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Wang J, Yin J, Liu X, Liu Y, Jin X. Gut commensal bacterium Bacteroides vulgatus exacerbates helminth-induced cardiac fibrosis through succinate accumulation. PLoS Pathog 2025; 21:e1013069. [PMID: 40238740 PMCID: PMC12002503 DOI: 10.1371/journal.ppat.1013069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2024] [Accepted: 02/21/2025] [Indexed: 04/18/2025] Open
Abstract
Trichinella spiralis (Ts) is known to cause cardiac fibrosis, which is a critical precursor to various heart diseases, and its progression is influenced by metabolic changes. However, the metabolic mechanisms remain unclear. Here, we observed that Ts-infected mice exhibited cardiac fibrosis along with elevated succinate levels in the heart using metabolomic analysis. Administration of succinate exacerbated fibrosis during Ts infection, while deficiency in succinate receptor 1 (Sucnr1) alleviated the condition, highlighting the role of the succinate-Sucnr1 axis in fibrosis development. Furthermore, metagenomics sequencing showed that Ts-infected mice had a higher abundance ratio of succinate-producing bacteria to succinate-consuming bacteria in the intestines. Notably, the succinate-producer Bacteroides vulgatus was enriched in Ts group. Oral supplementation with B. vulgatus aggravated Ts-induced cardiac fibrosis. In summary, our findings underscore the succinate-Sucnr1 axis as a critical pathway in helminth-induced cardiac fibrosis and highlight the potential of targeting this axis for therapeutic interventions. This study presents novel insights into the gut-heart axis, revealing innovative strategies for managing cardiovascular complications associated with helminth infections.
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Affiliation(s)
- Jiaqi Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
- College of Animal Sciences, Jilin University, Changchun, China
| | - Jiali Yin
- The Second Hospital of Jilin University, Changchun, China
| | - Xiaolei Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
| | - Yi Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
- College of Food Science and Engineering, Jilin University, Changchun, China
| | - Xuemin Jin
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, and College of Veterinary Medicine, Jilin University, Changchun, China
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Yenmis G, Kallenci I, Dokur M, Koc S, Yalinkilic SB, Atak E, Demirbilek M, Arkan H. The Distribution of Sport Performance Gene Variations Through COVID-19 Disease Severity. Diagnostics (Basel) 2025; 15:701. [PMID: 40150043 PMCID: PMC11941099 DOI: 10.3390/diagnostics15060701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2025] [Revised: 02/23/2025] [Accepted: 03/08/2025] [Indexed: 03/29/2025] Open
Abstract
Background/Objectives: Since its emergence in 2020, researchers worldwide have been collaborating to better understand the SARS-CoV-2 disease's pathophysiology. Disease severity can vary based on several factors, including comorbidities and genetic variations. Notably, recent studies have highlighted the role of genes associated with athletic performance, such as ACE, ACTN3, and PPARGC1A, in influencing muscle function, cardiovascular health, and the body's metabolic response. Given that these genes also impact oxidative metabolism, inflammation, and respiratory efficiency, we hypothesized that they might play a critical role in the host's response to SARS-CoV-2 infection. This study aimed to investigate the association between disease severity and genetic polymorphisms in these sport performance-related genes, specifically ACE rs4646994, ACTN3 rs1815739, and PPARGC1A rs8192678. Methods: A total of 422 COVID-19-positive patients were included in this study. The participants were divided into three groups: a severe group (77 patients) requiring intensive care unit (ICU) admission, a mild group (300 patients) exhibiting at least one symptom, and an asymptomatic control group. Genotyping was performed using restriction fragment length polymorphism PCR. Results: The D allele and DD genotype of ACE and the T allele and TT genotype of ACTN3 were found to confer protective effects against severe SARS-CoV-2 infection. Conversely, the PPARGC1A TC genotype and the ACE-PPARGC1A ins/ins + TC combined genotype were associated with increased disease severity (p < 0.05). Conclusions: Although vaccination has reduced the severity of SARS-CoV-2, the virus continues to impact human health. Inter-individual differences due to these genetic variations will broaden the horizon of knowledge on the pathophysiology of the disease.
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Affiliation(s)
- Guven Yenmis
- Department of Medical Biology, Tayfur Ata Sokmen School of Medicine, Hatay Mustafa Kemal University, Hatay 31060, Turkey
| | - Ilayda Kallenci
- Department of Molecular Biology and Genetics, Faculty of Natural Sciences and Engineering, Biruni University, Istanbul 34015, Turkey; (I.K.); (S.B.Y.)
| | - Mehmet Dokur
- Department of Emergency Medicine, Faculty of Medicine, Bilecik Seyh Edebali University, Bilecik 11230, Turkey;
| | - Suna Koc
- Department of Anesthesia and Reanimation, School of Medicine, Biruni University, Istanbul 34015, Turkey;
| | - Sila Basak Yalinkilic
- Department of Molecular Biology and Genetics, Faculty of Natural Sciences and Engineering, Biruni University, Istanbul 34015, Turkey; (I.K.); (S.B.Y.)
| | - Evren Atak
- Department of Bioinformatics and System Biology, Institute of Natural and Applied Sciences, Gebze Technical University, Kocaeli 41400, Turkey;
| | - Mahmut Demirbilek
- Department of Emergency Medicine, School of Medicine, Biruni University, Istanbul 34015, Turkey;
| | - Hulya Arkan
- Department of Biotechnology, Institute of Science, Yildiz Technical University, Istanbul 34210, Turkey;
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Stimart HL, Hipkins B. The negative effects of long COVID-19 on cardiovascular health and implications for the presurgical examination. J Osteopath Med 2025; 125:105-117. [PMID: 39417730 DOI: 10.1515/jom-2024-0109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 08/12/2024] [Indexed: 10/19/2024]
Abstract
CONTEXT In 2019, emergence of the novel and communicable severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection took scientific communities by surprise and imposed significant burden on healthcare systems globally. Although the advent of this disease piqued the interest of academic centers, healthcare systems, and the general public, there is still much yet to be elucidated regarding epidemiology, pathophysiology, and long-term impacts of coronavirus disease 2019 (COVID-19). It has been established that long COVID-19 can impact multiple organ systems, including the cardiovascular system, unfavorably. Although the pathophysiology of this damage is not well understood, adverse sequelae may range from chest pain and arrhythmias to heart failure (HF), myocardial infarction, or sudden cardiac death. For any postacute COVID-19 patient requiring a surgical procedure, the potential for cardiac injury secondary to long COVID-19 must be considered in the preoperative cardiac examination. OBJECTIVES This literature review serves to add to the growing body of literature exploring postacute cardiovascular outcomes of COVID-19, with a focus on presurgical cardiac clearance in the adult patient. Specifically, this review studies the prevalence of cardiovascular symptomatology including chest pain, arrhythmias, blood pressure changes, myo-/pericarditis, HF, cardiomyopathy, orthostatic intolerance, and thromboembolism. Although current evidence is scarce in both quality and quantity, it is the goal that this review will highlight the negative impacts of long COVID-19 on cardiovascular health and encourage providers to be cognizant of potential sequelae in the context of the presurgical examination. METHODS For this study, peer-reviewed and journal-published articles were selected based on established inclusion and exclusion criteria to address the question "How does long COVID-19 impact the presurgical cardiac examination of an adult scheduled to undergo a noncardiac procedure?" Inclusion criteria included human studies conducted in adult patients and published in peer-reviewed journals up until May 2024 examining the effects of long-COVID-19 infection on the cardiovascular system. Exclusion criteria eliminated unpublished reports, preprints, duplicate articles, literature regarding coronavirus strains other than COVID-19, studies regarding post-COVID-19 vaccination complications, animal studies, and studies conducted in people younger than 18 years of age. A total of 6,675 studies were retrieved from PubMed and Google Scholar. Following screening, 60 studies were included in final consideration. RESULTS Cardiovascular symptoms of postacute COVID-19 infection were encountered with the following percentages prevalence (total numbers of articles mentioning symptom/total number of articles [60]): chest pain (83.3), arrhythmias (88.3), hypertension (40.0), hypotension (16.7), myocarditis (80.0), pericarditis (51.7), HF (70.0), cardiomyopathy (55.0), orthostatic intolerance (56.7), and thromboembolic events (85.0). CONCLUSIONS The presence of persisting COVID symptoms may negatively impact the patient's physical examination, blood tests, electrocardiogram (ECG), imaging, and/or echocardiogram. Cardiac conditions associated with long COVID require special attention in the context of the presurgical candidate due to an increased risk of sudden cardiac death, myocarditis, stroke, and myocardial infarction - even in those who were healthy prior to acute COVID-19 infection. Until more specific scientific evidence comes to light, care of these patients should be viewed through the prism of the best practices already in use and clinicians should maintain a low threshold to pursue more extensive cardiac workup prior to surgery.
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Affiliation(s)
- Hannah L Stimart
- 447877 Edward Via College of Osteopathic Medicine , Spartanburg, SC, USA
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do Nascimento EP, do Nascimento LFE, Castro LDF, de Barros VC, Bandeira ERP, Wanderley e Lima TB, Otto-Yáñez M, Fregonezi GADF, Resqueti VR. Cardiac Hemodynamics, Tissue Oxygenation, and Functional Capacity in Post-COVID-19 Patients. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:124. [PMID: 39859106 PMCID: PMC11766540 DOI: 10.3390/medicina61010124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Revised: 10/10/2024] [Accepted: 10/29/2024] [Indexed: 01/27/2025]
Abstract
Background and Objectives: This study aimed to evaluate and compare the functional capacity of post-COVID-19 patients with a control group and analyze cardiac hemodynamics and muscle tissue oxygenation responses during assessment protocols in both groups. Materials and Methods: A cross-sectional study was conducted involving patients with COVID-19 and a control group who were all aged ≥18 years. Participants underwent two functional capacity tests: the one-minute sit-stand test (1-STS) and the six-minute walk test (6MWT). Cardiac hemodynamic responses were evaluated using impedance during the 1-STS, and tissue perfusion responses in the oxygenation were recorded during and after both tests. The Friedman test was used for within-group and the Mann-Whitney test was used for between-group comparisons. Results: Thirty-six post-COVID-19 patients (median age 36 years, BMI 26.51 kg/m2) and eleven control subjects (median age 25 years, BMI 23.71 kg/m2) were enrolled. The post-COVID-19 group showed a 20% decrease in 6MWT distance (p = 0.0001) and a 28% decrease in 1-STS repetitions (p = 0.01) versus the control group. Cardiac hemodynamic differences were observed in the post-COVID-19 group during the 1-STS, with reductions in the stroke volume index (18%, p = 0.004), cardiac index (21%, p = 0.0009), Contractility Index (78%, p = 0.0001), and Ejection Fraction (29%, p = 0.0003) and increases in Systemic Vascular Resistance (25%, p = 0.03) and the Systemic Vascular Resistance Index (27%, p = 0.0007). Tissue oxygenation during the 6MWT and 1-STS showed no significant differences between groups. Conclusions: The post-COVID-19 subjects exhibited a reduction in functional capacity, changes in hemodynamic responses related to cardiac and systemic vascular resistance, and a similar pattern of muscle oxygen delivery and consumption in both tests.
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Affiliation(s)
- Elizane Poquiviqui do Nascimento
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Larissa Fernanda Estevam do Nascimento
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Lhara de Freitas Castro
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Vilena Cavalcante de Barros
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Emily Rachel Pereira Bandeira
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Thiago Bezerra Wanderley e Lima
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Matías Otto-Yáñez
- Grupo de Investigación en Salud, Funcionalidad y Actividad Física (GISFAF), Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Santiago 8320000, Chile;
| | - Guilherme Augusto de Freitas Fregonezi
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
| | - Vanessa Regiane Resqueti
- Laboratório de Inovação Tecnológica em Reabilitação, Departamento de Fisioterapia, Universidade Federal do Rio Grande do Norte (UFRN), Campus Universitário Central, Natal 59078970, RN, Brazil; (E.P.d.N.); (L.F.E.d.N.); (L.d.F.C.); (V.C.d.B.); (E.R.P.B.); (T.B.W.e.L.); (G.A.d.F.F.)
- PneumoCardioVascular Lab/HUOL, Hospital Universitário Onofre Lopes, Universidade Federal do Rio Grande do Norte (UFRN), Natal 59012300, RN, Brazil
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Liu H, Brostoff T, Ramirez A, Wong T, Rowland DJ, Heffner M, Flores A, Willis B, Evans JJ, Lanoue L, Lloyd KCK, Coffey LL. Establishment and characterization of an h ACE2/hTMPRSS2 knock-in mouse model to study SARS-CoV-2. Front Immunol 2024; 15:1428711. [PMID: 39050847 PMCID: PMC11266032 DOI: 10.3389/fimmu.2024.1428711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Accepted: 06/25/2024] [Indexed: 07/27/2024] Open
Abstract
Despite a substantial body of research, we lack fundamental understanding of the pathophysiology of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) including pulmonary and cardiovascular outcomes, in part due to limitations of murine models. Most models use transgenic mice (K18) that express the human (h) angiotensin converting enzyme 2 (ACE2), ACE2 knock-in (KI) mice, or mouse-adapted strains of SARS-CoV-2. Further, many SARS-CoV-2 variants produce fatal neurologic disease in K18 mice and most murine studies focus only on acute disease in the first 14 days post inoculation (dpi). To better enable understanding of both acute (<14 dpi) and post-acute (>14 dpi) infection phases, we describe the development and characterization of a novel non-lethal KI mouse that expresses both the ACE2 and transmembrane serine protease 2 (TMPRSS2) genes (hACE2/hTMPRSS2). The human genes were engineered to replace the orthologous mouse gene loci but remain under control of their respective murine promoters, resulting in expression of ACE2 and TMPRSS2 instead of their murine counterparts. After intranasal inoculation with an omicron strain of SARS-CoV-2, hACE2/hTMPRSS2 KI mice transiently lost weight but recovered by 7 dpi. Infectious SARS-CoV-2 was detected in nasopharyngeal swabs 1-2 dpi and in lung tissues 2-6 dpi, peaking 4 dpi. These outcomes were similar to those in K18 mice that were inoculated in parallel. To determine the extent to which hACE2/hTMPRSS2 KI mice are suitable to model pulmonary and cardiovascular outcomes, physiological assessments measuring locomotion, behavior and reflexes, biomonitoring to measure cardiac activity and respiration, and micro computed tomography to assess lung function were conducted frequently to 6 months post inoculation. Male but not female SARS-CoV-2 inoculated hACE2/hTMPRSS2 KI mice showed a transient reduction in locomotion compared to control saline treated mice. No significant changes in respiration, oxygen saturation, heart rate variability, or conductivity were detected in SARS-CoV-2 inoculated mice of either sex. When re-inoculated 6 months after the first inoculation, hACE2/hTMPRSS2 KI became re-infected with disease signs similar to after the first inoculation. Together these data show that a newly generated hACE2/hTMPRSS2 KI mouse can be used to study mild COVID-19.
