Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations

被引：97

作者：

Diorio, Caroline ^{[1
,2
]}

McNerney, Kevin O. ^{[1
,2
]}

Lambert, Michele ^{[1
,3
]}

Paessler, Michele ^{[1
,4
]}

Anderson, Elizabeth M. ^{[5
]}

Henrickson, Sarah E. ^{[1
,6
]}

Chase, Julie ^{[1
,7
]}

Liebling, Emily J. ^{[7
]}

Burudpakdee, Chakkapong ^{[1
]}

Lee, Jessica H. ^{[1
]}

Balamuth, Frances B. ^{[8
]}

Blatz, Allison M. ^{[9
]}

Chiotos, Kathleen ^{[9
,10
]}

Fitzgerald, Julie C. ^{[1
,10
]}

Giglia, Therese M. ^{[11
]}

Gollomp, Kandace ^{[1
,3
]}

John, Audrey R. Odom ^{[9
]}

Jasen, Cristina ^{[6
]}

Leng, Tomas ^{[1
,2
]}

Petrosa, Whitney ^{[1
]}

Vella, Laura A. ^{[9
]}

Witmer, Char ^{[3
]}

Sullivan, Kathleen E. ^{[1
,6
]}

Laskin, Benjamin L. ^{[12
]}

Hensley, Scott E. ^{[5
]}

Bassiri, Hamid ^{[1
,9
]}

Behrens, Edward M. ^{[1
,7
]}

Teachey, David T. ^{[1
,2
]}

机构：

[1] Univ Penn, Immune Dysregulat Frontier Program, Childrens Hosp Philadelphia, Dept Pediat,Perelman Sch Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Div Oncol, Childrens Hosp Philadelphia, Dept Pediat,Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Childrens Hosp Philadelphia, Div Hematol, Perelman Sch Med, Philadelphia, PA 19104 USA

[4] Univ Penn, Perelman Sch Med, Dept Pathol, Philadelphia, PA 19104 USA

[5] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Allergy & Immunol,Dept Pediat, Philadelphia, PA 19104 USA

[7] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Rheumatol,Dept Pediat, Philadelphia, PA 19104 USA

[8] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Emergency Med,Dept Pediat, Philadelphia, PA 19104 USA

[9] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Infect Dis,Dept Pediat, Philadelphia, PA 19104 USA

[10] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Crit Care Med,Dept Anesthesiol & Crit Care Me, Philadelphia, PA 19104 USA

[11] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Cardiol,Dept Pediat, Philadelphia, PA 19104 USA

[12] Univ Penn, Perelman Sch Med, Childrens Hosp Philadelphia, Div Nephrol,Dept Pediat, Philadelphia, PA 19104 USA

来源：

BLOOD ADVANCES | 2020年 / 4卷 / 23期

基金：

美国医疗保健研究与质量局; 美国国家卫生研究院;

关键词：

DIAGNOSIS;

D O I：

10.1182/bloodadvances.2020003471

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C). Complement-mediated thrombotic microangiopathy (TMA) has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. We hypothesized that complement activation plays an important role in SARS-CoV-2 infection in children and sought to understand if TMA was present in these patients. We enrolled 50 hospitalized pediatric patientswith acute SARS-CoV-2 infection (n = 21, minimal coronavirus disease 2019 [COVID-19]; n = 11, severe COVID-19) or MIS-C (n = 18). As a biomarker of complement activation and TMA, soluble C5b9 (sC5b9, normal 247 ng/mL) was measured in plasma, and elevations were found in patients with minimal disease (median, 392 ng/mL; interquartile range [IQR], 244-622 ng/mL), severe disease (median, 646 ng/mL; IQR, 203-728 ng/mL), and MIS-C (median, 630 ng/mL; IQR, 359-932 ng/mL) compared with 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL; P < .001). Higher sC5b9 levels were associated with higher serum creatinine (P = .01) but not age. Of the 19 patients for whom complete clinical criteria were available, 17 (89%) met criteria for TMA. A high proportion of tested children with SARS-CoV-2 infection had evidence of complement activation and met clinical and diagnostic criteria for TMA. Future studies are needed to determine if hospitalized childrenwith SARS-CoV-2 should be screened for TMA, if TMA-directed management is helpful, and if there are any short- or long-term clinical consequences of complement activation and endothelial damage in children with COVID-19 or MIS-C.

引用

页码：6051 / 6063

页数：13

共 42 条

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