RESUMEN
BACKGROUND: COVID-19 is a new infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). Since the outbreak in December 2019, it has caused an unprecedented world pandemic, leading to a global human health crisis. Although SARS CoV-2 mainly affects the lungs, causing interstitial pneumonia and severe acute respiratory distress syndrome, a number of patients often have extensive clinical manifestations, such as gastrointestinal symptoms, cardiovascular damage and renal dysfunction. PURPOSE: This review article discusses the pathogenic mechanisms of cardiovascular damage in COVID-19 patients and provides some useful suggestions for future clinical diagnosis, treatment and prevention. METHODS: An English-language literature search was conducted in PubMed and Web of Science databases up to 12th April, 2024 for the terms "COVID-19", "SARS CoV-2", "cardiovascular damage", "myocardial injury", "myocarditis", "hypertension", "arrhythmia", "heart failure" and "coronary heart disease", especially update articles in 2023 and 2024. Salient medical literatures regarding the cardiovascular damage of COVID-19 were selected, extracted and synthesized. RESULTS: The most common cardiovascular damage was myocarditis and pericarditis, hypertension, arrhythmia, myocardial injury and heart failure, coronary heart disease, stress cardiomyopathy, ischemic stroke, blood coagulation abnormalities, and dyslipidemia. Two important pathogenic mechanisms of the cardiovascular damage may be direct viral cytotoxicity as well as indirect hyperimmune responses of the body to SARS CoV-2 infection. CONCLUSIONS: Cardiovascular damage in COVID-19 patients is common and portends a worse prognosis. Although the underlying pathophysiological mechanisms of cardiovascular damage related to COVID-19 are not completely clear, two important pathogenic mechanisms of cardiovascular damage may be the direct damage of the SARSCoV-2 infection and the indirect hyperimmune responses.
Asunto(s)
COVID-19 , Enfermedades Cardiovasculares , Pandemias , SARS-CoV-2 , Humanos , COVID-19/complicaciones , Enfermedades Cardiovasculares/etiología , Neumonía Viral/complicaciones , Neumonía Viral/inmunología , Neumonía Viral/virología , Neumonía Viral/patología , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/virología , Betacoronavirus , Miocarditis/etiología , Miocarditis/virologíaRESUMEN
IMPORTANCE: Although the role of bovine coronavirus (BCoV) in calf diarrhea and respiratory disorders is well documented, its contribution to neurological diseases is unclear. OBJECTIVE: This study conducted virological investigations of calves showing diarrhea and respiratory and neurological signs. METHODS: An outbreak of diarrhea, respiratory, and neurological disorders occurred among the 12 calves in July 2022 in Istanbul, Türkiye. Two of these calves exhibited neurological signs and died a few days after the appearance of symptoms. One of these calves was necropsied and analyzed using molecular and histopathological tests. RESULTS: BCoV RNA was detected in the brain, lung, spleen, liver, and intestine of the calf that had neurological signs by real-time reverse transcription polymerase chain reaction. Immunostaining was also observed in the intestine and brain. A 622 bp S1 gene product was noted on gel electrophoresis only in the brain. Phylogenetic analysis indicated that the BCoV detected in this study had a high proximity to the BCoV strain GIb with 99.19% nucleotide sequence homology to the strains detected in Poland, Israel, Türkiye, and France. No distinct genetic lineages were observed when the brain isolate was compared with the respiratory and enteric strains reported to GenBank. In addition, the highest identity (98,72%) was obtained with the HECV 4408 and L07748 strains of human coronaviruses. CONCLUSIONS AND RELEVANCE: The strain detected in a calf brain belongs to the GIb-European lineage and shares high sequence homology with BCoV strains detected in Europe and Israel. In addition, the similarity between the human coronaviruses (4408 and L07748) raises questions about the zoonotic potential of the strains detected in this study.
