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Qiu S, Hadidchi R, Vichare A, Lu JY, Hou W, Henry S, Akalin E, Duong TQ. SARS-CoV-2 Infection Is Associated with an Accelerated eGFR Decline in Kidney Transplant Recipients up to Four Years Post Infection. Diagnostics (Basel) 2025; 15:1091. [PMID: 40361909 PMCID: PMC12072077 DOI: 10.3390/diagnostics15091091] [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: 03/24/2025] [Revised: 04/15/2025] [Accepted: 04/22/2025] [Indexed: 05/15/2025] Open
Abstract
Background/Objectives: Although kidney transplant recipients (KTRs) who are immune-compromised have been shown to be at high risk of adverse acute COVID-19 outcomes (i.e., mortality and critical illness), the long-term outcomes of KTRs with a history of SARS-CoV-2 infection are unknown. We aimed to compare long-term outcomes of KTRs with and without exposure to SARS-CoV-2. Methods: This study retrospectively evaluated 1815 KTRs in the Montefiore Health System from 4 January 2001 to 31 January 2024. The final cohorts consisted of KTRs who survived COVID-19 (n = 510) and matched KTRs without COVID-19 (n = 510, controls). Outcomes were defined as all-cause mortality and changes in estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (UPCR) from 30 days up to four years post index date. Kaplan-Meier survival analysis and Cox proportional modeling were performed for mortality. Generalized estimating equations were used to analyze changes in eGFR and UPCR across time. Results: There was no significant group difference in long-term all-cause mortality (adjusted hazard ratio = 0.66, [0.43, 1.01] p = 0.057). eGFR in controls and COVID-19 patients before infection similarly decreased -0.98 units/year [-1.50, -0.46]. By contrast, eGFR declined at a significantly greater rate (-1.80 units/year [-2.45, -1.15]) in KTRs after COVID-19 compared to KTRs without COVID-19. This association was only seen among male and not female KTRs. COVID-19 status was not significantly associated with rate of change in UPCR or acute kidney rejection rate. Conclusions: SARS-CoV-2 infection was associated with an accelerated decline in eGFR up to four years post infection, suggesting potential long-term implications for graft health. These findings underscore the importance of vigilant monitoring and management of kidney function post SARS-CoV-2 infection in this vulnerable population.
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Affiliation(s)
- Shawn Qiu
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
| | - Roham Hadidchi
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
| | - Aditi Vichare
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
| | - Justin Y. Lu
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
| | - Wei Hou
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
| | - Sonya Henry
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
| | - Enver Akalin
- Department of Medicine (Nephrology), Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA;
| | - Tim Q. Duong
- Department of Radiology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY 10461, USA; (S.Q.); (R.H.); (A.V.); (J.Y.L.); (W.H.); (S.H.)
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Hawley HB. Long COVID: Clinical Findings, Pathology, and Endothelial Molecular Mechanisms. Am J Med 2025; 138:91-97. [PMID: 37704072 DOI: 10.1016/j.amjmed.2023.08.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Revised: 05/29/2023] [Accepted: 08/08/2023] [Indexed: 09/15/2023]
Abstract
Persistence of COVID-19 symptoms may follow severe acute respiratory syndrome coronavirus 2 infection. The incidence of long COVID increases with the severity of acute disease, but even mild disease can be associated with sequelae. The symptoms vary widely, with fatigue, shortness of breath, and cognitive dysfunction the most common. Abnormalities of multiple organs have been documented, and histopathology has revealed widespread microthrombi. Elevated levels of complement are present in acute COVID-19 patients and may persist at lower levels in long COVID. Evidence supports complement activation, with endotheliopathy-associated disease as the molecular mechanism causing both acute and long COVID.
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Affiliation(s)
- H Bradford Hawley
- Department of Medicine, Wright State University Boonshoft School of Medicine, Dayton, Ohio.
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Mata-Castro N, Castañeda-Vozmediano R, Perna C, Prada Puentes C, Sanz López L. Histological Findings of Resected Tracheal Ring in SARS-CoV-2-Positive and -Negative Tracheostomized Patients. Life (Basel) 2024; 14:1655. [PMID: 39768362 PMCID: PMC11679342 DOI: 10.3390/life14121655] [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: 11/11/2024] [Revised: 12/06/2024] [Accepted: 12/10/2024] [Indexed: 01/11/2025] Open
Abstract
INTRODUCTION The aim of this study was to compare the histopathological findings in the resected tracheal ring of tracheotomized critically ill patients with or without severe SARS-CoV-2 infection. MATERIAL AND METHODS This is a prospective case-control study. The data collection period was between May 2020 and 2022. Eighty tracheostomies were performed on patients with long intubation, and the resected tracheal ring was examined by standard microscopy. Forty consecutive tracheotomies were carried out in COVID-19-positive and -negative patients. RESULTS The mean age was 67.1 (6.9 SD) years in the COVID-19 group and 67.8 (9.6 SD) in the control group (p = 0.3). The number of men in each group was 30 (75.0%) versus 27 (67.5%), respectively (p = 0.5). No relevant histological alterations were found in 82.5% of samples. Chronic subepithelial inflammation was found in 13.8% of cases. Two cases presented with vasculitis (2.5%), and one case presented with thrombotic microangiopathy (1.2%), all of them in the COVID-19 group. We found no statistically significant dependence between relevant histologic findings versus no alterations (X2 = 0.779, p= 0.377) and no significant risk indices (RR = 1.8, OR = 2.032, PAR = 44%). CONCLUSION There is no evidence of increased risk of histopathological findings in the resected tracheal ring of patients with long intubation and COVID-19 disease.
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Affiliation(s)
- Nieves Mata-Castro
- Department of ENT, 12 de Octubre University Hospital, 28041 Madrid, Spain;
| | | | - Cristian Perna
- Department of Pathology, Ramon y Cajal Hospital, 28034 Madrid, Spain;
- RYCIS, School of Medicine Universidad de Alcala, 28801 Madrid, Spain
| | - Carlos Prada Puentes
- Department of Pathological Anatomy, Torrejón University Hospital, 28850 Madrid, Spain;
| | - Lorena Sanz López
- School of Medicine, Universidad Francisco de Vitoria, 28223 Madrid, Spain;
- Department of ENT, Torrejón University Hospital, Universidad Francisco de Vitoria, 28850 Madrid, Spain
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Schäfer A, Leist SR, Powers JM, Baric RS. Animal models of Long Covid: A hit-and-run disease. Sci Transl Med 2024; 16:eado2104. [PMID: 39536118 DOI: 10.1126/scitranslmed.ado2104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Accepted: 10/16/2024] [Indexed: 11/16/2024]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) pandemic has caused more than 7 million deaths globally. Despite the presence of infection- and vaccine-induced immunity, SARS-CoV-2 infections remain a major global health concern because of the emergence of SARS-CoV-2 variants that can cause severe acute coronavirus disease 2019 (COVID-19) or enhance Long Covid disease phenotypes. About 5 to 10% of SARS-CoV-2-infected individuals develop Long Covid, which, similar to acute COVID 19, often affects the lung. However, Long Covid can also affect other peripheral organs, especially the brain. The causal relationships between acute disease phenotypes, long-term symptoms, and involvement of multiple organ systems remain elusive, and animal model systems mimicking both acute and post-acute phases are imperative. Here, we review the current state of Long Covid animal models, including current and possible future applications.
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Affiliation(s)
- Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Sarah R Leist
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - John M Powers
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
| | - Ralph S Baric
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
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Chen F, Jiang F, Ma J, Alghamdi MA, Zhu Y, Yong JWH. Intersecting planetary health: Exploring the impacts of environmental stressors on wildlife and human health. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 283:116848. [PMID: 39116691 DOI: 10.1016/j.ecoenv.2024.116848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 07/30/2024] [Accepted: 08/05/2024] [Indexed: 08/10/2024]
Abstract
This comprehensive review articulates critical insights into the nexus of environmental stressors and their health impacts across diverse species, underscoring significant findings that reveal profound effects on both wildlife and human health systems. Central to our examination is the role of pollutants, climate variables, and pathogens in contributing to complex disease dynamics and physiological disruptions, with particular emphasis on immune and endocrine functions. This research brings to light emerging evidence on the severe implications of environmental pressures on a variety of taxa, including predatory mammals, raptorial birds, seabirds, fish, and humans, which are pivotal as indicators of broader ecosystem health and stability. We delve into the nuanced interplay between environmental degradation and zoonotic diseases, highlighting novel intersections that pose significant risks to biodiversity and human populations. The review critically evaluates current methodologies and advances in understanding the morphological, histopathological, and biochemical responses of these organisms to environmental stressors. We discuss the implications of our findings for conservation strategies, advocating for a more integrated approach that incorporates the dynamics of zoonoses and pollution control. This synthesis not only contributes to the academic discourse but also aims to influence policy by aligning with the Global Goals for Sustainable Development. It underscores the urgent need for sustainable interactions between humans and their environments, which are critical for preserving biodiversity and ensuring global health security. By presenting a detailed analysis of the interdependencies between environmental stressors and biological health, this review highlights significant gaps in current research and provides a foundation for future studies aimed at mitigating these pressing issues. Our study is significant as it proposes integrative and actionable strategies to address the challenges at the intersection of environmental change and public health, marking a crucial step forward in planetary health science.
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Affiliation(s)
- Fu Chen
- School of Public Administration, Hohai University, Nanjing 211100, China.
| | - Feifei Jiang
- School of Public Administration, Hohai University, Nanjing 211100, China.
| | - Jing Ma
- School of Public Administration, Hohai University, Nanjing 211100, China.
| | - Mohammed A Alghamdi
- Department of Laboratory & Blood Bank, Security Forces Hospital, Mecca, Saudi Arabia.
| | - Yanfeng Zhu
- School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou 221000, China.
| | - Jean Wan Hong Yong
- Department of Biosystems and Technology, Swedish University of Agricultural Sciences, Alnarp 23456, Sweden.
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Plasencia Martínez JM, García Tuells I, Bravo Pérez C, Blanco Barrio A. Target sign in COVID-19, radiological interpretation and diagnostic contribution of digital thoracic tomosynthesis. RADIOLOGIA 2024; 66 Suppl 1:S32-S39. [PMID: 38642959 DOI: 10.1016/j.rxeng.2023.07.005] [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: 06/06/2023] [Accepted: 07/16/2023] [Indexed: 04/22/2024]
Abstract
INTRODUCTION Our objectives are: To describe the radiological semiology, clinical-analytical features and prognosis related to the target sign (TS) in COVID-19. To determine whether digital thoracic tomosynthesis (DTT) improves the diagnostic ability of radiography. MATERIAL AND METHODS Retrospective, descriptive, single-centre, case series study, accepted by our ethical committee. Radiological, clinical, analytical and follow-up characteristics of patients with COVID-19 and TS on radiography and DTT between November 2020 and January 2021 were analysed. RESULTS Eleven TS were collected in 7 patients, median age 35 years, 57% male. All TS presented with a central nodule and a peripheral ring, and in at least 82%, the lung in between was of normal density. All TS were located in peripheral, basal regions and 91% in posterior regions. TS were multiple in 43%. Contiguous TS shared the peripheral ring. Other findings related to pneumonia were associated in 86% of patients. DTT detected 82% more TS than radiography. Only one patient underwent a CT angiography of the pulmonary arteries, positive for acute pulmonary thromboembolism. Seventy-one per cent presented with pleuritic pain. No distinctive laboratory findings or prognostic worsening were detected. CONCLUSIONS TS in COVID-19 predominates in peripheral and declining regions and can be multiple. Pulmonary thromboembolism was detected in one case. It occurs in young people, frequently with pleuritic pain and does not worsen the prognosis. DTT detects more than 80 % of TS than radiography.
