scholarly journals Clinical and pathomorphological analysis of deaths from COVID-19 in 2020

Pathologia ◽  
2021 ◽  
Vol 18 (3) ◽  
pp. 269-277
Author(s):  
O. V. Riabokon ◽  
L. M. Tumanska ◽  
V. V. Cherkaskyi ◽  
Yu. Yu. Riabokon

The aim of the work – to conduct clinical and pathomorphological analysis of deaths from COVID-19 in 2020. Materials and methods. We analyzed 41 case histories and results of pathological-anatomical examination of patients who were died of COVID-19 during 2020. Results. The lethal outcome of COVID-19 disease was recorded at day 22 (16; 27) of the disease. Among the dead, there is a high percentage of men (73.2 %), early old age and middle old age patients (75.6 %) with comorbid pathology (92.7 %). Early lung damage with COVID-19 in the deceased was determined by pronounced interstitial and interstitial-alveolar edema, the presence of erythrocyte stasis in the pulmonary microvessels, blood clots and hypoperfusion leukocyte stasis, as well as the presence of erythrocytes in the alveoli. Bilateral polysegmental subtotal viral pneumonia in 90.2 % of dead patients was characterized by significant edema and thickening of the alveolar walls with their moderate infiltration by lymphocytes, focal peribronchial and perivascular inflammatory polymorphonuclear infiltration, multiple and small exfoliated alveolar epithelium (87.8 %), as well as metaplasia of a few alveolocytes preserved on the luminal surface of the alveoli (82.9 %). Every tenth person who died of COVID-19 had signs of secondary bacterial microflora. In 85.4 % of patients who died on day 22–27 of the disease focal or sublobar pneumofibrosis was diagnosed. In those who died due to COVID-19, multiorgan failure was characterized by focal necrosis of the renal tubular epithelium (73.2 %), focal lymphocytic-leukocyte infiltration (12.2 %) and renal microvascular thrombosis (17.1 %), focal centro-lobular necrosis (90.2 %) and focal lymphocytic-leukocyte infiltration of lobes (7.3 %) of the liver. Thrombotic complications were confirmed in 22.0 % of deceased patients: ischemic cerebral infarction, transmural myocardial infarction, pulmonary embolism, deep vein thrombosis of the lower extremities under the pathology. These thrombotic complications were not diagnosed during life in all patients. The majority of deaths due to COVID-19 had morphological signs of chronic cardiovascular pathology. Ischemic heart disease and hypertension during the life of patients were not diagnosed in all cases. Conclusions. Early lung damage in COVID-19 in the deceased was determined by pronounced interstitial-alveolar edema, blood clots and leukocyte stasis in microvessels, less often – the presence of “hyaline membranes”. In 90.2 % of the dead patients bilateral polysegmental subtotal pneumonia with edema and lymphocytic infiltration of the pulmonary interstitium, inflammatory peribronchial and perivascular focal polymorphonuclear infiltrates, foci of atelectasis and dyscryphaseses was found. In 9.7 % of patients bilateral subtotal viral-bacterial fibrinous-purulent bronchopneumonia developed. In those who died on the 22nd–27th day of the disease focal pneumofibrosis was determined. Pathomorphologically, thrombotic complications, which were not diagnosed in all patients during their lifetime, were confirmed in 22.0 % of deceased patients. Most deaths from COVID-19 had morphological signs of chronic cardiovascular disease.

2021 ◽  
Vol 11 (1) ◽  
pp. 15-19
Author(s):  
Anastasia Babkina ◽  
Arkady Golubev ◽  
Alexey Volkov ◽  
Artem Kuzovlev ◽  
Maryam Khadzhieva ◽  
...  

The aim of the study was to evaluate the histopathological changes in the lungs of patients who died of a new coronavirus infection (COVID-19) in relation to the length of hospital stay. We evaluated lung autopsy material, autopsy reports, and death summaries of 39 patients who died of COVID-19. The length of hospital stay ranged from a few hours to 25 days. At all stages of the disease, lung alterations (desquamation of bronchial and alveolar epithelium), circulatory disorders (alveolar edema and hemorrhages, congestion in small blood vessels, thrombosis), compensatory response (fibrosis) were identified. The patients who died during the first week of hospitalization demonstrated predominant signs of circulatory disorders (alveolar edema, hyaline membranes, alveolar hemorrhages, congestion in small blood vessels). Fibrosis, usually not typical for the first week of acute respiratory distress syndrome, was detected in 46% of the deceased during the first week of hospitalization, which may be due to late hospitalization or patterns of fibrosis development in COVID-19. For those who died in the 2nd and 3rd weeks of hospitalization, the compensatory response and progression of fibrosis were noted. By the 3rd week, pulmonary fibrosis was detected in 91% of patients. Thrombotic complications (thrombosis, pulmonary artery thromboembolism) were observed in almost half of fatalities occurring during weeks 2–3. Hemorrhagic infarction was found in 43% (6 patients) who died during week 2 of hospitalization, three of them were diagnosed with pulmonary embolism, indicating progression of pulmonary vascular damage.