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Affiliation(s)
- Hongwei Liu
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, United States
| | - Terza Brostoff
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, United States
| | - Ana Ramirez
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, United States
| | - Talia Wong
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, United States
| | - Douglas J. Rowland
- Center for Molecular and Genomic Imaging, College of Engineering, University of California, Davis, Davis, CA, United States
| | - Mollie Heffner
- Mouse Biology Program, University of California, Davis, Davis, CA, United States
| | - Arturo Flores
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, United States
| | - Brandon Willis
- Mouse Biology Program, University of California, Davis, Davis, CA, United States
| | - Jeffrey J. Evans
- Mouse Biology Program, University of California, Davis, Davis, CA, United States
| | - Louise Lanoue
- Mouse Biology Program, University of California, Davis, Davis, CA, United States
| | - K. C. Kent Lloyd
- Mouse Biology Program, University of California, Davis, Davis, CA, United States
- Department of Surgery, School of Medicine, University of California, Davis, Davis, CA, United States
| | - Lark L. Coffey
- Department of Pathology, Microbiology, and Immunology, School of Veterinary Medicine, University of California, Davis, CA, United States
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Borczuk AC. Pathology of COVID-19 Lung Disease. Surg Pathol Clin 2024; 17:203-214. [PMID: 38692805 DOI: 10.1016/j.path.2023.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/03/2024]
Abstract
The pathology of severe COVID-19 lung injury is predominantly diffuse alveolar damage, with other reported patterns including acute fibrinous organizing pneumonia, organizing pneumonia, and bronchiolitis. Lung injury was caused by primary viral injury, exaggerated immune responses, and superinfection with bacteria and fungi. Although fatality rates have decreased from the early phases of the pandemic, persistent pulmonary dysfunction occurs and its pathogenesis remains to be fully elucidated.
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Affiliation(s)
- Alain C Borczuk
- Department of Pathology, Northwell Health, 2200 Northern Boulevard Suite 104, Greenvale, NY 11548, USA.
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Angiola F, Franchetti G, Cestonaro C, Agnolucci J, Giordano R, Viel G. Dying at home during the SARS-CoV-2 endemic: The importance of defining the exact mechanism of death. Leg Med (Tokyo) 2024; 66:102361. [PMID: 38039658 DOI: 10.1016/j.legalmed.2023.102361] [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: 06/23/2023] [Revised: 11/08/2023] [Accepted: 11/22/2023] [Indexed: 12/03/2023]
Abstract
INTRODUCTION Coronavirus Disease 2019 (COVID-19) has become endemic in Europe thanks to the presence of less deadly and more infectious variants and to the existence of a significant portion of unvaccinated people among the general population. SARS-Cov-2 related deaths are probably going to fade in the next years, but Covid-19 should still be considered a potential cause of death in the out-of-hospital setting in the next future. MATERIAL AND METHODS Three (3) cases of unexpected death at home are here presented. Each case has been investigated with the same methodological approach: death scene investigation (DSI), complete autopsy with histology, immunohistochemistry, RNA in situ hybridization for SARS-CoV-2 spike protein in lung tissue, toxicology and microbiology. RESULTS AND DISCUSSION All three cases had a COVID + post-mortem nasopharyngeal swab. Histology and immunohistochemistry revealed a SARS-CoV-2 lung involvement in only two of the cases (Cases 2 and 3), while a septic bacterial pneumonia was found in Case 1, where RNA-in situ hybridization for viral spike protein showed no reactivity in pneumocytes. The integration of all postmortem evidence allowed to attribute a different role of SARS-Cov-2 in the determinism of the death. CONCLUSION In the current post-pandemic context, SARS-CoV-2 remains a possible cause of death when investigating out-of-hospital unexpected deaths. Since a positive post-mortem swab does not automatically imply a COVID-19-related death, histology and immunohistochemistry are helpful for identifying SARS-CoV-2 lung involvement and, therefore, its potential active role in the determinism of death.
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Affiliation(s)
- Francesco Angiola
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy
| | - Giorgia Franchetti
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy
| | - Clara Cestonaro
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy
| | - Jacopo Agnolucci
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy
| | - Renzo Giordano
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy
| | - Guido Viel
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, Via Falloppio 50, 35121 Padova, Italy.
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Matthaiou AM, Bizymi N, Pagonidis K, Manousaki E, Fragkoulakis M, Lambiri I, Mitrouska I, Vasarmidi E, Tzanakis N, Antoniou KM. Reversibility of the Enlargement of the Pulmonary Artery in COVID-19 Pneumonia as a Marker of Remission of the Disease. J Pers Med 2024; 14:161. [PMID: 38392595 PMCID: PMC10890114 DOI: 10.3390/jpm14020161] [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: 01/15/2024] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 02/24/2024] Open
Abstract
Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients (p-value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed (p-value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT (p-value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.
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Affiliation(s)
- Andreas M Matthaiou
- Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 71500 Heraklion, Greece
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
| | - Nikoleta Bizymi
- Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 71500 Heraklion, Greece
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
| | - Konstantinos Pagonidis
- Department of Medical Imaging, Knossos Medical Diagnosis Centre, 71409 Heraklion, Greece
| | - Eirini Manousaki
- Department of Medical Imaging, Knossos Medical Diagnosis Centre, 71409 Heraklion, Greece
| | - Michail Fragkoulakis
- Department of Medical Imaging, Knossos Medical Diagnosis Centre, 71409 Heraklion, Greece
| | - Irini Lambiri
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
| | - Ioanna Mitrouska
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
| | - Eirini Vasarmidi
- Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 71500 Heraklion, Greece
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
| | - Nikolaos Tzanakis
- Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 71500 Heraklion, Greece
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
| | - Katerina M Antoniou
- Laboratory of Molecular and Cellular Pneumonology, Medical School, University of Crete, 71500 Heraklion, Greece
- Department of Respiratory Medicine, University Hospital of Heraklion, 71500 Heraklion, Greece
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9
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Milross L, Hunter B, McDonald D, Merces G, Thomson A, Hilkens CMU, Wills J, Rees P, Jiwa K, Cooper N, Majo J, Ashwin H, Duncan CJA, Kaye PM, Bayraktar OA, Filby A, Fisher AJ. Distinct lung cell signatures define the temporal evolution of diffuse alveolar damage in fatal COVID-19. EBioMedicine 2024; 99:104945. [PMID: 38142637 PMCID: PMC10788437 DOI: 10.1016/j.ebiom.2023.104945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 12/11/2023] [Accepted: 12/14/2023] [Indexed: 12/26/2023] Open
Abstract
BACKGROUND Lung damage in severe COVID-19 is highly heterogeneous however studies with dedicated spatial distinction of discrete temporal phases of diffuse alveolar damage (DAD) and alternate lung injury patterns are lacking. Existing studies have also not accounted for progressive airspace obliteration in cellularity estimates. We used an imaging mass cytometry (IMC) analysis with an airspace correction step to more accurately identify the cellular immune response that underpins the heterogeneity of severe COVID-19 lung disease. METHODS Lung tissue was obtained at post-mortem from severe COVID-19 deaths. Pathologist-selected regions of interest (ROIs) were chosen by light microscopy representing the patho-evolutionary spectrum of DAD and alternate disease phenotypes were selected for comparison. Architecturally normal SARS-CoV-2-positive lung tissue and tissue from SARS-CoV-2-negative donors served as controls. ROIs were stained for 40 cellular protein markers and ablated using IMC before segmented cells were classified. Cell populations corrected by ROI airspace and their spatial relationships were compared across lung injury patterns. FINDINGS Forty patients (32M:8F, age: 22-98), 345 ROIs and >900k single cells were analysed. DAD progression was marked by airspace obliteration and significant increases in mononuclear phagocytes (MnPs), T and B lymphocytes and significant decreases in alveolar epithelial and endothelial cells. Neutrophil populations proved stable overall although several interferon-responding subsets demonstrated expansion. Spatial analysis revealed immune cell interactions occur prior to microscopically appreciable tissue injury. INTERPRETATION The immunopathogenesis of severe DAD in COVID-19 lung disease is characterised by sustained increases in MnPs and lymphocytes with key interactions occurring even prior to lung injury is established. FUNDING UK Research and Innovation/Medical Research Council through the UK Coronavirus Immunology Consortium, Barbour Foundation, General Sir John Monash Foundation, Newcastle University, JGW Patterson Foundation, Wellcome Trust.
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Affiliation(s)
- Luke Milross
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Bethany Hunter
- Newcastle University Biosciences Institute, Newcastle upon Tyne, UK; Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - David McDonald
- Newcastle University Biosciences Institute, Newcastle upon Tyne, UK; Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - George Merces
- Newcastle University Biosciences Institute, Newcastle upon Tyne, UK; Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Amanda Thomson
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK; Newcastle University Biosciences Institute, Newcastle upon Tyne, UK; Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Catharien M U Hilkens
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - John Wills
- Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
| | - Paul Rees
- Department of Biomedical Engineering, Swansea University, Wales, UK; Imaging Platform, Broad Institute of MIT and Harvard, 415 Main Street, Boston, Cambridge, MA, USA
| | - Kasim Jiwa
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Nigel Cooper
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Joaquim Majo
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Helen Ashwin
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
| | - Christopher J A Duncan
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK; Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Paul M Kaye
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
| | | | - Andrew Filby
- Newcastle University Biosciences Institute, Newcastle upon Tyne, UK; Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK.
| | - Andrew J Fisher
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK; Institute of Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
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10
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Krishna N, K P S, G K R. Identifying diseases associated with Post-COVID syndrome through an integrated network biology approach. J Biomol Struct Dyn 2024; 42:652-671. [PMID: 36995291 DOI: 10.1080/07391102.2023.2195003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 03/17/2023] [Indexed: 03/31/2023]
Abstract
A growing body of research shows that COVID-19 is now recognized as a multi-organ disease with a wide range of manifestations that can have long-lasting repercussions, referred to as post-COVID-19 syndrome. It is unknown why the vast majority of COVID-19 patients develop post-COVID-19 syndrome, or why patients with pre-existing disorders are more likely to experience severe COVID-19. This study used an integrated network biology approach to obtain a comprehensive understanding of the relationship between COVID-19 and other disorders. The approach involved building a PPI network with COVID-19 genes and identifying highly interconnected regions. The molecular information contained within these subnetworks, as well as the pathway annotations, were used to reveal the link between COVID-19 and other disorders. Using Fisher's exact test and disease-specific gene information, significant COVID-19-disease associations were discovered. The study discovered diseases that affect multiple organs and organ systems, thus proving the theory of multiple organ damage caused by COVID-19. Cancers, neurological disorders, hepatic diseases, cardiac disorders, pulmonary diseases, and hypertensive diseases are just a few of the conditions linked to COVID-19. Pathway enrichment analysis of shared proteins revealed the shared molecular mechanism of COVID-19 and these diseases. The findings of the study shed new light on the major COVID-19-associated disease conditions and how their molecular mechanisms interact with COVID-19. The novelty of studying disease associations in the context of COVID-19 provides new insights into the management of rapidly evolving long-COVID and post-COVID syndromes, which have significant global implications.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Navami Krishna
- School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, India
| | - Sijina K P
- School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, India
| | - Rajanikant G K
- School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, India
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11
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Noack P, Grosse C, Bodingbauer J, Almeder M, Lohfink-Schumm S, Salzer HJF, Meier J, Lamprecht B, Schmitt CA, Langer R. Minimally invasive autopsies for the investigation of pulmonary pathology of COVID-19-experiences of a longitudinal series of 92 patients. Virchows Arch 2023; 483:611-619. [PMID: 37653260 PMCID: PMC10673967 DOI: 10.1007/s00428-023-03622-6] [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: 01/24/2023] [Revised: 07/20/2023] [Accepted: 08/07/2023] [Indexed: 09/02/2023]
Abstract
Minimally invasive autopsies (MIAs) allow the collection of tissue samples for diagnostic and research purposes in special situations, e.g., when there is a high risk of infection which is the case in the context of COVID-19 or restrictions due to legal or personal reasons. We performed MIA to analyze lung tissue from 92 COVID-19 patients (mean age 78 years; range 48-98; 35 women, 57 men), representing 44% of all patients who died from the disease between October 2020 and April 2021. An intercostal approach was used with removal of a 5-cm rib section followed by manual collection of four lung tissue samples (5-8 cm in size). Diffuse alveolar damage (DAD) was found in 89 (97%) patients at various stages. Exudative DAD (eDAD) predominated in 18 (20%) patients, proliferative DAD (pDAD) in 43 (47%) patients, and mixed DAD (mDAD) in 31 (34%) patients. There were no significant differences in the predominant DAD pattern between tissue samples from the same patient. Additional purulent components were present in 46 (50%) cases. Fungi were detected in 11 (12%) patients. The pDAD pattern was associated with longer hospital stay including intensive care unit (p=0.026 and p<0.001) and younger age (p=0.019). Positive bronchoalveolar lavage and blood cultures were observed more frequently in pDAD patterns (p<0.001; p=0.018). In contrast, there was no significant association between intravital positive microbiological results and superimposed bronchopneumonia or fungal infection at autopsy. Having demonstrated the characteristic lung changes in a large longitudinal autopsy series, we conclude that the presented MIA approach can be considered a reliable and safe method for performing post mortem lung diagnostics in COVID-19 and other high-risk situations. The lack of correlation between histological changes indicative of bacterial or fungal superinfection and microbiology could have clinical implications for disease and treatment surveillance.
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Affiliation(s)
- Petar Noack
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Claudia Grosse
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
| | - Jacob Bodingbauer
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Marion Almeder
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Sylvia Lohfink-Schumm
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria
- Medical Faculty, Johannes Kepler University, Linz, Austria
| | - Helmut J F Salzer
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Division of Infectious Diseases and Tropical Medicine, Department of Pulmonary Medicine, Kepler University Hospital, Linz, Austria
- Ignaz-Semmelweis-Institute, Interuniversity Institute for Infection Research, Vienna, Austria
| | - Jens Meier
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital, Linz, Austria
| | - Bernd Lamprecht
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Department of Pulmonary Medicine, Kepler University Hospital, Linz, Austria
| | - Clemens A Schmitt
- Medical Faculty, Johannes Kepler University, Linz, Austria
- Department of Hematology and Medical Oncology, Kepler University Hospital, Linz, Austria
| | - Rupert Langer
- Institute of Clinical Pathology, Kepler University Hospital, Krankenhausstr. 9, 4021, Linz, Austria.
- Medical Faculty, Johannes Kepler University, Linz, Austria.
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12
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Mikhaleva L, Gioeva Z, Varyasin V, Berezhnaja E, Vandysheva R, Gutyrchik N, Pechnikova V, Kontorshchikov A, Midiber K, Kakturskij L. Pathomorphological Features of the Novel Coronavirus Disease in Patients with Systemic Amyloidosis. Biomedicines 2023; 11:2811. [PMID: 37893183 PMCID: PMC10604009 DOI: 10.3390/biomedicines11102811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/10/2023] [Accepted: 10/14/2023] [Indexed: 10/29/2023] Open
Abstract
Amyloidosis is one of the rare systemic illnesses characterized by the deposition of amyloid fibrils in various organs and tissues. There is a common point between COVID-19 and systemic amyloidosis regarding the multiorgan involvement in the pathological process which leads to a heightened risk for severe morbidity and mortality in amyloidosis patients who contracted COVID-19. We performed a pathomorphological analysis of the autopsy records of 22 patients who had COVID-19 and pre-existing systemic amyloidosis. The premortem diagnosis of systemic amyloidosis was established in 55% of patients, and in other 45% of cases, amyloidosis was found at autopsy. Based on the results of immunohistochemical amyloid typing, amyloid A (AA) amyloidosis was detected in 23%, amyloid light chain (AL) lambda in 32%, AL kappa-in 9%, and transthyretin (ATTR) amyloidosis-in 36% of observations. Immunohistochemical staining with an antibody against SARS-CoV-2 Spike (S) protein revealed positive immune reactions in type II alveolocytes in 59% of deceased persons. The analysis of autopsy findings indicates that patients with systemic amyloidosis are more likely to experience an aggressive clinical course of COVID-19 which leads to a multiorgan failure and a higher risk of fatal outcome.
