Thrombotic complications in children with Coronavirus disease 2019 and Multisystem Inflammatory Syndrome of Childhood

Kumar, Riten; Rivkin, Michael J.; Raffini, Leslie

doi:10.1016/j.jtha.2023.05.020

Cited by 9 publications

(11 citation statements)

References 111 publications

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“…The importance of the inflammatory repsonce in the pathogenesis of cardiac commplications in the course of COVID-19 is well established in the have multisystem inflammatory syndrome in children, which is late immune-mediated complication occurring after SARS-CoV-2 infection 40 , 41 . Thus, beneficial impact of AP on hospital course and mortality in COVID-19 can be explained by anti-inflammatory effects of AP agents 15 – 18 , 42 .…”

Section: Discussionmentioning

confidence: 99%

Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study

Sokolski,

Reszka,

Adamik

et al. 2024

Sci Rep

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One of the major pathomechanisms of COVID-19 is the interplay of hyperinflammation and disruptions in coagulation processes, involving thrombocytes. Antiplatelet therapy (AP) by anti-inflammatory effect and inhibition of platelet aggregation may affect these pathways. The aim of this study was to investigate if AP has an impact on the in-hospital course and medium-term outcomes in hospitalized COVID-19 patients. The study population (2170 COVID-19 patients: mean ± SD age 60 ± 19 years old, 50% male) was divided into a group of 274 patients receiving any AP prior to COVID-19 infection (AP group), and after propensity score matching, a group of 274 patients without previous AP (non-AP group). Patients from the AP group were less frequently hospitalized in the intensive care unit: 9% vs. 15%, 0.55 (0.33–0.94), developed less often shock: 9% vs. 15%, 0.56 (0.33–0.96), and required less aggressive forms of therapy. The AP group had more coronary revascularizations: 5% vs. 1%, 3.48 (2.19–5.55) and strokes/TIA: 5% vs. 1%, 3.63 (1.18–11.2). The bleeding rate was comparable: 7% vs. 7%, 1.06 (0.54–2.06). The patients from the AP group had lower 3-month mortality: 31% vs. 39%, 0.69 (0.51–0.93) and didn’t differ significantly in 6-month mortality: 34% vs. 41%, 0.79 (0.60–1.04). When analyzing the subgroup with a history of myocardial infarction and/or coronary revascularization and/or previous stroke/transient ischemic attack and/or peripheral artery disease, AP had a beneficial effect on both 3-month: 37% vs. 56%, 0.58 (0.40–0.86) and 6-month mortality: 42% vs. 57%, 0.63 (0.44–0.92). Moreover, the favourable effect was highly noticeable in this subgroup where acetylsalicylic acid was continued during hospitalization with reduction of in-hospital: 19% vs. 43%, 0.31 (0.15–0.67), 3-month: 30% vs. 54%, 044 (0.26–0.75) and 6-month mortality: 33% vs. 54%, 0.49 (0.29–0.82) when confronted with the subgroup who had acetylsalicylic acid suspension during hospitalization. The AP may have a beneficial impact on hospital course and mortality in COVID-19 and shouldn’t be discontinued, especially in high-risk patients.

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Section: Discussionmentioning

confidence: 99%

Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study

Sokolski,

Reszka,

Adamik

et al. 2024

Sci Rep

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“…It suggests MIS-C as an immunometabolic condition 26 . Alterations in numerous coagulation factors with elevated procoagulants, reduced anticoagulants, and impaired fibrinolysis point towards a global hypercoagulability and may explain the risk of thrombosis in children with MIS-C 27 . Overall, our results align with those of a previous study, which also reported upregulated Fc Gamma Receptor IIIa, immune and complement activation and reduced lipid transport and clearance mechanisms 28 .…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children