2020 ◽  
Vol 127 (4) ◽  
pp. 571-587 ◽  
Author(s):  
James D. McFadyen ◽  
Hannah Stevens ◽  
Karlheinz Peter

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude. Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke. Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality. The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface. However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke. Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19. Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance. Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects. The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications. The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.


1977 ◽  
Vol 233 (1) ◽  
pp. H80-H86 ◽  
Author(s):  
E. A. Egan ◽  
R. M. Nelson ◽  
I. H. Gessner

Ten anesthetized dogs, 48 h postintravenous 131I-albumin injection, had a segment of lung airspace isolated by a balloon-tipped catheter lodged in a bronchus. An isotonic saline solution containing trace amounts of Blue Dextran, 125I-albumin, and 57Co-cyanocobalamin was instilled into the lung segment. During control periods, lung saline was absorbed at a rate of 0.133% per minute as measured by indicator dilution of Blue Dextran. Only 57Co-cyanocobalamin crossed the epithelium. Acute hemodynamic pulmonary edema was produced by aortic constriction plus saline overload. In pulmonary edema the fluid volume in the airspace increased at the rate of 0.96% per minute, and there was a significant influx of 131I-albumin into the lung saline from the blood in all animals. However, neither 125I-albumin nor Blue Dextran diffused from the airspace into blood during edema; both were merely diluted by fluid influx. The rate of diffusion of 57Co-cyanocobalamin increased fivefold during edema. A small number of discrete breaks in the lung epithelium allowing bulk flow of interstitial fluid is proposed to account for the one-way movement of albumin in hemodynamic alveolar edema.


2014 ◽  
Vol 88 (14) ◽  
pp. 8166-8179 ◽  
Author(s):  
Patricia Resa-Infante ◽  
René Thieme ◽  
Thomas Ernst ◽  
Petra C. Arck ◽  
Harald Ittrich ◽  
...  

ABSTRACTInfluenza A viruses recruit components of the nuclear import pathway to enter the host cell nucleus and promote viral replication. Here, we analyzed the role of the nuclear import factor importin-α7 in H1N1 influenza virus pulmonary tropism by using variousex vivoimaging techniques (magnetic resonance imaging, confocal laser scanning microscopy, and correlative light-electron microscopy). We infected importin-α7 gene-deficient (α7−/−) mice with a recombinant H1N1 influenza virus and compared thein vivoviral kinetics with those in wild-type (WT) mice. In WT mice, influenza virus replication in the bronchial and alveolar epithelium already occurred a few days after infection. Accordingly, extensive mononuclear infiltration and alveolar destruction were present in the lungs of infected WT mice, followed by 100% lethality. Conversely, in α7−/−mice, virus replication was restricted mostly to the bronchial epithelium with marginal alveolar infection, resulting in significantly reduced lung damage and enhanced animal survival. To investigate the host immune response during alveolar virus replication, we studied the role of primary macrophages in virus propagation and clearance. The ability of macrophages to support or clear the virus infection, as well as the host cellular immune responses, did not significantly differ between WT and α7−/−mice. However, cytokine and chemokine responses were generally elevated in WT mice, likely reflective of increased viral replication in the lung. In summary, these data show that a cellular factor, importin-α7, is required for enhanced virus replication in the alveolar epithelium, resulting in elevated cytokine and chemokine levels, extensive mononuclear infiltration, and thus, severe pneumonia and enhanced virulence in mice.IMPORTANCEInfluenza A viruses are respiratory pathogens that may cause pneumonia in humans. Viral infection and replication in the alveoli of the respiratory tract are believed to be crucial for the development of the acute respiratory distress syndrome associated with fatal outcomes in influenza virus-infected patients. Here, we report the requirement of a cellular factor, importin-α7, for efficient virus replication in the alveolar epithelium of mice. Using complementaryex vivoimaging approaches, we show that influenza virus replication is restricted to the bronchial epithelium, followed by enhanced survival in importin-α7-deficient mice. In contrast, the presence of this gene results in enhanced virus replication in the alveoli, elevated cytokine and chemokine responses, mononuclear infiltration, alveolar destruction, and 100% lethality in wild-type mice. Taken together, our results show that importin-α7 is particularly required for virus replication in the alveolar epithelium in association with severe pneumonia and death in mice.