Asunto(s)
Encéfalo , Enfermedades de los Bovinos , Infecciones por Coronavirus , Coronavirus Bovino , Filogenia , Animales , Bovinos , Coronavirus Bovino/genética , Coronavirus Bovino/aislamiento & purificación , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/patología , Enfermedades de los Bovinos/virología , Enfermedades de los Bovinos/patología , Encéfalo/virología , Encéfalo/patología , Turquía/epidemiología , Brotes de Enfermedades/veterinaria , Neumonía Viral/veterinaria , Neumonía Viral/virología , Neumonía Viral/patología , Enfermedades del Sistema Nervioso/veterinaria , Enfermedades del Sistema Nervioso/virología , Enfermedades del Sistema Nervioso/patologíaRESUMEN
COVID-associated coagulopathy seemly plays a key role in post-acute sequelae of SARS- CoV-2 infection. However, the underlying pathophysiological mechanisms are poorly understood, largely due to the lack of suitable animal models that recapitulate key clinical and pathological symptoms. Here, we fully characterized AC70 line of human ACE2 transgenic (AC70 hACE2 Tg) mice for SARS-CoV-2 infection. We noted that this model is highly permissive to SARS-CoV-2 with values of 50% lethal dose and infectious dose as ~ 3 and ~ 0.5 TCID50 of SARS-CoV-2, respectively. Mice infected with 105 TCID50 of SARS-CoV-2 rapidly succumbed to infection with 100% mortality within 5 days. Lung and brain were the prime tissues harboring high viral titers, accompanied by histopathology. However, viral RNA and inflammatory mediators could be detectable in other organs, suggesting the nature of a systemic infection. Lethal challenge of AC70 hACE2 Tg mice caused acute onset of leukopenia, lymphopenia, along with an increased neutrophil-to-lymphocyte ratio (NLR). Importantly, infected animals recapitulated key features of COVID-19-associated coagulopathy. SARS-CoV-2 could induce the release of circulating neutrophil extracellular traps (NETs), along with activated platelet/endothelium marker. Immunohistochemical staining with anti-platelet factor-4 (PF4) antibody revealed profound platelet aggregates especially within blocked veins of the lungs. We showed that acute SARS-CoV-2 infection triggered a hypercoagulable state coexisting with ill-regulated fibrinolysis. Finally, we highlighted the potential role of Annexin A2 (ANXA2) in fibrinolytic failure. ANXA2 is a calcium-dependent phospholipid-binding protein that forms a heterotertrameric complexes localized at the extracellular membranes with two S100A10 small molecules acting as a co-receptor for tissue-plasminogen activator (t-PA), tightly involved in cell surface fibrinolysis. Thus, our results revealing elevated IgG type anti-ANXA2 antibody production, downregulated de novo ANXA2/S100A10 synthesis, and reduced ANXA2/S100A10 association in infected mice, this protein might serve as druggable targets for development of antithrombotic and/or anti-fibrinolytic agents to attenuate pathogenesis of COVID-19.
Asunto(s)
Enzima Convertidora de Angiotensina 2 , COVID-19 , Modelos Animales de Enfermedad , Ratones Transgénicos , SARS-CoV-2 , Animales , COVID-19/patología , COVID-19/complicaciones , COVID-19/virología , COVID-19/metabolismo , Ratones , Enzima Convertidora de Angiotensina 2/metabolismo , Enzima Convertidora de Angiotensina 2/genética , Humanos , Trastornos de la Coagulación Sanguínea/virología , Trastornos de la Coagulación Sanguínea/patología , Neumonía Viral/virología , Neumonía Viral/patología , Neumonía Viral/metabolismo , Betacoronavirus , Pulmón/virología , Pulmón/patología , Pulmón/metabolismo , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/complicaciones , Pandemias , Trampas Extracelulares/metabolismoRESUMEN
CONTEXT: The changes in host membrane phospholipids are crucial in airway infection pathogenesis. Phospholipase A2 hydrolyzes host cell membranes, producing lyso-phospholipids and free fatty acids, including arachidonic acid (AA), which contributes significantly to lung inflammation. AIM: Follow these changes and their evolution from day 1, day 3 to day 7 in airway aspirates of 89 patients with COVID-19-associated acute respiratory distress syndrome and examine whether they correlate with the severity of the disease. The patients were recruited in three French intensive care units. The analysis was conducted from admission to the intensive care unit until the end of the first week of mechanical ventilation. RESULTS: In the airway aspirates, we found significant increases in the levels of host cell phospholipids, including phosphatidyl-serine and phosphatidyl-ethanolamine, and their corresponding lyso-phospholipids. This was accompanied by increased levels of AA and its inflammatory metabolite prostaglandin E2 (PGE2). Additionally, enhanced levels of ceramides, sphingomyelin, and free cholesterol were observed in these aspirates. These lipids are known to be involved in cell death and/or apoptosis, whereas free cholesterol plays a role in virus entry and replication in host cells. However, there were no significant changes in the levels of dipalmitoyl-phosphatidylcholine, the major surfactant phospholipid. A correlation analysis revealed an association between mortality risk and levels of AA and PGE2, as well as host cell phospholipids. CONCLUSION: Our findings indicate a correlation between heightened cellular phospholipid modifications and variations in AA and PGE2 with the severity of the disease in patients. Nevertheless, there is no indication of surfactant alteration in the initial phases of the illness.
