Preliminary Post-Mortem COVID-19 Evidence of Endothelial Injury and Factor VIII Hyperexpression
09 Aug 2020-Vol. 10, Iss: 8, pp 575
TL;DR: It is suggested that COVID-19 infection can cause different forms of acute respiratory distress syndrome (ARDS), due to diffuse alveolar damage and diffuse endothelial damage, and the data on Factor VIII discussed in this paper seem to suggest that the thrombogenicity of Sars-CoV2 infection might be linked to widespread endothelialDamage.
Abstract: (1) Background: The current outbreak of COVID-19 infection is an ongoing challenge and a major threat to public health that requires surveillance, prompt diagnosis, as well as research efforts to understand the viral pathogenesis. Despite this, to date, very few studies have been performed concerning autoptic specimens. Therefore, this study aimed: (i) to reiterate the importance of the autoptic examination, the only method able to precisely define the cause of death; (ii) to provide a complete post-mortem histological and immunohistochemical investigation pattern capable of diagnosing death from COVID-19 infection. (2) Methods: In this paper, the lung examination of two subjects who died from COVID-19 are discussed, comparing the obtained data with those of the control, a newborn who died from pneumonia in the same pandemic period. (3) Results: The results of the present study suggest that COVID-19 infection can cause different forms of acute respiratory distress syndrome (ARDS), due to diffuse alveolar damage and diffuse endothelial damage. Nevertheless, different patterns of cellular and cytokine expression are associated with anti-COVID-19 antibody positivity, compared to the control case. Moreover, in both case studies, it is interesting to note that COVID-19, ACE2 and FVIII positivity was detected in the same fields. (4) Conclusions: COVID-19 infection has been initially classified as exclusively interstitial pneumonia with varying degrees of severity. Subsequently, vascular biomarkers showed that it can also be considered a vascular disease. The data on Factor VIII discussed in this paper, although preliminary and limited in number, seem to suggest that the thrombogenicity of Sars-CoV2 infection might be linked to widespread endothelial damage. In this way, it would be very important to investigate the pro-coagulative substrate both in all subjects who died and in COVID-19 survivors. This is because it may be hypothesized that the different patterns with which the pathology is expressed could depend on different individual susceptibility to infection or a different personal genetic-clinical background. In light of these findings, it would be important to perform more post-mortem investigations in order to clarify all aspects of the vascular hypothesis in the COVID-19 infection.
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TL;DR: Several mechanisms of hypercoagulability in sepsis that may be upregulated in COVID‐19, including immune‐mediated thrombotic mechanisms, complement activation, macrophage activation syndrome, antiphospholipid antibody syndrome, hyperferritinemia, and renin‐angiotensin system dysregulation are reviewed.
Abstract: Thrombotic complications are frequent in COVID-19 and contribute significantly to mortality and morbidity. We review several mechanisms of hypercoagulability in sepsis that may be upregulated in COVID-19. These include immune-mediated thrombotic mechanisms, complement activation, macrophage activation syndrome, antiphospholipid antibody syndrome, hyperferritinemia, and renin-angiotensin system dysregulation. We highlight biomarkers within each pathway with potential prognostic value in COVID-19. Lastly, recent observational studies have evaluated a role for the expanded use of therapeutic anticoagulation in COVID-19. We review strengths and weaknesses of these studies, and we also discuss the hypothetical benefit and anticipated challenges of fibrinolytic therapy in COVID-19.
214 citations
Cites background from "Preliminary Post-Mortem COVID-19 Ev..."
...increased in hospitalized COVID-19 patients, including C-reactive protein, erythrocyte sedimentation rate, and ferritin, as are several procoagulant factors such as von Willebrand factor and Factor VIII (Table 1).(48,58) In addition, numerous proinflammatory cytokines are increased including tumor necrosis factor alpha (TNF-α) and interleukin (IL)-2R, IL-6, IL-8, and IL-10....
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TL;DR: In this article, the effect of tocilizumab administration was evaluated in a subset of patients with SARS-CoV-2 infection and the results showed that the treatment resulted in at least partial reversion of the metabolic alterations due to SARS infection.
Abstract: The current pandemic emergence of novel coronavirus disease (COVID-19) poses a relevant threat to global health. SARS-CoV-2 infection is characterized by a wide range of clinical manifestations, ranging from absence of symptoms to severe forms that need intensive care treatment. Here, plasma-EDTA samples of 30 patients compared with age- and sex-matched controls were analyzed via untargeted nuclear magnetic resonance (NMR)-based metabolomics and lipidomics. With the same approach, the effect of tocilizumab administration was evaluated in a subset of patients. Despite the heterogeneity of the clinical symptoms, COVID-19 patients are characterized by common plasma metabolomic and lipidomic signatures (91.7% and 87.5% accuracy, respectively, when compared to controls). Tocilizumab treatment resulted in at least partial reversion of the metabolic alterations due to SARS-CoV-2 infection. In conclusion, NMR-based metabolomic and lipidomic profiling provides novel insights into the pathophysiological mechanism of human response to SARS-CoV-2 infection and to monitor treatment outcomes.