2021 ◽  
Vol 11 (6) ◽  
pp. 161-163
Author(s):  
Komal Gharsangi ◽  
Rajesh Bhawani ◽  
Nitesh Kumar

COVID -19 is not just a respiratory illness; it is a great masquerader with clinical manifestations from pneumonia, acute respiratory distress syndrome to endothelial dysfunction, hypercoagulability and multiorgan failure. Thrombotic complications due to Covid related coagulopathy is of concern as it further leads to poor clinical outcome in severe cases of Covid 19. Acute limb ischemia (ALI) is a rare manifestation of Covid related coagulopathy. Key words: COVID, coagulopathy, acute limb ischemia (ALI).


2021 ◽  
Author(s):  
Nathaniel L. Lartey ◽  
Salvador Valle-Reyes ◽  
Hilda Vargas-Robles ◽  
Karina E. Jiménez-Camacho ◽  
Idaira M. Guerrero-Fonseca ◽  
...  

Severe coronavirus disease 2019 (Covid-19) is characterized by lung injury, cytokine storm and increased neutrophil-to-lymphocyte ratio (NLR). Current therapies focus on reducing viral replication and inflammatory responses, but no specific treatment exists to prevent the development of severe Covid-19 in infected individuals. Angiotensin-converting enzyme-2 ACE-2) is the receptor for SARS-CoV-2, the virus causing Covid-19, but it is also critical for maintaining the correct functionality of lung epithelium and endothelium. Coronaviruses induce activation of a disintegrin and metalloprotease 17 (ADAM17) and shedding of ACE-2 from the cell surface resulting in exacerbated inflammatory responses. Thus, we hypothesized that ADAM17 inhibition ameliorates Covid-19-related lung inflammation. We employed a pre-clinical mouse model using intra-tracheal instillation of a combination of polyinosinic:polycytidylic acid (poly-I:C) and the receptor-binding domain of the SARS-CoV-2 spike protein (RBD-S) to mimic lung damage associated with Covid-19. Histological analysis of inflamed mice confirmed the expected signs of lung injury including edema, fibrosis, vascular congestion and leukocyte infiltration. Moreover, inflamed mice also showed an increased NLR as observed in critically ill Covid-19 patients. Administration of the ADAM17 inhibitors apratastat and TMI-1 significantly improved lung histology and prevented leukocyte infiltration. Reduced leukocyte recruitment could be explained by reduced production of pro-inflammatory cytokines and lower levels of the endothelial adhesion molecules ICAM-1 and VCAM-1. Additionally, the NLR was significantly reduced by ADAM17 inhibition. Thus, we propose inhibition of ADAM17 as a novel promising treatment strategy in SARS-CoV-2-infected individuals to prevent the progression towards severe Covid-19.


2006 ◽  
Vol 291 (3) ◽  
pp. L354-L361 ◽  
Author(s):  
Michael T. Ganter ◽  
Lorraine B. Ware ◽  
Marybeth Howard ◽  
Jérémie Roux ◽  
Brandi Gartland ◽  
...  

Previous studies have shown that heat shock protein 72 (Hsp72) is found in the extracellular space (eHsp72) and that eHsp72 has potent immunomodulatory effects. However, whether eHsp72 is present in the distal air spaces and whether eHsp72 could modulate removal of alveolar edema is unknown. The first objective was to determine whether Hsp72 is released within air spaces and whether Hsp72 levels in pulmonary edema fluid would correlate with the capacity of the alveolar epithelium to remove alveolar edema fluid in patients with ALI/ARDS. Patients with hydrostatic edema served as controls. The second objective was to determine whether activation of the stress protein response (SPR) caused the release of Hsp72 into the extracellular space in vivo and in vitro and to determine whether SPR activation and/or eHsp72 itself would prevent the IL-1β-mediated inhibition of the vectorial fluid transport across alveolar type II cells. We found that eHsp72 was present in plasma and pulmonary edema fluid of ALI patients and that eHsp72 was significantly higher in pulmonary edema fluid from patients with preserved alveolar epithelial fluid clearance. Furthermore, SPR activation in vivo in mice and in vitro in lung endothelial, epithelial, and macrophage cells caused intracellular expression and extracellular release of Hsp72. Finally, SPR activation, but not eHsp72 itself, prevented the decrease in alveolar epithelial ion transport induced by exposure to IL-1β. Thus SPR may protect the alveolar epithelium against oxidative stress associated with experimental ALI, and eHsp72 may serve as a marker of SPR activation in the distal air spaces of patients with ALI.