Asunto(s)
COVID-19 , Fosfolípidos , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Humanos , COVID-19/metabolismo , COVID-19/virología , COVID-19/patología , Fosfolípidos/metabolismo , Fosfolípidos/análisis , Masculino , Femenino , Persona de Mediana Edad , Anciano , Unidades de Cuidados Intensivos , Neumonía Viral/metabolismo , Neumonía Viral/virología , Neumonía Viral/patología , Ácido Araquidónico/metabolismo , Infecciones por Coronavirus/metabolismo , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/patología , Francia , Betacoronavirus , Dinoprostona/metabolismo , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/virología , Pandemias , Adulto , Respiración Artificial , Ceramidas/metabolismoRESUMEN
Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. METHODS: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. RESULTS: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (-) negative lungs (COVID-19-), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. CONCLUSIONS: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.
Asunto(s)
COVID-19 , Pulmón , Megacariocitos , SARS-CoV-2 , Trombosis , Receptor Toll-Like 2 , Regulación hacia Arriba , Humanos , COVID-19/patología , COVID-19/inmunología , COVID-19/metabolismo , Masculino , Femenino , Receptor Toll-Like 2/metabolismo , Receptor Toll-Like 2/genética , Megacariocitos/metabolismo , Megacariocitos/patología , Megacariocitos/virología , Anciano , Persona de Mediana Edad , Anciano de 80 o más Años , Pulmón/patología , Pulmón/virología , Pulmón/metabolismo , Regulación hacia Arriba/genética , Trombosis/patología , Integrina beta3/metabolismo , Integrina beta3/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Glicoproteína de la Espiga del Coronavirus/genética , Neumonía Viral/patología , Neumonía Viral/inmunología , Neumonía Viral/mortalidad , Neumonía Viral/virología , Neumonía Viral/metabolismo , Inmunidad Innata , PandemiasRESUMEN
Inflammation induced by lung infection is a double-edged sword, moderating both anti-viral and immune pathogenesis effects; the mechanism of the latter is not fully understood. Previous studies suggest the vasculature is involved in tissue injury. Here, we report that expression of Sparcl1, a secreted matricellular protein, is upregulated in pulmonary capillary endothelial cells (EC) during influenza-induced lung injury. Endothelial overexpression of SPARCL1 promotes detrimental lung inflammation, with SPARCL1 inducing 'M1-like' macrophages and related pro-inflammatory cytokines, while SPARCL1 deletion alleviates these effects. Mechanistically, SPARCL1 functions through TLR4 on macrophages in vitro, while TLR4 inhibition in vivo ameliorates excessive inflammation caused by endothelial Sparcl1 overexpression. Finally, SPARCL1 expression is increased in lung ECs from COVID-19 patients when compared with healthy donors, while fatal COVID-19 correlates with higher circulating SPARCL1 protein levels in the plasma. Our results thus implicate SPARCL1 as a potential prognosis biomarker for deadly COVID-19 pneumonia and as a therapeutic target for taming hyperinflammation in pneumonia.
Asunto(s)
COVID-19 , Células Endoteliales , Pulmón , Activación de Macrófagos , SARS-CoV-2 , Animales , Humanos , COVID-19/inmunología , COVID-19/virología , COVID-19/metabolismo , COVID-19/patología , Ratones , Células Endoteliales/metabolismo , Células Endoteliales/virología , Células Endoteliales/inmunología , SARS-CoV-2/fisiología , Pulmón/virología , Pulmón/patología , Pulmón/inmunología , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Proteínas de Unión al Calcio/metabolismo , Proteínas de Unión al Calcio/genética , Ratones Endogámicos C57BL , Neumonía Viral/inmunología , Neumonía Viral/patología , Neumonía Viral/virología , Neumonía Viral/metabolismo , Masculino , Macrófagos/metabolismo , Macrófagos/inmunología , Femenino , Ratones Noqueados , Proteínas de la Matriz ExtracelularRESUMEN
The most prevalent glycoprotein on the influenza virus envelope is called hemagglutinin (HA), yet little is known about its involvement in the pathophysiology and etiology of severe influenza pneumonia. Here, after stimulating human bronchial epithelial cells (16-HBE) and mice with HA of H1N1 for 12 h, we investigated the proliferation, migration, inflammatory cytokines expression, and apoptosis in 16-HBE and the pathological damage in mouse lung tissue. The expression of inflammatory cytokines plasminogen activator inhibitor 1(PAI-1), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators, and apoptosis were all enhanced by HA, which also prevented the proliferation and migration of bronchial epithelial cells. HA enhanced up-regulated PAI-1, uPA, and tPA protein expression within mouse lung tissue and caused lung injury. In conclusion, HA alone, but not the whole H1N1 virus, induces lung tissue injury by inhibiting cell proliferation and migration, while promoting the expression of inflammatory cytokines and apoptosis.
