the multifaceted nature of the condition. We explain the immunological mechanisms, hypercoagulability states, and viral reservoirs in the skull that feed NeuroCOVID in patients with long COVID. Also, this study hints toward a patient approach and how to prioritize treatment sequences in long COVID patients in hospitals and clinics.
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Affiliation(s)
| | - Sandy Rosko
- Clinicum St. George, Rosenheimer Str. 6-8, Bad Aibling, Germany
| | - Beate Jaeger
- Clinicum St. George, Rosenheimer Str. 6-8, Bad Aibling, Germany
| | - Joachim Gerlach
- Clinicum St. George, Rosenheimer Str. 6-8, Bad Aibling, Germany
| | - Hans Rausch
- Clinicum St. George, Rosenheimer Str. 6-8, Bad Aibling, Germany
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Shao HH, Yin RX. Pathogenic mechanisms of cardiovascular damage in COVID-19. Mol Med 2024; 30:92. [PMID: 38898389 PMCID: PMC11186295 DOI: 10.1186/s10020-024-00855-2] [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: 03/09/2024] [Accepted: 06/07/2024] [Indexed: 06/21/2024] Open
Abstract
BACKGROUND COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. PURPOSE This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. METHODS An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. RESULTS The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. CONCLUSIONS Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.
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Affiliation(s)
- Hong-Hua Shao
- Department of Infectious Diseases, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, No. 1 Erli, Changgang Road, Nanning, Guangxi, 530023, People's Republic of China
| | - Rui-Xing Yin
- Department of Infectious Diseases, HIV/AIDS Clinical Treatment Center of Guangxi (Nanning), The Fourth People's Hospital of Nanning, No. 1 Erli, Changgang Road, Nanning, Guangxi, 530023, People's Republic of China.
- Department of Cardiology, Institute of Cardiovascular Diseases, The First Affiliated Hospital, Guangxi Medical University, 6 Shuangyong Road, Nanning, Guangxi, 530021, People's Republic of China.
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Pandey S, Bapat V, Abraham JN, Abraham NM. Long COVID: From olfactory dysfunctions to viral Parkinsonism. World J Otorhinolaryngol Head Neck Surg 2024; 10:137-147. [PMID: 38855289 PMCID: PMC11156689 DOI: 10.1002/wjo2.175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 02/20/2024] [Accepted: 03/08/2024] [Indexed: 06/11/2024] Open
Abstract
Neurological and psychiatric complications continue to be a public health concern in long coronavirus disease 2019 (COVID-19). This varies from olfactory dysfunctions such as parosmia to cognitive and emotional challenges. Historically, the surge of neurological disorders followed the viral pandemics, for example, the emergence of Encephalitis Lethargica after the outbreak of Spanish Influenza. During and after COVID-19 infection, the problems associated with the sense of smell and the reports of affected olfactory and limbic brain areas are leading to a growing concern about the similarity with the symptoms and the pattern of degeneration observed at the onset of Parkinson's disease and Alzheimer's disease. These reports reveal the essentiality of long-term studies of olfactory and cognitive functions in the post-COVID era and the experiments using animal models to dissect the neural basis of these complications. In this manuscript, we summarize the research reporting the potential correlation between neurological disorders and viral pandemic outbreaks with a historical perspective. Further, we discuss the studies providing evidence of neurodegeneration due to severe acute respiratory syndrome coronavirus 2 infection by focusing on viral Parkinsonism.
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Affiliation(s)
- Sanyukta Pandey
- Department of Biology, Laboratory of Neural Circuits and Behaviour (LNCB)Indian Institute of Science Education and Research (IISER)PuneMaharashtraIndia
| | - Vibha Bapat
- Department of Biology, Laboratory of Neural Circuits and Behaviour (LNCB)Indian Institute of Science Education and Research (IISER)PuneMaharashtraIndia
| | - Jancy Nixon Abraham
- Department of Biology, Laboratory of Neural Circuits and Behaviour (LNCB)Indian Institute of Science Education and Research (IISER)PuneMaharashtraIndia
- Department of Life Sciences, Centre of Excellence in EpigeneticsShiv Nadar Institution of EminenceGautam Buddha NagarUttar PradeshIndia
| | - Nixon M. Abraham
- Department of Biology, Laboratory of Neural Circuits and Behaviour (LNCB)Indian Institute of Science Education and Research (IISER)PuneMaharashtraIndia
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Lee KE, Lee J, Lee SM, Lee HY. Risk factors for progressing to critical illness in patients with hospital-acquired COVID-19. Korean J Intern Med 2024; 39:477-487. [PMID: 38632896 PMCID: PMC11076898 DOI: 10.3904/kjim.2023.347] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 11/19/2023] [Accepted: 12/01/2023] [Indexed: 04/19/2024] Open
Abstract
BACKGROUND/AIMS Risk factors for progression to critical illness in hospital-acquired coronavirus disease 2019 (COVID-19) remain unknown. Here, we assessed the incidence and risk factors for progression to critical illness and determined their effects on clinical outcomes in patients with hospital-acquired COVID-19. METHODS This retrospective cohort study analyzed patients admitted to the tertiary hospital between January 2020 and June 2022 with confirmed hospital-acquired COVID-19. The primary outcome was the progression to critical illness of hospital- acquired COVID-19. Patients were stratified into high-, intermediate-, or low-risk groups by the number of risk factors for progression to critical illness. RESULTS In total, 204 patients were included and 37 (18.1%) progressed to critical illness. In the multivariable logistic analysis, patients with preexisting respiratory disease (OR, 3.90; 95% CI, 1.04-15.18), preexisting cardiovascular disease (OR, 3.49; 95% CI, 1.11-11.27), immunocompromised status (OR, 3.18; 95% CI, 1.11-9.16), higher sequential organ failure assessment (SOFA) score (OR, 1.56; 95% CI, 1.28-1.96), and higher clinical frailty scale (OR, 2.49; 95% CI, 1.62-4.13) showed significantly increased risk of progression to critical illness. As the risk of the groups increased, patients were significantly more likely to progress to critical illness and had higher 28-day mortality. CONCLUSION Among patients with hospital-acquired COVID-19, preexisting respiratory disease, preexisting cardiovascular disease, immunocompromised status, and higher clinical frailty scale and SOFA scores at baseline were risk factors for progression to critical illness. Patients with these risk factors must be prioritized and appropriately isolated or treated in a timely manner, especially in pandemic settings.
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Affiliation(s)
- Kyung-Eui Lee
- Department of Critical Care Medicine, Seoul National University Hospital, Seoul,
Korea
| | - Jinwoo Lee
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul,
Korea
| | - Sang-Min Lee
- Department of Critical Care Medicine, Seoul National University Hospital, Seoul,
Korea
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul,
Korea
| | - Hong Yeul Lee
- Department of Critical Care Medicine, Seoul National University Hospital, Seoul,
Korea
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Rasyid A, Harris S, Kurniawan M, Mesiano T, Hidayat R, Wiyarta E. Predictive value of admission D-dimer levels in patient with acute ischaemic stroke and COVID-19: a second-wave prospective cohort study. BMJ Open 2024; 14:e077500. [PMID: 38580372 PMCID: PMC11002405 DOI: 10.1136/bmjopen-2023-077500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 03/21/2024] [Indexed: 04/07/2024] Open
Abstract
OBJECTIVES This study aimed to evaluate the predictive value of admission D-dimer levels for in-hospital mortality in patients with COVID-19 and acute ischaemic stroke. DESIGN Cohort (prospective). SETTING Tertiary referral hospital in the capital city of Indonesia conducted from June to December 2021. PARTICIPANTS 60 patients with acute ischaemic stroke and COVID-19 were included. Patients were classified into D-dimer groups (low and high) according to a 2 110 ng/mL cut-off value, determined via receiver operating characteristic analysis. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was in-hospital mortality, with admission D-dimer levels as the major predictor. Secondary outcomes included associations between other demographic and clinical variables and the admission D-dimer value. Kaplan-Meier method was used to carry out survival analysis, with univariable and multivariable Cox regression performed to assess the association of D-dimer levels and other confounding variables (including demographic, clinical and laboratory parameters) with in-hospital mortality. RESULTS The findings demonstrated an association between elevated admission D-dimer levels (≥2 110 ng/mL) and an increased likelihood of death during hospitalisation. The adjusted HR was 14.054 (95% CI 1.710 to 115.519; p=0.014), demonstrating an increase in mortality risk after accounting for confounders such as age and diabetes history. Other significant predictors of mortality included a history of diabetes and increased white blood cell count. CONCLUSIONS Admission D-dimer levels may be a useful predictive indicator for the likelihood of death during hospitalisation in individuals with COVID-19 and acute ischaemic stroke.
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Affiliation(s)
- Al Rasyid
- Department of Neurology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Salim Harris
- Department of Neurology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Mohammad Kurniawan
- Department of Neurology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Taufik Mesiano
- Department of Neurology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Rakhmad Hidayat
- Department of Neurology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
| | - Elvan Wiyarta
- Department of Neurology, Faculty of Medicine, Universitas Indonesia-Dr Cipto Mangunkusumo National Hospital, Jakarta, Indonesia
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Assylbek MI, Kocyigit BF, Yessirkepov M, Zimba O. Post-stroke rehabilitation in the peri-pandemic COVID-19 era. Rheumatol Int 2024; 44:399-411. [PMID: 38253904 DOI: 10.1007/s00296-023-05520-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Accepted: 12/12/2023] [Indexed: 01/24/2024]
Abstract
The coronavirus disease 2019 (COVID-19), which arose in late 2019, caused extensive destruction, impacting a substantial proportion of the worldwide population and leading to millions of deaths. Although COVID-19 is mainly linked to respiratory and pulmonary complications, it has the potential to affect neurologic structures as well. Neurological involvement may manifest as minimal and reversible; however, a notable proportion of cases have exhibited pronounced neurological consequences, such as strokes. Endothelial inflammation, hypercoagulation, renin-angiotensin-aldosterone system alterations, and cardiogenic embolism are the pathophysiological mechanisms of stroke under COVID-19 circumstances. Physical activity and exercise have improved several aspects of post-stroke recovery, including cardiovascular health, walking capacity, and upper limb strength. They are commonly used to assist stroke survivors in overcoming their motor restrictions. Furthermore, stroke rehabilitation can incorporate a range of specific techniques, including body-weight-supported treadmill applications, constraint-induced movement therapy, robotic rehabilitation interventions, transcranial direct current stimulation, transcranial magnetic stimulation, and prism adaptation training. Under pandemic conditions, there were several barriers to neurological rehabilitation. The most significant of these were individual's fear of infection, which caused them to postpone their rehabilitation applications and rehabilitation areas being converted into COVID-19 units. The primary emphasis had turned to COVID-19 treatment. Several valuable data and views were gained in reorganizing rehabilitation during the pandemic, contributing to establishing future views in this regard.