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Affiliation(s)
- Liudmila Mikhaleva
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Zarina Gioeva
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | | | | | - Rositsa Vandysheva
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Nikita Gutyrchik
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
- Medical Institute, Peoples' Friendship University of Russia (RUDN University), 117198 Moscow, Russia
| | - Valentina Pechnikova
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Andrej Kontorshchikov
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Konstantin Midiber
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
| | - Lev Kakturskij
- Avtsyn Research Institute of Human Morphology, Federal State Budgetary Scientific Institution "Petrovsky National Research Centre of Surgery", 117418 Moscow, Russia
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13
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Wang J, Liu X, Sun R, Mao H, Liu M, Jin X. Akkermansia muciniphila participates in the host protection against helminth-induced cardiac fibrosis via TLR2. PLoS Pathog 2023; 19:e1011683. [PMID: 37788279 PMCID: PMC10547169 DOI: 10.1371/journal.ppat.1011683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 09/12/2023] [Indexed: 10/05/2023] Open
Abstract
Helminth Trichinella spiralis (Ts) is one of the major pathogens of human infective myocarditis that can lead to cardiac fibrosis (CF). The gut microbiota involved in this pathology are of interest. Here, we use mice infected with Ts as a model to examine the interactions between gut microbes and host protection to CF. Infected mice show enhanced CF severity. We find that antibiotics treatment to deplete the microbiota aggravates the disease phenotype. Attempts to restore microbiota using fecal microbiota transplantation ameliorates helminth-induced CF. 16S rRNA gene sequencing and metagenomics sequencing reveal a higher abundance of Akkermansia muciniphila in gut microbiomes of Ts-infected mice. Oral supplementation with alive or pasteurized A. muciniphila improves CF via TLR2. This work represents a substantial advance toward our understanding of causative rather than correlative relationships between the gut microbiota and CF.
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Affiliation(s)
- Jiaqi Wang
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, Institute of Zoonosis, College of Animal Sciences, Jilin University, Changchun, China
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Xiaolei Liu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Ruohang Sun
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Hanhai Mao
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
| | - Mingyuan Liu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
- Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China
| | - Xuemin Jin
- State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research of the Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China
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14
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Leng L, Bian XW. Injury mechanism of COVID-19-induced cardiac complications. CARDIOLOGY PLUS 2023; 8:159-166. [PMID: 37928775 PMCID: PMC10621642 DOI: 10.1097/cp9.0000000000000055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 06/06/2023] [Indexed: 11/07/2023] Open
Abstract
Heart dysfunction is one of the most life-threatening organ dysfunctions caused by coronavirus disease 2019 (COVID-19). Myocardial or cardiovascular damage is the most common extrapulmonary organ complication in critically ill patients. Understanding the pathogenesis and pathological characteristics of myocardial and vascular injury is important for improving clinical diagnosis and treatment approach. Herein, the mechanism of direct damage caused by severe acute respiratory syndrome coronavirus 2 to the heart and secondary damage caused by virus-driven inflammation was reviewed. The pathological mechanism of ischemia and hypoxia due to microthrombosis and inflammatory injury as well as the injury mechanism of tissue inflammation and single myocardial cell necrosis triggered by the viral infection of pericytes or macrophages, hypoxia, and energy metabolism disorders were described. The latter can provide a novel diagnosis, treatment, and investigation strategy for heart dysfunctions caused by COVID-19 or the Omicron variant.
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Affiliation(s)
- Ling Leng
- Stem Cell and Regenerative Medicine Lab, Department of Medical Science Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Translational Medicine Center, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China
| | - Xiu-Wu Bian
- Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University), and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing 400038, China
- Department of Pathology, the First Hospital Affiliated to University of Science and Technology of China (USTC), and Intelligent Pathology Institute, Division of Life Sciences and Medicine, USTC, Hefei 230036, China
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15
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Zheng Z, Peng F, Zhou Y. Pulmonary fibrosis: A short- or long-term sequelae of severe COVID-19? CHINESE MEDICAL JOURNAL PULMONARY AND CRITICAL CARE MEDICINE 2023; 1:77-83. [PMID: 37388822 PMCID: PMC9988550 DOI: 10.1016/j.pccm.2022.12.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 10/21/2022] [Accepted: 12/04/2022] [Indexed: 07/01/2023]
Abstract
The pandemic of coronavirus disease 2019 (COVID‑19), caused by a novel severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), has caused an enormous impact on the global healthcare. SARS-CoV-2 infection primarily targets the respiratory system. Although most individuals testing positive for SARS-CoV-2 present mild or no upper respiratory tract symptoms, patients with severe COVID-19 can rapidly progress to acute respiratory distress syndrome (ARDS). ARDS-related pulmonary fibrosis is a recognized sequelae of COVID-19. Whether post-COVID-19 lung fibrosis is resolvable, persistent, or even becomes progressive as seen in human idiopathic pulmonary fibrosis (IPF) is currently not known and remains a matter of debate. With the emergence of effective vaccines and treatments against COVID-19, it is now important to build our understanding of the long-term sequela of SARS-CoV-2 infection, to identify COVID-19 survivors who are at risk of developing chronic pulmonary fibrosis, and to develop effective anti-fibrotic therapies. The current review aims to summarize the pathogenesis of COVID-19 in the respiratory system and highlights ARDS-related lung fibrosis in severe COVID-19 and the potential mechanisms. It envisions the long-term fibrotic lung complication in COVID-19 survivors, in particular in the aged population. The early identification of patients at risk of developing chronic lung fibrosis and the development of anti-fibrotic therapies are discussed.
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Affiliation(s)
- Zhen Zheng
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Fei Peng
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
- Department of Respiratory Medicine, The Second Xiangya Hospital, Central-South University, Changsha, Hunan 410011, China
| | - Yong Zhou
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
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16
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Hirsch J, Uzun G, Zlamal J, Singh A, Bakchoul T. Platelet-neutrophil interaction in COVID-19 and vaccine-induced thrombotic thrombocytopenia. Front Immunol 2023; 14:1186000. [PMID: 37275917 PMCID: PMC10237318 DOI: 10.3389/fimmu.2023.1186000] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2023] [Accepted: 05/04/2023] [Indexed: 06/07/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) is known to commonly induce a thrombotic diathesis, particularly in severely affected individuals. So far, this COVID-19-associated coagulopathy (CAC) has been partially explained by hyperactivated platelets as well as by the prothrombotic effects of neutrophil extracellular traps (NETs) released from neutrophils. However, precise insight into the bidirectional relationship between platelets and neutrophils in the pathophysiology of CAC still lags behind. Vaccine-induced thrombotic thrombocytopenia (VITT) is a rare autoimmune disorder caused by auto-antibody formation in response to immunization with adenoviral vector vaccines. VITT is associated with life-threatening thromboembolic events and thus, high fatality rates. Our concept of the thrombophilia observed in VITT is relatively new, hence a better understanding could help in the management of such patients with the potential to also prevent VITT. In this review we aim to summarize the current knowledge on platelet-neutrophil interplay in COVID-19 and VITT.
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Affiliation(s)
- Johannes Hirsch
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
- Center for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
| | - Günalp Uzun
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
- Center for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
| | - Jan Zlamal
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
- Center for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
| | - Anurag Singh
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
| | - Tamam Bakchoul
- Institute of Clinical and Experimental Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
- Center for Clinical Transfusion Medicine, University Hospital of Tuebingen, Tuebingen, Germany
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17
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Lebrun L, Absil L, Remmelink M, De Mendonça R, D'Haene N, Gaspard N, Rusu S, Racu ML, Collin A, Allard J, Zindy E, Schiavo AA, De Clercq S, De Witte O, Decaestecker C, Lopes MB, Salmon I. SARS-Cov-2 infection and neuropathological findings: a report of 18 cases and review of the literature. Acta Neuropathol Commun 2023; 11:78. [PMID: 37165453 PMCID: PMC10170054 DOI: 10.1186/s40478-023-01566-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Accepted: 04/15/2023] [Indexed: 05/12/2023] Open
Abstract
INTRODUCTION COVID-19-infected patients harbour neurological symptoms such as stroke and anosmia, leading to the hypothesis that there is direct invasion of the central nervous system (CNS) by SARS-CoV-2. Several studies have reported the neuropathological examination of brain samples from patients who died from COVID-19. However, there is still sparse evidence of virus replication in the human brain, suggesting that neurologic symptoms could be related to mechanisms other than CNS infection by the virus. Our objective was to provide an extensive review of the literature on the neuropathological findings of postmortem brain samples from patients who died from COVID-19 and to report our own experience with 18 postmortem brain samples. MATERIAL AND METHODS We used microscopic examination, immunohistochemistry (using two different antibodies) and PCR-based techniques to describe the neuropathological findings and the presence of SARS-CoV-2 virus in postmortem brain samples. For comparison, similar techniques (IHC and PCR) were applied to the lung tissue samples for each patient from our cohort. The systematic literature review was conducted from the beginning of the pandemic in 2019 until June 1st, 2022. RESULTS In our cohort, the most common neuropathological findings were perivascular haemosiderin-laden macrophages and hypoxic-ischaemic changes in neurons, which were found in all cases (n = 18). Only one brain tissue sample harboured SARS-CoV-2 viral spike and nucleocapsid protein expression, while all brain cases harboured SARS-CoV-2 RNA positivity by PCR. A colocalization immunohistochemistry study revealed that SARS-CoV-2 antigens could be located in brain perivascular macrophages. The literature review highlighted that the most frequent neuropathological findings were ischaemic and haemorrhagic lesions, including hypoxic/ischaemic alterations. However, few studies have confirmed the presence of SARS-CoV-2 antigens in brain tissue samples. CONCLUSION This study highlighted the lack of specific neuropathological alterations in COVID-19-infected patients. There is still no evidence of neurotropism for SARS-CoV-2 in our cohort or in the literature.
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Affiliation(s)
- Laetitia Lebrun
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Lara Absil
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Myriam Remmelink
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Ricardo De Mendonça
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Nicky D'Haene
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Nicolas Gaspard
- Department of Neurology, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, Erasme University Hospital, Brussels, Belgium
| | - Stefan Rusu
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Marie-Lucie Racu
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Amandine Collin
- DIAPath, Center for Microscopy and Molecular Imaging (CMMI), ULB, Gosselies, Belgium
| | - Justine Allard
- DIAPath, Center for Microscopy and Molecular Imaging (CMMI), ULB, Gosselies, Belgium
| | - Egor Zindy
- DIAPath, Center for Microscopy and Molecular Imaging (CMMI), ULB, Gosselies, Belgium
| | - Andrea Alex Schiavo
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Sarah De Clercq
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium
| | - Olivier De Witte
- Department of Neurosurgery, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital ErasmeErasme University Hospital, Brussels, Belgium
| | - Christine Decaestecker
- DIAPath, Center for Microscopy and Molecular Imaging (CMMI), ULB, Gosselies, Belgium
- Laboratory of Image Synthesis and Analysis, Brussels School of Engineering/École Polytechnique de Brussels, ULB, Brussels, Belgium
| | - Maria-Beatriz Lopes
- Department of Pathology, University of Virginia Health System, Charlottesville, VA, USA
| | - Isabelle Salmon
- Department of Pathology, Erasme University Hospital, Université Libre de Bruxelles (ULB)Hôpital Universitaire de Bruxelles (HUB), CUB Hôpital Erasme, 808 Route de Lennik, B-1070, Brussels, Belgium.
- DIAPath, Center for Microscopy and Molecular Imaging (CMMI), ULB, Gosselies, Belgium.
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18
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Soleiman-Meigooni S, Yaghmayee R, Mohammadi S, Ahmadi M, Sakhabakhsh M, Hamidi-Farahani R, Hazrati E, Jazayeri SM, Fotoohi M, Motemaveleh A, Doulatabadi-Farahani V, Shahmohamadi F, Kazemi-Galougahi MH, Asgari A, Aminianfar M, Darvishi M, Mohajeri-Iravani M, Gholizadeh O. Cardio-Pulmonary Histopathology with Clinical Correlations of Deceased Patients with COVID-19: A Case Series in Tehran, Iran. ARCHIVES OF IRANIAN MEDICINE 2023; 26:252-260. [PMID: 38301088 PMCID: PMC10685862 DOI: 10.34172/aim.2023.39] [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: 09/25/2022] [Accepted: 04/08/2023] [Indexed: 02/03/2024]
Abstract
BACKGROUND SARS-CoV-2 may affect vital organs. The present study investigated the histopathology of pulmonary and cardiac tissues with clinical correlation in deceased patients with COVID-19. METHODS We obtained pulmonary and cardiac tissues from 30 deceased patients with COVID-19 in Tehran, Iran, from January to May 2021. Sampling was performed through a percutaneous needle biopsy. After slide preparation, two expert pathologists studied them. We assessed the correlation between clinical and pathological data by Fisher's exact test. RESULTS The mean age of the patients was 73.8±13.4 years, and the male-to-female ratio was 23/7. The most common underlying disease was hypertension (HTN) in 25 patients (83%). Fifty-five tissue samples were achieved, including 28 pulmonary and 27 cardiac samples. Our results showed that all patients (100%) developed diffuse alveolar damage (DAD), and 26 (93%) developed hyaline membrane formation. The most common phase of DAD was the exudative-proliferative phase in 16 (57.1%). Three cardiac samples (11%) revealed myocarditis, and seven (26%) showed cardiomyocyte hypertrophy. In univariate analysis using Fischer's exact test, myocarditis had significant relationships with C-reactive protein (CRP) levels higher than 80 mg/dL (P=0.008) and elevated cardiac troponin levels higher than two-fold (P=0.01). CONCLUSION COVID-19 can affect the major vital organs. However, only myocarditis had a significant relationship with the circulating levels of inflammatory factors.
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Affiliation(s)
| | - Ramin Yaghmayee
- Department of Pathology, Khanevadeh University Hospital, Aja University of Medical Sciences, Tehran, Iran
| | - Shadi Mohammadi
- Department of Obstetrics and Gynecology, Khanevadeh University Hospital, Aja University of Medical Sciences, Tehran, Iran
| | - Mousa Ahmadi
- Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Mehdi Sakhabakhsh
- Department of Neurology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Ramin Hamidi-Farahani
- Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Ebrahim Hazrati
- Department of Anesthesiology, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | | | - Mahtab Fotoohi
- Department of Pathology, Khanevadeh University Hospital, Aja University of Medical Sciences, Tehran, Iran
| | - Akram Motemaveleh
- Department of Pulmonology, Khanevadeh University Hospital, Aja University of Medical Sciences, Tehran, Iran
| | - Vahid Doulatabadi-Farahani
- Department of Cardiology, Khanevadeh University Hospital, Aja University of Medical Sciences, Tehran, Iran
| | - Farhad Shahmohamadi
- Department of Forensic Medicine, Khanevadeh University Hospital, Aja University of Medical Sciences, Tehran, Iran
| | | | - Ali Asgari
- Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Mohammad Aminianfar
- Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Mohammad Darvishi
- Department of Infectious Diseases, Faculty of Medicine, Aja University of Medical Sciences, Tehran, Iran
| | - Mojgan Mohajeri-Iravani
- Department of Anesthesiology, Faculty of Paramedical Sciences, Aja University of Medical Sciences, Tehran, Iran
| | - Omid Gholizadeh
- Research Center for Clinical Virology, Tehran University of Medical Sciences, Tehran, Iran
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19
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van den Berg J, Haslbauer JD, Stalder AK, Romanens A, Mertz KD, Studt JD, Siegemund M, Buser A, Holbro A, Tzankov A. Von Willebrand factor and the thrombophilia of severe COVID-19: in situ evidence from autopsies. Res Pract Thromb Haemost 2023; 7:100182. [PMID: 37333991 PMCID: PMC10192064 DOI: 10.1016/j.rpth.2023.100182] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 04/29/2023] [Accepted: 05/08/2023] [Indexed: 06/20/2023] Open
Abstract
Background COVID-19 is accompanied by a hypercoagulable state and characterized by microvascular and macrovascular thrombotic complications. In plasma samples from patients with COVID-19, von Willebrand factor (VWF) levels are highly elevated and predictive of adverse outcomes, especially mortality. Yet, VWF is usually not included in routine coagulation analyses, and histologic evidence of its involvement in thrombus formation is lacking. Objectives To determine whether VWF, an acute-phase protein, is a bystander, ie, a biomarker of endothelial dysfunction, or a causal factor in the pathogenesis of COVID-19. Methods We compared autopsy samples from 28 patients with lethal COVID-19 to those from matched controls and systematically assessed for VWF and platelets by immunohistochemistry. The control group comprised 24 lungs, 23 lymph nodes, and 9 hearts and did not differ significantly from the COVID-19 group in age, sex, body mass index (BMI), blood group, or anticoagulant use. Results In lungs, assessed for platelets by immunohistochemistry for CD42b, microthrombi were more frequent in patients with COVID-19 (10/28 [36%] vs 2/24 [8%]; P = .02). A completely normal pattern of VWF was rare in both groups. Accentuated endothelial staining was found in controls, while VWF-rich thrombi were only found in patients with COVID-19 (11/28 [39%] vs 0/24 [0%], respectively; P < .01), as were NETosis thrombi enriched with VWF (7/28 [25%] vs 0/24 [0%], respectively; P < .01). Forty-six percent of the patients with COVID-19 had VWF-rich thrombi, NETosis thrombi, or both. Trends were also seen in pulmonary draining lymph nodes (7/20 [35%] vs 4/24 [17%]; P = .147), where the overall presence of VWF was very high. Conclusion We provide in situ evidence of VWF-rich thrombi, likely attributable to COVID-19, and suggest that VWF may be a therapeutic target in severe COVID-19.
