Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis

José, Ricardo J.; Williams, Andrew E.; Manuel, Ari; Brown, Jeremy S.; Chambers, Rachel C.

doi:10.1183/16000617.0240-2020

Cited by 21 publications

(18 citation statements)

References 115 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Skendros et al, recently showed that complement and tissue factor were identified as a key driver in COVID-19 severity: (47). Tissue factor (TF) is initiating downstream cascades involving factor X (48). Here, we confirm that SARS-CoV-2-infected hamster exhibit distinct factor X as well as complement C3c protein level in inflamed lung biopsies (Supplementary Figures 1-4).…”

Section: Endothelialitis and Vasculitis In Lungs Of Golden Syrian Hamster (Hamster) At 3 And 6 Days Post Infection (Dpi)supporting

confidence: 77%

Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

Becker¹,

Beythien²,

Buhr

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) have been identified as one pathogenetic trigger in severe COVID-19 cases and therefore well-described animal models to understand the influence of NETs in COVID-19 pathogenesis are needed. SARS-CoV-2 infection causes infection and interstitial pneumonia of varying severity in humans and COVID-19 models. Pulmonary as well as peripheral vascular lesions represent a severe, sometimes fatal, disease complication of unknown pathogenesis in COVID-19 patients. Furthermore, neutrophil extracellular traps (NETs), which are known to contribute to vessel inflammation or endothelial damage, have also been shown as potential driver of COVID-19 in humans. Though most studies in animal models describe the pulmonary lesions characterized by interstitial inflammation, type II pneumocyte hyperplasia, edema, fibrin formation and infiltration of macrophages and neutrophils, detailed pathological description of vascular lesions or NETs in COVID-19 animal models are lacking so far. Here we report different types of pulmonary vascular lesions in the golden Syrian hamster model of COVID-19. Vascular lesions included endothelialitis and vasculitis at 3 and 6 days post infection (dpi), and were almost nearly resolved at 14 dpi. Importantly, virus antigen was present in pulmonary lesions, but lacking in vascular alterations. In good correlation to these data, NETs were detected in the lungs of infected animals at 3 and 6 dpi. Hence, the Syrian hamster seems to represent a useful model to further investigate the role of vascular lesions and NETs in COVID-19 pathogenesis.

show abstract

Section: Endothelialitis and Vasculitis In Lungs Of Golden Syrian Hamster (Hamster) At 3 And 6 Days Post Infection (Dpi)supporting

confidence: 77%

Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

Becker¹,

Beythien²,

Buhr

et al. 2021

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Several studies demonstrated that dysregulation of procoagulant and fibrinolytic pathways may uniquely contribute to the pathophysiology of sepsis. However, this issue should be further investigated to obtain more details ( Bouck et al., 2020 ; Colantuoni et al., 2020 ; Jose et al., 2020 ; Kang et al., 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Prediction of Sepsis in COVID-19 Using Laboratory Indicators

Tang

Luo

Feng

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

BackgroundThe outbreak of coronavirus disease 2019 (COVID-19) has become a global public health concern. Many inpatients with COVID-19 have shown clinical symptoms related to sepsis, which will aggravate the deterioration of patients’ condition. We aim to diagnose Viral Sepsis Caused by SARS-CoV-2 by analyzing laboratory test data of patients with COVID-19 and establish an early predictive model for sepsis risk among patients with COVID-19.MethodsThis study retrospectively investigated laboratory test data of 2,453 patients with COVID-19 from electronic health records. Extreme gradient boosting (XGBoost) was employed to build four models with different feature subsets of a total of 69 collected indicators. Meanwhile, the explainable Shapley Additive ePlanation (SHAP) method was adopted to interpret predictive results and to analyze the feature importance of risk factors.FindingsThe model for classifying COVID-19 viral sepsis with seven coagulation function indicators achieved the area under the receiver operating characteristic curve (AUC) 0.9213 (95% CI, 89.94–94.31%), sensitivity 97.17% (95% CI, 94.97–98.46%), and specificity 82.05% (95% CI, 77.24–86.06%). The model for identifying COVID-19 coagulation disorders with eight features provided an average of 3.68 (±) 4.60 days in advance for early warning prediction with 0.9298 AUC (95% CI, 86.91–99.04%), 82.22% sensitivity (95% CI, 67.41–91.49%), and 84.00% specificity (95% CI, 63.08–94.75%).InterpretationWe found that an abnormality of the coagulation function was related to the occurrence of sepsis and the other routine laboratory test represented by inflammatory factors had a moderate predictive value on coagulopathy, which indicated that early warning of sepsis in COVID-19 patients could be achieved by our established model to improve the patient’s prognosis and to reduce mortality.

show abstract

“…Indeed, vitamin C deficiency appears to be common among COVID-19 patients ( 110 , 111 ). COVID-19 is also associated with the formation of microthrombi and coagulopathy ( 112 ), which contribute to its characteristic lung pathology ( 113 ), but these symptoms can be ameliorated by early infusions of vitamin C to inhibit endothelial surface P-selectin expression and platelet-endothelial cell adhesion ( 114 ). Intravenous vitamin C also reduced D-dimer levels in a case study of 17 COVID-19 patients ( 115 ).…”

Section: Vitamin Cmentioning

confidence: 99%

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

2021

View full text Add to dashboard Cite

Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents may reduce the pandemic’s devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Such products include vitamin C, vitamin D, omega 3 polyunsaturated fatty acids, probiotics, and zinc, all of which are currently under clinical investigation. In this review, we critically appraise the evidence surrounding dietary supplements and nutraceuticals for the prophylaxis and treatment of COVID-19. Overall, further study is required before evidence-based recommendations can be formulated, but nutritional status plays a significant role in patient outcomes, and these products may help alleviate deficiencies. For example, evidence indicates that vitamin D deficiency may be associated with a greater incidence of infection and severity of COVID-19, suggesting that vitamin D supplementation may hold prophylactic or therapeutic value. A growing number of scientific organizations are now considering recommending vitamin D supplementation to those at high risk of COVID-19. Because research in vitamin D and other nutraceuticals and supplements is preliminary, here we evaluate the extent to which these nutraceutical and dietary supplements hold potential in the COVID-19 crisis. IMPORTANCE Sales of dietary supplements and nutraceuticals have increased during the pandemic due to their perceived “immune-boosting” effects. However, little is known about the efficacy of these dietary supplements and nutraceuticals against the novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) or the disease that it causes, CoV disease 2019 (COVID-19). This review provides a critical overview of the potential prophylactic and therapeutic value of various dietary supplements and nutraceuticals from the evidence available to date. These include vitamin C, vitamin D, and zinc, which are often perceived by the public as treating respiratory infections or supporting immune health. Consumers need to be aware of misinformation and false promises surrounding some supplements, which may be subject to limited regulation by authorities. However, considerably more research is required to determine whether dietary supplements and nutraceuticals exhibit prophylactic and therapeutic value against SARS-CoV-2 infection and COVID-19. This review provides perspective on which nutraceuticals and supplements are involved in biological processes that are relevant to recovery from or prevention of COVID-19.

show abstract

Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis

Cited by 21 publications

References 115 publications

Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

Vasculitis and Neutrophil Extracellular Traps in Lungs of Golden Syrian Hamsters With SARS-CoV-2

Prediction of Sepsis in COVID-19 Using Laboratory Indicators

Dietary Supplements and Nutraceuticals under Investigation for COVID-19 Prevention and Treatment

Contact Info

Product

Resources

About