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Affiliation(s)
| | - I García Tuells
- Servicio de Radiodiagnóstico, Hospital Universitario Morales Meseguer, Murcia, Spain
| | - C Bravo Pérez
- Servicio de Hematología, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, Instituto de Salud Carlos III - CIBERER, Madrid, Spain
| | - A Blanco Barrio
- Servicio de Radiodiagnóstico, Hospital Universitario Morales Meseguer, Murcia, Spain
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Bemtgen X, Kaier K, Rilinger J, Rottmann F, Supady A, von Zur Mühlen C, Westermann D, Wengenmayer T, Staudacher DL. Myocarditis mortality with and without COVID-19: insights from a national registry. Clin Res Cardiol 2024; 113:216-222. [PMID: 36565377 PMCID: PMC9789728 DOI: 10.1007/s00392-022-02141-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2022] [Accepted: 12/07/2022] [Indexed: 12/25/2022]
Abstract
BACKGROUND Myocarditis in context of a SARS-CoV-2 infection is vividly discussed in the literature. Real-world data however are sparse, and relevance of the myocarditis diagnosis to outcome in coronavirus disease (COVID-19) is unclear. PATIENTS AND METHODS Retrospective analysis of 75,304 patients hospitalized in Germany with myocarditis between 2007 and 2020 is reported by DESTATIS. Patients hospitalized between 01/2016 and 12/2019 served as reference cohort for the COVID-19 patients hospitalized in 2020. RESULTS A total of 75,304 patients were hospitalized between 2007 and 2020 (age 42.5 years, 30.1% female, hospital mortality 2.4%). In the reference cohort, 24,474 patients (age 42.8 years, 29.5% female, hospital mortality 2.2%) were registered. In 2020, annual myocarditis hospitalizations dropped by 19.6% compared to reference (4921 vs. 6119 annual hospitalization), of which 443/4921 (9.0%) were connected to COVID-19. In 2020, hospital mortality of myocarditis in non-COVID-19 patients increased significantly compared to reference (2.9% vs. 2.2%, p = 0.008, OR 1.31, 95% CI 1.08-1.60). In COVID-19 myocarditis, hospital mortality was even higher compared to reference (13.5% vs. 2.2%, p < 0.001, OR 6.93, 95% CI 5.18-9.18). CONCLUSION The burden of patients with myocarditis and COVID-19 in 2020 was low. Hospital mortality was more than sixfold higher in patients with myocarditis and COVID-19 compared to those with myocarditis but without COVID-19.
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Affiliation(s)
- Xavier Bemtgen
- Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
| | - Klaus Kaier
- Faculty of Medicine, Institute for Medical Biometry and Statistics, University of Freiburg, Freiburg, Germany
| | - Jonathan Rilinger
- Department of Cardiology and Angiology, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Felix Rottmann
- Department of Medicine IV - Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Alexander Supady
- Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, Germany
| | - Constantin von Zur Mühlen
- Department of Cardiology and Angiology, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Dirk Westermann
- Department of Cardiology and Angiology, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Tobias Wengenmayer
- Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Dawid L Staudacher
- Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
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Nikkhoo B, Naseri K, Rahimi Darehbagh R, Habiby M, Moasses-Ghafari B. Histopathological Examination of Lung Necropsy of 11 Patients Who Died Due to COVID-19: A Case Series. IRANIAN JOURNAL OF PATHOLOGY 2023; 19:126-131. [PMID: 38864091 PMCID: PMC11164306 DOI: 10.30699/ijp.2023.2008773.3153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 09/14/2023] [Indexed: 06/13/2024]
Abstract
COVID-19 is known to present with acute respiratory distress syndrome pathological manifestations. Studies have shown that patients with COVID-19 can develop diffuse alveolar damage, acute bronchopneumonia, necrotic bronchiolitis, and viral pneumonia. In this study, we investigated 11 cases. Needle necropsies of 11 patients, hospitalized at Tohid and Kowsar hospitals of Kurdistan University of Medical Sciences, with a positive antemortem SARS-CoV-2 (COVID-19) real-time PCR test, were fixated within 3 hours after death in the negative-pressure isolation morgue. The participants included six men (54%) and five women (46%) with a mean age of 73.82±10.58 (52-86) years old. The average hospitalization was 14.27±15.72 days. The results showed interstitial lymphocytic pneumonitis in most of the cases, varied from mild to moderate and up to severe in some cases. In 7 cases, anthracosis was noted, while one case demonstrated anthracosis with fibrosis. The hyaline membrane was reported in two patients. In one case, severe interstitial lymphocytic pneumonia with intra-alveolar exudate with organization, lithiasis, bronchiolitis pattern (BOOP), intra-alveolar hemorrhage, and mild fibrosis were seen. As a result, it is suggested to keep an eye on these pathologies in management of the severe cases of COVID-19 infection.
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Affiliation(s)
- Bahram Nikkhoo
- Department of Pathology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Karim Naseri
- Department of Anesthesiology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | | | - Mehrdad Habiby
- Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Bahar Moasses-Ghafari
- Department of Radiology, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran
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Erickson R, Huang C, Allen C, Ireland J, Roth G, Zou Z, Lu J, Lafont BAP, Garza NL, Brumbaugh B, Zhao M, Suzuki M, Olano L, Brzostowski J, Fischer ER, Twigg HL, Johnson RF, Sun PD. SARS-CoV-2 infection of human lung epithelial cells induces TMPRSS-mediated acute fibrin deposition. Nat Commun 2023; 14:6380. [PMID: 37821447 PMCID: PMC10567911 DOI: 10.1038/s41467-023-42140-6] [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: 06/09/2022] [Accepted: 09/27/2023] [Indexed: 10/13/2023] Open
Abstract
Severe COVID-associated lung injury is a major confounding factor of hospitalizations and death with no effective treatments. Here, we describe a non-classical fibrin clotting mechanism mediated by SARS-CoV-2 infected primary lung but not other susceptible epithelial cells. This infection-induced fibrin formation is observed in all variants of SARS-CoV-2 infections, and requires thrombin but is independent of tissue factor and other classical plasma coagulation factors. While prothrombin and fibrinogen levels are elevated in acute COVID BALF samples, fibrin clotting occurs only with the presence of viral infected but not uninfected lung epithelial cells. We suggest a viral-induced coagulation mechanism, in which prothrombin is activated by infection-induced transmembrane serine proteases, such as ST14 and TMPRSS11D, on NHBE cells. Our finding reveals the inefficiency of current plasma targeted anticoagulation therapy and suggests the need to develop a viral-induced ARDS animal model for treating respiratory airways with thrombin inhibitors.
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Affiliation(s)
- Rachel Erickson
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Chang Huang
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Cameron Allen
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Joanna Ireland
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Gwynne Roth
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Zhongcheng Zou
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Jinghua Lu
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Bernard A P Lafont
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Nicole L Garza
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Beniah Brumbaugh
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT, 59840, USA
| | - Ming Zhao
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Motoshi Suzuki
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Lisa Olano
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Joseph Brzostowski
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA
| | - Elizabeth R Fischer
- Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 903 South 4th Street, Hamilton, MT, 59840, USA
| | - Homer L Twigg
- Division of Pulmonary, Critical Care, Sleep, and Occupational Medicine, Indiana University Medical Center, 1120 West Michigan Street, CL 260A, Indianapolis, IN, 46202, USA
| | - Reed F Johnson
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
| | - Peter D Sun
- Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5625 Fishers Ln, Rockville, MD, 20852, USA.
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10
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Loch A, Siew KSW, Tan KL, Azman bin Raja Aman RR. Transient severe myocarditis and intraventricular thrombus associated with SARS-CoV-2 vaccination. Singapore Med J 2023; 64:366-372. [PMID: 35509213 PMCID: PMC10335633 DOI: 10.11622/smedj.2022042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 01/07/2022] [Indexed: 11/18/2022]
Affiliation(s)
- Alexander Loch
- Division of Cardiology, Department of Medicine, University Malaya Medical Centre, Malaysia
| | - Kelvin Shenq Woei Siew
- Division of Cardiology, Department of Medicine, University Malaya Medical Centre, Malaysia
| | - Kok Leng Tan
- Advanced Medical and Dental Institute, University Sains Malaysia, Malaysia
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11
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Khade S, Nalwa A, Rao M, Aggarwal D, Sharma V, Chugh A. Mucormycosis: An Epidemic Complicating the COVID-19 Pandemic. Oman Med J 2023; 38:e511. [PMID: 37313250 PMCID: PMC10259156 DOI: 10.5001/omj.2023.16] [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: 06/22/2021] [Accepted: 11/24/2021] [Indexed: 08/30/2023] Open
Abstract
COVID-19 is a relatively new disease whose complete pathogenesis and complications have not been elucidated. Apart from the morbidity and mortality caused by the virus itself, it is noted that patients affected with this virus have a higher susceptibility to bacterial and fungal co-infections. Mucormycosis is a rare and life-threatening fungal infection generally associated with uncontrolled diabetes mellitus and immunosuppression. It tends to rapid disease progression and poor prognosis if not diagnosed and managed promptly. There has been a sudden increase in the number of mucormycosis cases in patients with moderate to severe COVID-19 infection in the past few months. Herein, we present a series of 10 mucormycosis cases diagnosed over one week.
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Affiliation(s)
- Shalaka Khade
- Department of Pathology, All India Institute of Medical Sciences, Rajasthan, India
| | - Aasma Nalwa
- Department of Pathology, All India Institute of Medical Sciences, Rajasthan, India
| | - Meenakshi Rao
- Department of Pathology, All India Institute of Medical Sciences, Rajasthan, India
| | - Divya Aggarwal
- Department of Pathology, All India Institute of Medical Sciences, Rajasthan, India
| | - Vidhu Sharma
- Department of Pathology, All India Institute of Medical Sciences, Rajasthan, India
| | - Ankita Chugh
- Department of Pathology, All India Institute of Medical Sciences, Rajasthan, India
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Kanibolotskiy AA, Zayratyants OV. Morphological features of brain damage in severe COVID-19. КЛИНИЧЕСКАЯ ПРАКТИКА 2023; 14:21-30. [DOI: 10.17816/clinpract176827] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Background: The damage to the nervous system in COVID-19 reflects the systemic nature of the infection. The question of the neuroinvasive potential of SARS-CoV-2 remains open, the role of "pseudovirions" in the development of the endothelial dysfunction, as well as of the S1 subunit in the TLR activation, and the importance of the blood-brain barrier are discussed. The immunological, non-immunological, and cytopathic mechanisms of the virus's action are described; there is no clear understanding of the genesis of neuropathological changes caused by SARS-CoV-2. In this tragic pandemic, the lessons of the dead should help save lives and health. Aim: to study and explain the features of brain damage in COVID-19. Methods: Brain fragments from 20 patients who died due to severe COVID-19 were studied, the sections were stained with hematoxylin and eosin, according to van Gieson and Nissl, IHC reactions were performed with antibodies to the S-protein, CD68 and CD8, the changes were compared with those related to the lethal outcomes of pancreatic necrosis and ruptured aortic aneurysm. Results: The following changes in the olfactory analyzer were revealed: sharp edema, dystrophic changes in neurons, gliosis, accumulations of starchy bodies, which explains the neuronal pathway of SARS-CoV-2 invasion; vascular plethora, erythrostasis and thrombosis, perivenular hemorrhages, diffuse edema, macroglia proliferation, perivascular astrocytosis and satellite. A positive reaction with the antibodies to the S1 and S2 subunits of the spike protein was detected, while the result of the reaction with antibodies to the N-protein of the virus, confirming the active replication of the virus, was doubtful. The S-protein expression in individual endotheliocytes makes the transendothelial route of the virus entry unlikely, in contrast to the hematogenous and neuronal pathways. The viral DNA was not detected by PCR. A weak inflammatory reaction was revealed in the form of perivascular accumulations of lymphocytes, scattered T-lymphocytes. Conclusions: 2 groups of changes were identified, the first group included circulatory disorders with a tendency to thrombosis, edema, dystrophic-necrotic changes in neurons, glial proliferation, the second group included inflammatory-degenerative changes, a weak inflammatory reaction and amyloid-like bodies. Further morphometric and statistical studies are needed to obtain the reliable conclusions.
