Pathological Changes and Cause of Death Associated with the Global Novel Coronavirus Disease (COVID-19) / 法医学杂志

The coronavirus disease 2019 (COVID-19) has been a global epidemic for more than three years, causing more than 6.9 million deaths. COVID-19 has the clinical characteristics of strong infectivity and long incubation period, and can cause multi-system damage, mainly lung damage, clinical symptoms of acute respiratory distress syndrome (ARDS) and systemic multiple organ damage. The SARS-CoV-2 virus is still constantly mutating. At present, there is no global consensus on the pathological changes of COVID-19 associated deaths and even no consensus on the criteria for determining the cause of death. The investigation of the basic pathological changes and progression of the disease is helpful to guide the clinical treatment and the development of therapeutic drugs. This paper reviews the autopsy reports and related literature published worldwide from February 2020 to June 2023, with a clear number of autopsy cases and corresponding pathological changes of vital organs as the inclusion criteria. A total of 1 111 autopsy cases from 65 papers in 18 countries are included. Pathological manifestations and causes of death are classified and statistically analyzed, common pathological changes of COVID-19 are summarized, and analytical conclusions are drawn, suggesting that COVID-19 infection can cause life-threatening pathological changes in vital organs. On the basis of different health levels of infected groups, the direct cause of death is mainly severe lung damage and secondary systemic multiple organ failure.

Pathological findings in COVID-19: A conventional autopsy-based study from India

Background & objectives: Autopsy study has been considered the gold standard method for studying the effects of any disease on the body. Since COVID-19 is a novel disease, autopsy is crucial to understand its pathophysiology. This study was conducted to analyze the microscopic and macroscopic findings of various organs in COVID-19 and to associate those findings with clinical observations and laboratory findings. Methods: Conventional invasive autopsies were performed on 33 patients with COVID-19 from September 7, 2020 to December 23, 2020. All the organs were removed by routine dissection techniques and preserved in 10 per cent formalin. The tissues were processed and stained according to standard practices using haematoxylin-eosin (H & E) and periodic acid-schiff (PAS) stain. Results: The study included 28 males and 5 females with a median age of 61 yr (range 30-90 yr). Massive pulmonary oedema and thrombi in the lungs were the characteristic features macroscopically. On microscopic examination, diffuse alveolar damage in the exudative/proliferative phase was found in 29 (87.88%) cases. Among the other notable microscopic findings were bronchopneumonia and lung abscesses due to secondary bacterial infection (n=17, 51.52%), acute tubular injury (n=21, 63.64%) and thrombi in the lungs, heart, and kidneys. Interpretation & conclusions: COVID-19 primarily affected the respiratory and the renal systems in the vast majority of severely affected patients in our study. We also found signs of hypercoagulability, as evidenced by widespread thrombi in multiple organs, along with a raised d-dimer level and a hyperinflammatory state manifested by elevated inflammatory markers. Our autopsy findings and altered laboratory investigations support

Pathological findings and morphologic correlation of the lungs of autopsied patients with SARS-CoV-2 infection in the Brazilian Amazon using transmission electron microscopy

Abstract INTRODUCTION: Electron microscopy (EM) is a rapid and effective tool that can be used to create images of a whole spectrum of virus-host interactions and, as such, has long been used in the discovery and description of viral mechanisms. METHODS: Electron microscopy was used to evaluate the pulmonary pathologies of postmortem lung sections from three patients who died from infection with SARS-associated coronavirus 2 (SARS-CoV-2), a new member of the Coronaviridae family. RESULTS: Diffuse alveolar damage (DAD) was predominant in all three patients. The early exudative stage was characterized principally by edema and extravasation of red blood cells into the alveolar space with injury to the alveolar epithelial cells; this was followed by detachment, apoptosis, and necrosis of type I and II pneumocytes. The capillaries exhibited congestion, exposure of the basement membrane from denuded endothelial cells, platelet adhesion, fibrin thrombi, and rupture of the capillary walls. The proliferative stage was characterized by pronounced proliferation of type II alveolar pneumocytes and multinucleated giant cells. The cytopathic effect of SARS-CoV-2 was observed both in degenerated type II pneumocytes and freely circulating in the alveoli, with components from virions, macrophages, lymphocytes, and cellular debris. CONCLUSIONS: Viral particles consistent with the characteristics of SARS-CoV-2 were observed mainly in degenerated pneumocytes, in the endothelium, or freely circulating in the alveoli. In the final stage of illness, the alveolar spaces were replaced by fibrosis.