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Affiliation(s)
- Jana van den Berg
- Department of Hematology, University Hospital Basel, Basel, Switzerland
| | - Jasmin D Haslbauer
- Department of Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
- Department of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Anna K Stalder
- Department of Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
| | - Anna Romanens
- Department of Oncology, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Kirsten D Mertz
- Department of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland
| | - Jan-Dirk Studt
- Department of Medical Oncology and Hematology, University Hospital Zürich, Zürich, Switzerland
| | - Martin Siegemund
- Intensive Care Unit, Department of Acute Medicine, University Hospital, Basel, Switzerland
| | - Andreas Buser
- Department of Hematology, University Hospital Basel, Basel, Switzerland
- Regional Blood Transfusion Service, Swiss Red Cross, Basel, Switzerland
| | - Andreas Holbro
- Department of Hematology, University Hospital Basel, Basel, Switzerland
- Regional Blood Transfusion Service, Swiss Red Cross, Basel, Switzerland
| | - Alexandar Tzankov
- Department of Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
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20
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do Nascimento RF, de Carvalho Filho JAA, Napoleão DC, Ribeiro BG, da Silva Pereira Cabral JJ, de Paiva ALR. Presence Of Non-Steroidal Anti-Inflammatories In Brazilian Semiarid Waters. WATER, AIR, AND SOIL POLLUTION 2023; 234:225. [PMID: 37008655 PMCID: PMC10038380 DOI: 10.1007/s11270-023-06239-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Accepted: 03/15/2023] [Indexed: 06/19/2023]
Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs) act as antipyretics, analgesics and anti-inflammatories. Among them, diclofenac and ibuprofen are the most consumed drugs worldwide. During the COVID-19 pandemic, some NSAIDs, such as dipyrone and paracetamol, have been used to alleviate the symptoms of the disease, causing an increase in the concentrations of these drugs in water. However, due to the low concentration of these compounds in drinking water and groundwater, few studies have been carried out on the subject, especially in Brazil. Thus, this study aimed to evaluate the contamination of the surface water, groundwater, and water treated with diclofenac, dipyrone, ibuprofen, and paracetamol at 3 cities (Orocó, Santa Maria da Boa Vista and Petrolândia) in the Brazilian semiarid region, in addition to analyzing the removal of these drugs by conventional water treatment (coagulation, flocculation, sedimentation, filtration and disinfection) in stations to each city. All drugs analyzed were detected in surface and treated waters. In groundwater, only dipyrone was not found. Dipyrone was seen in surface water with a maximum concentration of 1858.02 μg.L-1, followed by ibuprofen (785.28 μg.L-1), diclofenac (759.06 μg.L-1) and paracetamol (533.64 μg.L-1). The high concentrations derive from the increased consumption of these substances during the COVID-19 pandemic. During the conventional water treatment, the maximum removal of diclofenac, dipyrone, ibuprofen and paracetamol was 22.42%; 3.00%; 32.74%; and 1.58%, respectively, which confirms the inefficiency of this treatment in removing drugs. The variation in removal rate of the analyzed drugs is due to the difference in the hydrophobicity of the compounds.
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Affiliation(s)
- Raquel Ferreira do Nascimento
- Department of Civil and Environmental Engineering (DECIV), Federal University of Pernambuco (UFPE), Av. da Arquitetura, s/n. Cidade Universitária, Recife, Pernambuco 50740-550 Brazil
| | - José Adson Andrade de Carvalho Filho
- Department of Civil and Environmental Engineering (DECIV), Federal University of Pernambuco (UFPE), Av. da Arquitetura, s/n. Cidade Universitária, Recife, Pernambuco 50740-550 Brazil
| | - Daniella Carla Napoleão
- Department of Chemical Engineering (DEQ), Federal University of Pernambuco (UFPE), Av. dos Economistas, s/n. Cidade Universitária, Recife, Pernambuco 50740-590 Brazil
| | - Beatriz Galdino Ribeiro
- Department of Chemical Engineering (DEQ), Federal University of Pernambuco (UFPE), Av. dos Economistas, s/n. Cidade Universitária, Recife, Pernambuco 50740-590 Brazil
| | - Jaime Joaquim da Silva Pereira Cabral
- Department of Civil and Environmental Engineering (DECIV), Federal University of Pernambuco (UFPE), Av. da Arquitetura, s/n. Cidade Universitária, Recife, Pernambuco 50740-550 Brazil
| | - Anderson Luiz Ribeiro de Paiva
- Department of Civil and Environmental Engineering (DECIV), Federal University of Pernambuco (UFPE), Av. da Arquitetura, s/n. Cidade Universitária, Recife, Pernambuco 50740-550 Brazil
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21
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Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). eLife 2023; 12:e86002. [PMID: 36947108 DOI: 10.7554/elife.86002:] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 03/10/2023] [Indexed: 08/28/2024] Open
Abstract
COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.
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Affiliation(s)
- Zaki A Sherif
- Department of Biochemistry & Molecular Biology, Howard University College of Medicine, Washington, District of Columbia, United States
| | - Christian R Gomez
- Division of Lung Diseases, National Institutes of Health (NIH), National Heart, Lung and Blood Institute (NHLBI), Bethesda, United States
| | - Thomas J Connors
- Department of Pediatrics, Division of Critical Care, Columbia University Vagelos College of Physicians and Surgeons and New York - Presbyterian Morgan Stanley Children's Hospital, New York, United States
| | - Timothy J Henrich
- Division of Experimental Medicine, University of California, San Francisco, United States
| | - William Brian Reeves
- Department of Medicine, Joe R. and Teresa Lozano Long School of Medicine, University of Texas, San Antonio, United States
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22
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Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). eLife 2023; 12:e86002. [PMID: 36947108 PMCID: PMC10032659 DOI: 10.7554/elife.86002] [Citation(s) in RCA: 108] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2023] [Accepted: 03/10/2023] [Indexed: 03/23/2023] Open
Abstract
COVID-19, with persistent and new onset of symptoms such as fatigue, post-exertional malaise, and cognitive dysfunction that last for months and impact everyday functioning, is referred to as Long COVID under the general category of post-acute sequelae of SARS-CoV-2 infection (PASC). PASC is highly heterogenous and may be associated with multisystem tissue damage/dysfunction including acute encephalitis, cardiopulmonary syndromes, fibrosis, hepatobiliary damages, gastrointestinal dysregulation, myocardial infarction, neuromuscular syndromes, neuropsychiatric disorders, pulmonary damage, renal failure, stroke, and vascular endothelial dysregulation. A better understanding of the pathophysiologic mechanisms underlying PASC is essential to guide prevention and treatment. This review addresses potential mechanisms and hypotheses that connect SARS-CoV-2 infection to long-term health consequences. Comparisons between PASC and other virus-initiated chronic syndromes such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome will be addressed. Aligning symptoms with other chronic syndromes and identifying potentially regulated common underlining pathways may be necessary for understanding the true nature of PASC. The discussed contributors to PASC symptoms include sequelae from acute SARS-CoV-2 injury to one or more organs, persistent reservoirs of the replicating virus or its remnants in several tissues, re-activation of latent pathogens such as Epstein-Barr and herpes viruses in COVID-19 immune-dysregulated tissue environment, SARS-CoV-2 interactions with host microbiome/virome communities, clotting/coagulation dysregulation, dysfunctional brainstem/vagus nerve signaling, dysautonomia or autonomic dysfunction, ongoing activity of primed immune cells, and autoimmunity due to molecular mimicry between pathogen and host proteins. The individualized nature of PASC symptoms suggests that different therapeutic approaches may be required to best manage specific patients.
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Affiliation(s)
- Zaki A Sherif
- Department of Biochemistry & Molecular Biology, Howard University College of MedicineWashington, District of ColumbiaUnited States
| | - Christian R Gomez
- Division of Lung Diseases, National Institutes of Health (NIH), National Heart, Lung and Blood Institute (NHLBI)BethesdaUnited States
| | - Thomas J Connors
- Department of Pediatrics, Division of Critical Care, Columbia University Vagelos College of Physicians and Surgeons and New York - Presbyterian Morgan Stanley Children's HospitalNew YorkUnited States
| | - Timothy J Henrich
- Division of Experimental Medicine, University of CaliforniaSan FranciscoUnited States
| | - William Brian Reeves
- Department of Medicine, Joe R. and Teresa Lozano Long School of Medicine, University of TexasSan AntonioUnited States
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23
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Septimiu-Radu S, Gadela T, Gabriela D, Oancea C, Rosca O, Lazureanu VE, Fericean RM, Bratosin F, Dumitrescu A, Stoicescu ER, Bagiu I, Murariu M, Mavrea A. A Systematic Review of Lung Autopsy Findings in Elderly Patients after SARS-CoV-2 Infection. J Clin Med 2023; 12:2070. [PMID: 36902856 PMCID: PMC10004532 DOI: 10.3390/jcm12052070] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 02/27/2023] [Accepted: 03/05/2023] [Indexed: 03/08/2023] Open
Abstract
Although COVID-19 may cause various and multiorgan diseases, few research studies have examined the postmortem pathological findings of SARS-CoV-2-infected individuals who died. Active autopsy results may be crucial for understanding how COVID-19 infection operates and preventing severe effects. In contrast to younger persons, however, the patient's age, lifestyle, and concomitant comorbidities might alter the morpho-pathological aspects of the damaged lungs. Through a systematic analysis of the available literature until December 2022, we aimed to provide a thorough picture of the histopathological characteristics of the lungs in patients older than 70 years who died of COVID-19. A thorough search was conducted on three electronic databases (PubMed, Scopus, and Web of Science), including 18 studies and a total of 478 autopsies performed. It was observed that the average age of patients was 75.6 years, of which 65.4% were men. COPD was identified in an average of 16.7% of all patients. Autopsy findings indicated significantly heavier lungs, with an average weight of the right lung of 1103 g, while the left lung mass had an average weight of 848 g. Diffuse alveolar damage was a main finding in 67.2% of all autopsies, while pulmonary edema had a prevalence of between 50% and 70%. Thrombosis was also a significant finding, while some studies described focal and extensive pulmonary infarctions in 72.7% of elderly patients. Pneumonia and bronchopneumonia were observed, with a prevalence ranging from 47.6% to 89.5%. Other important findings described in less detail comprise hyaline membranes, the proliferation of pneumocytes and fibroblasts, extensive suppurative bronchopneumonic infiltrates, intra-alveolar edema, thickened alveolar septa, desquamation of pneumocytes, alveolar infiltrates, multinucleated giant cells, and intranuclear inclusion bodies. These findings should be corroborated with children's and adults' autopsies. Postmortem examination as a technique for studying the microscopic and macroscopic features of the lungs might lead to a better knowledge of COVID-19 pathogenesis, diagnosis, and treatment, hence enhancing elderly patient care.
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Affiliation(s)
- Susa Septimiu-Radu
- Department XIII, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Doctoral School, ‘’Victor Babes’’ University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Tejaswi Gadela
- School of General Medicine, Bhaskar Medical College, Amdapur Road 156-162, Hyderabad 500075, India
| | - Doros Gabriela
- Department of Pediatrics, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Cristian Oancea
- Center for Research and Innovation in Precision Medicine of Respiratory Diseases, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Ovidiu Rosca
- Department XIII, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Voichita Elena Lazureanu
- Department XIII, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Roxana Manuela Fericean
- Department XIII, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Doctoral School, ‘’Victor Babes’’ University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Felix Bratosin
- Department XIII, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Doctoral School, ‘’Victor Babes’’ University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Andreea Dumitrescu
- Cardioprevent Foundation, Calea Dorobantilor 3, Timisoara 300134, Romania
| | - Emil Robert Stoicescu
- Doctoral School, ‘’Victor Babes’’ University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Department of Radiology and Medical Imaging, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Iulia Bagiu
- Department of Microbiology, Multidisciplinary Research Center on Antimicrobial Resistance, “Victor Babes” University of Medicine and Pharmacy, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Mircea Murariu
- Doctoral School, ‘’Victor Babes’’ University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Department of Pediatrics, Discipline of Infectious Disease, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Adelina Mavrea
- Department of Internal Medicine I, Cardiology Clinic, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
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Dillard JA, Martinez SA, Dearing JJ, Montgomery SA, Baxter AK. Animal Models for the Study of SARS-CoV-2-Induced Respiratory Disease and Pathology. Comp Med 2023; 73:72-90. [PMID: 36229170 PMCID: PMC9948904 DOI: 10.30802/aalas-cm-22-000089] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Emergence of the betacoronavirus SARS-CoV-2 has resulted in a historic pandemic, with millions of deaths worldwide. An unprecedented effort has been made by the medical, scientific, and public health communities to rapidly develop and implement vaccines and therapeutics to prevent and reduce hospitalizations and deaths. Although SARS-CoV-2 infection can lead to disease in many organ systems, the respiratory system is its main target, with pneumonia and acute respiratory distress syndrome as the hallmark features of severe disease. The large number of patients who have contracted COVID-19 infections since 2019 has permitted a detailed characterization of the clinical and pathologic features of the disease in humans. However, continued progress in the development of effective preventatives and therapies requires a deeper understanding of the pathogenesis of infection. Studies using animal models are necessary to complement in vitro findings and human clinical data. Multiple animal species have been evaluated as potential models for studying the respiratory disease caused by SARSCoV-2 infection. Knowing the similarities and differences between animal and human responses to infection is critical for effective translation of animal data into human medicine. This review provides a detailed summary of the respiratory disease and associated pathology induced by SARS-CoV-2 infection in humans and compares them with the disease that develops in 3 commonly used models: NHP, hamsters, and mice. The effective use of animals to study SARS-CoV-2-induced respiratory disease will enhance our understanding of SARS-CoV-2 pathogenesis, allow the development of novel preventatives and therapeutics, and aid in the preparation for the next emerging virus with pandemic potential.
