Elevated Soluble C5b9 Biomarker Found in SARS-CoV-2 Infected Children

Most children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have mild or minimal disease, with a small proportion developing severe disease or multisystem inflammatory syndrome in children (MIS-C).

A small proportion of acutely infected children, typically adolescents with significant comorbidities, develop severe respiratory symptoms requiring hospitalization or admission to the pediatric intensive care unit. High rates of thrombosis and thrombotic-related complications have been reported in adult patients with severe COVID-19.

A multidisciplinary team of medical scientists associated with the Children's Hospital of Philadelphia (Philadelphia, PA, USA) analyzed 50 pediatric patients, hospitalized at the Children’s Hospital of Philadelphia with acute SARS-CoV-2 infection between April 3 and July 7, 2020. Of the patients, 21 had minimal COVID-19 (median age, 13 years), or those with mild COVID-19 symptoms that did not require noninvasive mechanical ventilation, 11 had severe COVID-19 (median age, 15 years), while 18 were diagnosed with MIS-C (median age, 9 years). Additionally, 10% of minimal COVID-19, 36% of severe COVID-19, and 28% of MIS-C patients had evidence of acute kidney injury (AKI).

Blood draws were obtained in conjunction with the first clinical blood draw after consent was obtained, within the first two weeks of the positive SARS-CoV-2 test or admission for MIS-C. For most patients, blood samples were obtained within 48 hours of admission. Ten proinflammatory cytokines were measured (interferon-γ, interleukin IL-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumor necrosis factor-α) using V-Plex Pro-inflammatory Panel 1 Human Kits (Meso Scale Diagnostics, Rockville, MD, USA). Assays were read and analyzed on a Meso Scale Diagnostics QuickPlex SQ120. Plasma samples were assayed for serum C5b9 (sC5b9) at 2 dilutions by using a human C5b9 enzyme-linked immunosorbent assay (ELISA) set (BD Biosciences, San Jose, CA, USA).

The scientists reported that sC5b9 levels were elevated 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 those of 26 healthy control subjects (median, 57 ng/mL; IQR, 9-163 ng/mL). In addition, significantly higher sC5b9 levels were observed in patients with AKI (717 ng/mL; IQR, 404-1232 ng/mL) than in those without AKI (433 ng/mL; IQR, 232-706 ng/mL).

Meanwhile, among patients with severe COVID-19 and MIS-C, sC5b9 did not correlate significantly with markers of inflammation, hemolysis, and coagulopathy, including ferritin, C-reactive protein, LDH, prothrombin time, partial thromboplastin time, fibrinogen, D-dimer, aspartate transaminase, hemoglobin, and platelets. The team retrospectively evaluated a subgroup of 19 patients who had a blood smear, complete blood count, and lactate dehydrogenase level available, 17 (89%) met clinical criteria for thrombotic microangiopathy (TMA).

Caroline Diorio, MD, FRCPC, FAAP, a hematology and oncology specialist and first author of the study, said, “Complement-mediated TMA has been associated with SARS-CoV-2 infection in adults but has not been studied in the pediatric population. SC5b9 is a clinically available biomarker and has been implicated as an indicator of severity in hematopoietic stem cell transplant-associated TMA, as patients with markedly elevated sC5b9 have increased mortality.” The study was published on December 8, 2020 in the journal Blood Advances.

Related Links:
Children's Hospital of Philadelphia
Meso Scale Diagnostics
BD Biosciences