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Affiliation(s)
- Aleksander A. Kanibolotskiy
- N.V. Sklifosovsky Research Institute for Emergency Medicine
- Research Institute for Healthcare Organization and Medical Management
| | - Oleg V. Zayratyants
- Moscow State University of Medicine and Dentistry named after A.I. Evdokimov
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Pesti A, Danics K, Glasz T, Várkonyi T, Barbai T, Reszegi A, Kovalszky I, Vályi-Nagy I, Dobi D, Lotz G, Schaff Z, Kiss A. Liver alterations and detection of SARS-CoV-2 RNA and proteins in COVID-19 autopsies. GeroScience 2023; 45:1015-1031. [PMID: 36527584 PMCID: PMC9759055 DOI: 10.1007/s11357-022-00700-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 11/20/2022] [Indexed: 12/23/2022] Open
Abstract
The most severe alterations in Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection are seen in the lung. However, other organs also are affected. Here, we report histopathologic findings in the liver and detection of viral proteins and RNA in COVID-19 autopsies performed at the Semmelweis University (Budapest, Hungary). Between March 2020 through March 2022, 150 autopsies on patients who died of COVID-19 were analyzed. Cause-of-death categories were formed based on the association with SARS-CoV-2 as strong, contributive, or weak. Samples for histopathologic study were obtained from all organs, fixed in formalin, and embedded in paraffin (FFPE). Immunohistochemical study (IHC) to detect SARS-CoV-2 spike protein and nucleocapsid protein (NP), CD31, claudin-5, factor VIII, macrosialin (CD68), and cytokeratin 7, with reverse transcriptase polymerase chain reaction (RT-PCR), and in situ hybridization (ISH, RNAscope®) for SARS-CoV-2 RNA were conducted using FFPE samples of livers taken from 20 autopsies performed ≤ 2 days postmortem. All glass slides were scanned; the digital images were evaluated by semiquantitative scoring and scores were analyzed statistically. Steatosis, single-cell and focal/zonal hepatocyte necrosis, portal fibrosis, and chronic inflammation were found in varying percentages. Sinusoidal ectasia, endothelial cell disruption, and fibrin-filled sinusoids were seen in all cases; these were assessed semiquantitatively for severity (SEF scored). SEF scores did not correlate with cause-of-death categories (p = 0.92) or with severity of lung alterations (p = 0.96). SARS-CoV-2 RNA was detected in 13/20 cases by PCR and in 9/20 by ISH, with IHC demonstration of spike protein in 4/20 cases and NP in 15/20. Viral RNA and proteins were located in endothelial and Kupffer cells, and in portal macrophages, but not in hepatocytes and cholangiocytes. In conclusion, endothelial damage (SEF scores) was the most common alteration in the liver and was a characteristic, but not specific alteration in COVID-19, suggesting an important role in the pathogenesis of COVID-19-associated liver disease. Detection of SARS-CoV-2 RNA and viral proteins in liver non-parenchymal cells suggests that while the most extended primary viral cytotoxic effect occurs in the lung, viral components are present in other organs too, as in the liver. The necrosis/apoptosis and endothelial damage associated with viral infection in COVID-19 suggest that those patients who survive more severe COVID-19 may face prolonged liver repair and accordingly should be followed regularly in the post-COVID period.
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Affiliation(s)
- Adrián Pesti
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Krisztina Danics
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tibor Glasz
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tibor Várkonyi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Tamás Barbai
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Andrea Reszegi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Ilona Kovalszky
- Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
| | - István Vályi-Nagy
- Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary
| | - Deján Dobi
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Gábor Lotz
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
| | - Zsuzsa Schaff
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary.
| | - András Kiss
- Department of Pathology, Forensic and Insurance Medicine, Semmelweis University, Budapest, Hungary
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14
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Torbenson M, Erickson LA. Reprint of: Problems and solutions: a special issue of gastrointestinal, pancreatic, and liver pathology. Hum Pathol 2023; 132:S0046-8177(23)00031-X. [PMID: 36792477 DOI: 10.1016/j.humpath.2023.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 02/16/2023]
Affiliation(s)
- Michael Torbenson
- Professor, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN, 55905, USA.
| | - Lori A Erickson
- Professor, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN, 55905, USA
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15
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Eschbacher KL, Larsen RA, Moyer AM, Majumdar R, Reichard RR. Neuropathological findings in COVID-19: an autopsy cohort. J Neuropathol Exp Neurol 2022; 82:21-28. [PMID: 36355625 DOI: 10.1093/jnen/nlac101] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
The literature regarding the neuropathological findings in cases of SARS-CoV-2 infection, which causes coronavirus disease 2019 (COVID-19), is expanding. We identified 72 patients who died of COVID-19 (n = 48) or had recovered shortly before death (n = 24) and had autopsies performed at our institution (49 males, 23 females; median age at death 76.4 years, range: 0.0-95.0 years). Droplet digital polymerase chain reaction (ddPCR) for the detection of SARS-CoV-2 was performed (n = 58) in multiple brain regions. In cases the assay was successfully completed (n = 50), 98.0% were negative (n = 49) and 2% were indeterminate (n = 1). Most histologic findings were typical of the patient age demographic, such as neurodegenerative disease and arteriolosclerosis. A subset of cases demonstrated findings which may be associated with sequelae of critical illness. We identified 3 cases with destructive perivascular lesions with axonal injury, one of which also harbored perivascular demyelinating lesions. These rare cases may represent a parainfectious process versus sequelae of vascular injury. The lack of detectable SARS-CoV-2 by ddPCR or significant histologic evidence of direct infection suggests that active encephalitis is not a feature of COVID-19.
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Affiliation(s)
- Kathryn L Eschbacher
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Rachel A Larsen
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ann M Moyer
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Ramanath Majumdar
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
| | - Robert Ross Reichard
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA
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16
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Su L, Zhang J, Peng Z. The role of kidney injury biomarkers in COVID-19. Ren Fail 2022; 44:1280-1288. [PMID: 35930243 PMCID: PMC9359166 DOI: 10.1080/0886022x.2022.2107544] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 07/25/2022] [Accepted: 07/25/2022] [Indexed: 12/15/2022] Open
Abstract
The coronavirus disease-2019 (COVID-19) outbreak has been declared a global pandemic. COVID-19-associated acute kidney injury (COVID-19 AKI) is related to a high mortality rate and serves as an independent risk factor for hospital death in patients with COVID-19. Early diagnosis would allow for earlier intervention and potentially improve patient outcomes. The goal of early identification of AKI has been the primary impetus for AKI biomarker research, and several kidney injury biomarkers have been demonstrated to be beneficial in predicting COVID-19 AKI as well as disease progression in COVID-19. Furthermore, such data provide valuable insights into the molecular mechanisms underlying this complex and unique disease and serve as a molecular phenotyping tool that could be utilized to direct clinical intervention. This review focuses on a number of kidney injury biomarkers, such as CysC, NAGAL, KIM-1, L-FABP, IL-18, suPAR, and [TIMP-2] • [IGFBP7], which have been widely studied in common clinical settings, such as sepsis, cardiac surgery, and contrast-induced AKI. We explore the role of kidney injury biomarkers in COVID-19 and discuss what remains to be learned.
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Affiliation(s)
- Lianjiu Su
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
- Department of Cardiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
| | - Jiahao Zhang
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhiyong Peng
- Department of Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China
- Department of Critical Care Medicine, Center of Critical Care Nephrology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
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17
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Torbenson M, Erickson LA. Problems and solutions: a special issue of gastrointestinal, pancreatic, and liver pathology. Hum Pathol 2022; 129:56-59. [PMID: 35970422 DOI: 10.1016/j.humpath.2022.07.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 07/29/2022] [Indexed: 12/14/2022]
Affiliation(s)
- Michael Torbenson
- Professor, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN, 55905, USA.
| | - Lori A Erickson
- Professor, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester MN, 55905, USA
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18
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Poloni TE, Moretti M, Medici V, Turturici E, Belli G, Cavriani E, Visonà SD, Rossi M, Fantini V, Ferrari RR, Carlos AF, Gagliardi S, Tronconi L, Guaita A, Ceroni M. COVID-19 Pathology in the Lung, Kidney, Heart and Brain: The Different Roles of T-Cells, Macrophages, and Microthrombosis. Cells 2022; 11:3124. [PMID: 36231087 PMCID: PMC9563269 DOI: 10.3390/cells11193124] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 09/28/2022] [Accepted: 09/29/2022] [Indexed: 12/03/2022] Open
Abstract
Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease's pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer's Disease pathology was also assessed. PCR techniques were used to verify the presence of viral RNA. COVID-19 cases had a short clinical course (0-32 days) and their mean age was 77.4 y/o. Hypoxic changes and inflammatory infiltrates were present across all tissues. The lymphocytic component in the lungs and kidneys was predominant over that of other tissues (p < 0.001), with a significantly greater presence of T-lymphocytes in the lungs (p = 0.020), which showed the greatest presence of viral antigens. The heart showed scant SARS-CoV-2 traces in the endothelium-endocardium, foci of activated macrophages, and rare lymphocytes. The brain showed scarce SARS-CoV-2 traces, prominent microglial activation, and rare lymphocytes. The pons exhibited the highest microglial activation (p = 0.017). Microthrombosis was significantly higher in COVID-19 lungs (p = 0.023) compared with controls. The most characteristic pathological features of COVID-19 were an abundance of T-lymphocytes and microthrombosis in the lung and relevant microglial hyperactivation in the brainstem. This study suggests that the long-term sequelae of COVID-19 derive from persistent inflammation, rather than persistent viral replication.
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Affiliation(s)
- Tino Emanuele Poloni
- Department of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
- Department of Rehabilitation, ASP Golgi-Redaelli, Abbiategrasso, 20081 Milan, Italy
| | - Matteo Moretti
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Valentina Medici
- Department of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Elvira Turturici
- Department of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Giacomo Belli
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Elena Cavriani
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Silvia Damiana Visonà
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
| | - Michele Rossi
- Unit of Biostatistics, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Valentina Fantini
- Laboratory of Neurobiology and Neurogenetic, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Riccardo Rocco Ferrari
- Laboratory of Neurobiology and Neurogenetic, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Arenn Faye Carlos
- Department of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Stella Gagliardi
- Unit of Molecular Biology and Transcriptomics IRCCS Mondino Foundation, 27100 Pavia, Italy
| | - Livio Tronconi
- Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy
- Department of Forensic Medicine, IRCCS Mondino Foundation, 27100 Pavia, Italy
| | - Antonio Guaita
- Department of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
- Unit of Biostatistics, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
- Laboratory of Neurobiology and Neurogenetic, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
| | - Mauro Ceroni
- Department of Neurology and Neuropathology, Golgi-Cenci Foundation, Abbiategrasso, 20081 Milan, Italy
- Unit of Molecular Biology and Transcriptomics IRCCS Mondino Foundation, 27100 Pavia, Italy
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19
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Anwar MM, Sah R, Shrestha S, Ozaki A, Roy N, Fathah Z, Rodriguez-Morales AJ. Disengaging the COVID-19 Clutch as a Discerning Eye Over the Inflammatory Circuit During SARS-CoV-2 Infection. Inflammation 2022; 45:1875-1894. [PMID: 35639261 PMCID: PMC9153229 DOI: 10.1007/s10753-022-01674-5] [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: 03/03/2022] [Revised: 03/29/2022] [Accepted: 04/18/2022] [Indexed: 01/08/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the cytokine release syndrome (CRS) and leads to multiorgan dysfunction. Mitochondrial dynamics are fundamental to protect against environmental insults, but they are highly susceptible to viral infections. Defective mitochondria are potential sources of reactive oxygen species (ROS). Infection with SARS-CoV-2 damages mitochondria, alters autophagy, reduces nitric oxide (NO), and increases both nicotinamide adenine dinucleotide phosphate oxidases (NOX) and ROS. Patients with coronavirus disease 2019 (COVID-19) exhibited activated toll-like receptors (TLRs) and the Nucleotide-binding and oligomerization domain (NOD-), leucine-rich repeat (LRR-), pyrin domain-containing protein 3 (NLRP3) inflammasome. The activation of TLRs and NLRP3 by SARS-CoV-2 induces interleukin 6 (IL-6), IL-1β, IL-18, and lactate dehydrogenase (LDH). Herein, we outline the inflammatory circuit of COVID-19 and what occurs behind the scene, the interplay of NOX/ROS and their role in hypoxia and thrombosis, and the important role of ROS scavengers to reduce COVID-19-related inflammation.