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Key Words
- ace2, angiotensin-converting enzyme 2
- agm, african green monkey
- ali, acute lung injury
- ards, acute respiratory distress syndrome
- balf, bronchoalveolar lavage fluid
- cards, covid-19-associated acute respiratory distress syndrome
- dad, diffuse alveolar damage
- dpi, days postinfection
- ggo, ground glass opacities
- s, spike glycoprotein
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Affiliation(s)
- Jacob A Dillard
- Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Sabian A Martinez
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Justin J Dearing
- Biological and Biomedical Sciences Program, Office of Graduate Education, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Stephanie A Montgomery
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
| | - Andvictoria K Baxter
- Division of Comparative Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;,
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Zanon M, Neri M, Pizzolitto S, Radaelli D, Concato M, Peruch M, D'Errico S. Liver pathology in COVID-19 related death and leading role of autopsy in the pandemic. World J Gastroenterol 2023; 29:200-220. [PMID: 36683722 PMCID: PMC9850946 DOI: 10.3748/wjg.v29.i1.200] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 11/14/2022] [Accepted: 12/21/2022] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND Information on liver involvement in patients with coronavirus disease 2019 is currently fragmented. AIM To highlight the pathological changes found during the autopsy of severe acute respiratory syndrome coronavirus 2 positive patients. METHODS A systematic literature search on PubMed was carried out until June 21, 2022. RESULTS A literature review reveals that pre-existing liver disease and elevation of liver enzyme in these patients are not common; liver enzyme elevations tend to be seen in those in critical conditions. Despite the poor expression of viral receptors in the liver, it seems that the virus is able to infect this organ and therefore cause liver damage. Unfortunately, to date, the search for the virus inside the liver is not frequent (16% of the cases) and only a small number show the presence of the virus. In most of the autopsy cases, macroscopic assessment is lacking, while microscopic evaluation of livers has revealed the frequent presence of congestion (42.7%) and steatosis (41.6%). Less frequent is the finding of hepatic inflammation or necrosis (19%) and portal inflammation (18%). The presence of microthrombi, frequently found in the lungs, is infrequent in the liver, with only 12% of cases presenting thrombotic formations within the vascular tree. CONCLUSION To date, the greatest problem in interpreting these modifications remains the association of the damage with the direct action of the virus, rather than with the inflammation or alterations induced by hypoxia and hypovolemia in patients undergoing oxygen therapy and decompensated patients.
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Affiliation(s)
- Martina Zanon
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Margherita Neri
- Department of Medical Sciences, University of Ferrara, Ferrara 44121, Italy
| | - Stefano Pizzolitto
- Department of Pathology, Santa Maria della Misericordia University Hospital, Udine 33100, Italy
| | - Davide Radaelli
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Monica Concato
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Michela Peruch
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
| | - Stefano D'Errico
- Department of Medical Surgical and Health Sciences, University of Trieste, Trieste 34149, Italy
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26
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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: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [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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27
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Milross L, Majo J, Pulle J, Hoggard S, Cooper N, Hunter B, Duncan CJ, Filby A, Fisher AJ. The trajectory of COVID-19 cardiopulmonary disease: insights from an autopsy study of community-based, pre-hospital deaths. ERJ Open Res 2022; 8:00303-2022. [PMID: 36575708 PMCID: PMC9571221 DOI: 10.1183/23120541.00303-2022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 10/04/2022] [Indexed: 12/30/2022] Open
Abstract
Background Post mortem examination of lung and heart tissue has been vital to developing an understanding of COVID-19 pathophysiology; however studies to date have almost uniformly used tissue obtained from hospital-based deaths where individuals have been exposed to major medical and pharmacological interventions. Methods In this study we investigated patterns of lung and heart injury from 46 community-based, pre-hospital COVID-19-attributable deaths who underwent autopsy. Results The cohort comprised 22 females and 24 males, median age 64 years (range 19-91) at time of death with illness duration range 0-23 days. Comorbidities associated with poor outcomes in COVID-19 included obesity (body mass index >30 kg·m-2) in 19 out of 46 cases (41.3%). Diffuse alveolar damage in its early exudative phase was the most common pattern of lung injury; however significant heterogeneity was identified with bronchopneumonia, pulmonary oedema consistent with acute cardiac failure, pulmonary thromboembolism and microthrombosis also identified and often in overlapping patterns. Review of clinical records and next of kin accounts suggested a combination of unexpectedly low symptom burden, rapidly progressive disease and psychosocial factors may have contributed to a failure of hospital presentation prior to death. Conclusions Identifying such advanced acute lung injury in community-based deaths is extremely unusual and raises the question why some with severe COVID-19 pneumonitis were not hospitalised. Multiple factors including low symptom burden, rapidly progressive disease trajectories and psychosocial factors provide possible explanations.
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Affiliation(s)
- Luke Milross
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Joaquim Majo
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Julian Pulle
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Sam Hoggard
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Nigel Cooper
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Bethany Hunter
- Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Christopher J.A. Duncan
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
- Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Andrew Filby
- Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Andrew J. Fisher
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
- Institute of Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
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28
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Zinellu A, Mangoni AA. A systematic review and meta-analysis of the association between the neutrophil, lymphocyte, and platelet count, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio and COVID-19 progression and mortality. Expert Rev Clin Immunol 2022; 18:1187-1202. [PMID: 36047369 DOI: 10.1080/1744666x.2022.2120472] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND AND AIMS Severe manifestations of coronavirus disease 2019 (COVID-19) are associated with alterations in blood cells that regulate immunity, inflammation, and hemostasis. We conducted an updated systematic review and meta-analysis of the association between the neutrophil, lymphocyte, and platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), and COVID-19 progression and mortality. METHODS A systematic literature search was conducted in PubMed, Web of Science, and Scopus for studies published between January 2020 and June 2022. RESULTS In 71 studies reporting the investigated parameters within 48 hours of admission, higher NLR (HR 1.21, 95% CI 1.16 to 1.27, p < 0.0001), relative neutrophilia (HR 1.62, 95% CI 1.46 to 1.80, p < 0.0001), relative lymphopenia (HR 1.62, 95% CI 1.27 to 2.08, p < 0.001), and relative thrombocytopenia (HR 1.74, 95% CI 1.36 to 2.22, p < 0.001), but not PLR (p = 0.11), were significantly associated with disease progression and mortality. Between-study heterogeneity was large-to-extreme. The magnitude and direction of the effect size were not modified in sensitivity analysis. CONCLUSIONS NLR and neutrophil, lymphocyte, and platelet count significantly discriminate COVID-19 patients with different progression and survival outcomes. (PROSPERO registration number: CRD42021267875).
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Affiliation(s)
- Angelo Zinellu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
| | - Arduino A Mangoni
- Discipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, Australia.,Department of Clinical Pharmacology, Flinders Medical Centre, Southern Adelaide Local Health Network, Adelaide, Australia
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29
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Raviraj KG, Shobhana SS. Findings and inferences from full autopsies, minimally invasive autopsies and biopsy studies in patients who died as a result of COVID19 - A systematic review. Forensic Sci Med Pathol 2022; 18:369-381. [PMID: 35817946 PMCID: PMC9273702 DOI: 10.1007/s12024-022-00494-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/07/2022] [Indexed: 12/14/2022]
Abstract
Many articles on COVID19 deaths have been published since the pandemic has occurred. On reviewing the articles published until June 2021, the findings were very heterogeneous. Adding to the existing knowledge, there were also some unique observations made in the pathogenesis of COVID19. This review was done to determine the findings obtained and inferences drawn from various studies published globally among patients who died due to COVID19. PRISMA guidelines were used to conduct this systematic review. A search of databases like PubMed, ScienceDirect and Epistemonikos was done. The articles focusing on postmortem sample studies involving full autopsies, minimally invasive autopsies and tissue biopsy studies were screened and searched. The studies included were all the case reports, case series, narrative reviews and systematic reviews obtained in full text and in the English language containing study information, and samples obtained postmortem. The information obtained was tabulated using Microsoft excel sheets. The duplicates were removed at the beginning of the tabulation. Zotero referencing software was used for article sorting and citation and bibliography. Two authors independently reviewed the articles throughout the process to prevent bias. Adding to the heterogeneity of COVID19, the concept of lethality in preexisting disease conditions, the occurrence of secondary bacterial and fungal infections, and other pathogenetic mechanisms uniquely encountered are to be considered in treating the patients. Also, the presence of SARS-CoV-2 postmortem is established and should be considered a hazard.
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Affiliation(s)
- K. G. Raviraj
- Department of Forensic Medicine & Toxicology, East Point College of Medical Sciences and Research Center, Jnanaprabha Campus, Bidarahalli, Virgo Nagar Post, Bangalore, 560049 Karnataka India
| | - S. S. Shobhana
- Department of Forensic Medicine & Toxicology, St. Peter’s Medical College, Hospital and Research Institute, NH 44, Hosur, Tamil Nadu 635109 India
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30
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Pereira MAM, Silva LNLE, Lessa MPDA, Cunha J, Souza ACSD, Pantaleão L. An ancient examination in the face of a modern pandemic: systematic review of major clinicopathological autopsy findings. Rev Assoc Med Bras (1992) 2022; 68:1103-1108. [PMID: 36000598 PMCID: PMC9574983 DOI: 10.1590/1806-9282.20210098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 04/27/2021] [Indexed: 11/22/2022] Open
Affiliation(s)
| | | | | | - Jéssica Cunha
- Universidade Federal Fluminense - Niterói (RJ), Brazil
| | | | - Luciana Pantaleão
- Universidade Federal Fluminense, Departamento de Patologia - Niterói (RJ), Brazil
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31
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Wismüller A, DSouza AM, Abidin AZ, Ali Vosoughi M, Gange C, Cortopassi IO, Bozovic G, Bankier AA, Batra K, Chodakiewitz Y, Xi Y, Whitlow CT, Ponnatapura J, Wendt GJ, Weinberg EP, Stockmaster L, Shrier DA, Shin MC, Modi R, Lo HS, Kligerman S, Hamid A, Hahn LD, Garcia GM, Chung JH, Altes T, Abbara S, Bader AS. Early-stage COVID-19 pandemic observations on pulmonary embolism using nationwide multi-institutional data harvesting. NPJ Digit Med 2022; 5:120. [PMID: 35986059 PMCID: PMC9388980 DOI: 10.1038/s41746-022-00653-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Accepted: 07/06/2022] [Indexed: 11/29/2022] Open
Abstract
We introduce a multi-institutional data harvesting (MIDH) method for longitudinal observation of medical imaging utilization and reporting. By tracking both large-scale utilization and clinical imaging results data, the MIDH approach is targeted at measuring surrogates for important disease-related observational quantities over time. To quantitatively investigate its clinical applicability, we performed a retrospective multi-institutional study encompassing 13 healthcare systems throughout the United States before and after the 2020 COVID-19 pandemic. Using repurposed software infrastructure of a commercial AI-based image analysis service, we harvested data on medical imaging service requests and radiology reports for 40,037 computed tomography pulmonary angiograms (CTPA) to evaluate for pulmonary embolism (PE). Specifically, we compared two 70-day observational periods, namely (i) a pre-pandemic control period from 11/25/2019 through 2/2/2020, and (ii) a period during the early COVID-19 pandemic from 3/8/2020 through 5/16/2020. Natural language processing (NLP) on final radiology reports served as the ground truth for identifying positive PE cases, where we found an NLP accuracy of 98% for classifying radiology reports as positive or negative for PE based on a manual review of 2,400 radiology reports. Fewer CTPA exams were performed during the early COVID-19 pandemic than during the pre-pandemic period (9806 vs. 12,106). However, the PE positivity rate was significantly higher (11.6 vs. 9.9%, p < 10-4) with an excess of 92 PE cases during the early COVID-19 outbreak, i.e., ~1.3 daily PE cases more than statistically expected. Our results suggest that MIDH can contribute value as an exploratory tool, aiming at a better understanding of pandemic-related effects on healthcare.
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Affiliation(s)
- Axel Wismüller
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA
- Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, NY, USA
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
- Faculty of Medicine, Ludwig Maximilian University of Munich, Munich, Germany
| | - Adora M DSouza
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
| | - Anas Z Abidin
- Department of Biomedical Engineering, University of Rochester Medical Center, Rochester, NY, USA
| | - M Ali Vosoughi
- Department of Electrical and Computer Engineering, University of Rochester, Rochester, NY, USA
| | - Christopher Gange
- Department of Radiology & Biomedical Sciences, Yale University School of Medicine, New Haven, CT, USA
| | - Isabel O Cortopassi
- Department of Radiology, Mayo Clinic College of Medicine and Science, Jacksonville, FL, USA
| | - Gracijela Bozovic
- Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Alexander A Bankier
- Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Kiran Batra
- Department of Radiology, University of Texas, Southwestern Medical Center, Dallas, TX, USA
| | - Yosef Chodakiewitz
- Department of Imaging, S. Mark Taper Foundation Imaging Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Yin Xi
- Department of Radiology, University of Texas, Southwestern Medical Center, Dallas, TX, USA
| | | | | | - Gary J Wendt
- Department of Radiology, University of Wisconsin, Madison, WI, USA
| | - Eric P Weinberg
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA
| | - Larry Stockmaster
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA
| | - David A Shrier
- Department of Imaging Sciences, University of Rochester Medical Center, Rochester, NY, USA
| | - Min Chul Shin
- Department of Radiology, Christiana Care Health System, Newark, DE, USA
| | - Roshan Modi
- Department of Radiology, Christiana Care Health System, Newark, DE, USA
| | - Hao Steven Lo
- Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA
| | - Seth Kligerman
- Department of Radiology, University of California, San Diego, San Diego, CA, USA
| | - Aws Hamid
- Emory University School of Medicine, Department of Radiology and Imaging Sciences, Atlanta, GA, USA
| | - Lewis D Hahn
- Department of Radiology, University of California, San Diego, San Diego, CA, USA
| | | | - Jonathan H Chung
- Department of Radiology, University of Chicago, Chicago, IL, USA
| | | | - Suhny Abbara
- Department of Radiology, University of Texas, Southwestern Medical Center, Dallas, TX, USA
| | - Anna S Bader
- Department of Radiology & Biomedical Sciences, Yale University School of Medicine, New Haven, CT, USA.
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32
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Gawelek KL, Padera R, Connors J, Pinkus GS, Podznyakova O, Battinelli EM. Cardiac megakaryocytes in SARS-CoV-2 positive autopsies. Histopathology 2022; 81:600-624. [PMID: 35925828 PMCID: PMC9538948 DOI: 10.1111/his.14734] [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: 04/29/2022] [Revised: 06/08/2022] [Accepted: 06/10/2022] [Indexed: 01/08/2023]
Abstract
Thromboembolic phenomena are an important complication of infection by severe acute respiratory coronavirus 2 (SARS‐CoV‐2). Increasing focus on the management of the thrombotic complications of Coronavirus Disease 2019 (COVID‐19) has led to further investigation into the role of platelets, and their precursor cell, the megakaryocyte, during the disease course. Previously published postmortem evaluations of patients who succumbed to COVID‐19 have reported the presence of megakaryocytes in the cardiac microvasculature. Our series evaluated a cohort of autopsies performed on SARS‐CoV‐2‐positive patients in 2020 (n = 36) and prepandemic autopsies performed in early 2020 (n = 12) and selected to represent comorbidities common in cases of severe COVID‐19, in addition to infectious and noninfectious pulmonary disease and thromboembolic phenomena. Cases were assessed for the presence of cardiac megakaryocytes and correlated with the presence of pulmonary emboli and laboratory platelet parameters and inflammatory markers. Cardiac megakaryocytes were detected in 64% (23/36) of COVID‐19 autopsies, and 40% (5/12) prepandemic autopsies, with averages of 1.77 and 0.84 megakaryocytes per cm2, respectively. Within the COVID‐19 cohort, autopsies with detected megakaryocytes had significantly higher platelet counts compared with cases throughout; other platelet parameters were not statistically significant between groups. Although studies have supported a role of platelets and megakaryocytes in the response to viral infections, including SARS‐CoV‐2, our findings suggest cardiac megakaryocytes may be representative of a nonspecific inflammatory response and are frequent in, but not exclusive to, COVID‐19 autopsies.
