Abstract
BackgroundSARS-CoV-2 infection in children can present with varied clinical phenotypes and understanding the pathogenesis is essential, to inform about the clinical trajectory and management. MethodsWe performed a multiplex immune assay analysis and compared the plasma biomarkers of Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), acute COVID-19 infection (COVID-19), SARS-CoV-2 seropositive and control children admitted to a tertiary care children's hospital in Chennai, India. Pro-inflammatory cytokines, chemokines and growth factors were correlated with SARS-CoV-2 clinical phenotypes. FindingsPIMS-TS children had significantly elevated levels of cytokines, IFNγ, IL-2, TNFα, IL-1α, IFNα, IFNβ, IL-6, IL-15, IL-17A, GM-CSF, IL-10, IL-33 and IL-Ra; elevated chemokines, CCL2, CCL19, CCL20 and CXCL10 and elevated VEGF, Granzyme B and PDL-1 in comparison to COVID-19, seropositive and controls. COVID-19 children had elevated levels of IFNγ, IL-2, TNFα, IL-1α, IFNα, IFNβ, IL-6, IL-17A, IL-10, CCL2, CCL5, CCL11, CXCL10 and VEGF in comparison to seropositive and/or controls. Similarly, seropositive children had elevated levels of IFNγ, IL-2, IL-1α, IFNβ, IL-17A, IL-10, CCL5 and CXCL10 in comparison to control children. Plasma biomarkers in PIMS-TS and COVID-19 children showed a positive correlation with CRP and a negative correlation with the lymphocyte count and sodium levels. InterpretationWe describe a comprehensive plasma biomarker profile of children with different clinical spectrum of SARS-CoV-2 infection from a low- and middle-income country (LMIC) and observed that PIMS-TS is a distinct and unique immunopathogenic paediatric illness related to SARS-CoV-2 presenting with cytokine storm different from acute COVID-19 infection and other hyperinflammatory conditions.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children has generally been a mild or asymptomatic illness compared with adults [1]
To our knowledge this is the first study from a low- and middle-income countries (LMIC) setting describing the plasma biomarker profile of children with different clinical spectrum of SARS-CoV-2 infection namely PIMS-TS, acute COVID-19 infection and asymptomatic seropositive
We describe the immune profile of children presenting with different spectrum of SARS-CoV-2 infection, ranging from acute COVID19 disease to PIMS-TS, and identify immune biomarkers that could help differentiate the varied presentation of infection
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children has generally been a mild or asymptomatic illness compared with adults [1]. Understanding the pathogenesis is essential to help understand the differences and similarities between different clinical phenotypes and to inform about the clinical trajectory, so that optimal and effective treatment can be delivered. To our knowledge this is the first study from a LMIC setting describing the plasma biomarker profile of children with different clinical spectrum of SARS-CoV-2 infection namely PIMS-TS, acute COVID-19 infection and asymptomatic seropositive. Methods: We performed a multiplex immune assay analysis and compared the plasma biomarkers of Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), acute COVID-19 infection (COVID-19), SARS-CoV-2 seropositive and control children admitted to a tertiary care children’s hospital in Chennai, India. Pro-inflammatory cytokines, chemokines and growth factors were correlated with SARS-CoV-2 clinical phenotypes
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