Lung Pathology in Septic Shock with Leukopenia / 대한법의학회지

Sepsis-related deaths are occasionally encountered in forensic practice. However, forensic pathologists are reluctant to use the terminology “sepsis” or “septic shock” as a cause of death because of the lack of definite morphological evidence. When sepsis is considered a cause of death, pathologic assessment is essential to identify the foci of infection or consequences of sepsis, such as diffuse alveolar damage (DAD). Pneumonia is known to be a common source of sepsis and can develop into DAD with progression of sepsis. The histology of DAD varies according to the immunologic status. An autopsy of a 55-year-old man who died of septic shock with leukopenia revealed only abundant gram-negative bacilli in the alveoli without typical DAD pathology.

O que todo intensivista deve saber a respeito da síndrome do desconforto respiratório agudo e dano alveolar difuso? / What every intensivist should know about acute respiratory distress syndrome and diffuse alveolar damage

RESUMO A síndrome do desconforto respiratório agudo é um desafio para o intensivista. A característica principal desta doença aguda é o dano alveolar difuso, presente em cerca de metade dos pacientes com a síndrome. É claro que o suporte respiratório à síndrome do desconforto respiratório agudo tem melhorado gradualmente nas últimas décadas. É também evidente que todos estes procedimentos são benéficos, já que reduzem a lesão pulmonar e mantêm o paciente vivo. Isto deve ser interpretado como uma estratégia de ganho de tempo, até que o fator desencadeante ou de risco causal melhore, assim como a tempestade inflamatória diminua e o pulmão se cure. Por outro lado, todos - exceto dois tratamentos farmacológicos (bloqueadores neuromusculares e esteroides) - são incapazes de melhorar o desfecho da síndrome do desconforto respiratório agudo. A hipótese de que os resultados farmacológicos negativos podem ser explicados pela heterogeneidade histológica da síndrome do desconforto respiratório agudo tem sido apoiada pelas recentes demonstrações de que a síndrome com dano alveolar difuso tem característica clínico-patológica específica. O dano alveolar difuso é um diagnóstico patológico, e a biópsia pulmonar a céu aberto (a técnica mais comum para obtenção de tecido pulmonar) tem efeitos colaterais graves, sendo necessário que se desenvolvam biomarcadores substitutos para o dano alveolar difuso. O objetivo desta revisão é discutir três tópicos relacionados à síndrome do desconforto respiratório agudo: o relacionamento entre a síndrome do desconforto respiratório agudo e o dano alveolar difuso; como o dano alveolar difuso pode ser representado no quadro clínico; e como o enriquecimento pode melhorar os resultados de estudos clínicos farmacológicos realizados com pacientes com a síndrome e com dano alveolar difuso.

ABSTRACT Acute respiratory distress syndrome is a challenging entity for the intensivist. The pathological hallmark of the acute phase is diffuse alveolar damage, which is present in approximately half of living patients with acute respiratory distress syndrome. It is clear that respiratory support for acute respiratory distress syndrome has gradually been improving over recent decades. However, it is also evident that these procedures are beneficial, as they reduce lung injury and keep the patient alive. This could be interpreted as a time-gaining strategy until the trigger or causal or risk factor improves, the inflammatory storm decreases and the lung heals. However, all except two pharmacological treatments (neuromuscular blockers and steroids) were unable to improve the acute respiratory distress syndrome outcome. The hypothesis that pharmacological negative results may be explained by the histological heterogeneity of acute respiratory distress syndrome has been supported by the recent demonstration that acute respiratory distress syndrome with diffuse alveolar damage constitutes a specific clinical-pathological entity. Given that diffuse alveolar damage is a pathological diagnosis and that open lung biopsy (the most common technique to obtain lung tissue) has several side effects, it is necessary to develop surrogate biomarkers for diffuse alveolar damage. The aim of this narrative review is to address the following three topics related to acute respiratory distress syndrome: (a) the relationship between acute respiratory distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage could be surrogated in the clinical setting and (c) how enrichment in diffuse alveolar damage may improve the results of pharmacological clinical trials tried out on patients with acute respiratory distress syndrome.