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Affiliation(s)
- Kara L Gawelek
- Department of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA
| | - Robert Padera
- Department of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA
| | - Jean Connors
- Division of Hematology, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA
| | - Geraldine S Pinkus
- Department of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA
| | - Olga Podznyakova
- Department of Pathology, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA
| | - Elisabeth M Battinelli
- Division of Hematology, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA
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33
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Almamlouk R, Kashour T, Obeidat S, Bois MC, Maleszewski JJ, Omrani OA, Tleyjeh R, Berbari E, Chakhachiro Z, Zein-Sabatto B, Gerberi D, Tleyjeh IM, Paniz Mondolfi AE, Finn AV, Duarte-Neto AN, Rapkiewicz AV, Frustaci A, Keresztesi AA, Hanley B, Märkl B, Lardi C, Bryce C, Lindner D, Aguiar D, Westermann D, Stroberg E, Duval EJ, Youd E, Bulfamante GP, Salmon I, Auer J, Maleszewski JJ, Hirschbühl K, Absil L, Barton LM, Ferraz da Silva LF, Moore L, Dolhnikoff M, Lammens M, Bois MC, Osborn M, Remmelink M, Nascimento Saldiva PH, Jorens PG, Craver R, Aparecida de Almeida Monteiro R, Scendoni R, Mukhopadhyay S, Suzuki T, Mauad T, Fracasso T, Grimes Z. COVID-19-Associated cardiac pathology at the postmortem evaluation: a collaborative systematic review. Clin Microbiol Infect 2022; 28:1066-1075. [PMID: 35339672 PMCID: PMC8941843 DOI: 10.1016/j.cmi.2022.03.021] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 03/10/2022] [Accepted: 03/14/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND Many postmortem studies address the cardiovascular effects of COVID-19 and provide valuable information, but are limited by their small sample size. OBJECTIVES The aim of this systematic review is to better understand the various aspects of the cardiovascular complications of COVID-19 by pooling data from a large number of autopsy studies. DATA SOURCES We searched the online databases Ovid EBM Reviews, Ovid Embase, Ovid Medline, Scopus, and Web of Science for concepts of autopsy or histopathology combined with COVID-19, published between database inception and February 2021. We also searched for unpublished manuscripts using the medRxiv services operated by Cold Spring Harbor Laboratory. STUDY ELIGIBILITY CRITERIA Articles were considered eligible for inclusion if they reported human postmortem cardiovascular findings among individuals with a confirmed SARS coronavirus type 2 (CoV-2) infection. PARTICIPANTS Confirmed COVID-19 patients with post-mortem cardiovascular findings. INTERVENTIONS None. METHODS Studies were individually assessed for risk of selection, detection, and reporting biases. The median prevalence of different autopsy findings with associated interquartile ranges (IQRs). RESULTS This review cohort contained 50 studies including 548 hearts. The median age of the deceased was 69 years. The most prevalent acute cardiovascular findings were myocardial necrosis (median: 100.0%; IQR, 20%-100%; number of studies = 9; number of patients = 64) and myocardial oedema (median: 55.5%; IQR, 19.5%-92.5%; number of studies = 4; number of patients = 46). The median reported prevalence of extensive, focal active, and multifocal myocarditis were all 0.0%. The most prevalent chronic changes were myocyte hypertrophy (median: 69.0%; IQR, 46.8%-92.1%) and fibrosis (median: 35.0%; IQR, 35.0%-90.5%). SARS-CoV-2 was detected in the myocardium with median prevalence of 60.8% (IQR 40.4-95.6%). CONCLUSIONS Our systematic review confirmed the high prevalence of acute and chronic cardiac pathologies in COVID-19 and SARS-CoV-2 cardiac tropism, as well as the low prevalence of myocarditis in COVID-19.
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Affiliation(s)
| | - Tarek Kashour
- Department of Cardiac Sciences, King Fahad Cardiac Center, King Saud University Medical City, Riyadh, Saudi Arabia
| | - Sawsan Obeidat
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Melanie C Bois
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Joseph J Maleszewski
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Osama A Omrani
- The Royal London Hospital, Barts Health NHS Trust, London, UK; Barts and the London School of Medicine and Dentistry, Queen Mary University, London, UK
| | - Rana Tleyjeh
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
| | - Elie Berbari
- Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA
| | - Zaher Chakhachiro
- Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon
| | - Bassel Zein-Sabatto
- Department of Pathology and Laboratory Medicine, American University of Beirut, Beirut, Lebanon
| | - Dana Gerberi
- Mayo Clinic Libraries, Mayo Clinic, Rochester, MN, USA
| | - Imad M Tleyjeh
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia; Division of Infectious Diseases, Mayo Clinic College of Medicine and Science, Rochester, MN, USA; Infectious Diseases Section, Department of Medical Specialties King Fahad Medical City, Riyadh, Saudi Arabia; Division of Epidemiology, Mayo Clinic College of Medicine and Science, Rochester, MN, USA.
| | | | - Aloke V Finn
- CVPath Institute, Inc., Gaithersburg, and University of Maryland, Baltimore, MD, USA
| | - Amaro Nunes Duarte-Neto
- Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Amy V Rapkiewicz
- NYU Winthrop Hospital, Department of Pathology, Long Island School of Medicine, Long Island, NY, USA
| | - Andrea Frustaci
- Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, Rome, Italy; Cellular and Molecular Cardiology Lab, IRCCS L. Spallanzani, Rome, Italy
| | - Arthur-Atilla Keresztesi
- Fogolyan Kristof Emergency County Hospital, Covasna County Institution of Forensic Medicine, Covasna, Romania
| | - Brian Hanley
- Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK; Centre for Inflammatory Disease, Imperial College London, London, UK
| | - Bruno Märkl
- Institute of Pathology and Molecular Diagnostics, University Medical Center Augsburg, Augsburg, Germany
| | - Christelle Lardi
- University Center of Legal Medicine, Geneva University Hospital, Geneva, Switzerland
| | - Clare Bryce
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Diana Lindner
- Department of Cardiology, University Heart and Vascular Centre, Hamburg, Germany; DZHK-German Center for Cardiovascular Research, Partner site, Hamburg/Kiel/Lübeck, Germany
| | - Diego Aguiar
- University Center of Legal Medicine, Geneva University Hospital, Geneva, Switzerland
| | - Dirk Westermann
- Department of Cardiology, University Heart and Vascular Centre, Hamburg, Germany; DZHK-German Center for Cardiovascular Research, Partner site, Hamburg/Kiel/Lübeck, Germany
| | - Edana Stroberg
- Office of the Chief Medical Examiner, Oklahoma City, OK, USA
| | - Eric J Duval
- Office of the Chief Medical Examiner, Oklahoma City, OK, USA
| | - Esther Youd
- Forensic Medicine and Science, University of Glasgow, Glasgow, UK
| | - Gaetano Pietro Bulfamante
- Unità di Anatomia Patologica, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Milan, Italy; Struttura Complessa di Anatomia Patologica e Genetica Medica, ASST Santi Paolo e Carlo, Milan, Italy
| | - Isabelle Salmon
- Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium; Centre Universitaire inter Régional d'expertise en Anatomie Pathologique Hospitalière, Jumet, Belgium; DIAPath, Center for Microscopy and Molecular Imaging, ULB, Gosselies, Belgium
| | - Johann Auer
- Department of Cardiology and Intensive Care, St. Josef Hospital Braunau, Austria; Department of Cardiology and Intensive Care, Kepler University of Medicine Linz, Austria
| | - Joseph J Maleszewski
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA
| | - Klaus Hirschbühl
- Department of Hematology and Clinical Oncology, University Medical Center Augsburg, Augsburg, Germany
| | - Lara Absil
- Department of Pathology, Erasme Hospital, ULB, Brussels, Belgium
| | - Lisa M Barton
- Office of the Chief Medical Examiner, Oklahoma City, OK, USA
| | - Luiz Fernando Ferraz da Silva
- Departamento de Patologia, 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
| | - Luiza Moore
- Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Ageing and Somatic Mutation, Wellcome Sanger Institute, Cambridge, UK
| | - Marisa Dolhnikoff
- Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Martin Lammens
- Department of Pathology, Antwerp University Hospital, University of Antwerp, Edegem, Belgium
| | - Melanie C Bois
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA
| | - Michael Osborn
- Department of Cellular Pathology, Northwest London Pathology, Imperial College London NHS Trust, London, UK; Death Investigation Committee, Royal College of Pathologists, London, UK; Nightingale NHS Hospital, London, UK
| | - Myriam Remmelink
- Department of Pathology, Erasme Hospital, ULB, Brussels, Belgium
| | | | - Philippe G Jorens
- Infla-Med Research Consortium of Excellence, University of Antwerp, Antwerp, Belgium; Department of Medicine and Health Sciences, Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium; Department of Intensive Care Medicine, Antwerp University Hospital, University of Antwerp, Edegem, Belgium
| | - Randall Craver
- Children's Hospital of New Orleans and Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | | | - Roberto Scendoni
- Institute of Legal Medicine, Department of Law, University of Macerata, Macerata, Italy
| | | | - Tadaki Suzuki
- National Institute of Infectious Diseases, Tokyo, Japan
| | - Thais Mauad
- Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil
| | - Tony Fracasso
- University Center of Legal Medicine, Geneva University Hospital, Geneva, Switzerland
| | - Zachary Grimes
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
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COVID-19 and the injured patient: A multicenter review. J Surg Res 2022; 280:526-534. [PMID: 36084394 PMCID: PMC9263818 DOI: 10.1016/j.jss.2022.06.068] [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: 12/06/2021] [Revised: 06/17/2022] [Accepted: 06/30/2022] [Indexed: 12/02/2022]
Abstract
Introduction Coronavirus disease 2019 (COVID-19) has been shown to affect outcomes among surgical patients. We hypothesized that COVID-19 would be linked to higher mortality and longer length of stay of trauma patients regardless of the injury severity score (ISS). Methods We performed a retrospective analysis of trauma registries from two level 1 trauma centers (suburban and urban) from March 1, 2019, to June 30, 2019, and March 1, 2020, to June 30, 2020, comparing baseline characteristics and cumulative adverse events. Data collected included ISS, demographics, and comorbidities. The primary outcome was time from hospitalization to in-hospital death. Outcomes during the height of the first New York COVID-19 wave were also compared with the same time frame in the prior year. Kaplan–Meier method with log-rank test and Cox proportional hazard models were used to compare outcomes. Results There were 1180 trauma patients admitted during the study period from March 2020 to June 2020. Of these, 596 were never tested for COVID-19 and were excluded from the analysis. A total of 148 COVID+ patients and 436 COVID− patients composed the 2020 cohort for analysis. Compared with the 2019 cohort, the 2020 cohort was older with more associated comorbidities, more adverse events, but lower ISS. Higher rates of historical hypertension, diabetes, neurologic events, and coagulopathy were found among COVID+ patients compared with COVID− patients. D-dimer and ferritin were unreliable indicators of COVID-19 severity; however, C-reactive protein levels were higher in COVID+ relative to COVID− patients. Patients who were COVID+ had a lower median ISS compared with COVID− patients, and COVID+ patients had higher rates of mortality and longer length of stay. Conclusions COVID+ trauma patients admitted to our two level 1 trauma centers had increased morbidity and mortality compared with admitted COVID− trauma patients despite age and lower ISS. C-reactive protein may play a role in monitoring COVID-19 activity in trauma patients. A better understanding of the physiological impact of COVID-19 on injured patients warrants further investigation.
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Heldt S, Neuböck M, Kainzbauer N, Shao G, Tschoellitsch T, Duenser M, Kaiser B, Winkler M, Paar C, Meier J, Lamprecht B, Salzer HJF. qSOFA score poorly predicts critical progression in COVID-19 patients. Wien Med Wochenschr 2022; 172:211-219. [PMID: 34185216 PMCID: PMC8239483 DOI: 10.1007/s10354-021-00856-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 05/11/2021] [Indexed: 11/29/2022]
Abstract
BACKGROUND In December 2019, the new virus infection coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged. Simple clinical risk scores may improve the management of COVID-19 patients. Therefore, the aim of this pilot study was to evaluate the quick Sequential Organ Failure Assessment (qSOFA) score, which is well established for other diseases, as an early risk assessment tool predicting a severe course of COVID-19. METHODS We retrospectively analyzed data from adult COVID-19 patients hospitalized between March and July 2020. A critical disease progress was defined as admission to intensive care unit (ICU) or death. RESULTS Of 64 COVID-19 patients, 33% (21/64) had a critical disease progression from which 13 patients had to be transferred to ICU. The COVID-19-associated mortality rate was 20%, increasing to 39% after ICU admission. All patients without a critical progress had a qSOFA score ≤ 1 at admission. Patients with a critical progress had in only 14% (3/21) and in 20% (3/15) of cases a qSOFA score ≥ 2 at admission (p = 0.023) or when measured directly before critical progression, respectively, while 95% (20/21) of patients with critical progress had an impairment oxygen saturation (SO2) at admission time requiring oxygen supplementation. CONCLUSION A low qSOFA score cannot be used to assume short-term stable or noncritical disease status in COVID-19.
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Affiliation(s)
- Sven Heldt
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria
| | - Matthias Neuböck
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria
| | - Nora Kainzbauer
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria
| | - Guangyu Shao
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria
| | - Thomas Tschoellitsch
- Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital, Linz, Austria
| | - Martin Duenser
- Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital, Linz, Austria
| | - Bernhard Kaiser
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria
| | - Markus Winkler
- Department of Pathology and Microbiology, Kepler University Hospital, Linz, Austria
| | - Christian Paar
- Institute of Laboratory Medicine, Kepler University Hospital, Linz, Austria
| | - Jens Meier
- Department of Anesthesiology and Intensive Care Medicine, Kepler University Hospital, Linz, Austria
| | - Bernd Lamprecht
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria
| | - Helmut J F Salzer
- Department of Pulmonary Medicine, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria.
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Welty FK, Rajai N, Amangurbanova M. Comprehensive Review of Cardiovascular Complications of Coronavirus Disease 2019 and Beneficial Treatments. Cardiol Rev 2022; 30:145-157. [PMID: 35384908 PMCID: PMC8983616 DOI: 10.1097/crd.0000000000000422] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 and was first reported in December 2019 in Wuhan, China. Since then, it caused a global pandemic with 212,324,054 confirmed cases and 4,440,840 deaths worldwide as of August 22, 2021. The disease spectrum of COVID-19 ranges from asymptomatic subclinical infection to clinical manifestations predominantly affecting the respiratory system. However, it is now evident that COVID-19 is a multiorgan disease with a broad spectrum of manifestations leading to multiple organ injuries including the cardiovascular system. We review studies that have shown that the relationship between cardiovascular diseases and COVID-19 is indeed bidirectional, implicating that preexisting cardiovascular comorbidities increase the morbidity and mortality of COVID-19, and newly emerging cardiac injuries occur in the settings of acute COVID-19 in patients with no preexisting cardiovascular disease. We present the most up-to-date literature summary to explore the incidence of new-onset cardiac complications of coronavirus and their role in predicting the severity of COVID-19. We review the association of elevated troponin with the severity of COVID-19 disease, which includes mild compared to severe disease, in nonintensive care unit compared to intensive care unit patients and in those discharged from the hospital compared to those who die. The role of serum troponin levels in predicting prognosis are compared in survivors and non-survivors. The association between COVID-19 disease and myocarditis, heart failure and coagulopathy are reviewed. Finally, an update on beneficial treatments is discussed.