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Affiliation(s)
- Meirgul I Assylbek
- Department of Neurology, Psychiatry, Neurosurgery and Rehabilitation, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
- Department of Social Health Insurance and Public Health, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
- Medical Center ''Mediker'', Shymkent, Kazakhstan
| | - Burhan Fatih Kocyigit
- Department of Physical Medicine and Rehabilitation, Adana Health Practice and Research Center, University of Health Sciences, Adana, Turkey.
| | - Marlen Yessirkepov
- Department of Biology and Biochemistry, South Kazakhstan Medical Academy, Shymkent, Kazakhstan
| | - Olena Zimba
- Department of Clinical Rheumatology and Immunology, University Hospital in Krakow, Krakow, Poland
- National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland
- Department of Internal Medicine N2, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
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11
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Oleson CV, Olsen AC, Shermon S. Spinal cord infarction attributed to SARS-CoV-2, with post-acute sequelae of COVID-19: A case report. World J Clin Cases 2023; 11:8542-8550. [PMID: 38188200 PMCID: PMC10768511 DOI: 10.12998/wjcc.v11.i36.8542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Revised: 11/29/2023] [Accepted: 12/12/2023] [Indexed: 12/22/2023] Open
Abstract
BACKGROUND While stroke and lower extremity venous thromboemboli have been commonly reported following acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spinal cord infarction or ischemia has been extremely rare. Findings of long coronavirus disease (COVID) in this select population have not been studied. CASE SUMMARY We present the case of a 70-year-old female with sudden onset of trunk and lower extremity sensorimotor loss due to spinal cord infarction, attributed to acute infection with SARS-CoV-2. Diagnostic work up confirmed a T3 complete (ASIA impairment Scale A) paraplegia resulting from a thrombotic infarct. Her reported myalgias, neuropathic pain, spasticity, bladder spasms, and urinary tract infections exceeded the frequency and severity of many spinal cord injury (SCI) individuals of similar age and degree of neurologic impairment. In her first year after contracting COVID-19, she underwent 2 separate inpatient rehabilitation courses, but also required acute hospitalization 6 additional times for subsequent infections or uncontrolled pain. Yet other complications of complete non-traumatic SCI (NTSCI), including neurogenic bowel and temperature hypersensitivity, were mild, and pressure injuries were absent. She has now transitioned from the acute to chronic phase of spinal cord injury care, with subsequent development of post-acute sequelae of SARS-CoV-2 infection (PASC). CONCLUSION This individual experienced significant challenges with the combined effects of acute T3 NTSCI and acute COVID-19, with subsequent progression to PASC.
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Affiliation(s)
- Christina V Oleson
- Department of Physical Medicine and Rehabilitation, Case Western Reserve University, MetroHealth Rehabilitation Institute, Cleveland, OH 44109, United States
| | - Andrew C Olsen
- Department of Physical Medicine and Rehabilitation, Case Western Reserve University, MetroHealth Rehabilitation Institute, Cleveland, OH 44109, United States
| | - Suzanna Shermon
- Department of Physical Medicine and Rehabilitation, Case Western Reserve University, MetroHealth Rehabilitation Institute, Cleveland, OH 44109, United States
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12
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Yang Y, Song Y, Hou D. Obesity and COVID-19 Pandemics: Epidemiology, Mechanisms, and Management. Diabetes Metab Syndr Obes 2023; 16:4147-4156. [PMID: 38145256 PMCID: PMC10749174 DOI: 10.2147/dmso.s441762] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 12/08/2023] [Indexed: 12/26/2023] Open
Abstract
Obesity is a principle causative factor of various metabolic dysfunctions, chronic inflammation, and multi-organ impairment. The global epidemic of obesity has constituted the greatest threat to global health. Emerging evidence has associated obesity with an increased risk of severe infection and poor outcomes from coronavirus disease 2019 (COVID-19). During current COVID-19 pandemic, the interaction between COVID-19 and obesity has exaggerated the disease burden of obesity more than ever before. Thus, there is an urgent need for consideration of universal measures to reduce the risk of complications and severe illness from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in obesity population. In this review, we first summarized the clinical evidence on the effect of obesity on susceptibility, severity, and prognosis of COVID-19. Then we discussed and the underlying mechanisms, including respiratory pathophysiology of obesity, dysregulated inflammation, upregulated angiotensin-converting enzyme 2 (ACE2) expression, hyperglycemia, and adipokines. Finally, we proposed recommendations on how to reduce the spread and pandemic of SARS-CoV-2 infection by prevention and treatment of obesity.
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Affiliation(s)
- Yanping Yang
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China
| | - Yuanlin Song
- Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China
- Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
- Shanghai Respiratory Research Institute, Shanghai, People’s Republic of China
| | - Dongni Hou
- Shanghai Key Laboratory of Lung Inflammation and Injury, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China
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13
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Li J, Li X, Ye P, You Y, Wang Y, Zhang J, Zhao W, Yu Z, Yao R, Tang J. A retrospective observational study on maternal and neonatal outcomes of COVID-19: Does the mild SARS-CoV-2 infection affect the outcome? PeerJ 2023; 11:e16651. [PMID: 38107588 PMCID: PMC10725666 DOI: 10.7717/peerj.16651] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 11/20/2023] [Indexed: 12/19/2023] Open
Abstract
Background Currently, several SARS-CoV-2 variants, including Omicron, are still circulating globally. This underscores the necessity for a comprehensive understanding of their impact on obstetric and neonatal outcomes in pregnant women, even in cases of mild infection. Methods We conducted a retrospective, single-center observational study to investigate the association between gestational SARS-CoV-2 infection and maternal-fetal outcomes in the Chinese population. The study enrolled 311 pregnant patients with SARS-CoV-2 infection (exposure group) and 205 uninfected pregnant patients (control group). We scrutinized the hospital records to collect data on demographics, clinical characteristics, and maternal and neonatal outcomes for subsequently comparison. Results Similar characteristics were observed in both groups, including maternal age, height, BMI, gravidity, parity, and comorbidities (p > 0.05). A majority (97.4%) of pregnant women in the exposure group with COVID-19 experienced mild clinical symptoms, with fever (86.5%) and cough (74.3%) as the primary symptoms. The exposure group exhibited significantly higher incidences of cesarean section and fetal distress compared to the control group (p < 0.05). Furthermore, pregnant women in the exposure group showed reduced levels of hemoglobin and high-sensitivity C-reactive protein, while experiencing significantly increased levels of lymphocytes, prothrombin time, alanine aminotransferase, and aspartate aminotransferase (p < 0.05). Notably, recent SARS-CoV-2 infection prior to delivery appeared to have an adverse impact on liver function, blood and coagulation levels in pregnant women. When comparing the two groups, there were no significant differences in the postpartum hemorrhage rate, premature birth rate, birth weight, neonatal asphyxia rate, neonatal department transfer rate, and neonatal pneumonia incidence. Conclusions Our study suggests that mild COVID-19 infection during pregnancy does not have detrimental effects on maternal and neonatal outcomes. However, the increased risks of events such as fetal distress and cesarean section, coupled with potential alterations in physical function, reveal the consequences of SARS-CoV-2 infection during pregnancy, even in mild cases. These findings emphasize the importance of proactive management and monitoring of pregnant individuals with COVID-19.
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Affiliation(s)
- Jing Li
- Department of Gynecology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
- Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, Guangdong, China
| | - Xiang Li
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Peiying Ye
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Yun You
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Yu Wang
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Jing Zhang
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Weihua Zhao
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Zhiying Yu
- Department of Gynecology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Runsi Yao
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
| | - Jie Tang
- Department of Obstetrics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China
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14
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Zhang K, Loong SSE, Yuen LZH, Venketasubramanian N, Chin HL, Lai PS, Tan BYQ. Genetics in Ischemic Stroke: Current Perspectives and Future Directions. J Cardiovasc Dev Dis 2023; 10:495. [PMID: 38132662 PMCID: PMC10743455 DOI: 10.3390/jcdd10120495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Revised: 12/01/2023] [Accepted: 12/11/2023] [Indexed: 12/23/2023] Open
Abstract
Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein.
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Affiliation(s)
- Ka Zhang
- Division of Neurology, Department of Medicine, National University Hospital, Singapore 119074, Singapore;
| | - Shaun S. E. Loong
- Cardiovascular-Metabolic Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore;
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | - Linus Z. H. Yuen
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
| | | | - Hui-Lin Chin
- Khoo Teck Puat National University Children’s Medical Institute, National University Hospital, Singapore 119074, Singapore;
| | - Poh San Lai
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore;
| | - Benjamin Y. Q. Tan
- Division of Neurology, Department of Medicine, National University Hospital, Singapore 119074, Singapore;
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
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15
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Zhu J, Li X, Lv F, Zhou W. Bioinformatics Approach to Identify the Influences of COVID-19 on Ischemic Stroke. Biochem Genet 2023; 61:2222-2241. [PMID: 37184686 PMCID: PMC10184096 DOI: 10.1007/s10528-023-10366-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 03/09/2023] [Indexed: 05/16/2023]
Abstract
As severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is becoming more infectious and less virulent, symptoms beyond the lungs of the Coronavirus Disease 2019 (COVID-19) patients are a growing concern. Studies have found that the severity of COVID-19 patients is associated with an increased risk of ischemic stroke (IS); however, the underlying pathogenic mechanisms remain unknown. In this study, bioinformatics approaches were utilized to explore potential pathogenic mechanisms and predict potential drugs that may be useful in the treatment of COVID-19 and IS. The GSE152418 and GSE122709 datasets were downloaded from the GEO website to obtain the common differentially expressed genes (DEGs) of the two datasets for further functional enrichment, pathway analysis, and drug candidate prediction. A total of 80 common DEGs were identified in COVID-19 and IS datasets for GO and KEGG analysis. Next, the protein-protein interaction (PPI) network was constructed and hub genes were identified. Further, transcription factor-gene interactions and DEGs-miRNAs coregulatory network were investigated to explore their regulatory roles in disease. Finally, protein-drug interactions with common DEGs were analyzed to predict potential drugs. We successfully identified the top 10 hub genes that could serve as novel targeted therapies for COVID-19 and screened out some potential drugs for the treatment of COVID-19 and IS.
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Affiliation(s)
- Jiabao Zhu
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China
| | - Xiangui Li
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China
| | - Fanzhen Lv
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China
| | - Weimin Zhou
- Department of Vascular Surgery, The Second Affliated Hospital of Nanchang University, Minde Road 1, Nanchang City, Jiangxi Province, China.
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16
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Pinosanu EA, Burada E, Pirscoveanu D, Aldea M, Albu CV, Surugiu R, Sandu RE. Predictive Value of Pulmonary Involvement in Stroke Patients Co-Infected with COVID-19. CURRENT HEALTH SCIENCES JOURNAL 2023; 49:536-545. [PMID: 38559828 PMCID: PMC10976201 DOI: 10.12865/chsj.49.04.9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Accepted: 12/12/2023] [Indexed: 04/04/2024]
Abstract
In response to the intricate clinical challenges posed by the intersection of COVID-19 and acute ischemic stroke, the Neuropsychiatry Hospital of Craiova, Romania, initiated a comprehensive study. This research aims to unravel the impacts of pulmonary complications on ischemic stroke outcomes, comparing patients with concurrent SARS-CoV-2 infection to those without. The study integrates pulmonary assessments, acknowledging the significant role respiratory involvement plays in the progression and prognosis of stroke patients during the pandemic. By systematically examining individuals with both acute ischemic stroke and COVID-19, the study seeks to shed light on the complex interplay between cerebral and pulmonary health. The findings are expected to enhance patient care by informing clinical decisions and leading to more effective management approaches for stroke patients in the COVID-19 era.