Hallazgos histopatológicos en síndrome de dificultad respiratoria aguda / Histopathological findings in acute distress respiratory syndrome / Padrões histopatológicos na síndrome da angústia respiratória aguda

Resumen: El síndrome de insuficiencia respiratoria aguda engloba una constelación relativamente uniforme de características clínicas, radiológicas y fisiológicas en pacientes con falla respiratoria de inicio rápido. En la actualidad existen expertos que consideran la necesidad de denominar a este síndrome lesión alveolar difusa debido a sus reportes histopatológicos. El objetivo de este trabajo de revisión es dar a conocer los cambios histopatológicos de los pacientes con síndrome de insuficiencia respiratoria aguda y la relación que existe con las clasificaciones clínicas actuales.

Abstract: The acute respiratory distress syndrome, includes a relatively uniform radiological and physiological constellation of clinical features respiratory failure in patients with quick start. At present there are experts who consider the need to call this syndrome Diffuse alveolar injury, by histopathological reports this. The objective of this review paper is to make known the histopathologic changes of patients with acute respiratory distress syndrome and the relationship with current clinical classifications.

Resumo: A síndrome da angústia respiratória aguda (SARA) engloba uma constelação relativamente uniforme de características clínicas, radiológicas e fisiológicas em pacientes com falha respiratória de início rápido. Atualmente, existem especialistas que consideram a necessidade de chamar essa síndrome de Lesão Alveolar Difusa pelos relatórios de histopatologia desta. O objetivo deste artigo de revisão é aumentar a consciência das alterações histopatológicas dos pacientes com SARA e a relação com as classificações clínicas atuais.

Embolismo de líquido amniótico / Amniotic fluid embolism

Se valoró un caso de una femenina quien es internada por embarazo en vías de prolongación para inducción del mismo, posterior a su labor presenta sangrado transvaginal abundante por lo que es ingresada a sala de operaciones, no se le encuentra sitio de sangrado, le realizan histerectomía y fallece; es enviada para su respectiva autopsia, se determina como causa de muerte: embolismo de líquido amniótico. Este artículo pretende revisar la etiología de esta patología, fisiopatología, criterios diagnósticos del mismo, factores de riesgo, diagnósticos diferenciales y su tratamiento.

A case of a female who is hospitalized for pregnancy-way extension for induction thereof, after their work presents TVB abundant so it is entered into operating room were assessed, you will not find the bleeding site, we performed hysterectomy and dies; is sent to the respective autopsy determined the cause of death: amniotic fluid embolism. This article reviews the etiology of this pathology, pathophysiology, diagnostic criteria thereof, risk factors, differential diagnosis and treatment.

A Case of Pulmonary Infarction Caused by Diffuse Alveolar Damage Confirmed by Open-Lung Biopsy / 대한내과학회지

We report a case of a 63-year-old man with adult respiratory distress syndrome and pulmonary infarction. The patient presented with fever, dyspnea, pleuritic chest pain, and acute respiratory failure, and we applied mechanical ventilation and steroid therapy. Pulmonary infarction and diffuse alveolar damage were confirmed by open-lung biopsy. Diffuse alveolar damage activated the blood coagulation system, resulting in thrombosis in the pulmonary vasculature. After anticoagulation therapy, the patient improved rapidly. We report a rare pulmonary infarction caused by diffuse alveolar damage confirmed by open-lung biopsy.

