Hemophagocytosis in bone marrow aspirates in multisystem inflammatory syndrome in children

Gürlevik, Sibel Laçinel; Aksu, Tekin; Özen, Seza; Kesici, Selman; Gümrük, Fatma; Özsürekçi, Yasemin

doi:10.1002/pbc.28931

Cited by 7 publications

(5 citation statements)

References 9 publications

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“…Other features of MAS in patients with MIS-C have been reported in the literature, including overlapping cytokine phenotypes and hemophagocytosis on bone marrow aspirates 50 . Although the evidence suggests that MIS-C does share many things in common with MAS, the clinical presentation of MIS-C patients is not fully consistent with a complete MAS phenotype and may be better understood as an occult MAS 51 , 52 .…”

Section: Discussionmentioning

confidence: 69%

Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction

et al. 2021

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Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. Here we perform a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesize that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. We show that protein signatures demonstrate overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is an important marker of MIS-C that associates with TMA. We find that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.

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Section: Discussionmentioning

confidence: 69%

Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction

et al. 2021

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“…Our study focused upon adult patients. Interestingly, haemophagocytosis in bone marrow biopsies was also reported in two small series of three paediatric patients each with COVID‐19‐associated multisystemic inflammatory syndrome 25,26 …”

Section: Discussionmentioning

confidence: 78%

“…Interestingly, haemophagocytosis in bone marrow biopsies was also reported in two small series of three paediatric patients each with COVID-19-associated multisystemic inflammatory syndrome. 25,26 Patients who succumbed to COVID-19 showed more severe anaemia and a trend towards lower haemoglobin levels when erythrophagocytosis was detectable in the bone marrow. While non-replicative infection of erythroid precursors/progenitors has been demonstrated in previous studies, the mechanism of erythrophagocytosis in COVID-19 patients has remained elusive.…”

Section: Discussionmentioning

confidence: 99%

Bone marrow haematopoiesis in patients with COVID‐19

et al. 2023

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AimsSevere acute respiratory syndrome coronavirus type 2 (SARS‐CoV‐2) infection broadly affects organ homeostasis, including the haematopoietic system. Autopsy studies are a crucial tool for investigation of organ‐specific pathologies. Here we perform an in‐depth analysis of the impact of severe coronavirus disease 2019 (COVID‐19) on bone marrow haematopoiesis in correlation with clinical and laboratory parameters.Methods and resultsTwenty‐eight autopsy cases and five controls from two academic centres were included in the study. We performed a comprehensive analysis of bone marrow pathology and microenvironment features with clinical and laboratory parameters and assessed SARS‐CoV‐2 infection of the bone marrow by quantitative polymerase chain reaction (qPCR) analysis. In COVID‐19 patients, bone marrow specimens showed a left‐shifted myelopoiesis (19 of 28, 64%), increased myeloid–erythroid ratio (eight of 28, 28%), increased megakaryopoiesis (six of 28, 21%) and lymphocytosis (four of 28, 14%). Strikingly, a high proportion of COVID‐19 specimens showed erythrophagocytosis (15 of 28, 54%) and the presence of siderophages (11 of 15, 73%) compared to control cases (none of five, 0%). Clinically, erythrophagocytosis correlated with lower haemoglobin levels and was more frequently observed in patients from the second wave. Analysis of the immune environment showed a strong increase in CD68+ macrophages (16 of 28, 57%) and a borderline lymphocytosis (five of 28, 18%). The stromal microenvironment showed oedema (two of 28, 7%) and severe capillary congestion (one of 28, 4%) in isolated cases. No stromal fibrosis or microvascular thrombosis was found. While all cases had confirmed positive testing of SARS‐CoV‐2 in the respiratory system, SARS‐CoV‐2 was not detected in the bone marrow by high‐sensitivity PCR, suggesting that SARS‐CoV‐2 does not commonly replicate in the haematopoietic microenvironment.ConclusionsSARS‐CoV‐2 infection indirectly impacts the haematological compartment and the bone marrow immune environment. Erythrophagocytosis is frequent and associated with lower haemoglobin levels in patients with severe COVID‐19.

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“…CRP levels of almost all the CCHF cases were within reference limits throughout all time intervals, but median CRP levels in MIS-C cases were low, at 18.7 mg/dL in 1 study ( 41 ) and 19.6 mg/dL in another ( 42 ). Meanwhile, the CRP levels of the MIS-C cases associated with HLH were 7.5–21.9 mg/dL ( 43 ). Combined with a tick-bite history, low CRP levels should raise suspicion of CCHF in pediatric patients with HLH in endemic regions.…”

Section: Discussionmentioning

confidence: 99%

Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey

Oygar¹,

Gürlevik²,

Sag³

et al. 2023

Emerg. Infect. Dis.

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Crimean-Congo hemorrhagic fever (CCHF), endemic in certain regions of the world, is listed as a priority disease with pandemic potential. Since CCHF was first identified in Turkey, children have been known to experience milder disease than adults. However, during the COVID-19 pandemic, we observed an unusually severe disease course, including hemophagocytic lymphohistiocytosis (HLH). We examined cytokine/chemokine profiles of 9/12 case-patients compared with healthy controls at 3 time intervals. Interferon pathway–related cytokines/chemokines, including interleukin (IL) 18, macrophage inflammatory protein 3α, and IL-33, were elevated, but tumor necrosis factor-α, IL-6, CXCL8 (formerly IL-8), and cytokines acting through C-C chemokine receptor 2 and CCR5 were lower among case-patients than controls. Interferon pathway activation and cytokines/chemokines acting through CCR2 and CCR5 improved health results among children with severe CCHF. Children can experience severe CCHF, including HLH, and HLH secondary to CCHF can be successfully treated with intravenous immunoglobulin and steroid therapy.

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Hemophagocytosis in bone marrow aspirates in multisystem inflammatory syndrome in children

Cited by 7 publications

References 9 publications

Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction

Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction

Bone marrow haematopoiesis in patients with COVID‐19

Changing Disease Course of Crimean-Congo Hemorrhagic Fever in Children, Turkey

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