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Affiliation(s)
- Elena Anca Pinosanu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, Romania
| | - Emilia Burada
- Department of Physiology, University of Medicine and Pharmacy of Craiova, Romania
| | - Denisa Pirscoveanu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, Romania
| | - Madalina Aldea
- Department of Psychiatry, University of Medicine and Pharmacy of Craiova, Romania
| | - Carmen Valeria Albu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, Romania
| | - Roxana Surugiu
- Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Romania
| | - Raluca Elena Sandu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, Romania
- Department of Biochemistry, University of Medicine and Pharmacy of Craiova, Romania
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17
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Arshad F, Singh V, Prasad C, Yadav R, Alladi S. Alexia without agraphia in an elderly man due to stroke secondary to COVID-19 infection. Acta Neurol Belg 2023; 123:1979-1981. [PMID: 35750954 PMCID: PMC9243941 DOI: 10.1007/s13760-022-02014-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Accepted: 06/16/2022] [Indexed: 11/01/2022]
Affiliation(s)
- Faheem Arshad
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 5600029, Karnataka, India.
| | - Vikram Singh
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 5600029, Karnataka, India
| | - Chandrajit Prasad
- Department of Neuroimaging and Interventional Radiology, NIMHANS, Bangalore, 560029, India
| | - Ravi Yadav
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 5600029, Karnataka, India
| | - Suvarna Alladi
- Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Hosur Road, Bangalore, 5600029, Karnataka, India
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18
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Behnke-Borowczyk J, Korzeniewicz R, Łukowski A, Baranowska M, Jagiełło R, Bułaj B, Hauke-Kowalska M, Szmyt J, Behnke JM, Robakowski P, Kowalkowski W. Variability of Functional Groups of Rhizosphere Fungi of Norway Spruce ( Picea abies (L.) H.Karst.) in the Boreal Range: The Wigry National Park, Poland. Int J Mol Sci 2023; 24:12628. [PMID: 37628809 PMCID: PMC10454689 DOI: 10.3390/ijms241612628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/28/2023] [Accepted: 08/04/2023] [Indexed: 08/27/2023] Open
Abstract
Rhizosphere microbial communities can influence plant growth and development. Natural regeneration processes take place in the tree stands of protected areas, which makes it possible to observe the natural changes taking place in the rhizosphere along with the development of the plants. This study aimed to determine the diversity (taxonomic and functional) of the rhizosphere fungal communities of Norway spruce growing in one of four developmental stages. Our research was based on the ITS region using Illumina system sequencing. Saprotrophs dominated in the studied rhizospheres, but their percentage share decreased with the age of the development group (for 51.91 from 43.13%). However, in the case of mycorrhizal fungi, an opposite trend was observed (16.96-26.75%). The most numerous genera were: saprotrophic Aspergillus (2.54-3.83%), Penicillium (6.47-12.86%), Pyrenochaeta (1.39-11.78%), pathogenic Curvularia (0.53-4.39%), and mycorrhizal Cortinarius (1.80-5.46%), Pseudotomentella (2.94-5.64%) and Tomentella (4.54-15.94%). The species composition of rhizosphere fungal communities was favorable for the regeneration of natural spruce and the development of multi-generational Norway spruce stands. The ratio of the abundance of saprotrophic and mycorrhizal fungi to the abundance of pathogens was high and promising for the durability of the large proportion of spruce in the Wigry National Park and for forest ecosystems in general.
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Affiliation(s)
- Jolanta Behnke-Borowczyk
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Robert Korzeniewicz
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Adrian Łukowski
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Marlena Baranowska
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Radosław Jagiełło
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Bartosz Bułaj
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Maria Hauke-Kowalska
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Janusz Szmyt
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Jerzy M. Behnke
- School of Life Sciences, University Park Nottingham, Nottingham NG7 2RD, UK;
| | - Piotr Robakowski
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
| | - Wojciech Kowalkowski
- Faculty of Forestry and Wood Technology, Poznan University of Life Sciences, Wojska Polskiego 71C, 60-625 Poznań, Poland; (R.K.); (A.Ł.); (M.B.); (R.J.); (B.B.); (M.H.-K.); (J.S.); (P.R.); (W.K.)
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19
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Forero K, Buqaileh R, Sunderman C, AbouAlaiwi W. COVID-19 and Neurological Manifestations. Brain Sci 2023; 13:1137. [PMID: 37626493 PMCID: PMC10452375 DOI: 10.3390/brainsci13081137] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2023] [Revised: 07/21/2023] [Accepted: 07/28/2023] [Indexed: 08/27/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a newly emerged coronavirus, has sparked a global pandemic with its airborne transmission and ability to infect with asymptomatic patients. The pathophysiology is thought to relate to the binding of angiotensin converting enzyme 2 (ACE2) receptors in the body. These receptors are widely expressed in various body organs such as the lungs, the heart, the gastrointestinal tract (GIT), and the brain. This article reviews the current knowledge on the symptoms of coronavirus disease 2019 (COVID-19), highlighting the neurological symptoms that are associated with COVID-19, and discussing the possible mechanisms for SARS-CoV-2 virus infection in the body.
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Affiliation(s)
| | | | | | - Wissam AbouAlaiwi
- Department of Pharmacology and Experimental Therapeutics, University of Toledo, Toledo, OH 43614, USA; (K.F.); (R.B.); (C.S.)
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20
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Advani S, Hosseini SMM, Bozorgmehr R, Khameneh-Bagheri A, Mohammadzadeh S, Hasanzadeh T, Jalilian L, Vahidi M, Nofeli AH, Hooshyari Z. Abnormalities of brain imaging in COVID-19 patients with neurological symptoms. CURRENT JOURNAL OF NEUROLOGY 2023; 22:162-169. [PMID: 38011453 PMCID: PMC10626144 DOI: 10.18502/cjn.v22i3.13796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Accepted: 05/09/2023] [Indexed: 11/29/2023]
Abstract
Background: Coronavirus disease 2019 (COVID-19) is a multisystem disease, manifested by several symptoms of various degrees. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) can affect the central nervous system (CNS) through several mechanisms and brain imaging plays an essential role in the diagnosis and evaluation of the neurological involvement of COVID-19. Moreover, brain imaging of patients with COVID-19 would result in a better understanding of SARS-CoV-2 neuro-pathophysiology. In this study, we evaluated the brain imaging findings of patients with COVID-19 in Shohada-e Tajrish Hospital, Tehran, Iran. Methods: This was a single-center, retrospective, and observational study. The hospital records and chest and brain computed tomography (CT) scans of patients with confirmed COVID-19 were reviewed. Results: 161 patients were included in this study (39.1% women, mean age: 60.84). Thirteen patients (8%) had ischemic strokes identified by brain CT. Subdural hematoma, subdural effusion, and subarachnoid hemorrhage were confirmed in three patients. Furthermore, there were four cases of intracranial hemorrhage (ICH) and intraventricular hemorrhage (IVH). Patients with and without abnormal brain CTs had similar average ages. The rate of brain CT abnormalities in both genders did not differ significantly. Moreover, abnormal brain CT was not associated with increased death rate. There was no significant difference in lung involvement (according to lung CT scan) between the two groups. Conclusion: Our experience revealed a wide range of imaging findings in patients with COVID-19 and these findings were not associated with a more severe lung involvement or increased rate of mortality.
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Affiliation(s)
- Soroor Advani
- Men’s Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyyed Mohammad Mahdi Hosseini
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Rama Bozorgmehr
- Clinical Research Development Unit, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arash Khameneh-Bagheri
- Department of Radiology, Shohada-e Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sevda Mohammadzadeh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Taha Hasanzadeh
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Laya Jalilian
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Vahidi
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Hasan Nofeli
- School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Hooshyari
- Psychiatry and Psychology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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21
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Libruder C, Hershkovitz Y, Ben-Yaish S, Tanne D, Keinan-Boker L, Binyaminy B. An Increased Risk for Ischemic Stroke in the Short-Term Period following COVID-19 Infection: A Nationwide Population-Based Study. Neuroepidemiology 2023; 57:253-259. [PMID: 37399799 PMCID: PMC11251667 DOI: 10.1159/000531163] [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: 03/23/2023] [Accepted: 05/09/2023] [Indexed: 07/05/2023] Open
Abstract
INTRODUCTION The association disclosed between coronavirus disease 2019 (COVID-19) infection and ischemic stroke (IS) raises concern. The exact risk periods, which were not consistent between studies, require further investigation. METHODS We linked two national databases: the COVID-19 database and the Israeli National Stroke Registry. The self-controlled case series method was used to estimate the association between COVID-19 infection and a first IS. The study population included all Israeli residents who had both a first IS event and a first COVID-19 diagnosis during 2020. The date of the PCR test served to define the day of exposure, and the 28 days following it were categorized into three risk periods: days 1-7, 8-14, and 15-28. A relative incidence (RI) with a 95% confidence interval (95% CI) was calculated based on the incidence rate of events in a post-exposure period, compared to the incidence rate in a control period. RESULTS From January 1, 2020, to December 31, 2020, 308,015 Israelis aged 18+ were diagnosed with COVID-19 and 9,535 were diagnosed with a first IS. Linking the two databases, 555 persons had both diagnoses during 2020. The mean age of the study population was 71.5 ± 13.7, 55.1% were males, 77.8% had hypertension, 73.7% had hyperlipidemia, 51.9% had diabetes, and 28.5% had ischemic heart disease. Comparing the risk period and the control period, we found a very similar distribution of the cardiovascular risk factors. The risk for an acute IS was 3.3-fold higher in the first week following COVID-19 diagnosis, compared with a control period (RI = 3.3; 95% CI: 2.3-4.6). The RI among males (RI = 4.5; 95% CI: 2.9-6.8) was 2.2-fold higher compared to females. The increased risk did not last beyond the first week following exposure. CONCLUSION Physicians should be aware of the elevated risk for IS among patients experiencing COVID-19, particularly among men with high burden of cardiovascular risk factors.
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Affiliation(s)
- Carmit Libruder
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
| | - Yael Hershkovitz
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
| | - Shir Ben-Yaish
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
| | - David Tanne
- Rambam Health Care Campus, Haifa, Israel
- Rappaport Faculty of Medicine, Technion Israel Institute of Technology, Haifa, Israel
| | - Lital Keinan-Boker
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
- School of Public Health, University of Haifa, Haifa, Israel
| | - Binyamin Binyaminy
- Israel Center for Disease Control, Israel Ministry of Health, Ramat Gan, Israel
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22
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Kim Y, Parekh MA, Li X, Huang Y, Zhang GQ, Manwani B. Age and sex-specific stroke epidemiology in COVID-19. FRONTIERS IN STROKE 2023; 2:1172854. [PMID: 39606612 PMCID: PMC11600532 DOI: 10.3389/fstro.2023.1172854] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/29/2024]
Abstract
Background COVID-19 has emerged as an independent risk factor for stroke. We aimed to determine age and sex-specific stroke incidence and risk factors with COVID-19 in the US using a large electronic health record (EHR) that included both inpatients and outpatients. Methods A retrospective cohort study was conducted using individual-level data from Optum® de-identified COVID-19 EHR. A total of 387,330 individuals aged ≥18 with laboratory-confirmed COVID-19 between March 1, 2020 and December 31, 2020 were included. The primary outcome was cumulative incidence of stroke after COVID-19 confirmation within 180 days of follow-up or until death. Kaplan-Meier cumulative incidence curves for acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and a composite outcome of all strokes were stratified by sex and age, and the differences in curves were assessed using a log-rank test. The relative risk of stroke by demographics and risk factors was estimated using multivariable Cox-proportional hazards regressions and adjusted hazard ratios (aHRs). Results Of 387,330 COVID-19 patients, 2,752 patients (0.71%, 95% CI 0.68-0.74) developed stroke during the 180-day follow-up, AIS in 0.65% (95% CI 0.62-0.67), and ICH in 0.11% (95% CI 0.10-0.12). Of strokes among COVID-19 patients, 57% occurred within 3 days. Advanced age was associated with a substantially higher stroke risk, with aHR 6.92 (5.72-8.38) for ages 65-74, 9.42 (7.74-11.47) for ages 75-84, and 11.35 (9.20-14.00) for ages 85 and older compared to ages 18-44 years. Men had a 32% higher risk of stroke compared to women. African-American [aHR 1.78 (1.61-1.97)] and Hispanic patients [aHR 1.48 (1.30-1.69)] with COVID-19 had an increased risk of stroke compared to white patients. Conclusion This study has several important findings. AIS and ICH risk in patients with COVID-19 is highest in the first 3 days of COVID-19 positivity; this risk decreases with time. The incidence of stroke in patients with COVID-19 (both inpatient and outpatient) is 0.65% for AIS and 0.11% for ICH during the 180-day follow-up. Traditional stroke risk factors increase the risk of stroke in patients with COVID-19. Male sex is an independent risk factor for stroke in COVID-19 patients across all age groups. African-American and Hispanic patients have a higher risk of stroke from COVID-19.