A Case of Pulmonary Infarction Caused by Diffuse Alveolar Damage Confirmed by Open-Lung Biopsy / 대한내과학회지

We report a case of a 63-year-old man with adult respiratory distress syndrome and pulmonary infarction. The patient presented with fever, dyspnea, pleuritic chest pain, and acute respiratory failure, and we applied mechanical ventilation and steroid therapy. Pulmonary infarction and diffuse alveolar damage were confirmed by open-lung biopsy. Diffuse alveolar damage activated the blood coagulation system, resulting in thrombosis in the pulmonary vasculature. After anticoagulation therapy, the patient improved rapidly. We report a rare pulmonary infarction caused by diffuse alveolar damage confirmed by open-lung biopsy.

Demographic, etiological, and histological pulmonary analysis of patients with acute respiratory failure: a study of 19 years of autopsies

INTRODUCTION: Acute respiratory failure has been one of the most important causes of death in intensive care units, and certain aspects of its pulmonary pathology are currently unknown. OBJECTIVES: The objective was to describe the demographic data, etiology, and pulmonary histopathological findings of different diseases in the autopsies of patients with acute respiratory failure. METHOD: Autopsies of 4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed, and the following data were obtained: age, sex, and major associated diseases. The pulmonary histopathology was categorized as diffuse alveolar damage, pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial pneumonia. The odds ratio of the concordance between the major associated diseases and specific autopsy findings was calculated using logistic regression. RESULTS: Bacterial bronchopneumonia was present in 33.9 percent of the cases and cancer in 28.1 percent. The pulmonary histopathology showed diffuse alveolar damage in 40.7 percent (1,917) of the cases. A multivariate analysis showed a significant and powerful association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS, sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/ AIDS and liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in these cases. The most prevalent pulmonary histopathological pattern was diffuse alveolar damage, which was associated with different inflammatory conditions. Further studies are necessary to elucidate the complete pathophysiological mechanisms involved with each disease and the development of acute respiratory failure.

Autopsy Findings with Pathological Features of a Novel Human Influenza Virus Infection / 대한법의학회지

In 2009, the novel swine H1N1 influenza (SI) virus infection had been pandemic and in some patients it led to death. But autopsy findings with pathologic features have been rarely known in the deceased with the SI infection. Herein we presented the findings in three deceased cases with the infection of SI virus, compared with those of other literatures. In all cases, postmortem examination with legal autopsy was done due to sudden unexpected death. SI virus infection was confirmed by detection of SI viral RNA performed on Korea center for Disease Control and Prevention. The autopsy findings with pathologic features of our cases were similar to those of the cases on other reports and those of previous pandemic influenza virus infection on literatures. And these findings may be helpful for understanding the biology of SI virus, and for diagnosis, treatment, and prevention of the SI infection.

Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine-origin influenza type A/H1N1 and acute respiratory failure

BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co-infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment. OBJECTIVE: To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1. METHODS: Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS. RESULTS: The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response. Ultrastructural analysis showed viral-like particles in all cases. CONCLUSIONS: Viral-like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT-PCR on nasopharyngeal aspirates. Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.

Two cases of acute fibrinous and organizing pneumonia / 대한내과학회지

Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern consisting of intra-alveolar fibrin in the form of fibrin "balls" and organizing pneumonia, without hyaline membranes or prominent eosinophil infiltration. Some reports suggest that the clinical course and pathological findings of AFOP are different from typical findings of bronchiolitis obliterans organizing pneumonia (BOOP) or eosinophilic pneumonia (EP), and its prognosis can be better or similar to that of diffuse alveolar damage (DAD). We report two cases of pathologically demonstrated AFOP experienced recently at our institute. One fatal case revealed a rapid development of respiratory failure and the need for mechanical ventilation. Another nonfatal case revealed subacute diffuse bilateral lung infiltration without the need for mechanical ventilation. Judging from our experience, the patient who required a mechanical ventilator had a poorer prognosis than the one who did not need a mechanical ventilator.