61 citations
TL;DR: In this article, the authors present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.
Abstract: At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2-3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.
57 citations
TL;DR: The heterogeneity of fatal cases - persistence of viral infection in lung, clearance of virus but severe lung injury, thrombosis, and exaggerated immune response - suggest that antiviral, antithrombotic, anti-inflammatory, and supportive therapy play a role in treatment, but that the patientspecific cause and timing of the lung injury is important in choosing intervention as discussed by the authors.
Abstract: Purpose of review COVID-19 lung injury is a common manifestation of severe illness. Lung tissue examination has been largely derived from autopsy - a combination of case reports, small and moderately sized series with international scope. Common and uncommon histopathology provides insight into the progression of severe, fatal disease. Recent findings COVID-19 lung histology is most commonly diffuse alveolar damage as part of acute respiratory distress syndrome. Lung injury can be temporally heterogeneous, with patterns of healing alongside new injury. Viral studies, including immunohistochemistry, RNA in-situ hybridization, and tissue-based Polymerase chain reaction (PCR) assist in discerning complications of therapy (e.g. ventilator-associated pneumonia) from primary viral-induced injury. Response to viral infection produces systemic effects, and one major manifestation is thrombosis of micro-circulation and larger vessels. Less common patterns include neutrophil-rich inflammation, raising speculation that neutrophil extra-cellular traps may play a role in both viral control and exaggerated immune response. Summary The heterogeneity of fatal cases- persistence of viral infection in lung, clearance of virus but severe lung injury, thrombosis, and exaggerated immune response - suggest that antiviral, antithrombotic, anti-inflammatory, and supportive therapy play a role in treatment, but that the patient-specific cause and timing of the lung injury is important in choosing intervention.
46 citations
TL;DR: In this paper, the authors reviewed postmortem studies of patients with COVID-19 published in English through September 26, 2020, for histopathologic findings consistent with bacterial lung infections.
Abstract: Background Limited clinical data suggest a ~16% prevalence of bacterial superinfections among critically ill patients with coronavirus disease 2019 (COVID-19) Methods We reviewed postmortem studies of patients with COVID-19 published in English through September 26, 2020, for histopathologic findings consistent with bacterial lung infections Results Worldwide, 621 patients from 75 studies were included The quality of data was uneven, likely because identifying superinfections was not a major objective in 96% (72/75) of studies Histopathology consistent with a potential lung superinfection was reported in 32% (200/621) of patients (22-96 years old; 66% men) Types of infections were pneumonia (95%), abscesses or empyema (35%), and septic emboli (15%) Seventy-three percent of pneumonias were focal rather than diffuse The predominant histopathologic findings were intra-alveolar neutrophilic infiltrations that were distinct from those typical of COVID-19-associated diffuse alveolar damage In studies with available data, 79% of patients received antimicrobial treatment; the most common agents were beta-lactam/beta-lactamase inhibitors (48%), macrolides (16%), cephalosoprins (12%), and carbapenems (6%) Superinfections were proven by direct visualization or recovery of bacteria in 255% (51/200) of potential cases and 8% of all patients in postmortem studies In rank order, pathogens included Acinetobacter baumannii, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae Lung superinfections were the cause of death in 16% of potential cases and 3% of all patients with COVID-19 Conclusions Potential bacterial lung superinfections were evident at postmortem examination in 32% of persons who died with COVID-19 (proven, 8%; possible, 24%), but they were uncommonly the cause of death
40 citations
References
More filters
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
36,578 citations
TL;DR: Re-analysis of data from a phase 3 randomised controlled trial of IL-1 blockade (anakinra) in sepsis, showed significant survival benefit in patients with hyperinflammation, without increased adverse events.
7,493 citations
TL;DR: The findings are consistent with person-to-person transmission of this novel coronavirus in hospital and family settings, and the reports of infected travellers in other geographical regions.
7,392 citations
"Preliminary Post-Mortem COVID-19 Ev..." refers background in this paper
...The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019 is an ongoing challenge and a major threat to public health that requires surveillance, prompt diagnosis as well as research efforts to understand this emerging pathogen and to develop effective countermeasures [1,2]....
[...]
TL;DR: O surto do novo coronavÃrus (COVID-19) em Wuhan, China, iniciado em dezembro de 2019, evoluiu para se tornar uma pandemia global A.
6,850 citations
TL;DR: The vascular endothelium is an active paracrine, endocrine, and Endothelial cell infection and endotheliitis in COVID-19 and recruitment of immune cells can result in widespread endothelial dysfunction associated with apoptosis.
4,855 citations
"Preliminary Post-Mortem COVID-19 Ev..." refers background in this paper
...[43] reported a widespread endothelial inflammation in 3 positive cases of COVID-19, including 1 case with the presence of lymphocytic endothelitis in lung, heart, kidney and liver samples, assuming that endothelial dysfunction is the main determinant of COVID-19 disease, which induces vasoconstriction with subsequent organ ischemia, inflammation, edema and pro-coagulant state....
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