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Affiliation(s)
- Youngran Kim
- Department of Management, Policy and Community Health,
School of Public Health, University of Texas Health Science at Houston, Houston, TX,
United States
| | - Maria A. Parekh
- Department of Neurology, University of Texas Health Science
at Houston, Houston, TX, United States
| | - Xiaojin Li
- Department of Neurology, University of Texas Health Science
at Houston, Houston, TX, United States
| | - Yan Huang
- Department of Neurology, University of Texas Health Science
at Houston, Houston, TX, United States
| | - Guo-Qiang Zhang
- Department of Neurology, University of Texas Health Science
at Houston, Houston, TX, United States
| | - Bharti Manwani
- Department of Neurology, University of Texas Health Science
at Houston, Houston, TX, United States
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23
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Pattanaik A, Bhandarkar B S, Lodha L, Marate S. SARS-CoV-2 and the nervous system: current perspectives. Arch Virol 2023; 168:171. [PMID: 37261613 PMCID: PMC10232347 DOI: 10.1007/s00705-023-05801-x] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 04/15/2023] [Indexed: 06/02/2023]
Abstract
SARS-CoV-2 infection frequently causes neurological impairment in both adults and children. Recent publications have described significant aspects of the viral pathophysiology associated with neurological dysfunction. In theory, neurological manifestations following SARS-CoV-2 infection may be caused directly by the effects of the virus infecting the brain or indirectly by the local and systemic immune responses against the virus. Neurological manifestations can occur during the acute phase as well as in the post-acute phase of the infection. In this review, we discuss recent literature describing the association of nervous system disorders with COVID-19.
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Affiliation(s)
- Amrita Pattanaik
- Manipal Institute of Virology, Manipal Academy of Higher Education (MAHE), PIN-576104, Manipal, Karnataka, India.
| | - Sushma Bhandarkar B
- Manipal Institute of Virology, Manipal Academy of Higher Education (MAHE), PIN-576104, Manipal, Karnataka, India
| | - Lonika Lodha
- Department of Neurovirology, National Institute of Mental Health and Neurosciences (NIMHANS), PIN-560029, Bengaluru, Karnataka, India
| | - Srilatha Marate
- Manipal Institute of Virology, Manipal Academy of Higher Education (MAHE), PIN-576104, Manipal, Karnataka, India
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24
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Carney PR, Stevenson DW, Riggs E, Dervisevic M, Carney CX, Gomez CR. Thrombectomy of an Acute Ischemic Stroke in a Child with COVID-19 and MIS-C: Case Analysis and Literature Context. CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10050851. [PMID: 37238399 DOI: 10.3390/children10050851] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 03/27/2023] [Accepted: 04/27/2023] [Indexed: 05/28/2023]
Abstract
We describe a very young child who developed an acute ischemic stroke from a LAO, while affected by COVID-19 and MIS-C, and whom we treated successfully with thrombectomy. We compare his clinical and imaging findings with those of the existing case reports, and we explore the multifactorial nature of such a neurovascular complication, particularly in the context of the most recent publications regarding the multifactorial endothelial derangements produced by the illness.
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Affiliation(s)
- Paul R Carney
- Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA
- Department of Neurology, University of Missouri School of Medicine, Colombia, MO 65212, USA
| | - Dakota W Stevenson
- Department of Neurology, University of Missouri School of Medicine, Colombia, MO 65212, USA
| | - Edith Riggs
- Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA
| | - Matilda Dervisevic
- Department of Child Health, University of Missouri School of Medicine, Columbia, MO 65201, USA
| | - Constanza X Carney
- Department of Epidemiology, George Washington University, Washington, DC 20052, USA
| | - Camilo R Gomez
- Department of Neurology, University of Missouri School of Medicine, Colombia, MO 65212, USA
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25
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Wu H, Han F. Investigation of shared genes and regulatory mechanisms associated with coronavirus disease 2019 and ischemic stroke. Front Neurol 2023; 14:1151946. [PMID: 37090981 PMCID: PMC10115163 DOI: 10.3389/fneur.2023.1151946] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Accepted: 03/20/2023] [Indexed: 04/08/2023] Open
Abstract
ObjectiveClinical associations between coronavirus disease (COVID-19) and ischemic stroke (IS) have been reported. This study aimed to investigate the shared genes between COVID-19 and IS and explore their regulatory mechanisms.MethodsPublished datasets for COVID-19 and IS were downloaded. Common differentially expressed genes (DEGs) in the two diseases were identified, followed by protein–protein interaction (PPI) network analysis. Moreover, overlapping module genes associated with the two diseases were investigated using weighted correlation network analysis (WGCNA). Through intersection analysis of PPI cluster genes and overlapping module genes, hub-shared genes associated with the two diseases were obtained, followed by functional enrichment analysis and external dataset validation. Moreover, the upstream miRNAs and transcription factors (TFs) of the hub-shared genes were predicted.ResultsA total of 91 common DEGs were identified from the clusters of the PPI network, and 129 overlapping module genes were screened using WGCNA. Based on further intersection analysis, four hub-shared genes in IS and COVID-19 were identified, including PDE5A, ITGB3, CEACAM8, and BPI. These hub-shared genes were remarkably enriched in pathways such as ECM-receptor interaction and focal adhesion pathways. Moreover, ITGB3, PDE5A, and CEACAM8 were targeted by 53, 32, and 3 miRNAs, respectively, and these miRNAs were also enriched in the aforementioned pathways. Furthermore, TFs, such as lactoferrin, demonstrated a stronger predicted correlation with the hub-shared genes.ConclusionThe four identified hub-shared genes may participate in crucial mechanisms underlying both COVID-19 and IS and may exhibit the potential to be biomarkers or therapeutic targets for the two diseases.
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Affiliation(s)
- Hao Wu
- Department of Anesthesiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China
| | - Fei Han
- Department of Neurology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, China
- *Correspondence: Fei Han,
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26
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AlNafea HM, Korish AA. The interplay between hypovitaminosis D and the immune dysfunction in the arteriovenous thrombotic complications of the sever coronavirus disease 2019 (COVID-19) infection. Blood Coagul Fibrinolysis 2023; 34:129-137. [PMID: 36966750 PMCID: PMC10089932 DOI: 10.1097/mbc.0000000000001212] [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: 01/25/2023] [Accepted: 02/11/2023] [Indexed: 03/28/2023]
Abstract
Thromboembolic complications including cerebrovascular accidents, pulmonary embolism, myocardial infarction, deep vein thrombosis and disseminating intravascular coagulopathy are serious encounters in sever coronavirus disease 2019 (COVID-19) infected patients. This worsens the prognosis and may lead to death or life long morbidities. The laboratory finding of the disturbed haemostasias and the hyperinflammatory response are almost invariably present in COVID-19 patients. Multiple treatment modalities are utilized by the healthcare professionals to overcome the cytokine storm, oxidative stress, endothelial dysfunction, and coagulopathy in these patients. The combined actions of vitamin D (VitD) as a steroid hormone with anti-inflammatory, immunomodulatory, and antithrombotic properties increase the potential of the possible involvement of hypovitaminosis D in the thromboembolic complications of COVID-19 infection, and stimulated researchers and physicians to administer VitD therapy to prevent the infection and/or overcome the disease complications. The current review highlighted the immunomodulatory, anti-inflammatory, antioxidative and hemostatic functions of VitD and its interrelation with the renin-angiotensin-aldosterone system (RAAS) pathway and the complement system. Additionally, the association of VitD deficiency with the incidence and progression of COVID-19 infection and the associated cytokine storm, oxidative stress, hypercoagulability, and endothelial dysfunction were emphasized. Normalizing VitD levels by daily low dose therapy in patients with hypovitaminosis D below (25 nmol/l) is essential for a balanced immune response and maintaining the health of the pulmonary epithelium. It protects against upper respiratory tract infections and decreases the complications of COVID-19 infections. Understanding the role of VitD and its associated molecules in the protection against the coagulopathy, vasculopathy, inflammation, oxidative stress and endothelial dysfunction in COVID-19 infection could lead to new therapeutic strategies to prevent, treat, and limit the complications of this deadly virus infection.
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Affiliation(s)
- Haifa M. AlNafea
- Clinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud University
| | - Aida A. Korish
- Physiology Department (29), College of Medicine, King Saud University Medical City (KSUMC), King Saud university, Riyadh, Saudi Arabia
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27
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Ratajczak-Tretel B, Lambert AT, Al-Ani R, Arntzen K, Bakkejord GK, Bekkeseth HMO, Bjerkeli V, Eldøen G, Gulsvik AK, Halvorsen B, Høie GA, Ihle-Hansen H, Ingebrigtsen S, Kremer C, Krogseth SB, Kruuse C, Kurz M, Nakstad I, Novotny V, Naess H, Qazi R, Rezaj MK, Rørholt DM, Steffensen LH, Sømark J, Tobro H, Truelsen TC, Wassvik L, Ægidius KL, Atar D, Aamodt AH. Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation. BMC Neurol 2023; 23:115. [PMID: 36944929 PMCID: PMC10028765 DOI: 10.1186/s12883-023-03155-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2022] [Accepted: 03/09/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. METHODS Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. RESULTS After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.
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Affiliation(s)
- B Ratajczak-Tretel
- Department of Neurology, Østfold Hospital Trust, Postboks 300, Grålum, 1714, Norway.
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
| | - A Tancin Lambert
- Department of Neurology, Østfold Hospital Trust, Postboks 300, Grålum, 1714, Norway
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - R Al-Ani
- Department of Cardiology, Østfold Hospital Trust, Grålum, Norway
| | - K Arntzen
- Department for Neurology, Nordlandssykehuset, Bodø, Norway
| | - G K Bakkejord
- Department for Neurology, Nordlandssykehuset, Bodø, Norway
| | - H M O Bekkeseth
- Lillehammer Hospital, Department of Neurology, Innlandet Hospital Trust, Lillehammer, Norway
| | - V Bjerkeli
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - G Eldøen
- Department of Neurology, Molde Hospital, Molde, Norway
| | - A K Gulsvik
- Department of Internal Medicine, Diakonhjemmet Hospital, Oslo, Norway
| | - B Halvorsen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway
| | - G A Høie
- Department of Cardiology, Østfold Hospital Trust, Grålum, Norway
| | - H Ihle-Hansen
- Stroke Unit, Oslo University Hospital, Ullevål, Oslo, Norway
- Department of Internal Medicine, Vestre Viken Hospital Trust, Baerum Hospital, Gjettum, Norway
| | - S Ingebrigtsen
- Department of Neurology, University Hospital of North Norway, Tromsø, Norway
| | - C Kremer
- Department of Neurology, Skåne University Hospital, Malmö, Sweden
- Department of Clinical Sciences, Lund University, Lund, Sweden
| | - S B Krogseth
- Department of Neurology, Vestfold Hospital, Tønsberg, Norway
| | - C Kruuse
- Department of Neurology, Herlev Gentofte Hospital, Herlev, Denmark
| | - M Kurz
- Department of Neurology, Stavanger University Hospital, Stavanger, Norway
| | - I Nakstad
- Drammen Hospital, Department of Neurology, Vestre Viken Hospital Trust, Drammen, Norway
| | - V Novotny
- Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - H Naess
- Department of Neurology, Haukeland University Hospital, Bergen, Norway
| | - R Qazi
- Department of Internal Medicine, Diakonhjemmet Hospital, Oslo, Norway
| | - M K Rezaj
- Department of Neurology, Stavanger University Hospital, Stavanger, Norway
| | - D M Rørholt
- Department of Neurology, Molde Hospital, Molde, Norway
| | - L H Steffensen
- Department of Neurology, University Hospital of North Norway, Tromsø, Norway
| | - J Sømark
- Lillehammer Hospital, Department of Neurology, Innlandet Hospital Trust, Lillehammer, Norway
| | - H Tobro
- Department of Neurology, Telemark Hospital, Skien, Norway
| | - T C Truelsen
- Department of Neurology, Rigshospitalet University Hospital, Copenhagen, Denmark
| | - L Wassvik
- Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark
| | - K L Ægidius
- Department of Neurology, Bispebjerg University Hospital, Copenhagen, Denmark
| | - D Atar
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway
| | - A H Aamodt
- Department of Neurology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Department of Neuromedicine and Movement science, The Norwegian University of Science and Technology, Trondheim, Norway
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28
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Huang R, Liu J, Wan TK, Siriwanna D, Woo YMP, Vodencarevic A, Wong CW, Chan KHK. Stroke mortality prediction based on ensemble learning and the combination of structured and textual data. Comput Biol Med 2023; 155:106176. [PMID: 36805232 DOI: 10.1016/j.compbiomed.2022.106176] [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: 04/26/2022] [Revised: 09/12/2022] [Accepted: 10/01/2022] [Indexed: 11/23/2022]
Abstract
For severe cerebrovascular diseases such as stroke, the prediction of short-term mortality of patients has tremendous medical significance. In this study, we combined machine learning models Random Forest classifier (RF), Adaptive Boosting (AdaBoost), Extremely Randomised Trees (ExtraTree) classifier, XGBoost classifier, TabNet, and DistilBERT to construct a multi-level prediction model that used bioassay data and radiology text reports from haemorrhagic and ischaemic stroke patients to predict six-month mortality. The performances of the prediction models were measured using the area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve (AUPRC), precision, recall, and F1-score. The prediction models were built with the use of data from 19,616 haemorrhagic stroke patients and 50,178 ischaemic stroke patients. Novel six-month mortality prediction models for these patients were developed, which enhanced the performance of the prediction models by combining laboratory test data, structured data, and textual radiology report data. The achieved performances were as follows: AUROC = 0.89, AUPRC = 0.70, precision = 0.52, recall = 0.78, and F1 score = 0.63 for haemorrhagic patients, and AUROC = 0.88, AUPRC = 0.54, precision = 0.34, recall = 0.80, and F1 score = 0.48 for ischaemic patients. Such models could be used for mortality risk assessment and early identification of high-risk stroke patients. This could contribute to more efficient utilisation of healthcare resources for stroke survivors.