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Affiliation(s)
- Mohammed Moustapha Anwar
- Department of Biotechnology, Institute of Graduate Studies and Research (IGSR), Alexandria University, Alexandria, Egypt.
| | - Ranjit Sah
- Tribhuvan University Institute of Medicine, Kathmandu, Nepal
| | - Sunil Shrestha
- Department of Pharmaceutical and Health Service Research, Nepal Health Research and Innovation Foundation, Lalitpur, Nepal
| | - Akihiko Ozaki
- Department of Breast Surgery, Jyoban Hospital of Tokiwa Foundation, Iwaki, Japan
- Medical Governance Research Institute, Tokyo, Japan
| | - Namrata Roy
- SRM University, SRM Nagar, Kattankulathur, Chengalpattu, Tamil Nadu, 603203, India
| | - Zareena Fathah
- Kings College London, London, UK
- College of Medicine and Health Sciences, United Arab University, Abu Dhabi, United Arab Emirates
| | - Alfonso J Rodriguez-Morales
- Grupo de Investigación Biomedicina, Faculty of Medicine, Fundacion Universitaria Autonoma de Las Americas, Pereira, Risaralda, Colombia.
- Institución Universitaria Visión de Las Americas, Pereira, Risaralda, Colombia.
- Faculty of Health Sciences, Universidad Cientifica del Sur, Lima, Peru.
- School of Medicine, Universidad Privada Franz Tamayo (UNIFRANZ), Cochabamba, Bolivia.
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SARS-CoV-2 Infection during Pregnancy and Histological Alterations in the Placenta. Diagnostics (Basel) 2022; 12:diagnostics12092258. [PMID: 36140659 PMCID: PMC9498066 DOI: 10.3390/diagnostics12092258] [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: 08/27/2022] [Revised: 09/15/2022] [Accepted: 09/16/2022] [Indexed: 11/17/2022] Open
Abstract
(1) Background: Despite the high number of cases of COVID-19 during pregnancy, SARS-CoV-2 congenital infection is rare. The role of the placenta as a barrier preventing the transmission of SARS-CoV-2 from the mother to the fetus is still being studied. This study aimed to evaluate the impact of SARS-CoV-2 infection on placental tissue. (2) Methods: This was a transversal monocentric observational study. In the study, we included pregnant women with COVID-19 who delivered at “Sfântul Pantelimon” Clinical Emergency Hospital between 1 April 2020 and 30 March 2022. Histological analyses, both macroscopic and microscopic, were performed for placentas that came from these cases. (3) Results: To date, a characteristic placental lesion has not been clearly demonstrated, but most findings include features of maternal and fetal vascular malperfusion, which probably reflect the reduction in placental blood flow due to low oxygen level from the hypoxic respiratory disease and underlying hypercoagulable state induced by the COVID-19 infection. (4) Conclusions: The histopathological aspects found in placentas that came from COVID-19-positive pregnant women are common for many other diseases, but when they are found together, they are highly suggestive for viral infectious involvement of the placenta.
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Kanne JP, Little BP, Schulte JJ, Haramati A, Haramati LB. Long-term Lung Abnormalities Associated with COVID-19 Pneumonia. Radiology 2022; 306:e221806. [PMID: 36040336 PMCID: PMC9462591 DOI: 10.1148/radiol.221806] [Citation(s) in RCA: 43] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
In the 3rd year of the SARS-CoV-2 pandemic, much has been learned about the long-term effects of COVID-19 pneumonia on the lungs. Approximately one-third of patients with moderate-to-severe pneumonia, especially those requiring intensive care therapy or mechanical ventilation, have residual abnormalities at chest CT 1 year after presentation. Abnormalities range from parenchymal bands to bronchial dilation to frank fibrosis. Less is known about the long-term pulmonary vascular sequelae, but there appears to be a persistent, increased risk of venothromboembolic events in a small cohort of patients. Finally, the associated histologic abnormalities resulting from SARS-CoV-2 infection are similar to those seen in patients with other causes of acute lung injury.
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22
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Vidusa L, Kalejs O, Maca-Kaleja A, Strumfa I. Role of Endomyocardial Biopsy in Diagnostics of Myocarditis. Diagnostics (Basel) 2022; 12:diagnostics12092104. [PMID: 36140505 PMCID: PMC9497694 DOI: 10.3390/diagnostics12092104] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 07/29/2022] [Accepted: 08/25/2022] [Indexed: 11/19/2022] Open
Abstract
Endomyocardial biopsy as the cornerstone of diagnostics has been re-evaluated throughout the years, leaving unanswered questions on the precedence of it. The reported incidence of myocarditis has increased during the pandemic of coronavirus disease 2019 (COVID-19), reinforcing discussions on appropriate diagnostics of myocarditis. By analysis of evidence-based literature published within the last demi-decade, we aimed to summarize the most recent information in order to evaluate the current role of endomyocardial biopsy in diagnostics and management of myocarditis. For the most part, research published over the last five years showed ongoing uncertainty regarding the use, informativeness, safety and necessity of performing a biopsy. Special circumstances, such as fulminant clinical course or failure to respond to empirical treatment, were reconfirmed as justified indications, with a growing applicability of non-invasive diagnostic approaches for most other cases. We concluded that endomyocardial biopsy, if performed properly and with adjunct diagnostic methods, holds a critical role for treatment correction in specific histological subtypes of myocarditis and for differential diagnosis between immune-mediated myocarditis and secondary infections due to immunosuppressive treatment. A high level of possible misdiagnosing was detected, indicating the need to review terminology used to describe findings of myocardial inflammation that did not meet Dallas criteria.
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Affiliation(s)
- Liga Vidusa
- Department of Pathology, Riga Stradins University, 16 Dzirciema Street, LV-1007 Riga, Latvia
| | - Oskars Kalejs
- Department of Internal Medicine, Riga Stradins University, 16 Dzirciema Street, LV-1007 Riga, Latvia
- Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital, 13 Pilsonu Street, LV-1002 Riga, Latvia
| | - Aija Maca-Kaleja
- Department of Internal Medicine, Riga Stradins University, 16 Dzirciema Street, LV-1007 Riga, Latvia
- Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital, 13 Pilsonu Street, LV-1002 Riga, Latvia
| | - Ilze Strumfa
- Department of Pathology, Riga Stradins University, 16 Dzirciema Street, LV-1007 Riga, Latvia
- Correspondence:
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23
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Complicated Laryngotracheal Stenosis Occurring Early after COVID-19 Intubation. SURGERIES 2022. [DOI: 10.3390/surgeries3030023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Background: Airway stenosis is a known complication of prolonged intubation in hospitalized patients. With the high rate of intubations in patients with COVID-19 pneumonia, laryngotracheal stenosis (LTS) is a complication of COVID-19 that drastically reduces quality of life for patients who may remain tracheostomy-dependent. Methods: Patient medical history, laryngoscopy, and CT imaging were obtained from medical records. Results: We report four cases of complicated LTS following intubation after COVID-19 pneumonia and explore the current literature in a narrative review. Four patients developed LTS following intubation from COVID-19 pneumonia. Three patients remain tracheostomy-dependent, and the fourth required a heroic operative schedule to avoid tracheostomy. Conclusion: Intubation for COVID-19 pneumonia can result in severe LTS, which may persist despite endoscopic intervention.
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Waseem W, Anwar F, Saleem U, Ahmad B, Zafar R, Anwar A, Saeed Jan M, Rashid U, Sadiq A, Ismail T. Prospective Evaluation of an Amide-Based Zinc Scaffold as an Anti-Alzheimer Agent: In Vitro, In Vivo, and Computational Studies. ACS OMEGA 2022; 7:26723-26737. [PMID: 35936440 PMCID: PMC9352245 DOI: 10.1021/acsomega.2c03058] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 07/04/2022] [Indexed: 06/15/2023]
Abstract
Alzheimer's disease is the most common progressive neurodegenerative mental disorder associated with loss of memory, decline in cognitive function, and dysfunction of language. The prominent pathogenic causes of this disease involve deposition of amyloid-β plaques, acetylcholine neurotransmitter deficiency, and accumulation of neurofibrillary tangles. There are multiple pathways that have been targeted to treat this disease. The inhibition of the intracellular cyclic AMP regulator phosphodiesterase IV causes the increase in CAMP levels that play an important role in the memory formation process. Organometallic chemistry works in a different way in treating pharmacological disorders. In the field of medicinal chemistry and pharmaceuticals, zinc-based amide carboxylates have been shown to be a preferred pharmacophore. The purpose of this research work was to investigate the potential of zinc amide carboxylates in inhibition of phosphodiesterase IV for the Alzheimer's disease management. Swiss Albino mice under controlled conditions were divided into seven groups with 10 mice each. Group I was injected with carboxymethylcellulose (CMC) at 1 mL/100 g dose, group II was injected with Streptozotocin (STZ) at 3 mg/kg dose, group III was injected with Piracetam acting as a standard drug at 200 mg/kg dosage, while groups IV-VII were injected with a zinc scaffold at the dose regimen of 10, 20, 40, and 80 mg/kg through intraperitoneal injection. All groups except group I were injected with Streptozotocin on the first day and third day of treatment at the dose of 3 mg/kg through an intracerebroventricular route to induce Alzheimer's disease. Afterward, respective treatment was continued for all groups for 23 days. In between the treatment regimen, groups were analyzed for memory and learning improvement through various behavioral tests such as open field, elevated plus maze, Morris water maze, and passive avoidance tests. At the end of the study, different biochemical markers in the brain were estimated like neurotransmitters (dopamine, serotonin and adrenaline), oxidative stress markers (superoxide dismutase, glutathione, and catalase), acetylcholinesterase (AchE), tau proteins, and amyloid-β levels. A PCR study was also performed. Results showed that the LD50 of the zinc scaffold is greater than 2000 mg/kg. Research indicated that the zinc scaffold has the potential to improve the memory impairment and learning behavior in Alzheimer's disease animal models in a dose-dependent manner. At the dose of 80 mg/kg, a maximum response was observed for the zinc scaffold. Maximum reduction in the acetylcholinesterase enzyme was observed at 80 mg/kg dose, which was further strengthened and verified by the PCR study. Oxidative stress was restored by the zinc scaffold due to the significant activation of the endogenous antioxidant enzymes. This research ended up with the conclusion that the zinc-based amide carboxylate scaffold has the potential to improve behavioral disturbances and vary the biochemical markers in the brain.
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Affiliation(s)
- Wajeeha Waseem
- Riphah
Institute of Pharmaceutical Sciences, Riphah
International University, Lahore Campus, Lahore 54000, Pakistan
| | - Fareeha Anwar
- Riphah
Institute of Pharmaceutical Sciences, Riphah
International University, Lahore Campus, Lahore 54000, Pakistan
| | - Uzma Saleem
- Faculty
of Pharmaceutical Sciences, Government College
University (GCU) Faisalabad, Faisalabad 38000, Pakistan
| | - Bashir Ahmad
- Riphah
Institute of Pharmaceutical Sciences, Riphah
International University, Lahore Campus, Lahore 54000, Pakistan
| | - Rehman Zafar
- Department
of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Riphah International University, Islamabad 44000, Pakistan
| | - Asifa Anwar
- Department
of Pharmacy, Islamia University Bahawalpur, Bahawalpur 63100, Pakistan
| | | | - Umer Rashid
- Department
of Chemistry, Comsat University, Abbottabad 22060, Pakistan
| | - Abdul Sadiq
- Department
of Pharmacy, University of Malakand, Chakdara 18000, Dir, KPK, Pakistan
| | - Tariq Ismail
- Department
of Pharmacy, COMSAT University, Abbottabad 22060, Pakistan
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Orendáčová M, Kvašňák E. Effects of vaccination, new SARS-CoV-2 variants and reinfections on post-COVID-19 complications. Front Public Health 2022; 10:903568. [PMID: 35968477 PMCID: PMC9372538 DOI: 10.3389/fpubh.2022.903568] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
Post-COVID-19 complications involve a variety of long-lasting health complications emerging in various body systems. Since the prevalence of post-COVID-19 complications ranges from 8-47% in COVID-19 survivors, it represents a formidable challenge to COVID-19 survivors and the health care system. Post-COVID-19 complications have already been studied in the connection to risk factors linked to their higher probability of occurrence and higher severity, potential mechanisms underlying the pathogenesis of post-COVID-19 complications, and their functional and structural correlates. Vaccination status has been recently revealed to represent efficient prevention from long-term and severe post-COVID-19 complications. However, the exact mechanisms responsible for vaccine-induced protection against severe and long-lasting post-COVID-19 complications remain elusive. Also, to the best of our knowledge, the effects of new SARS-CoV-2 variants and SARS-CoV-2 reinfections on post-COVID-19 complications and their underlying pathogenesis remain to be investigated. This hypothesis article will be dedicated to the potential effects of vaccination status, SARS-CoV-2 reinfections, and new SARS-CoV-2 variants on post-COVID-19 complications and their underlying mechanisms Also, potential prevention strategies against post-COVID complications will be discussed.