Nygaard,

Nielsen,

Dungu

et al. 2024

Commun Biol

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Multisystem inflammatory syndrome in children (MIS-C) is a severe disease that emerged during the COVID-19 pandemic. Although recognized as an immune-mediated condition, the pathogenesis remains unresolved. Furthermore, the absence of a diagnostic test can lead to delayed immunotherapy. Using state-of-the-art mass-spectrometry proteomics, assisted by artificial intelligence (AI), we aimed to identify a diagnostic signature for MIS-C and to gain insights into disease mechanisms. We identified a highly specific 4-protein diagnostic signature in children with MIS-C. Furthermore, we identified seven clusters that differed between MIS-C and controls, indicating an interplay between apolipoproteins, immune response proteins, coagulation factors, platelet function, and the complement cascade. These intricate protein patterns indicated MIS-C as an immunometabolic condition with global hypercoagulability. Our findings emphasize the potential of AI-assisted proteomics as a powerful and unbiased tool for assessing disease pathogenesis and suggesting avenues for future interventions and impact on pediatric disease trajectories through early diagnosis.

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“…Venous thrombosis is predominantly described, while reports of arterial thrombosis in children with COVID-19 are scarce. [ 22 ] A recent study by Whitworth et al [ 18 ] found that the incidence of thrombosis in multisystem inflammatory syndrome in children was 6.5%, and was highest compared with acute SARS-CoV-2 infection (2.1%) and its asymptomatic form (0.7%). The incidence of thrombosis in our group of children with MIS-C was twice as high, at 13.3%; this is probably due to the fact that we included secondary thrombotic microangiopathy, which is usually described separately in the literature [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Thrombosis in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children: Retrospective Cohort Study Analysis and Review of the Literature

Bregel,

Efremova,

Kostyunin

et al. 2023

Biomedicines

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Background: The causative agent of the new coronavirus infection SARS-CoV-2 has unique properties causing hyperinflammatory syndrome and cytokine storm, as well as widespread endotheliitis and thrombotic microangiopathy, initially detected in the lungs of adult patients who died from a severe form of the disease. Venous and arterial thrombosis in adults were identified as common causes of severe complications and deaths in new coronavirus infections. There are very few reports of thrombotic events in children with COVID-19 in the literature. Methods: We conducted a retrospective analysis of the histories of 60 patients in the Irkutsk Regional Children’s Clinical Hospital from November 2020 to November 2022 with a MIS-C diagnosis established according to WHO criteria, of which 8 (13.3%) were diagnosed with venous and/or arterial thrombosis, confirmed by laboratory and ultrasound and/or X-ray methods. Results: The average age of children with thrombosis (Me) was 7.5 years (min 4 months, max 17 years), with a M:F ratio of 3.0. Venous thrombosis was detected in six of the eight patients, including in the deep veins of the lower extremities in four. Pulmonary embolism occurred in two (one of them was fatal), and cerebral venous sinus thrombosis and thrombosis of the branches of the upper and lower vena cava were found in one patient. Extensive bilateral stroke due to thrombosis of the large cerebral arteries occurred in two patients, including one in combination with distal gangrene. Secondary thrombotic renal microangiopathy took place in three of the eight patients. Among these three, atypical HUS was diagnosed in one case. Multiple thrombosis involving the venous and arterial bed was detected in four of the eight patients. High levels of D-dimer, thrombocytopenia, increased NT-proBNP, cerebral coma, and aseptic meningitis were the events most often associated with thrombosis. All patients received immunomodulatory therapy (immunoglobulin, dexamethasone/methylprednisolone), pathogenetic therapy for multiorgan failure, anticoagulant therapy with heparin/LMWH, and acetylsalicylic acid. Biologics were used in two patients. Conclusions: The main predictors of thrombosis in children with MIS-C were increased D-dimer, thrombocytopenia, hospitalization in the ICU, and noncardiogenic pulmonary edema. Thrombosis of the deep veins of the lower extremities, large cerebral arteries, and secondary thrombotic microangiopathy was common. There was a single death (12.5% of the eight patients), associated with PE.

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Thrombotic complications in children with Coronavirus disease 2019 and Multisystem Inflammatory Syndrome of Childhood

Cited by 9 publications

References 111 publications

Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study

Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study

Proteomic profiling reveals diagnostic signatures and pathogenic insights in multisystem inflammatory syndrome in children

Thrombosis in Multisystem Inflammatory Syndrome Associated with COVID-19 in Children: Retrospective Cohort Study Analysis and Review of the Literature

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