Asunto(s)
Apoptosis , Proliferación Celular , Glicoproteínas Hemaglutininas del Virus de la Influenza , Subtipo H1N1 del Virus de la Influenza A , Animales , Humanos , Ratones , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Movimiento Celular , Citocinas/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/virología , Pulmón/metabolismo , Pulmón/virología , Pulmón/patología , Línea Celular , Neumonía Viral/virología , Neumonía Viral/metabolismo , Neumonía Viral/patología , Gripe Humana/metabolismo , Gripe Humana/virología , Activador de Plasminógeno de Tipo Uroquinasa/genética , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/virología , Inhibidor 1 de Activador Plasminogénico/metabolismo , Inhibidor 1 de Activador Plasminogénico/genética , Neumonía/metabolismo , Neumonía/virologíaRESUMEN
BACKGROUND: SARS-CoV-2 infection is considered as a relapsing inflammatory process with a dysregulation of IL-6 signalling. Classic IL-6 signalling is thought to represent a defence mechanism against pathogens. In contrast, IL-6 trans-signalling has pro-inflammatory effects. In severe COVID-19, therapeutic strategies have focused on global inhibition of IL-6, with controversial results. We hypothesized that specific blockade of IL-6 trans-signalling could inhibit inflammatory response preserving the host defence activity inherent to IL-6 classic signalling. METHODS: To test the role of the specific IL-6 trans-signalling inhibition by sgp130Fc in short- and long-term consequences of COVID-19, we used the established K18-hACE2 transgenic mouse model. Histological as well as immunohistochemical analysis, and pro-inflammatory marker profiling were performed. To investigate IL-6 trans-signalling in human cells we used primary lung microvascular endothelial cells and fibroblasts in the presence/absence of sgp130Fc. FINDINGS: We report that targeting IL-6 trans-signalling by sgp130Fc attenuated SARS-CoV-2-related clinical symptoms and mortality. In surviving mice, the treatment caused a significant decrease in lung damage. In vitro, IL-6 trans-signalling induced strong and persisting JAK1/STAT3 activation in endothelial cells and lung fibroblasts with proinflammatory effects, which were attenuated by sgp130Fc. Our data also suggest that in those cells with scant amounts of IL-6R, the induction of gp130 and IL-6 by IL-6:sIL-6R complex sustains IL-6 trans-signalling. INTERPRETATION: IL-6 trans-signalling fosters progression of COVID-19, and suggests that specific blockade of this signalling mode could offer a promising alternative to mitigate both short- and long-term consequences without affecting the beneficial effects of IL-6 classic signalling. These results have implications for the development of new therapies of lung injury and endotheliopathy in COVID-19. FUNDING: The project was supported by ISCIII, Spain (COV-20/00792 to MB, PI23/01351 to MARH) and the European Commission-Next generation EU (European Union) (Regulation EU 2020/2094), through CSIC's Global Health Platform (PTI Salud Global, SGL2103029 to MB). PID2019-110587RB-I00 (MB) supported by MICIN/AEI/10.13039/501100011033/and PID2022-143034OB-I00 (MB) by MICIN/AEI/10.13039/501100011033/FEDER. MAR-H acknowledges support from ISCIII, Spain and the European Commission-Next generation EU (European Union), through CSIC's Global Health PTI.
Asunto(s)
COVID-19 , Receptor gp130 de Citocinas , Interleucina-6 , Ratones Transgénicos , SARS-CoV-2 , Transducción de Señal , Animales , Humanos , Ratones , Enzima Convertidora de Angiotensina 2/metabolismo , Betacoronavirus , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/patología , COVID-19/metabolismo , Tratamiento Farmacológico de COVID-19 , Receptor gp130 de Citocinas/metabolismo , Receptor gp130 de Citocinas/antagonistas & inhibidores , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Interleucina-6/metabolismo , Pulmón/patología , Pulmón/virología , Pulmón/metabolismo , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/virología , Neumonía Viral/patología , Neumonía Viral/metabolismo , Receptores de Interleucina-6/metabolismo , Receptores de Interleucina-6/antagonistas & inhibidores , Proteínas Recombinantes de Fusión/farmacología , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacosRESUMEN
We present the case of a 61-year-old man who developed coronavirus disease 2019 (COVID-19) and died during treatment for relapsing polychondritis. The patient was intubated and treated with steroid pulse therapy, remdecivir, antibacterial agents, baricitinib, and tocilizumab. However, his respiratory condition worsened, and he died 108 days after disease onset. An autopsy revealed diffuse alveolar damage in the fibrotic phase in all lung lobes, diffuse pulmonary ossification, and cytomegalovirus-infected cells in the middle lobe of the right lung. We herein discuss the clinical features and pathological findings of COVID-19 in immunosuppressed patients.
