fibrin and Pneumonia--Viral

In late December 2019 an outbreak of a novel coronavirus (SARS-CoV-2) causing severe pneumonia (COVID-19) was reported in Wuhan, Hubei Province, China. A common finding in most COVID-19 patients is high D-dimer levels which are associated with a worse prognosis. We aimed to evaluate coagulation abnormalities via traditional tests and whole blood thromboelastometry profiles in a group of 22 (mean age 67 ± 8 years, M:F 20:2) consecutive patients admitted to the Intensive Care Unit of Padova University Hospital for acute respiratory failure due to COVID-19. Cases showed significantly higher fibrinogen and D-dimer plasma levels versus healthy controls (

Topics: Acute Disease; Aged; Area Under Curve; Betacoronavirus; Blood Coagulation; Blood Coagulation Tests; Coronavirus Infections; COVID-19; Critical Care; Female; Fibrin; Fibrin Fibrinogen Degradation Products; Fibrinogen; Humans; Intensive Care Units; Italy; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prognosis; Respiration Disorders; SARS-CoV-2; Thrombelastography; Thrombophilia; Treatment Outcome

Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase "acute respiratory distress syndrome" (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.

Topics: Alveolar Epithelial Cells; Autopsy; Betacoronavirus; Coronavirus Infections; Cough; COVID-19; Diabetes Mellitus, Type 2; Fever; Fibrin; Fibrosis; Humans; Hyperplasia; Hypertension; Lung; Lymphocytes; Macrophages; Male; Megakaryocytes; Metaplasia; Middle Aged; Neutrophils; Pandemics; Pneumonia, Viral; Quarantine; SARS-CoV-2; Tachycardia; Thrombosis

A 75-year-old man presented to a French hospital with a 4-day fever after returning from a coronavirus disease-19 (COVID-19) cluster region. A reverse-transcription polymerase chain reaction test was positive for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using a nasopharyngeal swab sample. After he returned home and a telephone follow-up, he was found deceased 9 days after first showing symptoms. Whole-body, non-enhanced, post-mortem computed tomography (PMCT) and a forensic autopsy were performed approximately 48 h after death, with sanitary precautions. The PMCT showed bilateral and diffuse crazy-paving lung opacities, with bilateral pleural effusions. Post-mortem virology studies detected the presence of SARS-CoV-2 (B.1 lineage) in the nasopharynx, plasma, lung biopsies, pleural effusion and faeces confirming the persistence of viral ribonucleic acid 48 h after death. Microscopic examination showed that severe lung damage was responsible for his death. The main abnormality was diffuse alveolar damage, associated with different stages of inflammation and fibrosis. This case is one of the first to describe complete post-mortem data for a COVID-19 death and highlights the ability of PMCT to detect severe involvement of the lungs before autopsy in an apparently natural death. The present pathology results are concordant with previously reported findings and reinforce the disease pathogenesis hypothesis of combined viral replication with an inappropriate immune response.

Topics: Aged; Alveolar Epithelial Cells; Autopsy; Betacoronavirus; Coronavirus Infections; COVID-19; Fibrin; Humans; Hyperplasia; Lung; Male; Pandemics; Pleural Effusion; Pneumonia, Viral; Pulmonary Alveoli; SARS-CoV-2; Tomography, X-Ray Computed

Detrimental inflammation of the lungs is a hallmark of severe influenza virus infections. Endothelial cells are the source of cytokine amplification, although mechanisms underlying this process are unknown. Here, using combined pharmacological and gene-deletion approaches, we show that plasminogen controls lung inflammation and pathogenesis of infections with influenza A/PR/8/34, highly pathogenic H5N1 and 2009 pandemic H1N1 viruses. Reduction of virus replication was not responsible for the observed effect. However, pharmacological depletion of fibrinogen, the main target of plasminogen reversed disease resistance of plasminogen-deficient mice or mice treated with an inhibitor of plasminogen-mediated fibrinolysis. Therefore, plasminogen contributes to the deleterious inflammation of the lungs and local fibrin clot formation may be implicated in host defense against influenza virus infections. Our studies suggest that the hemostatic system might be explored for novel treatments against influenza.