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Affiliation(s)
- Ruixuan Huang
- Department of Electrical Engineering, City University of Hong Kong, Hong Kong, China
| | - Jundong Liu
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | - Tsz Kin Wan
- Department of Electrical Engineering, City University of Hong Kong, Hong Kong, China
| | - Damrongrat Siriwanna
- Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China
| | | | | | - Chi Wah Wong
- Department of Applied AI and Data Science, City of Hope National Medical Center, Duarte, CA, 91010, United States
| | - Kei Hang Katie Chan
- Department of Electrical Engineering, City University of Hong Kong, Hong Kong, China; Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China; Department of Epidemiology and Center for Global Cardiometabolic Health, School of Public Health, Department of Medicine, The Warrant Alpert School of Medicine, Brown University, Providence, RI, United States.
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29
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Carpio-Orantes LD, Solís-Sánchez I, Moreno-Aldama NP, Aguilar-Silva A, García-Méndez S, Sánchez-Díaz JS. Incidence of stroke in a population affected by COVID-19 in Veracruz, México. Brain Circ 2023; 9:55-56. [PMID: 37151790 PMCID: PMC10158656 DOI: 10.4103/bc.bc_87_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/01/2022] [Accepted: 12/07/2022] [Indexed: 05/09/2023] Open
Affiliation(s)
- Luis Del Carpio-Orantes
- Study Group for the Diagnosis and Treatment of COVID-19 in Veracruz, Mexico
- Address for correspondence: Dr. Luis Del Carpio-Orantes, Study Group for the Diagnosis and Treatment of COVID-19 in Veracruz, Mexico. E-mail:
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30
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Norouzi-Barough L, Asgari Khosroshahi A, Gorji A, Zafari F, Shahverdi Shahraki M, Shirian S. COVID-19-Induced Stroke and the Potential of Using Mesenchymal Stem Cells-Derived Extracellular Vesicles in the Regulation of Neuroinflammation. Cell Mol Neurobiol 2023; 43:37-46. [PMID: 35025001 PMCID: PMC8755896 DOI: 10.1007/s10571-021-01169-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 11/09/2021] [Indexed: 02/07/2023]
Abstract
Ischemic stroke (IS) is a known neurological complication of COVID-19 infection, which is associated with high mortality and disability. Following IS, secondary neuroinflammation that occurs can play both harmful and beneficial roles and lead to further injury or repair of damaged neuronal tissue, respectively. Since inflammation plays a pivotal role in the pathogenesis of COVID-19-induced stroke, targeting neuroinflammation could be an effective strategy for modulating the immune responses following ischemic events. Numerous investigations have indicated that the application of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) improves functional recovery following stroke, mainly through reducing neuroinflammation as well as promoting neurogenesis and angiogenesis. Therefore, MSC-EVs can be applied for the regulation of SARS-CoV-2-mediated inflammation and the management of COVID-19- related ischemic events. In this study, we have first described the advantages and disadvantages of neuroinflammation in the pathological evolution after IS and summarized the characteristics of neuroinflammation in COVID-19-related stroke. Then, we have discussed the potential benefit of MSC-EVs in the regulation of inflammatory responses after COVID-19-induced ischemic events.
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Affiliation(s)
- Leyla Norouzi-Barough
- Acquired Immunodeficiency Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Ali Gorji
- Epilepsy Research Center, Department of Neurosurgery, Westfälische Wilhelms-Universitat Münster, Munster, Germany
- Shefa Neuroscience Research Center, Khatam Alanbia Hospital, Tehran, Iran
| | - Fariba Zafari
- Cellular and Molecular Research Center, Research Institute for Prevention of Non- Communicable Disease, Qazvin University of Medical Sciences, Qazvin, Iran
| | | | - Sadegh Shirian
- Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.
- Shiraz Molecular Pathology Research Center, Dr. Daneshbod Pathol Lab, Shiraz, Iran.
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31
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Khan M, Hameed S, Soomro BA, Mairaj S, Malik A, Farooq S, Rukn SA, Wasay M. COVID-19 independently predicts poor outcomes in Acute Ischemic Stroke- Insights from a multicenter study from Pakistan and United Arab Emirates. J Stroke Cerebrovasc Dis 2023; 32:106903. [PMID: 36436361 PMCID: PMC9678825 DOI: 10.1016/j.jstrokecerebrovasdis.2022.106903] [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: 07/13/2022] [Revised: 11/05/2022] [Accepted: 11/19/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Ischemic stroke associated with coronavirus 2019 (COVID-19) has been well recognized by now. Few studies have compared COVID related versus unrelated strokes. We intend to report on a large group of Asian patients from two countries and compare COVID with non-COVID strokes admitted during the same time period. METHODS Consecutive cases of acute ischemic stroke either presenting or developing, between March 2020 and December 2021 in four tertiary care hospitals (1 in Dubai, UAE and 3 in Karachi, Pakistan) and testing positive for COVID-19 were included in the study. Patients admitted with ischemic stroke during the same time period and who tested negative for COVID-19 were also randomly selected from the four hospitals. All data was collected from the medical records of the patients and recorded on a standard questionnaire before it was entered in SPSS version 21 for analysis. RESULTS There were 139 COVID positive and 271 COVID negative patients with acute ischemic stroke included in the current study. There were significantly more males (80.6% vs 64.9%, p=0.001) and more large vessel strokes in the COVID positive group (41% vs 21.8%, p<0.001). Being COVID positive was an independent predictor of poor outcome at discharge, defined as a modified Rankin score of 3-6 (OR 3.87, 95% CI 2.21-6.77) after adjusting for country, age, sex, vascular comorbid conditions and stroke subtype. CONCLUSIONS In this largest series of patients with COVID related strokes from Asia, COVID-19 was an independent predictor of poor outcomes at discharge after adjusting for other variables.
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Affiliation(s)
- Maria Khan
- Department of Neurology-Rashid Hospital, Dubai Medical College for Girls, Dubai, UAE
| | - Sajid Hameed
- Department of Neurology, Aga Khan University, Karachi, Pakistan
| | | | - Samar Mairaj
- Dow University of Health sciences, Karachi, Pakistan
| | - Abdul Malik
- Liaquat University of Medicine and Dentistry, Karachi, Pakistan
| | - Saba Farooq
- Department of Neurology-Rashid Hospital, Dubai Medical College for Girls, Dubai, UAE
| | - Suhail Al Rukn
- Department of Neurology-Rashid Hospital, Dubai Medical College for Girls, Dubai, UAE
| | - Mohammad Wasay
- Department of Neurology, Aga Khan University, Karachi, Pakistan,Corresponding author
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Rosenblum JS, Tunacao JM, Nazari MA, Ronk H, Dang DD, Downing C, Zhuang Z, Heiss JD, Smirniotopoulos JG, Bluestone A, Badia J, White J. Acute worsening of CADASIL in a patient with COVID-19 infection: illustrative case. JOURNAL OF NEUROSURGERY. CASE LESSONS 2022; 4:CASE22413. [PMID: 36572976 PMCID: PMC9795827 DOI: 10.3171/case22413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/24/2022] [Accepted: 10/19/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Reports of cerebrovascular ischemia and stroke occurring as predominant neurological sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), are increasingly evident within the literature. While various pathophysiological mechanisms have been postulated, including hypercoagulability, endothelial invasion, and systemic inflammation, discrete mechanisms for viral neurotropism remain unclear and controversial. OBSERVATIONS The authors present a unique case study of a 64-year-old male with acute COVID-19 infection and acute worsening of previously stable cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare heritable arteriopathy due to mutation in the Notch3 gene, which is critical for vascular development and tone. Delayed cranial neuropathies, brainstem fluid-attenuated inversion recovery signal, and enhancement of olfactory and vagus nerves on magnetic resonance neurography in this patient further support viral neurotropism via cranial nerves in addition to cerebral vasculature. LESSONS To the authors' knowledge, this is the first case in the literature that not only demonstrates the consequences of COVID-19 infection in a patient with altered cerebrovascular autoregulation such as CADASIL but also highlights the tropism of SARS-CoV-2 for (1) cranial nerves as a mode of entry to the central nervous system and (2) vessels as a cause of cerebrovascular ischemia.
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Affiliation(s)
- Jared S. Rosenblum
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Jessa M. Tunacao
- Department of Radiology, Stony Brook University Medical Center, Stony Brook, New York
| | - Matthew A. Nazari
- Internal Medicine and Pediatrics, Georgetown Hospital, Washington, District of Columbia
| | - Halle Ronk
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Danielle D. Dang
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland,Department of Neurosurgery, Inova Fairfax Medical Campus, Inova Health System, Falls Church, Virginia
| | - Chad Downing
- Department of Radiology, Stony Brook University Medical Center, Stony Brook, New York
| | - Zhengping Zhuang
- Neuro-Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - John D. Heiss
- Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland
| | - James G. Smirniotopoulos
- Department of Radiology, George Washington University, Washington, District of Columbia,MedPix® National Library of Medicine, Bethesda, Maryland; and
| | - Avraham Bluestone
- Department of Radiology, Stony Brook University Medical Center, Stony Brook, New York
| | - James Badia
- Department of Radiology, Stony Brook University Medical Center, Stony Brook, New York
| | - Joseph White
- Department of Family Medicine, Mather Hospital, Northwell Health System, Port Jefferson, New York
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Brola W, Wilski M. Neurological consequences of COVID-19. Pharmacol Rep 2022; 74:1208-1222. [PMID: 36180640 PMCID: PMC9524739 DOI: 10.1007/s43440-022-00424-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 09/22/2022] [Accepted: 09/25/2022] [Indexed: 12/13/2022]
Abstract
In December 2019, cases of pneumonia caused by infection with the previously unknown severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leading to coronavirus disease 2019 (COVID-19), were identified. Typical manifestations of COVID-19 are fever, cough, fatigue and dyspnoea. Initially, it was thought that the mechanism of action of SARS-CoV-2 was only associated with respiratory tract invasion, but it was later revealed that the infection might involve many other organs and systems, including the central and peripheral nervous systems. Neurological complications associated with SARS-CoV-2 infection include encephalopathy, encephalitis, meningitis, acute disseminated encephalomyelitis (ADEM), ischaemic and haemorrhagic stroke and cerebral venous sinus thrombosis. In cases of peripheral nervous system involvement, smell and taste disorders, myopathy or the signs and symptoms of Guillain‒Barré syndrome are observed. The most common early neurological complications, particularly during the first year of the epidemic, were anosmia and taste disorders, which, according to some studies, occurred in over 80 percent of patients with COVID-19. The proportion of patients with serious neurological manifestations was small compared to the global number of patients, but the numbers of SARS-CoV-2 infections and critical patients increased substantially. The experience from 2 years of the pandemic has shown that approximately 13% of infected patients suffer from severe neurological complications. The relationship between SARS-CoV-2 and the nervous system is not only a cause of neurological complications in previously healthy individuals but also directly and indirectly affects the courses of many nervous system diseases.