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Affiliation(s)
- Mária Orendáčová
- Department of Medical Biophysics and Medical Informatics, Third Faculty of Medicine, Charles University in Prague, Prague, Czechia
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The Evaluation Value of Diffusion-Weighted Imaging for Brain Injury in Patients after Deep Hypothermic Circulatory Arrest. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:5985806. [PMID: 35685655 PMCID: PMC9162866 DOI: 10.1155/2022/5985806] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 04/15/2022] [Accepted: 05/09/2022] [Indexed: 12/17/2022]
Abstract
Objective Cerebral complications may occur after surgery with deep hypothermic circulatory arrest (DHCA). Diffusion-weighted imaging (DWI) has shown promising results in detecting early changes of cerebral ischemia. However, studies in human models are limited. Here, we examined the significance of DWI for detecting brain injury in postoperative patients after DHCA. Methods Twelve patients who had undergone selective cerebral perfusion with DHCA were enrolled. All patients underwent magnetic resonance imaging (MRI) examinations before and after the operation with T1-weighted phase (T1W) and T2-weighted phase (T2W). Magnetic resonance angiography (3D TOF) was applied to observe intracranial arterial communication situations. DWI was employed to calculate the apparent diffusion coefficient (ADC) values. The neurocognitive function of patients was assessed preoperatively and postoperatively using the Montreal Cognitive Assessment Scale (MoCA), Hamilton Depression Scale (HAMD), and Hamilton Anxiety Scale (HAMA). Results The ADC values of the whole brain of patients after surgery were significantly higher than before surgery (P = 0.003). However, no significant difference in the ADC values of other regions before and after the operation was observed. There was no significant effect on the postoperative cognitive function of patients after surgery, but visual-spatial and executive abilities were significantly reduced, while psychological anxiety (P = 0.005) and depression levels (P < 0.05) significantly increased. Correlation analysis revealed a significant association between ADC change values and depression change values (P < 0.05). Conclusion DHCA demonstrated no significant effect on the cognitive function of patients but could affect the mood of patients. On the other hand, DWI demonstrated promising efficiency and accuracy in evaluating brain injury after DHCA.
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Oikonomou E, Souvaliotis N, Lampsas S, Siasos G, Poulakou G, Theofilis P, Papaioannou TG, Haidich AB, Tsaousi G, Ntousopoulos V, Sakka V, Charalambous G, Rapti V, Raftopoulou S, Syrigos K, Tsioufis C, Tousoulis D, Vavuranakis M. Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study. Vascul Pharmacol 2022; 144:106975. [PMID: 35248780 PMCID: PMC8893931 DOI: 10.1016/j.vph.2022.106975] [Citation(s) in RCA: 83] [Impact Index Per Article: 27.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Revised: 02/15/2022] [Accepted: 02/27/2022] [Indexed: 12/26/2022]
Abstract
BACKGROUND Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function. METHODS In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages. RESULTS Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge. CONCLUSION COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.
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Affiliation(s)
- Evangelos Oikonomou
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece; 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece.
| | - Nektarios Souvaliotis
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece
| | - Stamatios Lampsas
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece
| | - Gerasimos Siasos
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece; 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece
| | - Garyphallia Poulakou
- 3rd Department of Medicine, Medical School, Sotiria Chest Disease Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Panagiotis Theofilis
- 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece
| | - Theodore G Papaioannou
- 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece
| | - Anna-Bettina Haidich
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Georgia Tsaousi
- Department of Anesthesiology and ICU, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Vasileios Ntousopoulos
- 3rd Department of Medicine, Medical School, Sotiria Chest Disease Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Vissaria Sakka
- 3rd Department of Medicine, Medical School, Sotiria Chest Disease Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Vasiliki Rapti
- 3rd Department of Medicine, Medical School, Sotiria Chest Disease Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Konstantinos Syrigos
- 3rd Department of Medicine, Medical School, Sotiria Chest Disease Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Costas Tsioufis
- 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece
| | - Dimitris Tousoulis
- 1st Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Hippokration General Hospital, Athens, Greece
| | - Manolis Vavuranakis
- 3rd Department of Cardiology, National and Kapodistrian University of Athens, Medical School, Sotiria Chest Disease Hospital, Athens, Greece
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Histopathological and molecular links of COVID-19 with novel clinical manifestations for the management of coronavirus-like complications. Inflammopharmacology 2022; 30:1219-1257. [PMID: 35637319 PMCID: PMC9150634 DOI: 10.1007/s10787-022-00999-9] [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: 03/31/2022] [Accepted: 04/12/2022] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19) causes transmissible viral illness of the respiratory tract prompted by the SARS-CoV-2 virus. COVID-19 is one of the worst global pandemics affecting a large population worldwide and causing catastrophic loss of life. Patients having pre-existing chronic disorders are more susceptible to contracting this viral infection. This pandemic virus is known to cause notable respiratory pathology. Besides, it can also cause extra-pulmonary manifestations. Multiple extra-pulmonary tissues express the SARS-CoV-2 entry receptor, hence causing direct viral tissue damage. This insightful review gives a brief description of the impact of coronavirus on the pulmonary system, extra-pulmonary systems, histopathology, multiorgan consequences, the possible mechanisms associated with the disease, and various potential therapeutic approaches to tackle the manifestations.
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Zuin M, Engelen MM, Bilato C, Vanassche T, Rigatelli G, Verhamme P, Vandenbriele C, Zuliani G, Roncon L. Prevalence of Acute Pulmonary Embolism at Autopsy in Patients With COVID-19. Am J Cardiol 2022; 171:159-164. [PMID: 35277253 PMCID: PMC8902912 DOI: 10.1016/j.amjcard.2022.01.051] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2021] [Revised: 01/19/2022] [Accepted: 01/26/2022] [Indexed: 12/25/2022]
Abstract
To date, the actual prevalence of acute pulmonary embolism (PE) in patients with SARS-CoV-2 infection remains unknown, as systematic screening for PE is cumbersome. We performed a systematic review and meta-analysis on autoptic data to estimate the prevalence of histopathologic findings of acute PE and its relevance as a cause of death on patients with COVID-19. We searched MEDLINE-PubMed and Scopus to locate all articles published in the English language, up to August 10, 2021, reporting the autoptic prevalence of acute PE and evaluating PE as the underlying cause of death in patients with COVID-19. The pooled prevalence for both outcomes was calculated using a random-effects model and presenting the related 95% confidence interval (CI). Statistical heterogeneity was measured using the Higgins I2 statistic. We analyzed autoptic data of 749 patients with COVID-19 (mean age 63.4 years) included in 14 studies. In 10 studies, based on 526 subjects (mean age 63.8 years), a random-effect model revealed that autoptic acute PE findings were present in 27.5% of cases (95% CI 15.0 to 45.0%, I2 89.9%). Conversely, in 429 COVID-19 subjects (mean age 64.0 years) enrolled in 9 studies, acute PE was the underlying cause of death in 19.9% of cases (95% CI 11.0 to 33.3%, I2 83.3%). Autoptic findings of acute PE in patients with COVID-19 are present in about 30% of subjects, whereas a venous thromboembolic event represents the underlying cause of death in about 1 of 4 patients.
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Affiliation(s)
- Marco Zuin
- Department of Translational Medicine, Section of Internal and Cardio-Respiratory Medicine, University of Ferrara, Ferrara, Italy.
| | - Matthias M Engelen
- Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium
| | - Claudio Bilato
- Department of Cardiology, West Vicenza Hospital, Arzignano, Italy
| | - Thomas Vanassche
- Department of Cardiology, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Gianluca Rigatelli
- Department of Cardiology, Santa Maria della Misericordia Hospital, Rovigo, Italy
| | - Peter Verhamme
- Department of Cardiovascular Diseases, University Hospitals Leuven, Leuven, Belgium
| | | | - Giovanni Zuliani
- Department of Translational Medicine, Section of Internal and Cardio-Respiratory Medicine, University of Ferrara, Ferrara, Italy
| | - Loris Roncon
- Department of Cardiology, Santa Maria della Misericordia Hospital, Rovigo, Italy
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Omer AK, Khorshidi S, Mortazavi N, Rahman HS. A Review on the Antiviral Activity of Functional Foods Against COVID-19 and Viral Respiratory Tract Infections. Int J Gen Med 2022; 15:4817-4835. [PMID: 35592539 PMCID: PMC9112189 DOI: 10.2147/ijgm.s361001] [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: 02/03/2022] [Accepted: 04/12/2022] [Indexed: 11/23/2022] Open
Abstract
Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.
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Affiliation(s)
- Abdullah Khalid Omer
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
- Razga Company, Sulaimaniyah, Kurdistan Region, Iraq
| | - Sonia Khorshidi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Negar Mortazavi
- Department of Food Hygiene and Quality Control, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran
| | - Heshu Sulaiman Rahman
- Department of Physiology, College of Medicine, University of Sulaimani, Sulaimaniyah, Iraq
- Department of Medical Laboratory Sciences, Komar University of Science and Technology, Sulaimaniyah, Iraq
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31
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Tintinago LF, Victoria W, Escobar Stein J, Gonzales LF, Fernandez MI, Candelo E. Laryngotracheal Stenoses Post-Acute Respiratory Distress Syndrome due to COVID-19: Clinical Presentation, Histopathological Findings and Management. A Series of 12 Cases. Indian J Otolaryngol Head Neck Surg 2022; 74:3262-3267. [PMID: 35402214 PMCID: PMC8983326 DOI: 10.1007/s12070-022-03076-3] [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: 10/26/2021] [Accepted: 01/01/2022] [Indexed: 11/25/2022] Open
Abstract
Coronavirus disease 2019 (COVID-19) has increased the risk of developing severe acute respiratory distress syndrome and subsequent moderate to severe laryngotracheal stenoses (LSTs) with an early presentation that occurs between two and three months after SARS-CoV-2 infection. We present a series of 12 cases of LST following SARS-CoV-2 infection. Dense lymphocyte infiltration with multinuclear giant cell granulomas was found on biopsy with intranuclear inclusions, suggestive of viral cytopathic effects in one case and intravascular fibrin thrombi with perivascular mononuclear infiltrate of CD3 + T lymphocytes. We present the largest and only series that describes clinical and histopathological characteristics of LTS and the management and outcomes after early laryngotracheal reconstruction in the context of the SARS-CoV-2 outbreak.