Asunto(s)
Autopsia , COVID-19 , Osificación Heterotópica , SARS-CoV-2 , Humanos , Masculino , COVID-19/complicaciones , COVID-19/patología , Persona de Mediana Edad , Resultado Fatal , Osificación Heterotópica/patología , Osificación Heterotópica/etiología , Policondritis Recurrente/complicaciones , Policondritis Recurrente/tratamiento farmacológico , Policondritis Recurrente/diagnóstico , Policondritis Recurrente/patología , Neumonía Viral/complicaciones , Neumonía Viral/patología , Pandemias , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/patología , Pulmón/patología , Pulmón/diagnóstico por imagen , Betacoronavirus , Huésped Inmunocomprometido , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/etiologíaRESUMEN
Although alterations in the autophagy-lysosome pathway have been observed in the SARS-CoV-2 infection and invasion process since the outbreak of the coronavirus disease in 2019, the in-depth mechanism of autophagic and lysosomal reprogramming by SARS-CoV-2 has yet to be well identified. Our recent study unveiled a pivotal role played by the open reading frame 7a (ORF7a) protein in the SARS-CoV-2 genome, particularly in the modulation of macroautophagy/autophagy flux and function during viral infection and pathogenesis. Our study elucidated the underlying molecular mechanisms by which SARS-CoV-2 ORF7a intercepts autophagic flux, evades host autophagy-lysosome degradation, and accelerates viral infection and progeny germination. Furthermore, our study highlights that ORF7a can be a therapeutic target, and glecaprevir may hold potential as a drug against SARS-CoV-2 by targeting ORF7a. The key observations revealed in this study also contribute to a growing understanding of the function of SARS-CoV-2 ORF7a and the mechanisms underlying COVID-2019 treatment.
Asunto(s)
Autofagia , COVID-19 , Lisosomas , SARS-CoV-2 , Autofagia/fisiología , SARS-CoV-2/fisiología , SARS-CoV-2/efectos de los fármacos , Humanos , COVID-19/virología , Lisosomas/metabolismo , Animales , Betacoronavirus/fisiología , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/patología , Neumonía Viral/virología , Neumonía Viral/patología , Pandemias , Proteínas no Estructurales Virales/metabolismo , Antivirales/farmacología , Tratamiento Farmacológico de COVID-19 , Proteínas ViralesRESUMEN
Objective: To investigate the clinicopathological characteristics of occupational lung diseases, to reduce the missed diagnoses and misdiagnoses of the diseases and to help standardize the diagnosis and treatment of these patients. Methods: A total of 4 813 lung biopsy specimens (including 1 935 consultation cases) collected at the Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China from January 1st, 2017 to December 31th, 2019 were retrospectively analyzed. Among them, 126 cases of occupational lung diseases were confirmed with clinical-radiological-pathological diagnosis. Special staining, PCR and scanning electron microscopy were also used to rule out the major differential diagnoses. Results: The 126 patients with occupational lung diseases included 102 males and 24 females. All of them had a history of exposure to occupational risk factor(s). Morphologically, 68.3% (86/126) of the cases mainly showed pulmonary fibrotic nodules, dust plaque formation or carbon end deposition in pulmonary parenchyma. 16.7% (21/126) of the cases mainly showed welding smoke particle deposition in the alveolar cavity and lung interstitium while 15.1% (19/126) of the cases showed granulomas with fibrous tissue hyperplasia, alveolar protein deposition or giant cell interstitial pneumonia. The qualitative and semi-quantitative analyses of residual dust components in the lung under scanning electron microscope were helpful for the diagnosis of welder's pneumoconiosis and hard metal lung disease. Conclusions: The morphological characteristics of lung biopsy tissue are important reference basis for the clinicopathological diagnosis and differential diagnosis of occupational lung diseases. Recognizing the characteristic morphology and proper use of auxiliary examination are the key to an accurate diagnosis of occupational lung diseases on biopsy specimens.
