Myeloid-Derived Suppressor Cells and Clinical Outcomes in Children With COVID-19

Abstract

BackgroundAlthough children with COVID-19 account for fewer hospitalizations than adults, many develop severe disease requiring intensive care treatment. Critical illness due to COVID-19 has been associated with lymphopenia and functional immune suppression. Myeloid-derived suppressor cells (MDSCs) potently suppress T cells and are significantly increased in adults with severe COVID-19. The role of MDSCs in the immune response of children with COVID-19 is unknown.AimsWe hypothesized that children with severe COVID-19 will have expansion of MDSC populations compared to those with milder disease, and that higher proportions of MDSCs will correlate with clinical outcomes.MethodsWe conducted a prospective, observational study on a convenience sample of children hospitalized with PCR-confirmed COVID-19 and pre-pandemic, uninfected healthy controls (HC). Blood samples were obtained within 48 h of admission and analyzed for MDSCs, T cells, and natural killer (NK) cells by flow cytometry. Demographic information and clinical outcomes were obtained from the electronic medical record and a dedicated survey built for this study.ResultsFifty children admitted to the hospital were enrolled; 28 diagnosed with symptomatic COVID-19 (10 requiring ICU admission) and 22 detected by universal screening (6 requiring ICU admission). We found that children with severe COVID-19 had a significantly higher percentage of MDSCs than those admitted to the ward and uninfected healthy controls. Increased percentages of MDSCs in peripheral blood mononuclear cells (PBMC) were associated with CD4+ T cell lymphopenia. MDSC expansion was associated with longer hospitalizations and need for respiratory support in children admitted with acute COVID-19.ConclusionThese findings suggest that MDSCs are part of the dysregulated immune responses observed in children with severe COVID-19 and may play a role in disease pathogenesis. Future mechanistic studies are required to further understand the function of MDSCs in the setting of SARS-CoV-2 infection in children.

Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies

“…These findings suggest that persistent SARS-CoV-2 antigenaemia can trigger hyperinflammatory presentation during multi-system inflammatory syndrome in children 57 and, as a consequence, possibly also in long COVID. This hypothesis is coherent with observation of myeloid-derived suppressor cells as part of the dysregulated immune responses observed in children with severe COVID-19, 58 in other inflammatory conditions and viral respiratory infections, 59 and also detected in mild and asymptomatic COVID-19 convalescents. 60 …”

Dapsone Lowers Neutrophil to Lymphocyte Ratio and Mortality in COVID-19 Patients Admitted to the ICU

“…MDSC numbers and immune suppressive activity increase in direct proportion to the NLR and become an important immunosuppressive element during severe COVID-19 [ 33 , 34 , 35 , 36 , 37 , 38 ]. Absolute neutrophil numbers and the NLR exist and function within a neutrophil-centered interacting multi-component inflammation system.…”