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Affiliation(s)
- Waldemar Brola
- Collegium Medicum, Jan Kochanowski University, Al. IX Wieków Kielc 19, 25-317, Kielce, Poland.
| | - Maciej Wilski
- Department of Adapted Physical Activity, Poznań University of Physical Education, Poznan, Poland
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Effects of Hypoxia-Inducible Factor 1 (HIF-1) Signaling Pathway on Acute Ischemic Stroke. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:1860925. [DOI: 10.1155/2022/1860925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/10/2022] [Revised: 08/09/2022] [Accepted: 09/05/2022] [Indexed: 11/18/2022]
Abstract
Background. Epidemiological surveys show that a large number of cerebrovascular diseases occur in China every year, and among these cerebrovascular diseases, ischemic diseases are predominant. Ischemia leads to irreversible degenerative necrosis of a large number of brain neurons and severe neurological deficits. Aims. This study is aimed at exploring the mechanism of the major regulatory effect of hypoxia-inducible factor 1 (HIF-1) pathway on proangiogenesis and providing new ideas for the treatment of ischemic stroke. Materials and Methods. The rats were randomly divided into normal and ischemic control groups, and the ischemic control group was subjected to the middle cerebral artery occlusion (MCAO) cerebral ischemia model by the wire embolization method, and the rats were executed in batches at 6 h, 1 d, and 3 d after ischemia-reperfusion, and the brain tissue specimens were taken for examination to investigate the effect of hypoxia-inducible factor 1 (HIF-l) signaling pathway on acute ischemic stroke. Results. At 3 d, the number of VEGFR2 positive cells increased significantly, and there was a significant difference compared with the control group (
). At 3 d, the number of HIF-1α-positive cells increased significantly, and there was a significant difference compared with the control group (
). The number of Hes1+factor VIII positive cells in the ischemic cortex increased significantly on the 1st and 3rd day, and there was a significant difference compared with the control group (
). The expression of Hes1 protein was significantly lower than the normal level after 6 h of ischemia, and the protein expression was significantly increased at 1 d and 3 d after ischemia (
). Conclusion. By detecting the expression changes of Hesl+factor VII in the ischemic area, the results show that ischemia and hypoxia activate the HIF-1, making the HIF-l the main regulatory pathway in the process of angiogenesis after ischemia.
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Pandit T, Pandit R, Goyal L. Uncommon Side Effects of COVID-19 Vaccination in the Pediatric Population. Cureus 2022; 14:e30276. [PMID: 36258808 PMCID: PMC9573128 DOI: 10.7759/cureus.30276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/13/2022] [Indexed: 11/06/2022] Open
Abstract
Introduction The rapid development of vaccines followed the Coronavirus disease 2019 (COVID-19) pandemic. There is still significant vaccine hesitancy, especially among parents. Large-scale pediatric population-based studies or reviews about vaccine side effects are limited. Data sources and methods The Centers for Disease Control and Prevention (CDC) recommends recipients or their providers notify possible adverse events to the Vaccine Adverse Event Reporting System (VAERS). We evaluated Delaware state data from the VAERS system for the pediatric age group. Results A total of 111 reports were reviewed, with summaries of the reported key side effects discussed, including seizures, myocarditis, stroke, multisystem inflammatory syndrome in children (MIS-C), chest pain, hematuria, menstrual disorder, appendicitis, behavioral and otological side effects, etc. Conclusions We noted the approximate prevalence of reported adverse events to be <0.2%. Further studies with larger sample sizes or those focused on each key side effect are needed to evaluate these side effects in detail. An open discussion about the possible side effects and reinforcing the individual, family, and community benefits are key to promoting COVID-19 vaccine acceptance.
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Affiliation(s)
- Trupti Pandit
- Pediatrics, Nemours Children's Health, Glen Mills, USA
| | - Ramesh Pandit
- Medicine, Independent Researcher, Philadelphia, USA
- Hospital Medicine, University of Pennsylvania / Chester County Hospital, Philadelphia, USA
| | - Lokesh Goyal
- Hospital Medicine, CHRISTUS Spohn Hospital Corpus Christi - Shoreline, Corpus Christi, USA
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Blanco S, Martínez-Lara E, Siles E, Peinado MÁ. New Strategies for Stroke Therapy: Nanoencapsulated Neuroglobin. Pharmaceutics 2022; 14:pharmaceutics14081737. [PMID: 36015363 PMCID: PMC9412405 DOI: 10.3390/pharmaceutics14081737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Revised: 08/15/2022] [Accepted: 08/17/2022] [Indexed: 01/12/2023] Open
Abstract
Stroke is a global health and socio-economic problem. However, no efficient preventive and/or palliative treatments have yet been found. Neuroglobin (Ngb) is an endogen neuroprotective protein, but it only exerts its beneficial action against stroke after increasing its basal levels. Therefore, its systemic administration appears to be an efficient therapy applicable to stroke and other neurodegenerative pathologies. Unfortunately, Ngb cannot cross the blood-brain barrier (BBB), making its direct pharmacological use unfeasible. Thus, the association of Ngb with a drug delivery system (DDS), such as nanoparticles (NPs), appears to be a good strategy for overcoming this handicap. NPs are a type of DDS which efficiently transport Ngb and increase its bioavailability in the infarcted area. Hence, we previously built hyaluronate NPS linked to Ngb (Ngb-NPs) as a therapeutic tool against stroke. This nanoformulation induced an improvement of the cerebral infarct prognosis. However, this innovative therapy is still in development, and a more in-depth study focusing on its long-lasting neuroprotectant and neuroregenerative capabilities is needed. In short, this review aims to update the state-of-the-art of stroke therapies based on Ngb, paying special attention to the use of nanotechnological drug-delivering tools.
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Aghajani Shahrivar A, Khakpourian Z, Majdi F, Sobhani S, Coleman-Fuller N, Gholami M, Motaghinejad M. Hypothesized neuroprotective effect of minocycline against COVID-19-induced stroke and neurological dysfunction: possible role of matrix metalloprotease signaling pathway. Biologia (Bratisl) 2022; 77:3027-3035. [PMID: 35966933 PMCID: PMC9360701 DOI: 10.1007/s11756-022-01162-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 06/16/2022] [Indexed: 11/26/2022]
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (COVID-19) is a respiratory disease that causes dysfunction in respiration. Since late 2019, this virus has infected and killed millions of people around the world and imposed many medical and therapeutic problems in the form of a pandemic. According to recent data, COVID-19 disease can increase the risk of stroke, which can be deadly or cause many neurological disorders after the disease. During the last two years, many efforts have been made to introduce new therapies for management of COVID-19-related complications, including stroke. To achieve this goal, several conventional drugs have been investigated for their possible therapeutic roles. Minocycline, a broad-spectrum, long-acting antibiotic with anti-inflammatory and antioxidant properties, is one such conventional drug that should be considered for treating COVID-19-related stroke, as indirect evidence indicates that it exerts neuroprotective effects, can modulate stroke occurrence, and can play an effective and strategic role in management of the molecular signals caused by stroke and its destructive consequences. The matrix metalloprotease (MMP) signaling pathway is one of the main signaling pathways involved in the occurrence and exacerbation of stroke; however, its role in COVID-19-induced stroke and the possible role of minocycline in the management of this signaling pathway in patients with COVID-19 is unclear and requires further investigation. Based on this concept, we hypothesize that minocycline might act via MMP signaling as a neuroprotective agent against COVID-19-induced neurological dysfunction, particularly stroke.
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Affiliation(s)
- Ali Aghajani Shahrivar
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Zahra Khakpourian
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fatemeh Majdi
- Department of Pharmaceutical Biomaterials, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Sarvenaz Sobhani
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Natalie Coleman-Fuller
- Department of Veterinary and Biomedical Sciences, University of Minnesota, Saint Paul, MN 55108 USA
| | - Mina Gholami
- College of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Majid Motaghinejad
- Chronic Respiratory Disease Research Center (CRDRC), National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Wiszniewska M, Sankowska M. Stroke in the COVID-19 pandemic era. POSTEPY PSYCHIATRII NEUROLOGII 2022; 31:69-73. [PMID: 37082091 PMCID: PMC9881573 DOI: 10.5114/ppn.2022.116881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/28/2022] [Indexed: 04/22/2023]
Abstract
Purpose The aim of this article is to outline the impact of COVID-19 on the frequency of occurrence, course of stroke treatment, and to highlight the cause-effect relationship between SARS-CoV-2 infection and stroke on the basis of a literature overview. Views Since the end of 2019, the whole world has been struggling with the effects of the pandemic caused by the coronavirus SARS-CoV-2. The virus induces a wide spectrum of symptoms, ranging from mild or serious ones, which may lead to a severe multiorgan failure. Acute ischaemic stroke (AIS) might be associated with COVID-19 as a potentially fatal complication, while hemorrhagic stroke is less frequent. In most cases, stroke is caused by large artery occlusion. One of its reasons is hypercoagulation with a complex mechanism, which has not been fully explained. Research has shown that during COVID-19 pandemic, the number of patients admitted to hospitals due to AIS decreased. During the first pandemic wave there was no change regarding the proportion of patients with cerebral vessel obstruction who received endovascular treatment. Conclusions In the COVID-19 pandemic era, rapid intravenous administration of tissue plasminogen activator remains the main treatment for acute ischaemic stroke. Patients often fail to report to hospital for the fear of SARS-CoV-2 infection. It is of the utmost importance to raise society's awareness of the necessity to report to hospital when experiencing serious symptoms, including stroke.
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Affiliation(s)
- Małgorzata Wiszniewska
- Emergency Medical Services, University of Applied Sciences, Piła, Poland
- Neurological Department with Stroke Unit, Specialist Hospital, Piła, Poland
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Dehghani A, Zokaei E, Kahani SM, Alavinejad E, Dehghani M, Meftahi GH, Afarinesh MR. The potential impact of Covid-19 on CNS and psychiatric sequels. Asian J Psychiatr 2022; 72:103097. [PMID: 35405524 PMCID: PMC8982477 DOI: 10.1016/j.ajp.2022.103097] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/19/2022] [Accepted: 04/02/2022] [Indexed: 01/08/2023]
Abstract
Due to its high prevalence and fatality, the current Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) virus, which first emerged in China in 2019, quickly spread around the world and immediately became a serious global health concern. Although respiratory issues were initially the most prominent symptom of coronavirus disease 2019 (COVID-19), it became obvious rapidly that COVID-19, like many other coronavirus family members, could affect the central nervous system (CNS). During the pandemic, CNS involvement expressed itself in a variety of forms, including insomnia, anosmia, headaches, encephalopathies, encephalitis, cerebrovascular accidents, cognitive and memory impairment, and increased psychiatric disorders. Almost everyone who has been infected has at least one of these neurological symptoms, demonstrating that the virus has a high ability to impact the CNS. As the coronavirus pandemic passes its second year, the manifestations it can cause in the long run, such as its psychological sequels, have not yet been thoroughly studied. Given the high importance of this issue in today's society and due to the lack of reliable knowledge about the COVID-19 landscape on psychiatric disorders, we intend to investigate coronavirus's possible effect on mental illnesses based on available literature. Because the majority of the psychological effects of the coronavirus can continue for a long period after the pandemic ends, our research can give insight into potential psychiatric sequels associated with COVID-19.