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Affiliation(s)
- Francine K. Welty
- From the Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Nazanin Rajai
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Maral Amangurbanova
- From the Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
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Martín-Martín J, Martín-Cazorla F, Suárez J, Rubio L, Martín-de-Las-Heras S. Comorbidities and autopsy findings of COVID-19 deaths and their association with time to death: a systematic review and meta-analysis. Curr Med Res Opin 2022; 38:785-792. [PMID: 35254193 DOI: 10.1080/03007995.2022.2050110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE Examination of postmortem findings can help establish effective therapeutic strategies to reduce mortality. The aim of this study was therefore to review complete autopsy cases and their postmortem findings and comorbidities associated with death caused by COVID-19, in order to establish a profile of the deceased and the likelihood of time to death. METHODS A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and meets Cochrane criteria recommendations (PROSPERO registration number CRD 42020209649). An electronic search in the databases Pubmed, Scopus, Web of Science, Wiley Online Library, and Scientific Electronic Library Online (SciELO) was performed. RESULTS The search strategy yielded a total of 25 articles where 140 cases of complete autopsies were reported. The most prevalent comorbidity was vascular diseases. Patients with vascular disease, heart disease, and diabetes died significantly in a shorter period of time. Autopsies mainly focused on the lungs. The proliferative phase of Diffuse Alveolar Damage (DAD) was the most reported in the microscopic postmortem findings, and these patients died in a shorter period of time. However, individuals aged over 80 years significantly presented fibrotic phase of DAD at the time of death. The kidney was the second most affected organ with thrombosis and tubular damage, followed by the liver with congestion and necrosis. CONCLUSION Given that accurate information of complete autopsies findings is still scarce, it is necessary to perform complete autopsies by examining organs other than the lungs in order to provide information to improve new treatment strategies in patients with a high risk of mortality.
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Affiliation(s)
- Jaime Martín-Martín
- Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
- Department of Legal and Forensic Medicine. Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Fernando Martín-Cazorla
- Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
- Instituto de Medicina Legal, Servicio de Patología Forense, Málaga, Spain
| | - Juan Suárez
- Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
- Department of Legal and Forensic Medicine. Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Leticia Rubio
- Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
- Department of Legal and Forensic Medicine. Facultad de Medicina, Universidad de Málaga, Málaga, Spain
| | - Stella Martín-de-Las-Heras
- Instituto de Investigación Biomédica de Málaga-IBIMA, Málaga, Spain
- Department of Legal and Forensic Medicine. Facultad de Medicina, Universidad de Málaga, Málaga, Spain
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Ergen P, Koçoğlu ME, Nural M, Kuşkucu MA, Aydin Ö, İnal FY, Öztürk H, Üçişik AC, Çaşkurlu H, Güneysu B, Yildirim B, Midilli K, Çağ Y, Arslan F, Vahaboglu H. Carbapenem-resistant Klebsiella pneumoniae outbreak in a COVID-19 intensive care unit; a case-control study. J Chemother 2022; 34:517-523. [PMID: 35470780 DOI: 10.1080/1120009x.2022.2064698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
We analysed a carbapenem-resistant Klebsiella pneumoniae (CRKP) outbreak in the coronavirus disease (COVID) ICU. We retrospectively collected data from ICU records. We identified 25 cases between 12 November 2020 and 19 December 2020, and compared them to 42 controls present in the ICU during the same period. The presence of a femoral haemodialysis catheter was strongly associated with invasive CRKP infections (cases, 9 [36%]; controls, 0 [0%]; odds ratio [OR] 95% confidence intervals [CIs], 21 (5; 89)). We found a significant association between old age and CRKP infection with adverse outcomes. Sequence analysis revealed three distinct carbapenemase genes: blaNDM-1, blaOXA-48 and blaKPC-2. We launched rectal swab sampling upon admission to the ICU, cohorted colonized patients and cases and conducted an intensive training programme for newly employed staff. This study revealed that the emergence and dissemination of CRKP in COVID ICUs were associated with increased adverse outcomes. The presence of a femoral haemodialysis catheter was a significant risk factor for CRKP infections.
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Affiliation(s)
- Pınar Ergen
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - M Esra Koçoğlu
- Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Müge Nural
- Anestesi ve Rehabilitasyon Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Mert Ahmet Kuşkucu
- Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Cerrahpaşa Tıp Fakültes, İstanbul Üniversitesi, İstanbul, Turkiye
| | - Özlem Aydin
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Ferda Y İnal
- Anestesi ve Rehabilitasyon Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Hande Öztürk
- Anestesi ve Rehabilitasyon Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Ayşe C Üçişik
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Hülya Çaşkurlu
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Büşra Güneysu
- Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Büşra Yildirim
- Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Kenan Midilli
- Mikrobiyoloji ve Klinik Mikrobiyoloji Anabilim Dalı, Cerrahpaşa Tıp Fakültes, İstanbul Üniversitesi, İstanbul, Turkiye
| | - Yasemin Çağ
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Ferhat Arslan
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
| | - Haluk Vahaboglu
- Enfeksiyon Hastalıkları Anabilim Dalı, Tıp Fakultesi, İstanbul Medeniyet Üniversitesi, İstanbul, Turkiye
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Pandolfi S, Valdenassi L, Bjørklund G, Chirumbolo S, Lysiuk R, Lenchyk L, Doşa MD, Fazio S. COVID-19 Medical and Pharmacological Management in the European Countries Compared to Italy: An Overview. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:4262. [PMID: 35409942 PMCID: PMC8998583 DOI: 10.3390/ijerph19074262] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 03/16/2022] [Accepted: 03/30/2022] [Indexed: 02/01/2023]
Abstract
(1) Background: Italy accounts for more than 150,000 deaths due to the COVID-19 pandemic, leading the top rank in SARS-CoV-2-caused deceases in Europe. A survey on the different ways by which the COVID-19 pandemic emergency was managed in the foreign European countries compared to Italy is the purpose of this paper. (2) Methods: A literature search and various mathematical algorithms to approach a rank scoring scale were used to describe in detail the different approaches used by European countries to manage the COVID-19 pandemic emergency. (3) Results: The study showed that Italy stands at the bottom ranking for COVID-19 management due to its high mortality rate. Possible causes of the observed huge numbers of hospitalization and deaths were (a) the demographic composition of the European country; (b) its decentralized healthcare system organization; (c) the role of correct pharmacology in the early stages before hospitalization. Post-mortem examinations were of paramount importance to elucidate the etiopathogenesis of COVID-19 and to tailor a suitable and proper therapy in the early symptomatic stages of COVID-19, preventing hospitalization. (4) Conclusions: Factors such as the significant impact on elderly people, the public health organization prevalently state-owned and represented mainly by hospitals, and criticism of the home therapy approach toward SARS-CoV-2-infected people, may have concurred in increasing the number of COVID-19 deaths in Italy.
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Affiliation(s)
- Sergio Pandolfi
- High School Master of Oxygen-Ozone Therapy, University of Pavia, 27100 Pavia, Italy; (S.P.); (L.V.)
| | - Luigi Valdenassi
- High School Master of Oxygen-Ozone Therapy, University of Pavia, 27100 Pavia, Italy; (S.P.); (L.V.)
| | - Geir Bjørklund
- Council for Nutritional and Environmental Medicine (CONEM), 8610 Mo i Rana, Norway;
| | - Salvatore Chirumbolo
- Council for Nutritional and Environmental Medicine (CONEM), 8610 Mo i Rana, Norway;
| | - Roman Lysiuk
- Department of Pharmacognosy and Botany, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine;
| | - Larysa Lenchyk
- Department of Standardization Kharkiv, National University of Pharmacy, 61002 Kharkiv, Ukraine;
| | - Monica Daniela Doşa
- Department of Pharmacology, Faculty of Medicine, Ovidius University, 900527 Constanța, Romania;
| | - Serafino Fazio
- Department of Internal Medicine, University of Naples Federico II, 80138 Naples, Italy;
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Driggers KE, Sadowski BW, Shagla E, Kwok RM. Care of the Hepatology Patient in the COVID-19 Era. CURRENT HEPATOLOGY REPORTS 2022; 21:9-20. [PMID: 35382426 PMCID: PMC8970972 DOI: 10.1007/s11901-021-00581-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 10/15/2020] [Accepted: 12/16/2021] [Indexed: 01/08/2023]
Abstract
Background and Purpose of Review The COVID-19 pandemic has resulted in over 800,000 deaths worldwide and resulted in fundamental changes in practice in nearly every aspect of medicine. The majority of symptomatic patients experience liver-associated enzyme (LAE) elevations which appear to be correlated to disease severity. Furthermore, there are unique considerations of COVID-19 on chronic liver disease. Background, including epidemiology, pathophysiologic mechanisms and therapeutics, as well as the impact of COVID-19 on specific chronic liver disease, is discussed. Findings Studies suggest that degree of LAE elevation correlates with illness severity, although it is unclear whether this represents true liver injury. Numerous proposed treatments for COVID-19 have been linked with drug induced liver injury and may have clinically significant drug-drug interactions. Others may have unintended consequences on chronic liver disease treatment including reactivation of hepatitis B. The risk of severe COVID-19 in patients with chronic liver disease is largely unknown; metabolic dysfunction-associated fatty liver disease may be linked to higher risk for severe illness. Implications for cirrhosis of other etiologies, autoimmune hepatitis, and viral hepatitis are less well defined. The treatment of chronic liver disease has been severely impacted by the pandemic. The societal factors created by the pandemic have led to decreased in person visits, evolving access to invasive screening modalities, food and financial insecurity, and likely increased alcohol use. Conclusions The impacts of COVID-19 on the liver range from a potential increased risk of severe infection in chronic liver disease patients, to hepatotoxic effects of proposed treatments, to second and third order impacts on the care of patients with chronic liver disease.
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Affiliation(s)
- Kathryn E. Driggers
- Internal Medicine, Walter Reed National Military Medical Center, Bethesda, MD USA
| | - Brett W. Sadowski
- Gastroenterology/Hepatology, Portsmouth Naval Medical Center, Portsmouth, VA USA
| | - Eva Shagla
- Gastro-Hepatology Department, Mother Theresa University Hospital Center, Tirana, Albania
| | - Ryan M. Kwok
- Chief Department of Gastroenterology/Hepatology, Madigan Army Medical Center, Tacoma WA, USA
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Maitz T, Parfianowicz D, Vojtek A, Rajeswaran Y, Vyas AV, Gupta R. COVID-19 Cardiovascular Connection: A Review of Cardiac Manifestations in COVID-19 Infection and Treatment Modalities. Curr Probl Cardiol 2022:101186. [PMID: 35351486 PMCID: PMC8957382 DOI: 10.1016/j.cpcardiol.2022.101186] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 03/22/2022] [Indexed: 01/08/2023]
Abstract
The coronavirus pandemic has crippled healthcare system since its outbreak in 2020, and has led to over 2.6 million deaths worldwide. Clinical manifestations of COVID-19 range from asymptomatic carrier to severe pneumonia, to life-threatening acute respiratory distress syndrome (ARDS). The early efforts of the pandemic surrounded treating the pulmonary component of COVID-19, however, there has been robust data surrounding the cardiac complications associated with the virus. This is suspected to be from a marked inflammatory response as well as direct viral injury. Arrhythmias, acute myocardial injury, myocarditis, cardiomyopathy, thrombosis, and myocardial fibrosis are some of the observed cardiac complications. There have been high morbidity and mortality rates in those affected by cardiac conditions associated with COVID-19. Additionally, there have been documented cases of patients presenting with typical cardiac symptoms who are subsequently discovered to have COVID-19 infection. In those who test positive for COVID-19, clinical awareness of the significant cardiac components of the virus is pertinent to prevent morbidity and mortality. Unfortunately, treatment and preventative measures developed for COVID-19 have been shown to be also be associated with cardiac complications. This is a comprehensive review of the cardiac complications and manifestations of COVID-19 infection in addition to those associated with both treatment and vaccination.
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Affiliation(s)
- Theresa Maitz
- Department of Medicine, Lehigh Valley Health Network, Allentown, PA
| | | | - Ashley Vojtek
- Department of Medicine, Lehigh Valley Health Network, Allentown, PA
| | | | - Apurva V Vyas
- Department of Cardiology, Lehigh Valley Health Network, Allentown, PA
| | - Rahul Gupta
- Department of Cardiology, Lehigh Valley Health Network, Allentown, PA.
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Frisoni P, Neri M, D’Errico S, Alfieri L, Bonuccelli D, Cingolani M, Di Paolo M, Gaudio RM, Lestani M, Marti M, Martelloni M, Moreschi C, Santurro A, Scopetti M, Turriziani O, Zanon M, Scendoni R, Frati P, Fineschi V. Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α. Forensic Sci Med Pathol 2022; 18:4-19. [PMID: 34463916 PMCID: PMC8406387 DOI: 10.1007/s12024-021-00414-9] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/27/2021] [Indexed: 12/12/2022]
Abstract
This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1β, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1β in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.
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Affiliation(s)
- Paolo Frisoni
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Margherita Neri
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Stefano D’Errico
- Department of Surgical, Medical and Health Sciences, University of Trieste, Trieste, Italy
| | - Letizia Alfieri
- Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Diana Bonuccelli
- Department of Legal Medicine, Territorial Unit USL Toscana Nordovest Lucca, Pisa, Italy
| | - Mariano Cingolani
- Department of Law, Institute of Legal Medicine, University of Macerata, Macerata, Italy
| | - Marco Di Paolo
- Department of Surgical Pathology, Medical, Molecular and Critical Area, Institute of Legal Medicine, University of Pisa, 56126 Pisa, PI Italy
| | - Rosa Maria Gaudio
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Maurizio Lestani
- Pathology Unit, Territorial Unit ULSS 7 Pedemontana, Alto Vicentino Hospital, Thiene, Italy
| | - Matteo Marti
- Department of Translational Medicine, University of Ferrara, Ferrara, Italy
| | - Massimo Martelloni
- Department of Legal Medicine, Territorial Unit USL Toscana Nordovest Lucca, Pisa, Italy
| | - Carlo Moreschi
- Department of Medical Area (DAME), University of Udine, Udine, Italy
| | - Alessandro Santurro
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences (SAIMLAL), Sapienza University of Rome, Rome, Italy
| | - Matteo Scopetti
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences (SAIMLAL), Sapienza University of Rome, Rome, Italy
| | - Ombretta Turriziani
- Department of Molecular Medicine, Laboratory of Virology, Sapienza University of Rome, Rome, Italy
| | - Martina Zanon
- Department of Surgical, Medical and Health Sciences, University of Trieste, Trieste, Italy
| | - Roberto Scendoni
- Department of Law, Institute of Legal Medicine, University of Macerata, Macerata, Italy
| | - Paola Frati
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences (SAIMLAL), Sapienza University of Rome, Rome, Italy
| | - Vittorio Fineschi
- Department of Anatomical, Histological, Forensic and Orthopaedic Sciences (SAIMLAL), Sapienza University of Rome, Rome, Italy
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Menezes RG, Rizwan T, Saad Ali S, Hassan W, Khetpal A, Aqil M, Madadin M, Jamal Siddiqi T, Shariq Usman M. Postmortem findings in COVID-19 fatalities: A systematic review of current evidence. Leg Med (Tokyo) 2022; 54:102001. [PMID: 34952452 PMCID: PMC8648585 DOI: 10.1016/j.legalmed.2021.102001] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2020] [Revised: 08/18/2021] [Accepted: 12/01/2021] [Indexed: 12/12/2022]
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). Almost 17 months after the first COVID-19 case was reported, the exact pathogenesis of the virus is still open to interpretation. Postmortem studies have been relatively scarce due to the high infectivity rate of the virus. We systematically reviewed the literature available for studies that reported gross, histological, microscopic, and immunohistochemical findings in COVID-19 fatalities with the aim of reporting any recurrent findings among different demographics. PubMed and Scopus were searched up till the second of May 2021 and 46 studies with a total of 793 patients were shortlisted after the application of inclusion and exclusion criteria. The selected studies reported gross, histological, microscopic, and immunohistochemical autopsy findings in the lungs, heart, liver, gallbladder, bowels, kidney, spleen, bone marrow, lymph nodes, CNS, pancreas, endocrine/exocrine glands, and a few other miscellaneous locations. The SARS-CoV-2 virus was detected in multiple organs and so was the presence of widespread microthrombi. This finding suggests that the pathogenesis of this highly infectious virus might be linked to some form of coagulopathy. Further studies should focus on analyzing postmortem findings in a larger number of patients from different demographics in order to obtain more generalizable results.
