tetano
Editor, Senior Moderator
Blood Adv
. 2020 Dec 8;4(23):6051-6063.
doi: 10.1182/bloodadvances.2020003471.
Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations
Caroline Diorio[SUP] 1 2 [/SUP], Kevin O McNerney[SUP] 1 2 [/SUP], Michele Lambert[SUP] 1 3 [/SUP], Michele Paessler[SUP] 1 4 [/SUP], Elizabeth M Anderson[SUP] 5 [/SUP], Sarah E Henrickson[SUP] 1 6 [/SUP], Julie Chase[SUP] 1 7 [/SUP], Emily J Liebling[SUP] 7 [/SUP], Chakkapong Burudpakdee[SUP] 1 [/SUP], Jessica H Lee[SUP] 1 [/SUP], Frances B Balamuth[SUP] 8 [/SUP], Allison M Blatz[SUP] 9 [/SUP], Kathleen Chiotos[SUP] 9 10 [/SUP], Julie C Fitzgerald[SUP] 1 10 [/SUP], Therese M Giglia[SUP] 11 [/SUP], Kandace Gollomp[SUP] 1 3 [/SUP], Audrey R Odom John[SUP] 9 [/SUP], Cristina Jasen[SUP] 6 [/SUP], Tomas Leng[SUP] 1 2 [/SUP], Whitney Petrosa[SUP] 1 [/SUP], Laura A Vella[SUP] 9 [/SUP], Char Witmer[SUP] 3 [/SUP], Kathleen E Sullivan[SUP] 1 6 [/SUP], Benjamin L Laskin[SUP] 12 [/SUP], Scott E Hensley[SUP] 5 [/SUP], Hamid Bassiri[SUP] 1 9 [/SUP], Edward M Behrens[SUP] 1 7 [/SUP], David T Teachey[SUP] 1 2 [/SUP]
Affiliations
Abstract
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 patients with 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 children with 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.
. 2020 Dec 8;4(23):6051-6063.
doi: 10.1182/bloodadvances.2020003471.
Evidence of thrombotic microangiopathy in children with SARS-CoV-2 across the spectrum of clinical presentations
Caroline Diorio[SUP] 1 2 [/SUP], Kevin O McNerney[SUP] 1 2 [/SUP], Michele Lambert[SUP] 1 3 [/SUP], Michele Paessler[SUP] 1 4 [/SUP], Elizabeth M Anderson[SUP] 5 [/SUP], Sarah E Henrickson[SUP] 1 6 [/SUP], Julie Chase[SUP] 1 7 [/SUP], Emily J Liebling[SUP] 7 [/SUP], Chakkapong Burudpakdee[SUP] 1 [/SUP], Jessica H Lee[SUP] 1 [/SUP], Frances B Balamuth[SUP] 8 [/SUP], Allison M Blatz[SUP] 9 [/SUP], Kathleen Chiotos[SUP] 9 10 [/SUP], Julie C Fitzgerald[SUP] 1 10 [/SUP], Therese M Giglia[SUP] 11 [/SUP], Kandace Gollomp[SUP] 1 3 [/SUP], Audrey R Odom John[SUP] 9 [/SUP], Cristina Jasen[SUP] 6 [/SUP], Tomas Leng[SUP] 1 2 [/SUP], Whitney Petrosa[SUP] 1 [/SUP], Laura A Vella[SUP] 9 [/SUP], Char Witmer[SUP] 3 [/SUP], Kathleen E Sullivan[SUP] 1 6 [/SUP], Benjamin L Laskin[SUP] 12 [/SUP], Scott E Hensley[SUP] 5 [/SUP], Hamid Bassiri[SUP] 1 9 [/SUP], Edward M Behrens[SUP] 1 7 [/SUP], David T Teachey[SUP] 1 2 [/SUP]
Affiliations
- PMID: 33290544
- DOI: 10.1182/bloodadvances.2020003471
Abstract
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 patients with 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 children with 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.