Defibrotide for the Treatment of Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 2 Pediatric Patients

Lang, Peter; Eichholz, Thomas; Bakchoul, Tamam; Streiter, Monika; Petrasch, Maurice; Bösmüller, Hans; Klein, Reinhild; Rabsteyn, Armin; Lang, Annemarie; Adams, Constantin; Klingel, Karin; Geßner, Michaela; Rosenberger, Peter; Ruef, Peter; Handgretinger, Rupert

doi:10.1093/jpids/piaa117

Cited by 16 publications

(21 citation statements)

References 12 publications

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“…After reading the full texts, 7 were excluded (summarized in the Supplementary Table ) [13] , [14] , [15] , [16] , [11] , [17] , [18] . Twelve articles were case reports ( Table 1 ) [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] . In addition, an international survey [31] and a prospective multicenter study were included [32] ( Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Thrombotic risk in children with COVID-19 infection: A systematic review of the literature

Zaffanello

Piacentini

Nosetti

et al. 2021

Thrombosis Research

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Coagulation and inflammatory parameters are mildly altered in children with SARS-CoV-2 (COVID-19) infection, and laboratory evidence of a proinflammatory and procoagulant state has been noted in multisystem inflammatory syndrome in children (MIS-C). It is not clear whether this pediatric condition is related to thrombotic events. With this study we reviewed the literature for thrombotic complications in children with COVID-19 infection and MIS-C. Data sources: We searched the Medline PubMed Advanced Search Builder, Scopus, Web Of Science, and Google Scholar electronic databases (until 1 January 2021) using the medical subject headings (MeSH) terms and text words (their combinations and truncated synonyms): (THROMBOSIS OR THROMBOPHILIA) AND (CHILD OR CHILDREN OR INFANT) AND (COVID-19 OR SARS-CoV-2). Study eligibility criteria: Inclusion criteria were children with COVID-19 or SARS-COV-2 infection. The search was limited to articles published in English. Exclusion criteria were: reviews of published studies, studies published only as abstracts, letters or conference proceedings, discussion papers, animal studies, or editorials. Results: After screening for duplicates, the initial search yielded 86 records: 12 were case reports involving 19 children; comorbidities were absent or mild in 73.7%. The most common site of thrombosis the lung (21%); the most often used drug was heparin (42%). Two studies were an international survey (n = 337 patients) and a large multicenter study (n = 186 patients with MIS-C). The risk of ischemic stroke in SARS-CoV-2 infection (0.82%) and deep venous thrombosis in MIS-C (4.3%) was lower in children than in adults. Conclusions: Thrombodic or thromboembolic events are rare in pediatric patients with COVID-19 infection and MIS-C. Nonetheless, as in adults, a high index of suspicion should be maintained in children with COVID-19 infection or MIS-C, particularly in those with comorbidities predisposing to thrombotic events.

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Section: Resultsmentioning

confidence: 99%

Thrombotic risk in children with COVID-19 infection: A systematic review of the literature

Zaffanello

Piacentini

Nosetti

et al. 2021

Thrombosis Research

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“…Under treatment, thromboelastometry returned to normal after 8 days. A detailed report about her course of disease has been published [ 17 ]. Ribavirin was administered to the girl who had undergone HSCT a year before.…”

Section: Resultsmentioning

confidence: 99%

“…Data assessed from children admitted with COVID-19 was shared with ISARIC. A detailed report about patient N° 6 has been published in the Journal of the Pediatric Infectious Diseases Society [ 17 ]. A case report about patient N° 3 is currently in progress, but not yet submitted to a journal (Kumpf M. and Bösmüller H., unpublished data).…”

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confidence: 99%

A case series of children and young people admitted to a tertiary care hospital in Germany with COVID-19

Remppis

Ganzenmueller²,

Vasconcelos

et al. 2021

BMC Infect Dis

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Background While our knowledge about COVID-19 in adults has rapidly increased, data on the course of disease and outcome in children with different comorbidities is still limited. Methods Prospective, observational study at a tertiary care children’s hospital in southern Germany. Clinical and virology data from all paediatric patients admitted with SARS-CoV-2 infection at our hospital were prospectively assessed. Results Between March and November 2020, 14 patients were admitted with COVID-19. One patient was admitted a second time with COVID-19 6 months after initial disease. Among seven patients with severe underlying comorbidities, three developed multisystem inflammatory syndrome (MIS-C), two were admitted to the paediatric intensive care unit. One patient needed invasive ventilation. Another patient died shortly after discharge of COVID-19-related complications. Conclusions While COVID-19 generally causes mild disease in children, severe respiratory illness and MIS-C occur, in some cases with fatal outcome. Children with underlying diseases might be at special risk for severe disease.

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“…DF may similarly regulate complement hyperactivation observed in patients with severe COVID-19. In fact, two patients with pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection received DF, leading to symptomatic resolution and normalization of complement levels [ 154 ].…”

Section: Therapeutic Strategies To Protect the Endotheliummentioning

confidence: 99%

Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?

Castro

Palomo

Moreno-Castaño

et al. 2021

Cardiovasc Drugs Ther

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Patients with COVID-19 present a wide spectrum of disease severity, from asymptomatic cases in the majority to serious disease leading to critical care and even death. Clinically, four different scenarios occur within the typical disease timeline: first, an incubation and asymptomatic period; second, a stage with mild symptoms due mainly to the virus itself; third, in up to 20% of the patients, a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome; and finally, a post-acute sequelae (PASC) phase, which present symptoms that can range from mild or annoying to actually quite incapacitating. Although the most common manifestation is acute respiratory failure of the lungs, other organs are also frequently involved. The clinical manifestations of the COVID-19 infection support a key role for endothelial dysfunction in the pathobiology of this condition. The virus enters into the organism via its interaction with angiotensin-converting enzyme 2-receptor that is present prominently in the alveoli, but also in endothelial cells, which can be directly infected by the virus. Cytokine release syndrome can also drive endothelial damage independently. Consequently, a distinctive feature of SARS-CoV-2 infection is vascular harm, with severe endothelial injury, widespread thrombosis, microangiopathy, and neo-angiogenesis in response to endothelial damage. Therefore, endothelial dysfunction seems to be the pathophysiological substrate for severe COVID-19 complications. Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity. In addition, the endothelium could represent a very attractive target to both prevent and treat these complications. To establish an adequate therapy, the underlying pathophysiology and corresponding clinical stage should be clearly identified. In this review, the clinical features of COVID-19, the central role of the endothelium in COVID-19 and in other pathologies, and the potential of specific therapies aimed at protecting the endothelium in COVID-19 patients are addressed.

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Defibrotide for the Treatment of Pediatric Inflammatory Multisystem Syndrome Temporally Associated With Severe Acute Respiratory Syndrome Coronavirus 2 Infection in 2 Pediatric Patients

Cited by 16 publications

References 12 publications

Thrombotic risk in children with COVID-19 infection: A systematic review of the literature

Thrombotic risk in children with COVID-19 infection: A systematic review of the literature

A case series of children and young people admitted to a tertiary care hospital in Germany with COVID-19

Is the Endothelium the Missing Link in the Pathophysiology and Treatment of COVID-19 Complications?

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