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Affiliation(s)
- Ritesh G Menezes
- Department of Pathology, College of Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
| | - Tehlil Rizwan
- Department of Medicine, AMITA Health Saint Joseph Hospital, Chicago, IL, USA
| | - Syed Saad Ali
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Wardah Hassan
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Akash Khetpal
- Department of Internal Medicine, Dow Medical College, Dow University of Health Sciences, Karachi, Pakistan
| | - Mohammad Aqil
- Deanship of Library Affairs, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammed Madadin
- Department of Pathology, College of Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Tariq Jamal Siddiqi
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA
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44
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Esteban-Zubero E, García-Muro C, Alatorre-Jiménez MA, Johal V, López-García CA, Marín-Medina A. High Flow Nasal Cannula Therapy in the Emergency Department: Main Benefits in Adults, Pediatric Population and against COVID-19: A Narrative Review. ACTA MEDICA (HRADEC KRALOVE, CZECH REPUBLIC) 2022; 65:45-52. [DOI: 10.14712/18059694.2022.17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Abstract
This review aims to summarize the literature’s main results about high flow nasal cannula therapy (HFNC) HFNC benefits in the Emergency Department (ED) in adults and pediatrics, including new Coronavirus Disease (COVID-19). HFNC has recently been established as the usual treatment in the ED to provide oxygen support. Its use has been generalized due to its advantages over traditional oxygen therapy devices, including decreased nasopharyngeal resistance, washing out of the nasopharyngeal dead space, generation of positive pressure, increasing alveolar recruitment, easy adaptation due to the humidification of the airways, increased fraction of inspired oxygen and improved mucociliary clearance. A wide range of pathologies has been studied to evaluate the potential benefits of HFNC; some examples are heart failure, pneumonia, chronic pulmonary obstructive disease, asthma, and bronchiolitis. The regular use of this oxygen treatment is not established yet due to the literature’s controversial results. However, several authors suggest that it could be useful in several pathologies that generate acute respiratory failure. Consequently, the COVID-19 irruption has generated the question of HFNC as a safety and effective treatment. Our results suggested that HFNC seems to be a useful tool in the ED, especially in patients affected by acute hypoxemic respiratory failure, acute heart failure, pneumonia, bronchiolitis, asthma and acute respiratory distress syndrome in patients affected by COVID-19. Its benefits in hypercapnic respiratory failure are more discussed, being only observed benefits in patients with mild-moderate disease. These results are based in clinical as well as cost-effectiveness outcomes. Future studies with largest populations are required to confirm these results as well as establish a practical guideline to use this device.
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45
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Milross L, Majo J, Cooper N, Kaye PM, Bayraktar O, Filby A, Fisher AJ. Post-mortem lung tissue: the fossil record of the pathophysiology and immunopathology of severe COVID-19. THE LANCET. RESPIRATORY MEDICINE 2022; 10:95-106. [PMID: 34871544 PMCID: PMC8641959 DOI: 10.1016/s2213-2600(21)00408-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 08/05/2021] [Accepted: 08/21/2021] [Indexed: 12/15/2022]
Abstract
The lungs are the main site that is affected in severe COVID-19, and post-mortem lung tissue provides crucial insights into the pathophysiology of severe disease. From basic histology to state-of-the-art multiparameter digital pathology technologies, post-mortem lung tissue provides snapshots of tissue architecture, and resident and inflammatory cell phenotypes and composition at the time of death. Contrary to early assumptions that COVID-19 in the lungs is a uniform disease, post-mortem findings have established a high degree of disease heterogeneity. Classic diffuse alveolar damage represents just one phenotype, with disease divisible by early and late progression as well as by pathophysiological process. A distinct lung tissue state occurs with secondary infection; extrapulmonary causes of death might also originate from a pathological process in the lungs linked to microthrombosis. This heterogeneity of COVID-19 lung disease must be recognised in the management of patients and in the development of novel treatment strategies.
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Affiliation(s)
- Luke Milross
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Joaquim Majo
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Nigel Cooper
- Department of Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Paul M Kaye
- York Biomedical Research Institute, Hull York Medical School, University of York, York, UK
| | - Omer Bayraktar
- Cellular Genetics Institute, Wellcome Sanger Institute, Cambridge, UK
| | - Andrew Filby
- Innovation Methodology and Application Research Theme, Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Andrew J Fisher
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK; Institute of Transplantation, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.
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46
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Scendoni R, Gattari D, Cingolani M. COVID-19 Pulmonary Pathology, Ventilator-Induced Lung Injury (VILI), or Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)? Healthcare Considerations Arising From an Autopsy Case and Miny-Review. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2022; 15:2632010X221083223. [PMID: 35284825 PMCID: PMC8905213 DOI: 10.1177/2632010x221083223] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Accepted: 01/30/2022] [Indexed: 01/20/2023]
Abstract
Acute respiratory distress syndrome (ARDS) caused by coronavirus disease (COVID-19) is a serious complication that requires early recognition. Autopsy reports or biopsies of the lungs in patients with COVID-19 revealed diffuse alveolar damage (DAD) at different stages; the fibrotic phase is usually associated with long-standing severe disease. Care management of hospitalized patients is not easy, given that the risk of incurring a ventilator-induced lung injury (VILI) is high. Additionally, if the patient develops nosocomial infections, sepsis-induced ARDS should be considered in the study of the pathophysiological processes. We present an autopsy case of a hospitalized patient whose death was linked to COVID-19 infection, with the histopathological pattern of advanced pulmonary fibrosis. After prolonged use of non-invasive and invasive ventilation, the patient developed polymicrobial superinfection oh the lungs. After analyzing the individual’s clinical history and pulmonary anatomopathological findings, we consider healthcare issues that should lead to an improvement in diagnosis and to more adequate standards of care management among health professionals.
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Affiliation(s)
- Roberto Scendoni
- Department of Law, Institute of Legal Medicine, University of Macerata, Macerata, Italy
| | - Diego Gattari
- Anesthesia and Resuscitation Unit, ASUR Marche AV3, Macerata, Italy
| | - Mariano Cingolani
- Department of Law, Institute of Legal Medicine, University of Macerata, Macerata, Italy
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47
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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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48
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Bassat Q, Varo R, Hurtado JC, Marimon L, Ferrando M, Ismail MR, Carrilho C, Fernandes F, Castro P, Maixenchs M, Rodrigo-Calvo MT, Guerrero J, Martínez A, Lacerda MVG, Mandomando I, Menéndez C, Martinez MJ, Ordi J, Rakislova N. Minimally Invasive Tissue Sampling as an Alternative to Complete Diagnostic Autopsies in the Context of Epidemic Outbreaks and Pandemics: The Example of Coronavirus Disease 2019 (COVID-19). Clin Infect Dis 2021; 73:S472-S479. [PMID: 34910176 PMCID: PMC8672745 DOI: 10.1093/cid/ciab760] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
Background Infectious diseases’ outbreak investigation requires, by definition, conducting a thorough epidemiological assessment while simultaneously obtaining biological samples for an adequate screening of potential responsible pathogens. Complete autopsies remain the gold-standard approach for cause-of-death evaluation and characterization of emerging diseases. However, for highly transmissible infections with a significant associated lethality, such as COVID-19, complete autopsies are seldom performed due to biosafety challenges, especially in low-resource settings. Minimally invasive tissue sampling (MITS) is a validated new approach based on obtaining postmortem samples from key organs and body fluids, a procedure that does not require advanced biosafety measures or a special autopsy room. Methods We aimed to review the use of MITS or similar procedures for outbreak investigation up to 27 March 2021 and their performance for evaluating COVID-19 deaths. Results After a literature review, we analyzed in detail the results of 20 studies conducted at international sites, whereby 216 COVID-19–related deaths were investigated. MITS provided a general and more granular understanding of the pathophysiological changes secondary to the infection and high-quality samples where the extent and degree of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related damage could be evaluated. Conclusions MITS is a useful addition in the investigation and surveillance of infections occurring in outbreaks or epidemics. Its less invasive nature makes the tool more acceptable and feasible and reduces the risk of procedure-associated contagion, using basic biosafety measures. Standardized approaches protocolizing which samples should be collected—and under which exact biosafety measures—are necessary to facilitate and expand its use globally.
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Affiliation(s)
- Quique Bassat
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.,ICREA, Catalan Institution for Research and Advanced Studies, Barcelona, Madrid, Spain.,Pediatrics Department, Hospital Sant Joan de Déu (University of Barcelona), Barcelona, Spain.,Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain
| | - Rosauro Varo
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique
| | - Juan Carlos Hurtado
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Department of Microbiology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Lorena Marimon
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
| | - Melania Ferrando
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain
| | - Mamudo R Ismail
- Department of Pathology, Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.,Department of Pathology, Maputo Central Hospital, Maputo, Mozambique
| | - Carla Carrilho
- Department of Pathology, Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.,Department of Pathology, Maputo Central Hospital, Maputo, Mozambique
| | - Fabiola Fernandes
- Department of Pathology, Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique.,Department of Pathology, Maputo Central Hospital, Maputo, Mozambique
| | - Pedro Castro
- Medical Intensive Care Unit, Hospital Clínic, Institut D'investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Maria Maixenchs
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique
| | | | - José Guerrero
- Department of Pathology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Antonio Martínez
- Department of Pathology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Marcus V G Lacerda
- Fundação de Medicina Tropical Dr Heitor Vieira Dourado, Manaus, Brazil.,Fundação Oswaldo Cruz, Instituto Leônidas e Maria Deane-ILMD, Manaus, Brazil
| | - Inacio Mandomando
- Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.,Instituto Nacional de Saúde (INS), Maputo, Mozambique
| | - Clara Menéndez
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.,Consorcio de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Spain
| | - Miguel J Martinez
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Department of Microbiology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Jaume Ordi
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Department of Pathology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
| | - Natalia Rakislova
- ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.,Department of Pathology, Hospital Clinic of Barcelona, Universitat de Barcelona, Barcelona, Spain
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49
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Brener MI, Hulke ML, Fukuma N, Golob S, Zilinyi RS, Zhou Z, Tzimas C, Russo I, McGroder C, Pfeiffer RD, Chong A, Zhang G, Burkhoff D, Leon MB, Maurer MS, Moses JW, Uhlemann AC, Hibshoosh H, Uriel N, Szabolcs MJ, Redfors B, Marboe CC, Baldwin MR, Tucker NR, Tsai EJ. Clinico-histopathologic and single nuclei RNA sequencing insights into cardiac injury and microthrombi in critical COVID-19. JCI Insight 2021; 7:154633. [PMID: 34905515 PMCID: PMC8855793 DOI: 10.1172/jci.insight.154633] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2021] [Accepted: 12/08/2021] [Indexed: 11/17/2022] Open
Abstract
Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality. Its etiology remains debated, as initially presumed causes--- myocarditis and cardiac necrosis--- have proven uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted a prospective study of the first 69 consecutive COVID-19 decedents at Columbia University Irving Medical Center in New York City. Of six acute cardiac histopathologic features, microthrombi was the most commonly detected amongst our cohort (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak erythrocyte sedimentation rate and c-reactive protein were independently associated with increased odds of microthrombi, supporting an immunothrombotic etiology. Using single nuclei RNA-sequencing analysis on 3 patients with and 4 patients without cardiac microthrombi, we discovered an enrichment of pro-thrombotic/anti-fibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling amongst cardiac fibroblasts in microthrombi-positive, relative to microthrombi-negative, COVID-19 hearts. Non-COVID-19 non-failing hearts were used as reference controls. Our study identifies a specific transcriptomic signature in cardiac fibroblasts as a salient feature of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts may represent a potential therapeutic target for COVID-19-associated cardiac microthrombi.
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Affiliation(s)
- Michael I Brener
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Michelle L Hulke
- Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, United States of America
| | - Nobuaki Fukuma
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Stephanie Golob
- Department of Medicine, Columbia University Irving Medical Center, New York, United States of America
| | - Robert S Zilinyi
- Department of Medicine, Columbia University Irving Medical Center, New York, United States of America
| | - Zhipeng Zhou
- Department of Biostatistics, Cardiovascular Research Foundation, New York, United States of America
| | - Christos Tzimas
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Ilaria Russo
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Claire McGroder
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, United States of America
| | - Ryan D Pfeiffer
- Department of Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, United States of America
| | - Alexander Chong
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, United States of America
| | - Geping Zhang
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United States of America
| | - Daniel Burkhoff
- Department of Heart Failure, Hemodynamics and MCS Research, Cardiovascular Research Foundation, New York, United States of America
| | - Martin B Leon
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Mathew S Maurer
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Jeffrey W Moses
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Anne-Catrin Uhlemann
- Division of Infectious Diseases, Columbia University Irving Medical Center, New York, United States of America
| | - Hanina Hibshoosh
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United States of America
| | - Nir Uriel
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
| | - Matthias J Szabolcs
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United States of America
| | - Björn Redfors
- Department of Biostatistics, Cardiovascular Research Foundation, New York, United States of America
| | - Charles C Marboe
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, United States of America
| | - Matthew R Baldwin
- Division of Pulmonary, Allergy, and Critical Care Medicine, Columbia University Irving Medical Center, New York, United States of America
| | - Nathan R Tucker
- Biomedical Research and Translational Medicine, Masonic Medical Research Institute, Utica, United States of America
| | - Emily J Tsai
- Division of Cardiology, Columbia University Irving Medical Center, New York, United States of America
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50
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Abstract
BACKGROUND Analyses for the presence of SARS-CoV‑2 in the tissues of COVID-19 patients is important in order to improve our understanding of the disease pathophysiology for interpretation of diagnostic histopathological findings in autopsies, biopsies, or surgical specimens and to assess the potential for occupational infectious hazard. MATERIAL AND METHODS In this review we identified 136 published studies in PubMed's curated literature database LitCovid on SARS-CoV‑2 detection methods in tissues and evaluated them regarding sources of error, specificity, and sensitivity of the methods, taking into account our own experience. RESULTS Currently, no sufficiently specific histomorphological alterations or diagnostic features for COVID-19 are known. Therefore, three approaches for SARS-CoV‑2 detection are used: RNA, proteins/antigens, or morphological detection by electron microscopy. In the preanalytical phase, the dominant source of error is tissue quality, especially the different intervals between sample collection and processing or fixation (and its duration) and specifically the interval between death and sample collection in autopsies. However, this information is found in less than half of the studies (e.g., in only 42% of autopsy studies). Our own experience and first studies prove the significantly higher sensitivity and specificity of RNA-based detection methods compared to antigen or protein detection by immunohistochemistry or immunofluorescence. Detection by electron microscopy is time consuming and difficult to interpret. CONCLUSIONS Different methods are available for the detection of SARS-CoV‑2 in tissue. Currently, RNA detection by RT-PCR is the method of choice. However, extensive validation studies and method harmonization are not available and are absolutely necessary.
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Affiliation(s)
| | - Peter Boor
- Institute of Pathology, University Hospital of RWTH Aachen, Aachen, Germany.
- Medical Clinic II (Nephrology and Immunology), University Hospital of RWTH Aachen, Pauwelsstr. 30, 52074, Aachen, Germany.
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