Two cases of acute fibrinous and organizing pneumonia / 대한내과학회지

Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern consisting of intra-alveolar fibrin in the form of fibrin "balls" and organizing pneumonia, without hyaline membranes or prominent eosinophil infiltration. Some reports suggest that the clinical course and pathological findings of AFOP are different from typical findings of bronchiolitis obliterans organizing pneumonia (BOOP) or eosinophilic pneumonia (EP), and its prognosis can be better or similar to that of diffuse alveolar damage (DAD). We report two cases of pathologically demonstrated AFOP experienced recently at our institute. One fatal case revealed a rapid development of respiratory failure and the need for mechanical ventilation. Another nonfatal case revealed subacute diffuse bilateral lung infiltration without the need for mechanical ventilation. Judging from our experience, the patient who required a mechanical ventilator had a poorer prognosis than the one who did not need a mechanical ventilator.

Pathological findings in influenza A (H5N1) infection.

This report includes pathological findings in the two patients who died of avian flu infection in Thailand. One of them was the first confirmed human case of H5N1 infection reported in Thailand. The other was the first case that was probably infected by person-to-person transmission. The most affected organ systems are respiratory and reticuloendothelial systems. Both cases revealed diffuse alveolar damage, which is the major cause of death. The former also showed superimposed pulmonary fungal infection.

A Case of Diffuse Alveolar Damage Induced by Cyclophosphamide / 결핵

Approximately 100 drugs have been reported to affect the lungs adversely. Among these, pulmonary toxicity caused by antieneoplastic agent is being recognized more frequently. Cyclophosphamide is an immunosuppressive alkylating agent used for the treatment of a wide variety of malignant and nonmalignant diseases. The incidence of pulmonary toxicity is probably less than 1 percent The first case was reported in 1967. Since then, more than 20 well-documented cases of pulmonary toxicity associated with cyclophosphamide have been reported in the literature. In Korea, three patients were identified with cyclophosphamide-induced lung disease. The typical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchangs abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. The best approach to management is early diagnosis, discontinuation of the offending drug and administration of corticosteroid therapy. Recently, we experienced a case of diffuse alveolar damage induced by cyclophosphamide. The patient presented with early-onset pulmonary toxicity and died of repiratory failure despite early use of corticosteroid.

Pneumocystis carinii Pneumonia Presented as Diffuse Alveolar Damage: Report of a case

Pneumocystis carinii is the most common cause of diffuse pulmonary infiltrates in the immunocompromised patients. Microscopically, Pneumocystis carinii pneumonia(PCP) shows characteristic frothy intraalveolar exudate and interstitial lymphocytic and plasma cell infiltrate. However, sometimes the only histologic finding of PCP on routine hematoxylin-eosin stain is that of diffuse alveolar damage(DAD), when we can miss the diagnosis without aid of special stains. We report a case of Pneumocystis carinii pneumonia presenting as DAD in a 50-year old man after chemotherapy due to malignant lymphoma. Open lung biopsy specimen reveals the early stage of DAD without any characteristic findings, such as foamy exudate. However many cysts of Pneumocystis carinii were found on Gomori's methenamine silver(GMS) stain. Therefore, GMS stain should be routinely performed on all biopsy specimens obtained from immunocompromised patients.

Diffuse Alveolar Damage Associated with Polymyositis / 결핵

Interstitial pneumonitis may be the presenting manifestation of polymyositis-dermatomyositis (PM-DM), or may occur later in the evolution of disease. The clinical picture is characterized by non-productive cough, dyspnea and hypoxemia. The chest radiograph demonstrates interstitial infiltrates with predilection for the lung bases, often with an alveolar pattern in addition. We experienced a case of polymyositis associated with diffuse alveolar damage(DAD) that was proven in open lung biopsy. The patient was a 52 year-old woman who was presented with 6 months' duration of generalized ache, edema on ankle and wrist, non-productive cough and mild dyspnea. She had typical symptoms and physical findings of interstitial pneuminitis, and elevated muscle enzyme levels in serum with characteristic histologic findings of myositis on muscle biopsy. She also had typical interstitial lung disease pattern on high resolution CT and restrictive pattern on pulmonary function tests. The findings of open lung biopsy was compatible with diffuse alveolar damage(DAD). She failed to respond to the therapeutic trials with corticosteroid and cyclophosphamide, and finally expired due to acute respiratory distress syndrome.