Blood ◽  
2009 ◽  
Vol 114 (2) ◽  
pp. 444-451 ◽  
Author(s):  
Sonja Oehmcke ◽  
Oonagh Shannon ◽  
Maren von Köckritz-Blickwede ◽  
Matthias Mörgelin ◽  
Adam Linder ◽  
...  

Abstract Sepsis and septic shock remain an important medical problem, emphasizing the need to identify novel therapeutic opportunities. Hypovolemic hypotension, coagulation dysfunction, disturbed microcirculation, and multiorgan failure resulting from vascular leakage are often observed in these severe conditions. In the present study, we find that HKH20, a peptide derived from human high molecular weight kininogen (HK), down-regulates inflammatory reactions caused by Streptococcus pyogenes in a mouse model of sepsis. HK is a component of the pro-inflammatory and pro-coagulant contact system. Activation of the contact system in the bloodstream by S pyogenes leads to massive tissue damage in the lungs of the infected mice, which eventually results in the death of the animals. HKH20 inhibits activation of the contact system and protects mice with invasive S pyogenes infection from lung damage. In combination with clindamycin treatment, the peptide also significantly prolongs the survival of infected mice.


2021 ◽  
Vol 9 (1) ◽  
pp. 159
Author(s):  
Mai M. Zafer ◽  
Hadir A. El-Mahallawy ◽  
Hossam M. Ashour

The ongoing outbreak of the novel coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has taken a significant toll on people and countries all over the world. The pathogenesis of COVID-19 has not been completely elucidated yet. This includes the interplay between inflammation and coagulation which needs further investigation. The massive production of proinflammatory cytokines and chemokines results in the so-called cytokine storm, leading to plasma leakage, vascular hyperpermeability, and disseminated vascular coagulation. This is usually accompanied by multiorgan failure. The extensive changes in the serum levels of cytokines are thought to play a crucial role in the COVID-19 pathogenesis. Additionally, the viral load and host inflammation factors are believed to have a significant role in host damage, particularly lung damage, from SARS-CoV-2. Interestingly, patients exhibit quantitative and qualitative differences in their immune responses to the virus, which can impact the clinical manifestation and outcomes of COVID-19. There needs to be a better understanding of the dynamic events that involve immune responses, inflammatory reactions, and viral replication in the context of the COVID-19 infection. Here, we discuss the main aspects of COVID-19 pathogenesis while supporting the hypothesis that inflammatory immune responses are involved in the progression of the disease to a more critical and fatal phase. We also explore the similarities and differences between severe COVID-19 and sepsis. A deeper understanding of the COVID-19 clinical picture as it relates to better-known conditions such as sepsis can provide useful clues for the management, prevention, and therapy of the disease.


2017 ◽  
Vol 163 ◽  
pp. 527-540
Author(s):  
Anna Zura

The picture of old age in the late works of Jaroslav Seifert Morový sloup, Deštník z Piccadilly, Býti básníkemThe analysis is an attempt to scrutinize the linguistic picture of old age in the late works of the Czech Nobel laureate J. Seifert. The following study focuses on the last three poetry volumes of the author. The article presents an analysis of the semantic field of the old age as well as the function and the way in which the metaphors are applied in the works of the Czech poet. The article is based on the research methodology of the ‘linguistic picture of the world’. Nine major metaphorical schemes were distinguished and taken under examination. When describing old age, the dominant theme was: time, travelling, farewell, sand, water, fading fire, denial of youth, meeting the dead and reflections about life after death.Obraz světa stáří vpozdní tvorbě Jaroslava Seiferta Morový sloup, Deštník z Piccadilly, Býti básníkemCílem studie je pokus oodhalení specifického autorského obrazu stáří vpozdní tvorbě českého nositele Nobelovy ceny Jaroslava Seiferta, jež zahrnuje tři poslední sbírky: Morový sloup, Deštník z Piccadilly, Býti básníkem. Hlavní pozornost byla zaměřená na rozbor sémantického pole stáří asoučasně byly analyzovány funkce azpůsoby užití metafor. Článek vychází zmetodologie opírající se oprincipy zkoumaní jazykového obrazu světa resp. textového obrazu světa. Během práce bylo vyčleněno devět hlavních metaforických schémat, znichž dominantními jsou: čas, cestovaní, loučení, písek, voda, uhaslý oheň, negace mladí, setkaní sezesnulými, uvažování oživotě po smrti.


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