Asunto(s)
Neumoconiosis , Neumonía Viral , Masculino , Femenino , Humanos , Estudios Retrospectivos , Neumoconiosis/diagnóstico , Neumoconiosis/patología , Pulmón/patología , Polvo , Neumonía Viral/patología , BiopsiaRESUMEN
Organoids are tissue cultures formed by culturing cells in three-dimensional environments that simulate the physiological or pathological conditions of the human body. The cultivation of organoids is used to study the temporal and spatial transformation of cells during the development of tissues or organs, to investigate changes in cellular functions and inter-communications caused by various risk factors, and to discover potential therapeutic targets. This article provided an overview of the cultivation and identification methods of alveolar organoids, as well as the research progress in their application to common respiratory diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, viral pneumonia, and so on. The limitations and future applications of alveolar organoids are also analyzed and discussed.
Asunto(s)
Enfermedades Pulmonares , Neumonía Viral , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Pulmón/patología , Enfermedades Pulmonares/patología , Neumonía Viral/patología , Organoides/patología , Organoides/fisiología , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
This article reviews the radiologic and pathologic findings of the epithelial and endothelial injuries in COVID-19 pneumonia to help radiologists understand the fundamental nature of the disease. The radiologic and pathologic manifestations of COVID-19 pneumonia result from epithelial and endothelial injuries based on viral toxicity and immunopathologic effects. The pathologic features of mild and reversible COVID-19 pneumonia involve nonspecific pneumonia or an organizing pneumonia pattern, while the pathologic features of potentially fatal and irreversible COVID-19 pneumonia are characterized by diffuse alveolar damage followed by fibrosis or acute fibrinous organizing pneumonia. These pathologic responses of epithelial injuries observed in COVID-19 pneumonia are not specific to SARS-CoV-2 but rather constitute universal responses to viral pneumonia. Endothelial injury in COVID-19 pneumonia is a prominent feature compared with other types of viral pneumonia and encompasses various vascular abnormalities at different levels, including pulmonary thromboembolism, vascular engorgement, peripheral vascular reduction, a vascular tree-in-bud pattern, and lung perfusion abnormality. Chest CT with different imaging techniques (eg, CT quantification, dual-energy CT perfusion) can fully capture the various manifestations of epithelial and endothelial injuries. CT can thus aid in establishing prognosis and identifying patients at risk for deterioration.
Asunto(s)
COVID-19 , Enfermedades Pulmonares , Neumonía Viral , Neumonía , Humanos , COVID-19/patología , SARS-CoV-2 , Neumonía Viral/patología , Enfermedades Pulmonares/patología , Radiólogos , Pulmón/patologíaRESUMEN
Objective: To investigate the clinicopathological characteristics of occupational lung diseases, to reduce the missed diagnoses and misdiagnoses of the diseases and to help standardize the diagnosis and treatment of these patients. Methods: A total of 4 813 lung biopsy specimens (including 1 935 consultation cases) collected at the Department of Pathology, Nanjing Drum Tower Hospital, Nanjing, China from January 1st, 2017 to December 31th, 2019 were retrospectively analyzed. Among them, 126 cases of occupational lung diseases were confirmed with clinical-radiological-pathological diagnosis. Special staining, PCR and scanning electron microscopy were also used to rule out the major differential diagnoses. Results: The 126 patients with occupational lung diseases included 102 males and 24 females. All of them had a history of exposure to occupational risk factor(s). Morphologically, 68.3% (86/126) of the cases mainly showed pulmonary fibrotic nodules, dust plaque formation or carbon end deposition in pulmonary parenchyma. 16.7% (21/126) of the cases mainly showed welding smoke particle deposition in the alveolar cavity and lung interstitium while 15.1% (19/126) of the cases showed granulomas with fibrous tissue hyperplasia, alveolar protein deposition or giant cell interstitial pneumonia. The qualitative and semi-quantitative analyses of residual dust components in the lung under scanning electron microscope were helpful for the diagnosis of welder's pneumoconiosis and hard metal lung disease. Conclusions: The morphological characteristics of lung biopsy tissue are important reference basis for the clinicopathological diagnosis and differential diagnosis of occupational lung diseases. Recognizing the characteristic morphology and proper use of auxiliary examination are the key to an accurate diagnosis of occupational lung diseases on biopsy specimens.