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Affiliation(s)
| | - William Victoria
- Head and Neck and Airway Surgery Department, Fundacion Valle del Lili, Cali, Colombia
| | | | | | | | - Estephania Candelo
- Head and Neck and Airway Surgery Department, Fundacion Valle del Lili, Cali, Colombia
- Clinical Research Center, Fundacion Valle del Lili, Cali, Colombia
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Caruso PF, Angelotti G, Greco M, Guzzetta G, Cereda D, Merler S, Cecconi M. Early prediction of SARS-CoV-2 reproductive number from environmental, atmospheric and mobility data: A supervised machine learning approach. Int J Med Inform 2022; 162:104755. [PMID: 35390590 PMCID: PMC8970608 DOI: 10.1016/j.ijmedinf.2022.104755] [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: 11/12/2021] [Revised: 02/04/2022] [Accepted: 03/27/2022] [Indexed: 11/16/2022]
Abstract
INTRODUCTION SARS-CoV-2 was declared a pandemic by the WHO on March 11th, 2020. Public protective measures were enforced in every country to limit the diffusion of SARS-CoV-2. Its transmission, mainly by droplets, has been measured by the effective reproduction number (Rt) that counts the number of secondary cases caused in a population by an average infectious individual at time t. Current strategies to calculate Rt reflect the number of secondary cases after several days, due to a delay from symptoms onset to reporting. We propose a complementary Rt estimation using supervised machine learning techniques to predict short term variations with more timely results. MATERIAL AND METHODS Our primary goal was to predict Rt of the current day in the twelve provinces of Lombardy with the highest possible accuracy, and with no influence of the local testing strategies. We gathered data about mobility, weather, and pollution from different public sources as a proxy of human behavior and public health measures. We built four supervised machine learning algorithms with different strategies: the outcome variable was the daily median Rt values per province obtained from officially adopted algorithms. RESULTS Data from 243 days for every province were presented to our four models (from February 15th, 2020, to October 14th, 2020). Two models using differential calculation of Rt instead of the raw values showed the highest mean coefficient of determination (0.93 for both) and residuals reported the lowest mean error (-0.03 and 0.01) and standard deviation (0.13 for both) as well. The one with access to the value of Rt of the day before heavily relied on that feature for prediction, while the other one had more distributed weights. DISCUSSION The model that had not access to the Rt value of the previous day and used Rt differential value as outcome (FDRt) was considered the most robust according to the metrics. Its forecasts were able to predict the trend that Rt values would have developed over different weeks, but it was not particularly accurate in predicting the precise value of Rt. A correlation among mobility, atmospheric, features, pollution and Rt values is plausible, but further testing should be performed.
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Affiliation(s)
- Pier Francesco Caruso
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele - Milan, Italy; Department of Anesthesiology and Intensive Care, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano - Milan, Italy
| | - Giovanni Angelotti
- Aritifcial Intelligence Center, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano - Milan, Italy
| | - Massimiliano Greco
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele - Milan, Italy; Department of Anesthesiology and Intensive Care, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano - Milan, Italy.
| | - Giorgio Guzzetta
- Center for Health Emergencies, Fondazione Bruno Kessler, Trento, Italy
| | | | - Stefano Merler
- Center for Health Emergencies, Fondazione Bruno Kessler, Trento, Italy
| | - Maurizio Cecconi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20072 Pieve Emanuele - Milan, Italy; Department of Anesthesiology and Intensive Care, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Rozzano - Milan, Italy
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Hess CN, Capell WH, Bristow MR, Ruf W, Szarek M, Morrow DA, Nicolau JC, Graybill CA, Marshall D, Hsia J, Bonaca MP. Rationale and design of a study to assess the safety and efficacy of rNAPc2 in COVID-19: the Phase 2b ASPEN-COVID-19 trial. Am Heart J 2022; 246:136-143. [PMID: 34986394 PMCID: PMC8720379 DOI: 10.1016/j.ahj.2021.12.010] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 12/11/2021] [Accepted: 12/21/2021] [Indexed: 12/22/2022]
Abstract
Background The interaction between thrombosis and inflammation appears central to COVID-19-associated coagulopathy and likely contributes to poor outcomes. Tissue factor is a driver of disordered coagulation and inflammatory signaling in viral infections and is important for viral replication; therefore, tissue factor may be an important therapeutic target in COVID-19. Study Design ASPEN-COVID-19 (NCT04655586) is a randomized, prospective open-label blinded endpoint (PROBE), active comparator Phase 2b trial to evaluate the safety and efficacy of recombinant Nematode Anticoagulant Protein c2 (rNAPc2), a potent tissue factor inhibitor, in patients hospitalized with COVID-19 with elevated D-dimer levels. This report describes the design of the Phase 2b dose ranging and proof of concept study. Participants are randomly assigned, in a 1:1:2 ratio, to lower or higher dose rNAPc2 by subcutaneous injection on days 1, 3, and 5 or to heparin according to local standard of care; randomization is stratified by baseline D-dimer level (at 2X upper limit of normal). The primary efficacy endpoint for Phase 2b is proportional change in D-dimer concentration from baseline to Day 8 or day of discharge, whichever is earlier. The primary safety endpoint is major or non-major clinically relevant bleeding through Day 8. Phase 2b enrollment began in December 2020 and is projected to complete ∼160 participants by Q4 2021. Conclusions ASPEN-COVID-19 will provide important data on a novel therapeutic approach that may improve outcomes in hospitalized COVID-19 patients beyond available anticoagulants by targeting tissue factor, with potential effects on not only thrombosis but also inflammation and viral propagation.
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Abstract
To measure inspiratory airflow resistance in patients with acute respiratory distress syndrome (ARDS) due to COVID-19.
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Shafqat A, Shafqat S, Salameh SA, Kashir J, Alkattan K, Yaqinuddin A. Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review. Front Immunol 2022; 13:835104. [PMID: 35401519 PMCID: PMC8989408 DOI: 10.3389/fimmu.2022.835104] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/02/2022] [Indexed: 12/15/2022] Open
Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes coronavirus-19 (COVID-19), has caused significant morbidity and mortality globally. In addition to the respiratory manifestations seen in severe cases, multi-organ pathologies also occur, making management a much-debated issue. In addition, the emergence of new variants can potentially render vaccines with a relatively limited utility. Many investigators have attempted to elucidate the precise pathophysiological mechanisms causing COVID-19 respiratory and systemic disease. Spillover of lung-derived cytokines causing a cytokine storm is considered the cause of systemic disease. However, recent studies have provided contradictory evidence, whereby the extent of cytokine storm is insufficient to cause severe illness. These issues are highly relevant, as management approaches considering COVID-19 a classic form of acute respiratory distress syndrome with a cytokine storm could translate to unfounded clinical decisions, detrimental to patient trajectory. Additionally, the precise immune cell signatures that characterize disease of varying severity remain contentious. We provide an up-to-date review on the immune dysregulation caused by COVID-19 and highlight pertinent discussions in the scientific community. The response from the scientific community has been unprecedented regarding the development of highly effective vaccines and cutting-edge research on novel therapies. We hope that this review furthers the conversations held by scientists and informs the aims of future research projects, which will potentially further our understanding of COVID-19 and its immune pathogenesis.
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Affiliation(s)
- Areez Shafqat
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | | | | | - Junaid Kashir
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
- Center of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Khaled Alkattan
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Le AB, Brown CK, Gibbs SG, Uhrig A, Green AD, Broch Brantsæter A, Herstein JJ, Vasa A, Shugart J, Wilson Egbe W, Lowe JJ. Best practices of highly infectious decedent management: Consensus recommendations from an international expert workshop. JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE 2022; 19:129-138. [PMID: 35025726 DOI: 10.1080/15459624.2022.2027427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
With the increasing number of highly infectious disease incidents, outbreaks, and pandemics in our society (e.g., Ebola virus disease, Lassa fever, coronavirus diseases), the need for consensus and best practices on highly infectious decedent management is critical. In January 2020, a workshop of subject matter experts from across the world convened to discuss highly infectious live patient transport and highly infectious decedent management best practices. This commentary focuses on the highly infectious decedent management component of the workshop. The absence of guidance or disparate guidance on highly infectious decedent management can increase occupational safety and health risks for death care sector workers. To address this issue, the authorship presents these consensus recommendations on best practices in highly infectious decedent management, including discussion of what is considered a highly infectious decedent; scalability and storage for casualty events; integration of key stakeholders; infection control and facility considerations; transport; care and autopsy; psychological, ethical, and cultural considerations as well as multi-national care perspectives. These consensus recommendations are not intended to be exhaustive but rather to underscore this overlooked area and serve as a starting point for much-needed conversations.
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Affiliation(s)
- Aurora B Le
- Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan
| | - Christopher K Brown
- Division of Emergency Operations, Center for Preparedness and Response, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Shawn G Gibbs
- Department of Environmental and Occupational Health, Texas A&M University School of Public Health, College Station, Texas
| | - Alexander Uhrig
- Department of Infectious Diseases, Pulmonary and Critical Care Medicine, Charité University Medical Center, Berlin, Germany
| | | | - Arne Broch Brantsæter
- Department of Infectious Diseases and Department of Acute Medicine, Oslo University Hospital, Oslo, Norway
| | - Jocelyn J Herstein
- Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center College of Public Health, Omaha, Nebraska
| | | | - Jill Shugart
- Center for State, Tribal, Local and Territorial Support, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Wanda Wilson Egbe
- Department of Health and Human Services, Assistant Secretary for Preparedness and Response, Washington, DC
| | - John J Lowe
- Department of Environmental, Agricultural and Occupational Health, University of Nebraska Medical Center College of Public Health, Omaha, Nebraska
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Filograna L, Manenti G, Ampanozi G, Calcagni A, Ryan CP, Floris R, Thali MJ. Potentials of post-mortem CT investigations during SARS-COV-2 pandemic: a narrative review. Radiol Med 2022; 127:383-390. [PMID: 35226246 PMCID: PMC8884096 DOI: 10.1007/s11547-022-01457-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Accepted: 01/21/2022] [Indexed: 12/22/2022]
Abstract
In December 2019, a new coronavirus, SARS-COV-2, caused a cluster of cases of pneumonia in China, and rapidly spread across the globe. It was declared a pandemic by the World Health Organization on March 11th, 2020. Virtual autopsy by post-mortem CT (PMCT) and its ancillary techniques are currently applied in post-mortem examinations as minimally or non-invasive techniques with promising results. In this narrative review, we speculate on the potentials of PMCT and its ancillary techniques, as a viable investigation technique for analysis of suspected or confirmed SARS-COV-2 deaths. An online literature search was performed by using three prefix search terms (postmortem, post-mortem, post mortem) individually combined with the suffix radiology, imaging, computed tomography, CT and with the search terms ‘SARS-CoV-2’ and ‘COVID-19’ to identify papers about PMCT and its ancillary techniques in SARS-COV-2 positive cadavers. PMCT findings suggestive for pulmonary COVID-19 in deceased positive SARS-COV-2 infection are reported in the literature. PMCT ancillary techniques were never applied in such cases. PMCT imaging of the lungs has been proposed as a pre-autopsy screening method for SARS-COV-2 infection. Further studies are needed to ascertain the value of PMCT in determining COVID-19 as the cause of death without autopsy histopathological confirmation. We advocate the application of PMCT techniques in the study of ascertained or suspected SARS-COV-2 infected deceased individuals as a screening technique and as a method of post-mortem investigation, to augment the numbers of case examined and significantly reducing infection risk for the operators.