Topics: Animals; Antiviral Agents; Female; Fibrin; Fibrin Clot Lysis Time; Fibrinogen; Fibrinolysis; Fibrinolytic Agents; Host-Pathogen Interactions; Inflammation; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Orthomyxoviridae Infections; Plasminogen; Pneumonia, Viral; Virus Replication

Varicella (chickenpox) is one of the most frequent highly infectious diseases in childhood. It is caused by varicella-zoster virus. Lethal complications are rare. Focused on histological findings, we present a case of a sudden unexpected death of an otherwise healthy 18-month-old girl due to varicella-induced pneumonia. The histological and immunohistochemical investigations of the lung tissue revealed typical findings of a varicella pneumonia: haemorrhagic and necrotic nodules, intra-alveolar fibrin, numerous neutrophilic granulocytes, lymphocytes, plasmacells, macrophages, multinucleated giant cells and hyaline membranes. Varicella-related deaths are preventable by vaccine. To prevent complications and lethal outcome of varicella as reported here, the recommendations concerning vaccination against varicella must be taken into account in paediatric practice.

Topics: Adolescent; Chickenpox; Death, Sudden; Female; Fibrin; Forensic Pathology; Hemorrhage; Humans; Lung; Lymphocytes; Macrophages, Alveolar; Necrosis; Neutrophils; Plasma Cells; Pneumonia, Viral

Three cases of life-endangering airway obstruction by fibrin membranes are reviewed which developed in a 17-year-old girl with virus pneumonia, in a 21-year-old girl with a history of thrombopathy after general anaesthesia with naso-tracheal intubation and in a 23-year-old woman after short anaesthesia with orotracheal intubation. Possible causal factors, the clinical symptoms and the therapeutic measures taken by the anaesthetist are discussed. Since these cases are generally in a state of severe respiratory collapse by the time treatment is initiated general anaesthesia with muscle relaxation should be attempted only if the anaesthesist is certain that he can effectively ventilate the patient before and during the operation. Otherwise it is better to apply assisted ventilation with oxygen and halothane via a mask until a clear air passage has been restored. Administration of anticholine drugs and control of shock are essential.

Topics: Adolescent; Adult; Airway Obstruction; Dyspnea; Female; Fibrin; Humans; Intubation, Intratracheal; Pneumonia, Viral; Succinylcholine; Tracheitis; Tracheotomy; Tubocurarine

Chronic pneumonia experimentally produced in 14 pigs with African swine fever (ASF) virus was studied by immunofluorescene (IF) and histopathologic techniques. Frozen sections prepared from pulmonary tissues of the infected pigs were stained with fluorescein-conjugated antiserums against ASF viral antigen, porcine immunoglobulin G (IgG), procine complement (C), and porcine fibrinogen. The viral antigen(s) was mainly seen in macrophages and cell debris in alveolar walls and lumens. This finding indicates that the virus replicated in the cytoplasm of alveolar macrophages that subsequently degenerated and released the viral antigen. Diffuse immunoglobulin (Ig) deposition was found in necrotic cells and debris. Immunoglobulin also was seen bound to intracytoplasmic inclusion bodies in some degenerating alveolar macrophages. This finding indicates that antibody against ASF viral antigen(s) excluded from blood circulation or produced by local immunocytes (or both) reacted with viral antigen at intramacrophage and extramacrophage levels and resulted in the formation of insoluble antigen-antibody (Ag-Ab) complexes. The participation of C in the immune complex was evident in the early stage of the pneumonia, but was less evident in the subsequent extensive, progressive necrotic processes. Fibrin deposits were visible only in the early necrotic area of alveolar walls and lumens. Possible mechanisms inducing extensive necrosis are discussed.

Topics: African Swine Fever; Animals; Antigen-Antibody Complex; Antigens, Viral; Complement System Proteins; DNA Viruses; Fibrin; Fibrinogen; Fluorescent Antibody Technique; Immune Sera; Immunoglobulin G; Lung; Macrophages; Necrosis; Pneumonia, Viral; Pulmonary Alveoli; Rabbits; Swine; Swine Diseases

Topics: Adult; Aged; Autopsy; Bronchi; Chronic Disease; Epithelium; Female; Fibrin; Humans; Influenza, Human; Lung; Male; Middle Aged; Orthomyxoviridae; Pneumonia, Viral; Pulmonary Alveoli; Pulmonary Embolism