Asunto(s)
Masculino , Femenino , Humanos , Estudios Retrospectivos , Neumoconiosis/patología , Pulmón/patología , Polvo , Neumonía Viral/patología , BiopsiaRESUMEN
A case of the development of multifocal leukoencephalopathy and hemorrhage after infection with SARS-CoV-2 in a female patient with Alzheimer's disease, aged 67 years, is described. The patient was hospitalized by an ambulance. Computed tomography (CT) of the brain showed the signs of cerebral infarction in the basin of the left middle cerebral artery with hemorrhagic transformation, multiple low-density foci that do not accumulate contrast in the white matter of the brain, the presence of sickle-shaped lesions in the cerebellum. CT of the chest revealed bilateral diffuse COVID-associated pneumonitis, alveolitis. The percentage of lesion was 75%. A smear express test for a new coronavirus infection was positive. Treatment was started, and a sudden death occurred. A sectional study in the brain revealed signs of ischemic cerebral infarction and multifocal leukoencephalomalacia - foci of demyelination (from 1 mm to 1 cm) had a multifocal lesion located in different parts of the white matter. Fibrinoid necrosis of vessel walls, destructive-productive vasculitis, ischemic small-focal perivascular necrosis, ischemic lesions of neurons and glial cells, neuronal and glial spongiosis were noted. In conclusion, the cause of death of the patient was a new coronavirus infection COVID-19, which caused diffuse viral COVID-associated pneumonitis, alveolitis with the development of acute respiratory distress syndrome in adults, respiratory failure and COVID-associated ischemic infarction, multifocal leukoencephalopathy (or malacia), cerebral edema complicated by neuromorphological changes in the brain.
Asunto(s)
COVID-19 , Leucoencefalopatía Multifocal Progresiva , Neumonía Viral , Accidente Cerebrovascular , Adulto , Femenino , Humanos , COVID-19/complicaciones , SARS-CoV-2 , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico , Neumonía Viral/patología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/complicaciones , Infarto Cerebral/complicacionesRESUMEN
Pulmonary fibrosis (PF) is a feared outcome of many pulmonary diseases which results in a reduction in lung compliance and capacity. The development of PF is relatively rare, but it can occur secondary to viral pneumonia, especially COVID-19 infection. While COVID-19 infection and its complications are still under investigation, we can look at a similar outbreak in the past to gain better insight as to the expected long-term outcomes of COVID-19 patient lung function. In the current article, we review the literature relative to PF via PubMed. We also performed a literature search for COVID-related pathological changes in the lungs. Finally, the paper was reviewed and summarized based on the studies' integrity, relative, or power calculations. This article provides a narrative review that endeavors to elucidate the current understanding of the pathophysiological mechanisms underlying PF and therapeutic strategies. We also discussed the potential for preventing progression to the fibrotic state within the context of the COVID-19 pandemic. With the massive scale of the COVID-19 pandemic, we expect there should more instances of PF due to COVID-19 infection. Patients who survive severe COVID-19 infection may suffer from a high incidence of PF.
Asunto(s)
COVID-19 , Neumonía Viral , Fibrosis Pulmonar , Humanos , Pulmón/patología , Pandemias , Neumonía Viral/patología , Fibrosis Pulmonar/complicaciones , Fibrosis Pulmonar/tratamiento farmacológicoRESUMEN
BACKGROUND: Despite a reported cardiac injury in patients with new coronavirus infection, the possibility and specifics of genuine viral myocarditis in COVID-19 remains not fully clear. PURPOSE: To study the presence of SARS-CoV-2 in the myocardium and the morphological properties of myocarditis in patients with severe coronavirus infection (COVID-19). METHODS: Autopsy data of eight elderly patients (75.6 ± 7.4 years), four male and four female, with severe new coronavirus infection were studied. The lifetime diagnosis of COVID-19 is based on a positive result of the PCR study. The inclusion criterion was the presence of morphological signs of myocarditis according to the Dallas criteria. A standard histological examination included staining by hematoxylin and eosin, toluidin blue and Van Gieson. An immunohistochemical study was performed using antibodies to CD3, CD 68, CD20, perforin, toll-like receptor (TLR) types 4 and 9. PCR in real-time was performed to determine the viral RNA in the myocardium. RESULTS: All patients had severe bilateral viral pneumonia. In all cases, myocarditis was not clinically diagnosed. Morphological examination of the heart found signs of active lymphocytic myocarditis. PCR identified the SARS-Cov2 RNA in all cases. There were also signs of destructive coronaritis in all cases, thrombovasculitis, lymphocytic pericarditis (in 3 cases) and endocarditis (in 2 cases). The absence of neutrophils confirms the aseptic nature of inflammation. An immunohistochemical study showed the CD3-positive T lymphocytes in the infiltrates. Increased expression of TLR type 4 and less 9 was also detected. CONCLUSION: Morphological and immunohistochemical evidence of myocarditis in COVID-19 was presented. Lymphocytic infiltrations and positive PCR confirm the viral nature of inflammation. Myocarditis in COVID-19 is also characterized by coronaritis with microvascular thrombosis and associated with lymphocytic endo- and pericarditis.