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Affiliation(s)
- Laura Filograna
- Department of Radiological Sciences, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Lazio, IT, Italy.
| | - Guglielmo Manenti
- Department of Radiological Sciences, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Lazio, IT, Italy
| | - Garyfalia Ampanozi
- Institute of Forensic Medicine, Department of Forensic Medicine and Imaging, University of Zurich, Winterthurerstrasse 190/52, CH-8057, Zurich, Switzerland
| | - Antonello Calcagni
- Department of Radiological Sciences, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Lazio, IT, Italy
| | - Colleen Patricia Ryan
- Department of Radiological Sciences, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Lazio, IT, Italy
| | - Roberto Floris
- Department of Radiological Sciences, Fondazione PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, Rome, Lazio, IT, Italy
| | - Michael John Thali
- Institute of Forensic Medicine, Department of Forensic Medicine and Imaging, University of Zurich, Winterthurerstrasse 190/52, CH-8057, Zurich, Switzerland
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Air trapping in COVID-19 patients following hospital discharge: retrospective evaluation with paired inspiratory/expiratory thin-section CT. Eur Radiol 2022; 32:4427-4436. [PMID: 35226158 PMCID: PMC8884095 DOI: 10.1007/s00330-022-08580-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2021] [Revised: 01/14/2022] [Accepted: 01/15/2022] [Indexed: 12/13/2022]
Abstract
Objectives The study reports our experience with paired inspiration/expiration thin-section computed tomographic (CT) scans in the follow-up of COVID-19 patients with persistent respiratory symptoms. Methods From August 13, 2020, to May 31, 2021, 48 long-COVID patients with respiratory symptoms (27 men and 21 women; median age, 62.0 years; interquartile range: 54.0–69.0 years) underwent follow-up paired inspiration-expiration thin-section CT scans. Patient demographics, length of hospital stay, intensive care unit admission rate, and clinical and laboratory features of acute infection were also included. The scans were obtained on a median of 72.5 days after onset of symptoms (interquartile range: 58.5–86.5) and at least 30 days after hospital discharge. Thin-section CT findings included ground-glass opacity, mosaic attenuation pattern, consolidation, traction bronchiectasis, reticulation, parenchymal bands, bronchial wall thickening, and air trapping. We used a quantitative score to determine the degree of air trapping in the expiratory scans. Results Parenchymal abnormality was found in 50% (24/48) of patients and included air trapping (37/48, 77%), ground-glass opacities (19/48, 40%), reticulation (18/48, 38%), parenchymal bands (15/48, 31%), traction bronchiectasis (9/48, 19%), mosaic attenuation pattern (9/48, 19%), bronchial wall thickening (6/48, 13%), and consolidation (2/48, 4%). The absence of air trapping was observed in 11/48 (23%), mild air trapping in 20/48 (42%), moderate in 13/48 (27%), and severe in 4/48 (8%). Independent predictors of air trapping were, in decreasing order of importance, gender (p = 0.0085), and age (p = 0.0182). Conclusions Our results, in a limited number of patients, suggest that follow-up with paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping. Key Points • Our experience indicates that paired inspiratory/expiratory CT in long-COVID patients with persistent respiratory symptoms commonly displays air trapping. • Iterative reconstruction and dose-reduction options are recommended for demonstrating air trapping in long-COVID patients.
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Teixeira JP, Barone S, Zahedi K, Soleimani M. Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets. Int J Mol Sci 2022; 23:2242. [PMID: 35216358 PMCID: PMC8877127 DOI: 10.3390/ijms23042242] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 02/07/2022] [Accepted: 02/08/2022] [Indexed: 01/08/2023] Open
Abstract
As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.
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Affiliation(s)
- J. Pedro Teixeira
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA
| | - Sharon Barone
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Research/Medicine Services, New Mexico Veterans Healthcare Medical Center, Albuquerque, NM 87108, USA
| | - Kamyar Zahedi
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Research/Medicine Services, New Mexico Veterans Healthcare Medical Center, Albuquerque, NM 87108, USA
| | - Manoocher Soleimani
- Department of Internal Medicine, Division of Nephrology, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA; (S.B.); (K.Z.)
- Research/Medicine Services, New Mexico Veterans Healthcare Medical Center, Albuquerque, NM 87108, USA
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Filograna L, Grassi S, Manenti G, Di Donna C, Tatulli D, Nardoni F, Masini V, Ausania F, Grassi VM, Floris R, Colosimo C, Arena V, Pascali VL, Oliva A. Postmortem CT pulmonary findings in SARS-CoV-2-positive cases: correlation with lung histopathological findings and autopsy results. Int J Legal Med 2022; 136:1407-1415. [PMID: 35157128 PMCID: PMC8853405 DOI: 10.1007/s00414-022-02793-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 01/26/2022] [Indexed: 12/12/2022]
Abstract
Introduction/purpose Postmortem computed tomography (PMCT) is a valuable tool for analyzing the death of patients with SARS-CoV-2 infection. The purpose of this study was to investigate the correlation between PMCT lung findings in autopsy cadavers positive for SARS-CoV-2 infection and the severity of COVID-19 lung disease by histopathological analysis. Materials and methods We reviewed chest PMCT findings, paying particular attention to the lung parenchyma, in 8 autopsy cases positive for SARS-CoV-2. Correlations between chest PMCT and histopathological findings were assessed. Clinical conditions and comorbidities were also recorded and discussed. The primary cause of death was finally considered. Results In 6/8 cases, pulmonary PMCT findings were massive consolidation (4/8) and bilateral diffuse mixed densities with a crazy-paving pattern (2/8). These cases showed severe pulmonary signs of COVID-19 at histopathological analysis. In the remaining 2/8 cases, pulmonary PMCT findings were scant antideclive ground-glass opacities in prevalent gradient densities attributed to hypostasis. In 4/8 cases with massive consolidations, important comorbidities were noted. In 6/8 cases with severe pulmonary histopathological signs of lung COVID-19, autopsy found that the cause of death was cardiorespiratory failure. In the remaining 2/8 cases, histopathological analysis revealed lung alterations due to edema and some signs of SARS-CoV-2 infection; the cause of death was not attributed to SARS-CoV-2 infection (Table 1). Discussion and conclusion Chest PMCT findings correlate with the severity of COVID-19 lung disease at histopathology examination. According to our results, there may also be a relationship between cause of death and PMCT findings in COVID-19, which must be critically analyzed considering clinical antemortem data.
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Affiliation(s)
- Laura Filograna
- Department of Integrated Care Processes, Diagnostic Imaging Area, Tor Vergata University, PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, FondazioneRome, Italy.
| | - Simone Grassi
- Department of Health Surveillance and Bioethics, Section of Legal Medicine, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Guglielmo Manenti
- Department of Integrated Care Processes, Diagnostic Imaging Area, Tor Vergata University, PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, FondazioneRome, Italy
| | - Carlo Di Donna
- Department of Integrated Care Processes, Diagnostic Imaging Area, Tor Vergata University, PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, FondazioneRome, Italy
| | - Doriana Tatulli
- Department of Integrated Care Processes, Diagnostic Imaging Area, Tor Vergata University, PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, FondazioneRome, Italy
| | - Francesco Nardoni
- Department of Health Surveillance and Bioethics, Section of Legal Medicine, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Valentina Masini
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology - Diagnostic Imaging Area, Catholic University of Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Francesco Ausania
- Department of Health Surveillance and Bioethics, Section of Legal Medicine, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Vincenzo Maria Grassi
- Department of Health Surveillance and Bioethics, Section of Legal Medicine, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Roberto Floris
- Department of Integrated Care Processes, Diagnostic Imaging Area, Tor Vergata University, PTV Policlinico Tor Vergata, Viale Oxford 81, 00133, FondazioneRome, Italy
| | - Cesare Colosimo
- Department of Diagnostic Imaging, Oncological Radiotherapy and Hematology - Diagnostic Imaging Area, Catholic University of Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Vincenzo Arena
- Department of Woman and Child Health and Public Health, Area of Pathology, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Vincenzo Lorenzo Pascali
- Department of Health Surveillance and Bioethics, Section of Legal Medicine, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
| | - Antonio Oliva
- Department of Health Surveillance and Bioethics, Section of Legal Medicine, Catholic University of Sacred Heart, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Francesco Vito, 1, 00168, Rome, Italy
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Nunes MC, Hale MJ, Mahtab S, Mabena FC, Dludlu N, Baillie VL, Thwala BN, Els T, du Plessis J, Laubscher M, Mckenzie S, Mtshali S, Menezes C, Serafin N, van Blydenstein S, Tsitsi M, Dulisse B, Madhi SA. Clinical characteristics and histopathology of COVID-19 related deaths in South African adults. PLoS One 2022; 17:e0262179. [PMID: 35051205 PMCID: PMC8775212 DOI: 10.1371/journal.pone.0262179] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2021] [Accepted: 12/17/2021] [Indexed: 12/22/2022] Open
Abstract
Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.
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Affiliation(s)
- Marta C. Nunes
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Martin J. Hale
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Division of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sana Mahtab
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Fikile C. Mabena
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Paediatrics and Child Health, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Noluthando Dludlu
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Vicky L. Baillie
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Bukiwe N. Thwala
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Toyah Els
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Jeanine du Plessis
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Marius Laubscher
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Shakeel Mckenzie
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sihle Mtshali
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Colin Menezes
- Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Natali Serafin
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Sarah van Blydenstein
- Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Merika Tsitsi
- Department of Internal Medicine, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Brian Dulisse
- BDII Analytics, Atlanta, GA, United States of America
| | - Shabir A. Madhi
- South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- Department of Science and Technology/National Research Foundation, South African Research Chair Initiative in Vaccine Preventable Diseases, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
- African Leadership in Vaccinology Expertise, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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Alkattan W, Yaqinuddin A, Shafqat A, Kashir J. NET-Mediated Pathogenesis of COVID-19: The Role of NETs in Hepatic Manifestations. JOURNAL OF HEALTH AND ALLIED SCIENCES NU 2022. [DOI: 10.1055/s-0041-1741418] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AbstractSome coronavirus disease-2019 (COVID-19) patients exhibit multi-organ failure, which often includes the liver. Indeed, liver disease appears to be an emerging feature of COVID-19 infections. However, the exact mechanism behind this remains unknown. Neutrophil extracellular traps (NETs) have increasingly been attributed as major contributors to various liver pathologies, including sepsis, ischemic-reperfusion (I/R) injury, and portal hypertension in the setting of chronic liver disease. Although vital in normal immunity, excessive NET formation can drive inflammation, particularly of the endothelium. Collectively, we propose that NETs observed to be elevated in severe COVID-19 infection play principal roles in liver injury in addition to acute lung injury. Herein, we discuss the potential mechanisms underlying COVID-induced liver injury including cytopathic effects from direct liver infection, systemic inflammatory response syndrome, and hypoxic injury, encompassing I/R injury and coagulopathy. Further research is required to further elucidate the role of NETs in COVID. This holds potential therapeutic significance, as inhibition of NETosis could alleviate the symptoms of acute respiratory distress syndrome and liver injury, as well as other organs.
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Affiliation(s)
- Wael Alkattan
- College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
| | - Ahmed Yaqinuddin
- College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
| | - Areez Shafqat
- College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
| | - Junaid Kashir
- College of Medicine, Alfaisal University, Riyadh, Kingdom of Saudi Arabia
- Department of Comparative Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Kingdom of Saudi Arabia
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Xie H, Han W, Xie Q, Xu T, Zhu M, Chen J. Face mask-A potential source of phthalate exposure for human. JOURNAL OF HAZARDOUS MATERIALS 2022; 422:126848. [PMID: 34403943 PMCID: PMC8496910 DOI: 10.1016/j.jhazmat.2021.126848] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 07/20/2021] [Accepted: 08/04/2021] [Indexed: 05/19/2023]
Abstract
Face masks are necessary for fighting against the coronavirus disease 2019 around the world. As the face mask is usually made from polymers and phthalates are widely-used additives into the polymers, the face mask could be a potential source of phthalate exposure to humans. However, limited knowledge is available on the occurrence and risks of the phthalates from the face mask. In this study, twelve phthalates were determined in 56 mask samples collected from different countries. The phthalates were detected in all the samples with total levels ranging from 115 ng/g to 37,700 ng/g. Estimated daily intakes (EDIs) of the phthalates from the masks ranged from 3.71 to 639 ng/kg-bw/day, and the EDIs of the phthalates from masks for toddlers were approximately 4-5 times higher than those for adults. Non-carcinogenic risks in relation to the phthalates in masks were found to be within safe levels, yet 89.3% of the mask samples exhibited potential carcinogenic effects to humans. The extent of the risks for wearing masks located at a moderate level comparing with other skin-contacted products. This study unveiled a potential source of phthalate exposure to human, and indicated necessity of managing types and levels of additives in the face masks.
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Affiliation(s)
- Huaijun Xie
- Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, China
| | - Wenjing Han
- Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, China
| | - Qing Xie
- Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, China
| | - Tong Xu
- Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, China
| | - Minghua Zhu
- Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, China
| | - Jingwen Chen
- Key Laboratory of Industrial Ecology and Environmental Engineering (Ministry of Education), Dalian Key Laboratory on Chemicals Risk Control and Pollution Prevention Technology, School of Environmental Science and Technology, Dalian University of Technology, Linggong Road 2, Dalian 116024, China.
