Nuts and bolts of COVID-19 associated coagulopathy: the essentials for management and treatment

Lindsay, Patrick; Rosovsky, Rachel; Bittner, Edward A.; Chang, Marvin G.

doi:10.1080/00325481.2021.1974212

Cited by 5 publications

(1 citation statement)

References 82 publications

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“…In addition, a meta-analysis in 2021 suggested that almost 3% of COVID-19 patients may develop DIC and this condition may increase the likelihood of mortality by more than 2.4 times [ 42 ]. Therefore, monitoring and diagnosis of CAC is a major challenge in the management of COVID-19 patients [ 43 ]. Reports have revealed that COVID-19 patients, particularly with ARDS, may represent hypercoagulability state, i.e., higher levels of D-dimer, mild prolongation of PT and PTT, and thrombocytopenia [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

et al. 2023

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Background and aims The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients. Materials and methods COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention. Results A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041). Conclusion MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073.

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Section: Discussionmentioning

confidence: 99%

Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

et al. 2023

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Novel mechanism of the COVID-19 associated coagulopathy (CAC) and vascular thromboembolism

Singh,

Pushpakumar,

Zheng

et al. 2023

npj Viruses

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Previous studies from our laboratory revealed that SARS-CoV-2 spike protein (SP) administration to a genetically engineered model expressing the human angiotensin-converting enzyme 2; ACE2 receptor (i.e., hACE2 humanized mouse) mimicked the coronavirus disease-19 (COVID-19) pathology. In humans the cause of high morbidity, and mortality is due to ‘cytokine-storm’ led thromboembolism; however, the exact mechanisms of COVID-19 associated coagulopathy (CAC) have yet to be discovered. Current knowledge suggests that CAC is distinct from the standard coagulopathy, in that the intrinsic and extrinsic thrombin-dependent coagulation factors, and the pathway(s) that are common to coagulopathy, are not recruited by SARS-CoV-2. Findings from patients revealed that there is little change in their partial thromboplastin, or the prothrombin time coupled with a significant decline in platelets. Further, there appears to be an endothelial dysfunction during COVID-19 suggesting an interaction of the endothelia with immune cells including neutrophils. There are also reports that inflammatory NGAL is elevated during COVID-19. Furthermore, the levels of NPT are also increased indicating an increase in inflammatory M1 macrophage iNOS which sequesters BH4; an essential enzyme co-factor that acts as a potent antioxidant thus causing damage to endothelia. SARS-CoV-2 entry into the host cells is facilitated by a co-operative action between TMPRSS2 and the main ACE2 receptor. Interestingly, after infection ADAMTS13; a von Willebrand factor; VWF cleaving enzyme is found to be decreased. Based on these facts, we hypothesize that vascular thromboembolism is associated with serine and metalloproteinase, and in that context, we opine that inhibition of iNOS might help mitigate COVID-19 harmful effects. To test this hypothesis, we administered SP to the hACE2 mice that were subsequently treated with amino guanidine (AG; a potent inhibitor of glycoxidation, lipoxidation and oxidative vicious cycles). Our results revealed increase in TMPRSS2, and NGAL by SP but treatment with AG mitigated their levels. Similarly, levels of MMP-2, and -9 were increased; however, AG treatment normalized these levels. Our findings suggest that occurrence of CAC is influenced by TMPRSS2, ADAMTS13, NGAL and MMP- 2, and -9 factors, and an intervention with iNOS blocker helped mitigate the CAC condition in experimental settings.

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Ground-glass opacity on emergency department chest X-ray: a risk factor for in-hospital mortality and organ failure in elderly admitted for COVID-19

Roig-Marín

Roig-Rico

2022

Postgraduate Medicine

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Nuts and bolts of COVID-19 associated coagulopathy: the essentials for management and treatment

Cited by 5 publications

References 82 publications

Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

Novel mechanism of the COVID-19 associated coagulopathy (CAC) and vascular thromboembolism

Ground-glass opacity on emergency department chest X-ray: a risk factor for in-hospital mortality and organ failure in elderly admitted for COVID-19

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