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Affiliation(s)
- Ali Dehghani
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Elham Zokaei
- Department of Biology, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran
| | - Seyyed Mohammad Kahani
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Elaheh Alavinejad
- Department of Medical Genetics, Faculty of Medical Sciences, Tehran University of Medical Science, Tehran, Iran
| | - Mohammad Dehghani
- Department of Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | | | - Mohammad Reza Afarinesh
- Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
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Ahmad SJ, Feigen CM, Vazquez JP, Kobets AJ, Altschul DJ. Neurological Sequelae of COVID-19. J Integr Neurosci 2022; 21:77. [PMID: 35633158 DOI: 10.31083/j.jin2103077] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 01/31/2022] [Accepted: 02/21/2022] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND Though primarily a pulmonary disease, Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus can generate devastating disease states that affect multiple organ systems including the central nervous system (CNS). The various neurological disorders associated with COVID-19 range in severity from mild symptoms such as headache, or myalgias to more severe symptoms such as stroke, psychosis, and anosmia. While some of the COVID-19 associated neurological complications are mild and reversible, a significant number of patients suffer from stroke. Studies have shown that COVID-19 infection triggers a wave of inflammatory cytokines that induce endothelial cell dysfunction and generate coagulopathy that increases the risk of stroke or thromboses. Inflammation of the endothelium following infection may also destabilize atherosclerotic plaque and induce thrombotic stroke. Although uncommon, there have also been reports of hemorrhagic stroke associated with COVID-19. The proposed mechanisms include a blood pressure increase caused by infection leading to a reduction in angiotensin converting enzyme-2 (ACE-2) levels that results in an imbalance of the renin-angiotensin system ultimately manifesting inflammation and vasoconstriction. Coagulopathy, as demonstrated by elevated prothrombin time (PT), has also been posited as a factor contributing to hemorrhagics stroke in patients with COVID-19. Other neurological conditions associated with COVID-19 include encephalopathy, anosmia, encephalitis, psychosis, brain fog, headache, depression, and anxiety. Though there are several hypotheses reported in the literature, a unifying pathophysiological mechanism of many of these disorders remains unclear. Pulmonary dysfunction leading to poor oxygenation of the brain may explain encephalopathy and other disorders in COVID-19 patients. Alternatively, a direct invasion of the CNS by the virus or breach of the blood-brain barrier by the systemic cytokines released during infection may be responsible for these conditions. Notwithstanding, the relationship between the inflammatory cytokine levels and conditions such as depression and anxiety is contradictory and perhaps the social isolation during the pandemic may in part be a contributing factor to some of the reported CNS disorders. OBJECTIVE In this article, we review the current literature pertaining to some of the most significant and common neurological disorders such as ischemic and hemorrhagic stroke, encephalopathy, encephalitis, brain fog, Long COVID, headache, Guillain-Barre syndrome, depression, anxiety, and sleep disorders in the setting of COVID-19. We summarize some of the most relevant literature to provide a better understanding of the mechanistic details regarding these disorders in order to help physicians monitor and treat patients for significant COVID-19 associated neurologic impairments. METHODS A literature review was carried out by the authors using PubMed with the search terms "COVID-19" and "Neurology", "Neurological Manifestations", "Neuropsychiatric Manifestations", "Stroke", "Encephalopathy", "Headache", "Guillain-Barre syndrome", "Depression", "Anxiety", "Encephalitis", "Seizure", "Spasm", and "ICUAW". Another search was carried out for "Long-COVID" and "Post-Acute COVID-19" and "Neurological Manifestations" or "Neuropsychiatric Manifestations". Articles such as case reports, case series, and cohort studies were included as references. No language restrictions were enforced. In the case of anxiety and depression, attempts were made to focus mainly on articles describing these conditions in infected patients. RESULTS A total of 112 articles were reviewed. The incidence, clinical outcomes, and pathophysiology of selected neurological disorders are discussed below. Given the recent advent of this disease, the incidence of certain neurologic sequelae was not always available. Putative mechanisms for each condition in the setting of COVID-19 are outlined.
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Affiliation(s)
- Samuel J Ahmad
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Chaim M Feigen
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Juan P Vazquez
- Albert Einstein College of Medicine, Bronx, NY 10461, USA
| | - Andrew J Kobets
- Department of Neurological Surgery, Montefiore Medical, Bronx, NY 10467, USA
| | - David J Altschul
- Department of Neurovascular Surgery, Montefiore Medical, Bronx, NY 10467, USA
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COVID-19 and thrombosis: The role of hemodynamics. Thromb Res 2022; 212:51-57. [PMID: 35219932 PMCID: PMC8864963 DOI: 10.1016/j.thromres.2022.02.016] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 01/24/2022] [Accepted: 02/18/2022] [Indexed: 12/16/2022]
Abstract
Severe coronavirus disease 2019 (COVID-19) is characterized by an increased risk of thromboembolic events, a leading cause for adverse outcomes in patients afflicted by the more serious manifestation of the disease. These thromboembolic complications expressed as sepsis-induced coagulopathy, disseminated intravascular coagulation, venous and arterial thromboembolism, pulmonary embolism, microthrombosis, and thrombotic microangiopathy have been observed to affect different organs such as the lungs, heart, kidneys, and brain. Endothelial injury and dysfunction have been identified as the critical pathway towards thrombogenesis, and contributions of other mechanisms such as hypercoagulability, cytokine storm, neutrophils have been studied. However, the contribution of hemodynamic pathways towards thrombosis in severe COVID-19 cases has not been investigated. From the classical theory of Virchow's triad to the contemporary studies on the effect of shear enhanced platelet activation, it is well established that hemodynamics plays a role in the initiation and growth of thrombosis. This article reviews recent studies on COVID-19 related thrombotic events and offers hypotheses on how hemodynamics may be responsible for some of the adverse outcomes observed in severe COVID-19 cases. While thrombogenesis through endothelial injury and the effects of hypercoagulability on thrombosis are briefly addressed, the crux of the discussion is focused on hemodynamic factors such as stasis, turbulent flow, and non-physiological shear stress and their effects on thrombosis. In addition, hemodynamics-dependent venous, arterial, and microvascular thrombosis in COVID-19 cases is discussed. We also propose further investigation of diagnostic and therapeutic options that address the hemodynamics aspects of COVID-19 thrombus formation to assess their potential in patient care.
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Endovascular-first approach for symptomatic carotid artery stenosis in a COVID-19 positive patient: expected and unexpected advantages. Ann Vasc Surg 2022; 83:e1-e2. [PMID: 35247539 PMCID: PMC8890792 DOI: 10.1016/j.avsg.2022.01.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2022] [Accepted: 01/30/2022] [Indexed: 11/20/2022]
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Kim M, George A, Ganti L, Huang D, Carman M. The Burden of Hypercoagulability in COVID-19. TH OPEN 2022; 6:e96-e98. [PMID: 35707624 PMCID: PMC9054923 DOI: 10.1055/a-1760-0445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Accepted: 01/20/2022] [Indexed: 11/25/2022] Open
Abstract
The novel coronavirus disease 2019 (COVID-19) infection has widespread impact on multiple organ systems, including damage to endothelial cells. Various studies have found evidence for direct mechanisms by which interaction between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and endothelial cells lead to extensive damage to the latter, and indirect mechanisms, such as excessively elevated cytokines, can also result in the same outcome. Damage to the endothelium results in release of thrombotic factors and inhibition of fibrinolysis. This confers a significant hypercoagulability burden on patients infected or recovering from COVID-19 infection. In this case report, the authors report the case of a gentleman presenting with extensive deep vein thrombosis and pulmonary embolism, in the context of recent COVID-19 infection. The postulated mechanisms and management are discussed.
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Affiliation(s)
| | | | - Latha Ganti
- University of Central Florida, Orlando, United States
| | - Derrick Huang
- University of Central Florida College of Medicine, Orlando, United States
| | - Matthew Carman
- Emergency Medicine, Lakeland Regional Health Medical Center, Lakeland, United States
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Stamm B, Huang D, Royan R, Lee J, Marquez J, Desai M. Pathomechanisms and Treatment Implications for Stroke in COVID-19: A Review of the Literature. Life (Basel) 2022; 12:207. [PMID: 35207494 PMCID: PMC8877423 DOI: 10.3390/life12020207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 01/17/2022] [Accepted: 01/25/2022] [Indexed: 11/25/2022] Open
Abstract
Stroke in patients with COVID-19 has received increasing attention throughout the global COVID-19 pandemic, perhaps due to the substantial disability and mortality that can result when the two conditions co-occur. We reviewed the existing literature and found that the proposed pathomechanism underlying COVID-19-associated ischemic stroke is broadly divided into the following three categories: vasculitis, endothelialitis, and endothelial dysfunction; hypercoagulable state; and cardioembolism secondary to cardiac dysfunction. There has been substantial debate as to whether there is a causal link between stroke and COVID-19. However, the distinct phenotype of COVID-19-associated strokes, with multivessel territory infarcts, higher proportion of large vessel occlusions, and cryptogenic stroke mechanism, that emerged in pooled analytic comparisons with non-COVID-19 strokes is compelling. Further, in this article, we review the various treatment approaches that have emerged as they relate to the proposed pathomechanisms. Finally, we briefly cover the logistical challenges, such as delays in treatment, faced by providers and health systems; the innovative approaches utilized, including the role of tele-stroke; and the future directions in COVID-19-associated stroke research and healthcare delivery.
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Affiliation(s)
- Brian Stamm
- Department of Neurology, School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA; (D.H.); (J.L.)
| | - Deborah Huang
- Department of Neurology, School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA; (D.H.); (J.L.)
| | - Regina Royan
- Department of Emergency Medicine, School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA;
| | - Jessica Lee
- Department of Neurology, School of Medicine, Northwestern University Feinberg, Chicago, IL 60611, USA; (D.H.); (J.L.)
| | - Joshua Marquez
- Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, NM 87144, USA;
| | - Masoom Desai
- Department of Neurology, School of Medicine, University of New Mexico, Albuquerque, NM 87144, USA;
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Wang C, Yu C, Novakovic VA, Xie R, Shi J. Circulating Microparticles in the Pathogenesis and Early Anticoagulation of Thrombosis in COVID-19 With Kidney Injury. Front Cell Dev Biol 2022; 9:784505. [PMID: 35118071 PMCID: PMC8804312 DOI: 10.3389/fcell.2021.784505] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Accepted: 12/16/2021] [Indexed: 12/15/2022] Open
Abstract
As more is learned about the pathophysiological mechanisms of COVID-19, systemic thrombosis has been recognized as being associated with more severe clinical manifestations, mortality and sequelae. As many as 40% of patients admitted to the hospital due to COVID-19 have acute kidney injury, with coagulation abnormalities the main cause of impaired function. However, the mechanism of renal thrombosis and the process leading to kidney injury are unclear. Microparticles (MPs) are membrane bubbles released in response to activation, injury or apoptosis of cells. The phosphatidylserine (PS) exposed on the surface of MPs provides binding sites for endogenous and exogenous FXase complexes and prothrombin complexes, thus providing a platform for the coagulation cascade reaction and facilitating clot formation. In the context of COVID-19 infection, viral attack leads immune cells to release cytokines that damage circulating blood cells and vascular endothelial cells, resulting in increased MPs levels. Therefore, MPs can be used as a risk factor to predict renal microthrombosis and kidney injury. In this paper, we have summarized the latest data on the pathophysiological mechanism and treatment of renal thrombosis caused by MPs in COVID-19, revealing that the coagulation abnormality caused by MP and PS storms is a universal progression that aggravates the mortality and sequelae of COVID-19 and potentially other pandemic diseases. This paper also describes the risk factors affecting renal thrombosis in COVID-19 from the perspective of the Virchow’s triad: blood hypercoagulability, vascular endothelial injury, and decreased blood flow velocity. In summary, given the serious consequences of thrombosis, current guidelines and clinical studies suggest that early prophylactic anticoagulant therapy reduces mortality and improves clinical outcomes. Early anticoagulation, through inhibition of PS-mediated coagulopathy, allows maintenance of unobstructed blood circulation and oxygen delivery thereby facilitating the removal of inflammatory factors, viruses, MPs, and dead or damaged cells, and expediting patient rehabilitation.