Asunto(s)
COVID-19/patología , Miocarditis/patología , Neumonía Viral/patología , SARS-CoV-2/aislamiento & purificación , Anciano , Anciano de 80 o más Años , Autopsia , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/virología , Femenino , Corazón/virología , Humanos , Inmunohistoquímica , Inflamación , Linfocitos/patología , Masculino , Persona de Mediana Edad , Miocarditis/complicaciones , Miocarditis/diagnóstico , Miocarditis/virología , Miocardio/patología , Neumonía Viral/diagnóstico , Neumonía Viral/virología , SARS-CoV-2/genéticaRESUMEN
HCoV-OC43 is one of the mildly pathogenic coronaviruses with high infection rates in common population. Here, 43 HCoV-OC43 related cases with pneumonia were reported, corresponding genomes of HCoV-OC43 were obtained. Phylogenetic analyses based on complete genome, orf1ab and spike genes revealed that two novel genotypes of HCoV-OC43 have emerged in China. Obvious recombinant events also can be detected in the analysis of the evolutionary dynamics of novel HCoV-OC43 genotypes. Estimated divergence time analysis indicated that the two novel genotypes had apparently independent evolutionary routes. Efforts should be conducted for further investigation of genomic diversity and evolution analysis of mildly pathogenic coronaviruses.
Asunto(s)
Resfriado Común/epidemiología , Infecciones por Coronavirus/epidemiología , Coronavirus Humano OC43/genética , Genoma Viral , Genotipo , Neumonía Viral/epidemiología , Secuencia de Bases , Teorema de Bayes , Niño , Niño Hospitalizado , Preescolar , China/epidemiología , Resfriado Común/patología , Resfriado Común/transmisión , Resfriado Común/virología , Infecciones por Coronavirus/patología , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Coronavirus Humano OC43/clasificación , Coronavirus Humano OC43/patogenicidad , Monitoreo Epidemiológico , Femenino , Humanos , Lactante , Masculino , Método de Montecarlo , Mutación , Filogenia , Neumonía Viral/patología , Neumonía Viral/transmisión , Neumonía Viral/virología , Recombinación GenéticaRESUMEN
The acute respiratory distress syndrome (ARDS) is a common complication of severe COVID-19 (coronavirus disease 2019) caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. Knowledge of molecular mechanisms driving host responses to SARS-CoV-2 is limited by the lack of reliable preclinical models of COVID-19 that recapitulate human illness. Further, existing COVID-19 animal models are not characterized as models of experimental acute lung injury (ALI) or ARDS. Acknowledging differences in experimental lung injury in animal models and human ARDS, here we systematically evaluate a model of experimental acute lung injury as a result of SARS-CoV-2 infection in Syrian golden hamsters. Following intranasal inoculation, hamsters demonstrate acute SARS-CoV-2 infection, viral pneumonia, and systemic illness but survive infection with clearance of virus. Hamsters exposed to SARS-CoV-2 exhibited key features of experimental ALI, including histologic evidence of lung injury, increased pulmonary permeability, acute inflammation, and hypoxemia. RNA sequencing of lungs indicated upregulation of inflammatory mediators that persisted after infection clearance. Lipidomic analysis demonstrated significant differences in hamster phospholipidome with SARS-CoV-2 infection. Lungs infected with SARS-CoV-2 showed increased apoptosis and ferroptosis. Thus, SARS-CoV-2 infected hamsters exhibit key features of experimental lung injury supporting their use as a preclinical model of COVID-19 ARDS.
Asunto(s)
COVID-19/patología , Modelos Animales de Enfermedad , Pulmón/patología , Neumonía Viral/patología , SARS-CoV-2/patogenicidad , Animales , COVID-19/virología , Cricetinae , Masculino , Mesocricetus , Neumonía Viral/virología , SARS-CoV-2/aislamiento & purificaciónRESUMEN
Thoracic air leak syndromes (TALS) are very rare among the noninfectious pulmonary complications (PCs). They can either be idiopathic or have several risk factors such as allogeneic hematopoietic stem cell transplantation (allo-HSCT), graft versus host disease and rarely pulmonary aspergillosis. We present a 14-year-old girl with hypoplastic myelodysplastic syndrome who developed graft versus host disease on day 60, TALS on day 150, bronchiolitis obliterans syndrome on day 300, pulmonary aspergillosis on day 400 and COVID-19 pneumonia on day 575 after allo-HSCT. This is the first report of a child who developed these subsequent PCs after allo-HSCT. Therefore, the manifestations of these unfamiliar PCs like TALS and COVID-19 pneumonia, and concomitant pulmonary aspergillosis with management options are discussed.