Association between antithrombin and mortality in patients with COVID-19. A possible link with obesity

Gazzaruso, Carmine; Paolozzi, Enrico; Valenti, Cinzia; Brocchetta, M.; Naldani, Daniela; Grignani, Claudio; Salvucci, Fabrizio; Marino, F; Coppola, Adriana; Gallotti, Pietro

doi:10.1016/j.numecd.2020.07.040

Cited by 56 publications

(64 citation statements)

References 18 publications

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“…Indeed, DIC has been reported in a few patients, usually in the advanced stages of the disease 33 , 37 , 38 . Recently, low antithrombin levels were linked to poor outcomes in COVID-19, especially among patients with obesity 39 . Hence, it is possible that antithrombin activity changes as SARS-CoV-2 infection worsens and a putative mechanism might be the cytokine-driven imbalance in endogenous anticoagulant levels 40 .…”

Section: Immunothrombosis In Covid-19mentioning

confidence: 99%

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

et al. 2021

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Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs. Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels. Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions. Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful. Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection. The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.

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Section: Immunothrombosis In Covid-19mentioning

confidence: 99%

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

et al. 2021

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“…Since, severely ill COVID-19 patients are often associated with coagulopathy/thrombosis and obesity could potentially make it worse. A study by Gazzaruso et al on a cohort of 49 patients hospitalized with COVID-19 infection and reported that low antithrombin (AT) levels were strongly associated with increased mortality [ 132 ]. The authors further show that BMI was the only variable that showed a significant difference between patients with low and high levels of AT.…”

Section: Role Of Coagulopathy /Thrombosis In Sars-cov-2 Pathogenesismentioning

confidence: 99%

“…The authors reported that obese COVID-19 patients were more likely to be admitted to ICU than non-obese subjects but obesity was not significantly associated with mortality, mortality in ICU and length of hospital stay [ 137 ]. However, majority of the studies have reported that obese subjects are an increased risk of severe disease and increased mortality due to COVID-19 [ 59 , 132 , 138 – 143 ].…”

Section: Does Obesity Survival Paradox Occur In Covid-19 Patients?mentioning

confidence: 99%

Obesity and COVID-19: what makes obese host so vulnerable?

et al. 2021

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The disease (COVID-19) novel coronavirus pandemic has so far infected millions resulting in the death of over a million people as of Oct 2020. More than 90% of those infected with COVID-19 show mild or no symptoms but the rest of the infected cases show severe symptoms resulting in significant mortality. Age has emerged as a major factor to predict the severity of the disease and mortality rates are significantly higher in elderly patients. Besides, patients with underlying conditions like Type 2 diabetes, cardiovascular diseases, hypertension, and cancer have an increased risk of severe disease and death due to COVID-19 infection. Obesity has emerged as a novel risk factor for hospitalization and death due to COVID-19. Several independent studies have observed that people with obesity are at a greater risk of severe disease and death due to COVID-19. Here we review the published data related to obesity and overweight to assess the possible risk and outcome in Covid-19 patients based on their body weight. Besides, we explore how the obese host provides a unique microenvironment for disease pathogenesis, resulting in increased severity of the disease and poor outcome.

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“…Certain coagulation parameters were found to be increased, i.e., fibrinogen, D-Dimer, factor VIII, von Willebrand factor antigen, and protein C levels, whereas others were found to be decreased: AT and free protein S levels [ 19 ]. There are reports that linked mortality and decreased AT levels in COVID-19 patients [ 20 , 21 ]. However, decreased levels of AT are typical in severe infections, sepsis, and DIC [ 22 ].…”

Section: Overviewmentioning

confidence: 99%

Antithrombin and Its Role in Host Defense and Inflammation

Schlömmer

Brandtner

Bachler

2021

IJMS

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Antithrombin (AT) is a natural anticoagulant that interacts with activated proteases of the coagulation system and with heparan sulfate proteoglycans (HSPG) on the surface of cells. The protein, which is synthesized in the liver, is also essential to confer the effects of therapeutic heparin. However, AT levels drop in systemic inflammatory diseases. The reason for this decline is consumption by the coagulation system but also by immunological processes. Aside from the primarily known anticoagulant effects, AT elicits distinct anti-inflammatory signaling responses. It binds to structures of the glycocalyx (syndecan-4) and further modulates the inflammatory response of endothelial cells and leukocytes by interacting with surface receptors. Additionally, AT exerts direct antimicrobial effects: depending on AT glycosylation it can bind to and perforate bacterial cell walls. Peptide fragments derived from proteolytic degradation of AT exert antibacterial properties. Despite these promising characteristics, therapeutic supplementation in inflammatory conditions has not proven to be effective in randomized control trials. Nevertheless, new insights provided by subgroup analyses and retrospective trials suggest that a recommendation be made to identify the patient population that would benefit most from AT substitution. Recent experiment findings place the role of various AT isoforms in the spotlight. This review provides an overview of new insights into a supposedly well-known molecule.

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Association between antithrombin and mortality in patients with COVID-19. A possible link with obesity

Cited by 56 publications

References 18 publications

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19

Obesity and COVID-19: what makes obese host so vulnerable?

Antithrombin and Its Role in Host Defense and Inflammation

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