Alpha‐defensins: risk factor for thrombosis in COVID‐19 infection

Abdeen, Suhair; Bdeir, Khalil; Abu‐Fanne, Rami; Maraga, Emad; Higazi, Mohamed; Khurram, Nigar; Feldman, Michael; Deshpande, Charuhas; Litzky, Leslie A.; Heyman, Samuel N.; Montone, Kathleen T.; Cines, Douglas B.; Higazi, Abd Al‐Roof

doi:10.1111/bjh.17503

Cited by 17 publications

(21 citation statements)

References 42 publications

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Section: Resultssupporting

confidence: 78%

“…In contrast to TCZ and as previously reported, colchicine 18 inhibited IL‐6‐mediated release of α‐Def from neutrophils (Fig 2B ) . These data support the hypothesis that an increase of α‐Def released from neutrophils promotes coagulation in patients with COVID‐19, evident by an increase in D‐dimer levels, 18 and that by inhibiting the release α‐Def from neutrophils (Fig 2B ), colchicine attenuates pro‐thrombotic pathways with a consequent decline in D‐dimers (Fig 2A ). This hypothesis is in line with previous data showing that colchicine decreases the coagulation tendency and lowers D‐dimers in patients with familial Mediterranean fever (FMF), 24 as well as in mice expressing α‐Def in their neutrophils.…”

Section: Resultssupporting

confidence: 78%

“… 19 We also reported that plasma levels of α‐Def are increased in patients with COVID‐19, which is associated with an increase in IL‐6 and D‐dimers. 18 Therefore, it would be expected that inhibiting signal transduction in neutrophils by blocking IL‐6 receptors (IL‐6R) would decrease α‐Def and D‐dimers.…”

Section: Resultsmentioning

confidence: 99%

“…Measurement of plasma components and statistical analyses were performed as previously reported. 18 For more details, see 18 and the Supplementary Material.…”

Section: Methodsmentioning

confidence: 99%

“…Colchicine was given to 16 patients [mean (SD) age 51·4 (6·5) years, nine males and seven females] admitted to the Department of Internal Medicine with ‘moderate’ symptoms as previously defined 18 . Patients in the treatment arm were given colchicine 1 mg twice a day on day 1 and 0·5 mg twice a day for a mean (SD) of 7 (4) days thereafter, in addition to standard care.…”

Section: Methodsmentioning

confidence: 99%

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Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins

et al. 2021

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Summary Patients who are severely affected by coronavirus disease 2019 (COVID‐19) may develop a delayed onset ‘cytokine storm’, which includes an increase in interleukin‐6 (IL‐6). This may be followed by a pro‐thrombotic state and increased D‐dimers. It was anticipated that tocilizumab (TCZ), an anti‐IL‐6 receptor monoclonal antibody, would mitigate inflammation and coagulation in patients with COVID‐19. However, clinical trials with TCZ have recorded an increase in D‐dimer levels. In contrast to TCZ, colchicine reduced D‐dimer levels in patients with COVID‐19. To understand how the two anti‐inflammatory agents have diverse effects on D‐dimer levels, we present data from two clinical trials that we performed. In the first trial, TCZ was administered (8 mg/kg) to patients who had a positive polymerase chain reaction test for COVID‐19. In the second trial, colchicine was given (0·5 mg twice a day). We found that TCZ significantly increased IL‐6, α‐Defensin (α‐Def), a pro‐thrombotic peptide, and D‐dimers. In contrast, treatment with colchicine reduced α‐Def and Di‐dimer levels. In vitro studies show that IL‐6 stimulated the release of α‐Def from human neutrophils but in contrast to colchicine, TCZ did not inhibit the stimulatory effect of IL‐6; raising the possibility that the increase in IL‐6 in patients with COVID‐19 treated with TCZ triggers the release of α‐Def, which promotes pro‐thrombotic events reflected in an increase in D‐dimer levels.

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Section: Resultssupporting

confidence: 78%

Section: Resultssupporting

confidence: 78%

Section: Resultsmentioning

confidence: 99%

“…Measurement of plasma components and statistical analyses were performed as previously reported. 18 For more details, see 18 and the Supplementary Material.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins

et al. 2021

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Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19

Bolla

Loretelli

Montefusco

et al. 2022

Diabetes Metabolism Res

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Aims Several reports indicate that diabetes determines an increased mortality risk in patients with coronavirus disease 19 (COVID‐19) and a good glycaemic control appears to be associated with more favourable outcomes. Evidence also supports that COVID‐19 pneumonia only accounts for a part of COVID‐19 related deaths. This disease is indeed characterised by abnormal inflammatory response and vascular dysfunction, leading to the involvement and failure of different systems, including severe acute respiratory distress syndrome, coagulopathy, myocardial damage and renal failure. Inflammation and vascular dysfunction are also well‐known features of hyperglycemia and diabetes, making up the ground for a detrimental synergistic combination that could explain the increased mortality observed in hyperglycaemic patients. Materials and methods In this work, we conduct a narrative review on this intriguing connection. Together with this, we also present the clinical characteristics, outcomes, laboratory and histopathological findings related to this topic of a cohort of nearly 1000 subjects with COVID‐19 admitted to a third‐level Hospital in Milan. Results We found an increased mortality in subjects with COVID‐19 and diabetes, together with an altered inflammatory profile. Conclusions This may support the hypothesis that diabetes and COVID‐19 meet at the crossroads of inflammation and vascular dysfunction. (ClinicalTrials.gov NCT04463849 and NCT04382794).

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Use of α-Defensins to Help Diagnose Nosocomial Ventriculitis

Doub

2022

Neurocrit Care

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Ventriculitis is a severe complication of indwelling neurosurgical devices that is associated with significant morbidity and mortality. The incidence rate of ventriculitis is approximately 10% with external ventricular drains. Obstinately, patients with these indwelling neurosurgical devices are prone to have traditional cerebral spinal fluid parameters that lack sensitivity and specificity in diagnosing nosocomial ventriculitis. In addition, diagnosis can be arduous given that indolent pathogens are commonly implicated. Therefore, diagnosis is difficult but paramount to thwart the morbidity and mortality associated with this infectious condition as well as to reduce the prolonged use of broad-spectrum antibiotics. As we extrapolate from prosthetic joint infections, for which diagnosis can also be challenging, we learn that the use of α-defensins as a diagnostic biomarker for nosocomial ventriculitis may hold promise. Herein, the viewpoint of using α-defensins as a diagnostic biomarker for nosocomial ventriculitis is discussed.

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Alpha‐defensins: risk factor for thrombosis in COVID‐19 infection

Cited by 17 publications

References 42 publications

Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins

Divergent impacts of tocilizumab and colchicine in COVID‐19‐associated coagulopathy: the role of alpha‐defensins

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19

Use of α-Defensins to Help Diagnose Nosocomial Ventriculitis

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