SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19

Anderson, Elizabeth M.; Diorio, Caroline; Goodwin, Eileen; McNerney, Kevin O.; Weirick, Madison E.; Gouma, Sigrid; Bolton, Marcus J.; Arevalo, Claudia P.; Chase, Julie; Hicks, Philip; Manzoni, Tomaz B.; Baxter, Amy E.; Andrea, Kurt P; Burudpakdee, Chakkapong; Lee, Jessica H.; Vella, Laura A.; Henrickson, Sarah E.; Harris, Rebecca M.; Wherry, E. John; Bates, Paul; Bassiri, Hamid; Behrens, Edward M.; Teachey, David T.; Hensley, Scott E.

doi:10.1101/2020.08.17.20176552

Cited by 28 publications

(45 citation statements)

References 15 publications

(25 reference statements)

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“…The latter would be consistent with the variable antibody responses now determined for the spectrum of pediatric disease [44]. For EIA-based antibody studies otherwise, we have learned so far that the type and severity of disease and age may have bearing on the quality and quantity of antibody responses [34,[45][46][47][48]. Gender may also possibly affect antibody responses or other relevant immune responses [34,49].…”

Section: Provisional Acceptance Of What Constitutes Immunitysupporting

confidence: 63%

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Cimolai

2020

SN Compr. Clin. Med.

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Until either efficacious therapy or vaccination for COVID-19 is achieved, there will be a need to regain world economic stability while yet controlling the pandemic with current approaches. For those infected thus far, there is a prevailing perspective that devising recognition for protective immunity will progressively allow segments of society to return to some functionality more than is existing. At this time, the best correlates with protection from natural coronavirus infections are systemic neutralizing antibody and mucosal IgA. Serum neutralizing antibody more easily fulfills the latter requisite, but current live virus methods for neutralization prevent large-scale application. It is conceivable that the exposure of previously infected individuals can allow for the definition of protective thresholds of neutralizing antibody. Thereafter, many other antibody assays will be able to screen for surrogate protection after correlations with protective neutralizing antibody are made. Specificity of common antibody tests would benefit from confirmatory blocking systems or confirmatory immunoblotting fingerprints with well-defined antigen(s). The opportunity for the scientific community to make these assessments is evident in the current context of the COVID-19 epidemic given the large numbers of infected individuals worldwide. Such information will also be vital to guide vaccine development and/or immunotherapy.

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Section: Provisional Acceptance Of What Constitutes Immunitysupporting

confidence: 63%

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Cimolai

2020

SN Compr. Clin. Med.

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“…In the United States, almost all MIS-C patients are seropositive for SARS-CoV-2 specific antibodies, consistent with a delayed clinical presentation compared to acute SARS-CoV-2 infection 40,[108][109][110] . Both pediatric COVID-19 and MIS-C had similar frequencies of naive B cells, CD27-IgD-B cells, non-switched memory, and switched memory B cells (Fig S5A-C).…”

Section: Humoral Immunity In Mis-c Is Dysregulatedmentioning

confidence: 84%

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

Vella

Giles

Baxter

et al. 2020

Preprint

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111

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Pediatric COVID-19 following SARS-CoV-2 infection is associated with fewer hospitalizations and often milder disease than in adults. A subset of children, however, present with Multisystem Inflammatory Syndrome in Children (MIS-C) that can lead to vascular complications and shock, but rarely death. The immune features of MIS-C compared to pediatric COVID-19 or adult disease remain poorly understood. We analyzed peripheral blood immune responses in hospitalized SARS-CoV-2 infected pediatric patients (pediatric COVID-19) and patients with MIS-C. MIS-C patients had patterns of T cell-biased lymphopenia and T cell activation similar to severely ill adults, and all patients with MIS-C had SARS-CoV-2 spike-specific antibodies at admission. A distinct feature of MIS-C patients was robust activation of vascular patrolling CX3CR1+ CD8 T cells that correlated with use of vasoactive medication. Finally, whereas pediatric COVID-19 patients with acute respiratory distress syndrome (ARDS) had sustained immune activation, MIS-C patients displayed clinical improvement over time, concomitant with decreasing immune activation. Thus, non-MIS-C versus MIS-C SARS-CoV-2 associated illnesses are characterized by divergent immune signatures that are temporally distinct and implicate CD8 T cells in clinical presentation and trajectory of MIS-C.

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“…Of particular interest to TMA is the neutrophil chemotactic factor IL-8, due to its role as a marker of endothelial damage. 31…”

Section: Proinflammatory Cytokine Profilingmentioning

confidence: 99%

“…30 We previously showed that most patients, and specifically patients with MIS-C, had elevations in anti-SARS-CoV-2 antibody titers. 31 We considered whether sC5b9 elevations may be related to classical pathway activation from antiviral antibody-antigen complexes rather than the alternative complement activation of TMA. SARS-CoV-2-specific antibodies were measured by using ELISA as previously described.…”

Section: Sars-cov-2-specific Antibodiesmentioning

confidence: 99%

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

Diorio¹,

McNerney²,

et al. 2020

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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.

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SARS-CoV-2 antibody responses in children with MIS-C and mild and severe COVID-19

Cited by 28 publications

References 15 publications

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

A Minimalist Strategy Towards Temporarily Defining Protection for COVID-19

Deep Immune Profiling of MIS-C demonstrates marked but transient immune activation compared to adult and pediatric COVID-19

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

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