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Affiliation(s)
- Chengyue Wang
- Department of Hematology, The First Hospital of Harbin, Harbin Medical University, Harbin, China
- Department of Nephrology, The First Hospital of Harbin, Harbin Medical University, Harbin, China
| | - Chengyuan Yu
- Department of Hematology, The First Hospital of Harbin, Harbin Medical University, Harbin, China
- Department of Geriatric, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, China
| | - Valerie A. Novakovic
- Department of Research, VA Boston Healthcare System, Harvard Medical School, Boston, MA, United States
| | - Rujuan Xie
- Department of Nephrology, The First Hospital of Harbin, Harbin Medical University, Harbin, China
- *Correspondence: Rujuan Xie, ; Jialan Shi,
| | - Jialan Shi
- Department of Hematology, The First Hospital of Harbin, Harbin Medical University, Harbin, China
- Department of Research, VA Boston Healthcare System, Harvard Medical School, Boston, MA, United States
- Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
- *Correspondence: Rujuan Xie, ; Jialan Shi,
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Gryczyńska W, Litvinov N, Bitew B, Bartosz Z, Kośmider W, Bogdański P, Skrypnik D. Excess Body Mass-A Factor Leading to the Deterioration of COVID-19 and Its Complications-A Narrative Review. Viruses 2021; 13:v13122427. [PMID: 34960696 PMCID: PMC8708912 DOI: 10.3390/v13122427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 11/30/2021] [Indexed: 01/08/2023] Open
Abstract
Currently, the world is facing two serious pandemics: obesity and COVID-19. It is well-established that the prevalence of obesity has risen dramatically, causing a deterioration in the health quality of the population and increasing susceptibility for the unfavourable course of acute infections. It has been observed that excess body mass significantly influences the COVID-19 outcome. The aim of this review is to present the latest scientific reports on the impact of excess body mass on the course and complications of COVID-19. The Web of Science, PubMed, and Google Scholar databases were searched. Only studies reporting patients stated to be COVID-19 positive based on the results of a nasopharyngeal swab and the ribonucleic acid test were included. It is shown that thromboembolic and ischemic complications, namely stroke, disseminated intravascular coagulation, severe hyperglycaemia, and leukoencephalopathy are more likely to appear in COVID-19 positive patients with obesity compared to non-obese subjects. COVID-19 complications such as cardiomyopathy, dysrhythmias, endothelial dysfunction, acute kidney injury, dyslipidaemia, lung lesions and acute respiratory distress syndrome have a worse outcome among obese patients.
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Affiliation(s)
- Weronika Gryczyńska
- Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (W.G.); (N.L.); (B.B.); (Z.B.); (W.K.)
| | - Nikita Litvinov
- Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (W.G.); (N.L.); (B.B.); (Z.B.); (W.K.)
| | - Bezawit Bitew
- Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (W.G.); (N.L.); (B.B.); (Z.B.); (W.K.)
- Ethiopian Medical Students’ Association, Zambia Street, Addis Ababa P.O. Box 9302, Ethiopia
| | - Zuzanna Bartosz
- Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (W.G.); (N.L.); (B.B.); (Z.B.); (W.K.)
| | - Weronika Kośmider
- Faculty of Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (W.G.); (N.L.); (B.B.); (Z.B.); (W.K.)
| | - Paweł Bogdański
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland;
| | - Damian Skrypnik
- Department of Treatment of Obesity, Metabolic Disorders and Clinical Dietetics, Poznan University of Medical Sciences, 60-569 Poznan, Poland;
- Correspondence:
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Liu JL, Shah K, Marji A, Sareini R, Bhasin A, Rao S, Mohamed W, Rajamani K, Chamiraju P, Khawaja A. Descriptive analysis of Acute Ischemic stroke in COVID-19 patients through the course of the COVID-19 pandemic. J Clin Neurosci 2021; 96:221-226. [PMID: 34801399 PMCID: PMC8554005 DOI: 10.1016/j.jocn.2021.10.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2021] [Revised: 10/04/2021] [Accepted: 10/22/2021] [Indexed: 02/06/2023]
Abstract
Coronavirus disease 2019 (COVID-19) has been associated with Acute Ischemic Stroke (AIS). Here, we characterize our institutional experience with management of COVID-19 and AIS. Baseline demographics, clinical, imaging, and outcomes data were determined in patients with COVID-19 and AIS presenting within March 2020 to October 2020, and November 2020 to August 2021, based on institutional COVID-19 hospitalization volume. Of 2512 COVID-19 patients, 35 (1.39%, mean age 63.3 years, 54% women) had AIS. AIS recognition was frequently delayed after COVID-19 symptoms (median 19.5 days). Four patients (11%) were on therapeutic anticoagulation at AIS recognition. AIS mechanism was undetermined or due to multiple etiologies in most cases (n = 20, 57%). Three patients underwent IV TPA, and three underwent mechanical thrombectomy, of which two suffered re-occlusion. Three patients had incomplete mRNA vaccination course. Fourteen (40%) died, with 26 (74%) having poor outcomes. Critical COVID-19 severity was associated with worsened mortality (p = 0.02). More patients (12/16; 75%) had either worsened or similar 3-month functional outcomes, than those with improvement, indicating the devastating impact of co-existing AIS and COVID-19. Comparative analysis showed that patients in the later cohort had earlier AIS presentation, fewer stroke risk factors, more comprehensive workup, more defined stroke mechanisms, less instance of critical COVID-19 severity, more utilization of IV TPA, and a trend towards worse outcomes for the sub-group of mild-to-moderate COVID-19 severity. AIS incidence, NIHSS, and overall outcomes were similar. Further studies should investigate outcomes beyond 3 months and their predictive factors, impact of completed vaccination course, and access to neurologic care.
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Affiliation(s)
- Jay Liuhong Liu
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | - Keval Shah
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | - Amin Marji
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | - Ricky Sareini
- Wayne State University School of Medicine, Detroit, MI, USA
| | - Amman Bhasin
- Wayne State University School of Medicine, Detroit, MI, USA
| | - Shishir Rao
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | - Wazim Mohamed
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | - Kumar Rajamani
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA
| | | | - Ayaz Khawaja
- Department of Neurology, Wayne State University-Detroit Medical Center, Detroit, MI, USA.
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48
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COVID-19 as a new risk factor for the development of acute vascular diseases of the optic nerve and retina. OPHTHALMOLOGY JOURNAL 2021. [DOI: 10.17816/ov64115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
The new coronavirus disease (COVID-19) is a viral respiratory infection accompanied by systemic endotheliitis. COVID-19 patients usually encounter changes related to hypercoagulability, hypofibrinolysis, and increased intravascular platelet aggregation. There is also a vascular wall thromboresistance decrease and impaired vasomotor function, which significantly increase the risk of thromboembolic complications. Currently, pathogenic aspects of the relationship between COVID-19 and vascular and inflammatory conditions of the optic nerve and retina are actively investigated. One of the triggers of impaired blood flow in ocular vessels may be a perfusion pressure decrease, observed in the acute period of the infectious process. This is related to both COVID-19 clinical course features and to resuscitation specificity as well. Secondary autoimmune inflammation is being considered as a mechanism of damage to the vascular wall in the post-infectious period. In this publication, possible pathogenic links of these diseases are considered for the first time in a specific context of the example of ischemic optic neuropathy associated with coronavirus infection.
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Tsuchiya T, Koizumi S, Tomioka A, Miyawaki S, Saito N. Acute Ischemic Stroke Due to Basilar Artery Occlusion with Coronavirus Disease 2019: A Case Report. NMC Case Rep J 2021; 8:579-585. [PMID: 35079520 PMCID: PMC8769431 DOI: 10.2176/nmccrj.cr.2021-0043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 04/14/2021] [Indexed: 11/20/2022] Open
Abstract
Although it is increasingly recognized that coronavirus disease 2019 (COVID-19) can cause multi-organ disease, including acute ischemic stroke, the incidence of coagulation disorder is reported to be lower in Asian countries. We report a case of a 47-year-old Asian man with mild COVID-19 respiratory symptoms who had acute basilar artery occlusion. Despite successful recanalization with mechanical thrombectomy, the patient developed extensive cerebral infarction in the posterior circulation, necessitating decompressive craniotomy. Our findings suggest that severe large vessel occlusion (LVO) can occur even in young Asian patients with mild COVID-19 respiratory symptoms and that its outcome can be extremely severe despite successful recanalization. The management of COVID-19-related LVO can be very challenging, as both the prevention of possible nosocomial infection and early recanalization are required simultaneously.
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Affiliation(s)
| | - Satoshi Koizumi
- Department of Neurosurgery, The University of Tokyo, Tokyo, Japan
| | - Arisa Tomioka
- Department of Neurosurgery, The University of Tokyo, Tokyo, Japan
| | - Satoru Miyawaki
- Department of Neurosurgery, The University of Tokyo, Tokyo, Japan
| | - Nobuhito Saito
- Department of Neurosurgery, The University of Tokyo, Tokyo, Japan
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50
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Luan YY, Yin CH, Yao YM. Update Advances on C-Reactive Protein in COVID-19 and Other Viral Infections. Front Immunol 2021; 12:720363. [PMID: 34447386 PMCID: PMC8382792 DOI: 10.3389/fimmu.2021.720363] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 07/21/2021] [Indexed: 01/08/2023] Open
Abstract
Severe coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan dysfunction. It has been documented that severe COVID-19 is associated with higher levels of inflammatory mediators than a mild disease, and tracking these markers may allow early identification or even prediction of disease progression. It is well known that C-reactive protein (CRP) is the acute-phase protein and the active regulator of host innate immunity, which is highly predictive of the need for mechanical ventilation and may guide escalation of treatment of COVID-19-related uncontrolled inflammation. There are numerous causes of an elevated CRP, including acute and chronic responses, and these can be infectious or non-infectious in etiology. CRP are normally lacking in viral infections, while adaptive immunity appears to be essential for COVID-19 virus clearance, and the macrophage activation syndrome may explain the high serum CRP contents and contribute to the disease progression. Nevertheless, for the assessment of host inflammatory status and identification of viral infection in other pathologies, such as bacterial sepsis, the acute-phase proteins, including CRP and procalcitonin, can provide more important information for guiding clinical diagnosis and antibiotic therapy. This review is aimed to highlight the current and most recent studies with regard to the clinical significance of CRP in severe COVID-19 and other viral associated illnesses, including update advances on the implication of CRP and its form specifically on the pathogenesis of these diseases. The progressive understanding in these areas may be translated into promising measures to prevent severe outcomes and mitigate appropriate treatment modalities in critical COVID-19 and other viral infections.
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Affiliation(s)
- Ying-Yi Luan
- Translational Medicine Research Center, Medical Innovation Research Division and the Fourth Medical Center of PLA General Hospital, Beijing, China.,Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
| | - Cheng-Hong Yin
- Department of Central Laboratory, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China
| | - Yong-Ming Yao
- Translational Medicine Research Center, Medical Innovation Research Division and the Fourth Medical Center of PLA General Hospital, Beijing, China
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