Immunothrombosis in Acute Respiratory Dysfunction of COVID-19

Fang, Xiang; Wang, Ya Xin; Xu, Ji; He, Ya Jun; Peng, Zhe; Shang, You

doi:10.3389/fimmu.2021.651545

Cited by 21 publications

(18 citation statements)

References 157 publications

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“…3B). Tissue factor activation is the initiator of the extrinsic coagulation cascade, and it has been implicated as a key to the process of microvascular thrombi formation and immunothrombosis in severe ARDS, including COVID-19 (14, 15). Although we have not elucidated the exact mechanism of the increase in tissue factor, our hypothesis is that it is due to the nicotine-dependent increases in type 1 inflammatory cytokine genes, which were also highly expressed in the lung tissue in our model (Fig.…”

Section: Discussionmentioning

confidence: 99%

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Hinds

Nick

Vallin

et al. 2022

Preprint

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IntroductionE-cigarette vaping has become a major portion of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of sub-acute and chronic e-cigarette vaping exposure have shown many pro-inflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting SARS-CoV-2 without genetic alteration to the animal or virus.MethodsUsing a two-day, whole-body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant (p-value <0.05), post-hoc Tukey-Kramer and Dunn’s tests, respectively, were performed to make pairwise comparisons between groups.ResultsIn nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-β), and a nicotine-independent decrease in the vasculogenesis/angiogenesis gene VEGF-A. In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1β, TNF-α, and CXCL-10), fibrosis (TGF-β and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified.ConclusionTo our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig induced inhalational injury. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation in the respiratory tract of pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Hinds

Nick

Vallin

et al. 2022

Preprint

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“…Following the increased formation of clots, the fibrinolysis process is activated whereby plasminogen is converted into the active plasmin under the influence of tissue plasminogen activator (t-PA) and urokinase plasminogen activator (u-PA). The active plasmin then breaks down the fibrin in the vasculature [87] , [88] , [89] ( Fig. 1 C).…”

Section: Interaction Of the Immune And Coagulation Systems In Critica...mentioning

confidence: 99%

Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation

Mortazavi-Jahromi

Aslani

2022

International Immunopharmacology

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“…Durch intrazelluläre Replikation und Exozytose des Virus in die Blutstrombahn werden Schädigungen von Alveolarzellen und Endothelien verursacht. Diese führen pulmonal zu entzündlichen Infiltraten, Thromben in der Mikrozirkulation und einer starken systemischen Akute-Phase-Reaktion, oft mit überschießender Produktion proinflammatorischer Zytokine sowie prothrombotischer Aktivierung des Hämostasesystems [9][10][11].…”

Section: Pathophysiologie Der Thrombogenese Bei Covid-19unclassified

Antikoagulation bei „coronavirus disease 2019“ (COVID-19) – Gesichertes und Kontroverses

Rauch-Kröhnert

Riess

2022

Internist

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ZusammenfassungDie Infektion mit dem „severe acute respiratory syndrome coronavirus 2“ (SARS-CoV-2) ist mit einem hohen Risiko mikrovaskulärer Immunthrombosen sowie symptomatischer und inzidenteller Thromboembolien vorrangig im venösen, aber auch im arteriellen System vergesellschaftet. Dies begründet unter anderem die hohe kardiovaskuläre Morbidität und Mortalität der Patienten. Der heutige Kenntnisstand zur Pathophysiologie der Immunthrombosen und zu derzeitigen Strategien der Antikoagulation bei an „coronavirus disease 2019“ (COVID-19) erkrankten Patienten wird in diesem Beitrag zusammenfassend beleuchtet. Gemäß den aktuellen Leitlinien sollen moderat bis schwer erkrankte Infizierte, die sich in stationärer Krankenhausbehandlung befinden, frühzeitig eine Thromboseprophylaxe mit niedermolekularem oder unfraktioniertem Heparin oder alternativ mit Fondaparinux erhalten, sofern kein deutlich erhöhtes Blutungsrisiko vorliegt. Außerhalb der etablierten Therapieindikationen sollte eine intensivierte oder therapeutisch dosierte Prophylaxe auch aufgrund vermehrter Blutungskomplikationen bei diesen kritisch erkrankten Patienten sehr zurückhaltend erwogen werden. Die routinemäßige Fortführung einer prophylaktischen Antikoagulation nach der Krankenhausentlassung wird derzeit nicht empfohlen.

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Immunothrombosis in Acute Respiratory Dysfunction of COVID-19

Cited by 21 publications

References 157 publications

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

Dysregulated miRNAs network in the critical COVID-19: An important clue for uncontrolled immunothrombosis/thromboinflammation

Antikoagulation bei „coronavirus disease 2019“ (COVID-19) – Gesichertes und Kontroverses

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