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Mirzaie M, Sarmadi S, Omranipour A, Mirzaian E, Ahangari R, Yazdi Z, Asgarian A. Placental pathologies and fetal outcome in pregnant women with COVID-19: A retrospective study. ASIAN PACIFIC JOURNAL OF REPRODUCTION 2022. [DOI: 10.4103/2305-0500.346091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Kayaaslan B, Guner R. COVID-19 and the liver: A brief and core review. World J Hepatol 2021; 13:2013-2023. [PMID: 35070005 PMCID: PMC8727220 DOI: 10.4254/wjh.v13.i12.2013] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Revised: 06/23/2021] [Accepted: 11/27/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 has a wide range of clinical spectrum from asymptomatic infection to severe infection resulting in death within a short time. Currently, it is known that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) does not only cause a respiratory tract infection but a more complicated disease that can lead to multiple system involvement including the liver. Herein, we evaluate the epidemiology, the impact of liver injury/ dysfunction on disease prognosis, the pathophysiological mechanisms and management of liver injury. More than one-fourth of the patients have abnormal liver function tests, mostly a mild-to-moderate liver dysfunction. Liver injury is significantly associated with a poor clinical outcome. Direct cytotoxic effect of SARS-CoV-2, the immune response ("cytokine storm"), the complications related to the disease, and drugs used in the treatments are the pathophysiological mechanisms responsible for liver injury. However, the exact mechanism is not yet clearly explained. The binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 receptors and entering the hepatocyte and cholangiocytes can cause cytotoxic effects on the liver. Excessive immune response has an important role in disease progression and causes acute respiratory distress syndrome and multi-organ failures accompanied by liver injury. Treatment drugs, particularly lopinavir/ritonavir, remdesivir and antibiotics are a frequent reason for liver injury. The possible reasons should be meticulously investigated and resolved.
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Affiliation(s)
- Bircan Kayaaslan
- Department of Infectious Disease and Clinical Microbiology, Ankara City Hospital, Ankara Yildirim Beyazit University, Ankara 06800, Turkey.
| | - Rahmet Guner
- Department of Infectious Disease and Clinical Microbiology, Ankara City Hospital, Ankara Yildirim Beyazit University, Ankara 06800, Turkey
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Yurdaisik I, Demiroz AS, Oz AB, Akker M, Agirman A, Aksoy SH, Nurili F. Postmortem Biopsies of the Lung, Heart, Liver, and Spleen of COVID-19 Patients. Cureus 2021; 13:e20734. [PMID: 35111427 PMCID: PMC8792123 DOI: 10.7759/cureus.20734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2021] [Indexed: 12/15/2022] Open
Abstract
Objective We aimed to evaluate histopathologic alterations in the lung, heart, liver, and spleen of coronavirus disease 2019 (COVID-19) decedents through postmortem core needle biopsies. Materials and methods Patients who died of reverse transcription-polymerase chain reaction-proven COVID-19 were included in this postmortem case series. Postmortem percutaneous ultrasound-guided biopsies of the lungs, heart, liver, and spleen were performed using 14- and 16-gauge needles. Biopsy samples were stained with hematoxylin-eosin and examined under a light microscope. Clinicodemographic characteristics, chest computed tomography (CT) images, and COVID-19-related treatments of the patients were also collected. Results Seven patients were included in this study. Liver and heart tissue samples were available from all patients, and lung and spleen tissue samples were available from five and three patients, respectively. Chest CT images predominantly revealed bibasilar ground-glass opacities. Lung biopsies showed diffuse alveolar damage in all biopsy specimens. Heart findings were nonspecific and largely compatible with the underlying disease. Patchy necrosis, steatosis, and mononuclear cell infiltration were the main findings in the liver biopsies. Splenic histopathological examination showed that splenic necrosis and neutrophil infiltration were common findings in all patients. Conclusion Tissue acquisition was complete for the heart and liver and acceptable for the lungs. The amount of tissue was sufficient for a proper histopathologic examination. Histopathological findings were generally in accordance with previous autopsy studies. Radiological findings of the lung were also correlated with the histopathologic findings. We consider that a postmortem biopsy is a feasible alternative for histopathological examinations in COVID-19 decedents.
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Duarte-Neto AN, Ferraz da Silva LF, Monteiro RADA, Theodoro Filho J, Leite TLLF, de Moura CS, Gomes-Gouvêa MS, Pinho JRR, Kanamura CT, de Oliveria EP, Bispo KCS, Arruda C, Dos Santos AB, Aquino FCG, Caldini EG, Mauad T, Saldiva PHN, Dolhnikoff M. Ultrasound-Guided Minimally Invasive Tissue Sampling: A Minimally Invasive Autopsy Strategy During the COVID-19 Pandemic in Brazil, 2020. Clin Infect Dis 2021; 73:S442-S453. [PMID: 34910174 PMCID: PMC8672862 DOI: 10.1093/cid/ciab885] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Minimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)-guided MITS as a strategy. METHODS This case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases. RESULTS US-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction. CONCLUSIONS Our data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.
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Affiliation(s)
- Amaro Nunes Duarte-Neto
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.,Instituto Adolfo Lutz, São Paulo, Brazil
| | - Luiz Fernando Ferraz da Silva
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.,Serviço de Verificação de Óbitos da Capital, Universidade de São Paulo, São Paulo, Brazil
| | - Renata Aparecida de Almeida Monteiro
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Jair Theodoro Filho
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Thabata Larissa Luciano Ferreira Leite
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Catia Sales de Moura
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | | | | | | | | | - Kely Cristina Soares Bispo
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Cássia Arruda
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Aline Brito Dos Santos
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Flavia Cristina Gonçalves Aquino
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Elia Garcia Caldini
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.,Departamento de Patologia, Laboratório de Investigação Médica 59, São Paulo, Brazil
| | - Thais Mauad
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Paulo Hilário Nascimento Saldiva
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Marisa Dolhnikoff
- Brazilian Image Autopsy Study Group, Departamento de Patologia, Laboratório de Investigação Médica 05, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
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Mudenda V, Mumba C, Pieciak RC, Mwananyanda L, Chimoga C, Ngoma B, Mupila Z, Kwenda G, Forman L, Lapidot R, MacLeod WB, Thea DM, Gill CJ. Histopathological Evaluation of Deceased Persons in Lusaka, Zambia With or Without Coronavirus Disease 2019 (COVID-19) Infection: Results Obtained From Minimally Invasive Tissue Sampling. Clin Infect Dis 2021; 73:S465-S471. [PMID: 34910177 PMCID: PMC8672753 DOI: 10.1093/cid/ciab858] [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] [Indexed: 11/13/2022] Open
Abstract
Background Although much has been learned about the pathophysiology of coronavirus disease 2019 (COVID-19) infections, pathology data from patients who have died of COVID-19 in low- and middle-income country settings remain sparse. We integrated minimally invasive tissue sampling (MITS) into an ongoing postmortem surveillance study of COVID-19 in deceased individuals of all ages in Lusaka, Zambia. Methods We enrolled deceased subjects from the University Teaching Hospital Morgue in Lusaka, Zambia within 48 hours of death. We collected clinical and demographic information, a nasopharyngeal swab, and core tissue biopsies from the lung, liver, and kidneys for pathologic analysis. Individuals were considered eligible for MITS if they had a respiratory syndrome prior to death or a COVID-19+ polymerase chain reaction (PCR) nasopharyngeal swab specimen. Samples were retested using quantitative reverse transcriptase PCR. Results From June to September 2020 we performed MITS on 29 deceased individuals. PCR results were available for 28/29 (96.5%) cases. Three had a COVID-19+ diagnosis antemortem, and 5 more were identified postmortem using the recommended cycle threshold cut-point <40. When expanding the PCR threshold to 40 ≤ cycle threshold (Ct) ≤ 45, we identified 1 additional case. Most cases were male and occurred in the community The median age at death was 47 years (range 40–64). Human immunodeficiency virus (HIV)/AIDS, tuberculosis, and diabetes were more common among the COVID-19+ cases. Diffuse alveolar damage and interstitial pneumonitis were common among COVID-19+ cases; nonspecific findings of hepatic steatosis and acute kidney injury were also prevalent in the COVID-19+ group. Vascular thrombi were rarely detected. Conclusions Lung abnormalities typical of viral pneumonias were common among deceased COVID-19+ individuals, as were nonspecific findings in the liver and kidneys. Pulmonary vascular thrombi were rarely detected, which could be a limitation of the MITS technique. Nonetheless, MITS offers a valuable alternative to open autopsy for understanding pathological changes due to COVID-19.
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Affiliation(s)
- Victor Mudenda
- University Teaching Hospital, Department of Pathology, Lusaka, Zambia
| | - Chibamba Mumba
- University Teaching Hospital, Department of Pathology, Lusaka, Zambia
| | - Rachel C Pieciak
- Boston University School of Public Health, Department of Global Health, Boston, Massachusetts, USA
| | - Lawrence Mwananyanda
- Boston University School of Public Health, Department of Global Health, Boston, Massachusetts, USA.,Right to Care Zambia, Lusaka, Zambia
| | | | | | | | - Geoffrey Kwenda
- University of Zambia, School of Health Sciences, Department of Biomedical Sciences, Lusaka, Zambia
| | - Leah Forman
- Boston University School of Public Health, Biostatistics and Epidemiology Data Analytics Center (BEDAC), Boston, Massachusetts, USA
| | - Rotem Lapidot
- Boston University School of Medicine, Boston, Massachusetts, USA
| | - William B MacLeod
- Boston University School of Public Health, Department of Global Health, Boston, Massachusetts, USA
| | - Donald M Thea
- Boston University School of Public Health, Department of Global Health, Boston, Massachusetts, USA
| | - Christopher J Gill
- Boston University School of Public Health, Department of Global Health, Boston, Massachusetts, USA
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Immunotherapy of multisystem inflammatory syndrome in children (MIS-C) following COVID-19 through mesenchymal stem cells. Int Immunopharmacol 2021. [DOI: oi.org/10.1016/j.intimp.2021.108217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Suksatan W, Chupradit S, Yumashev AV, Ravali S, Shalaby MN, Mustafa YF, Kurochkin A, Siahmansouri H. Immunotherapy of multisystem inflammatory syndrome in children (MIS-C) following COVID-19 through mesenchymal stem cells. Int Immunopharmacol 2021; 101:108217. [PMID: 34627083 PMCID: PMC8487784 DOI: 10.1016/j.intimp.2021.108217] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/28/2021] [Accepted: 09/30/2021] [Indexed: 02/06/2023]
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus causing coronavirus 2019 (COVID-19) that was first observed in Wuhan, China, in Dec. 2019. An inflammatory immune response targeting children appeared during the pandemic, which was associated with COVID-19 named multisystem inflammatory syndrome in children (MIS-C). Characteristics of MIS-C include the classic inflammation findings, multi-organ dysfunction, and fever as the cardinal feature. Up to now, no specific therapy has been identified for MIS-C. Currently, considerable progress has been obtained in the MIS-C treatment by cell therapy, specially Mesenchymal stem cells (MSCs). Unique properties have been reported for MSCs, such as various resources for purification of cell, high proliferation, self-renewal, non-invasive procedure, tissue regenerator, multidirectional differentiation, and immunosuppression. As indicated by a recent clinical research, MSCs have the ability of reducing disease inflammation and severity in children with MIS-C. In the present review study, the benefits and characteristics of MSCs and exosomes are discussed for treating patients with MIS-C.
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Affiliation(s)
- Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Supat Chupradit
- Department of Occupational Therapy, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand
| | | | - Sahithya Ravali
- Department of Pharmacy Practice, SRM College of Pharmacy, SRM Institute of Science and Technology, Chennai, India
| | | | - Yasser Fakri Mustafa
- Department of Pharmaceutical Chemistry, College of Pharmacy, University of Mosul, Mosul 41001, Iraq
| | | | - Homayoon Siahmansouri
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
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