Clonal dynamics of SARS-CoV-2-specific T cells in children and adults with COVID-19

Children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop less severe coronavirus disease 2019 (COVID-19) than adults. The mechanisms for the age-specific differences and the implications for infection-induced immunity are beginning to be uncovered. We show by longitudinal multimodal analysis that SARS-CoV-2 leaves a small footprint in the circulating T cell compartment in children with mild/asymptomatic COVID-19 compared to adult household contacts with the same disease severity who had more evidence of systemic T cell interferon activation, cytotoxicity and exhaustion. Children harbored diverse polyclonal SARS-CoV- 2-specific naive T cells whereas adults harbored clonally expanded SARS-CoV-2-specific memory T cells. More naive interferon-activated CD4+ T cells were recruited into the memory compartment and recovery was associated with the development of robust CD4+ memory T cell responses in adults but not children. These data suggest that rapid clearance of SARS-CoV-2 in children may compromise their cellular immunity and ability to resist reinfection. HIGHLIGHTSO_LIChildren have diverse polyclonal SARS-CoV-2-specific naive T cells C_LIO_LIAdults have clonally expanded exhausted SARS-CoV-2-specific memory T cells C_LIO_LIInterferon-activated naive T cells differentiate into memory T cells in adults but not children C_LIO_LIAdults but not children develop robust memory T cell responses to SARS-CoV-2 C_LI O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/478400v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@e9586org.highwire.dtl.DTLVardef@17aaf37org.highwire.dtl.DTLVardef@18575e0org.highwire.dtl.DTLVardef@fde4ae_HPS_FORMAT_FIGEXP M_FIG C_FIG

No evidence that plasmablasts transdifferentiate into developing neutrophils in severe COVID-19 disease

A recent study by Wilk et al. of the transcriptome of peripheral blood mononuclear cells (PBMCs) in seven patients hospitalized with COVID-19 described a population of "developing neutrophils" that were "phenotypically related by dimensionality reduction" to plasmablasts, and that these two cell populations represent a "linear continuum of cellular phenotype"1. The authors suggest that, in the setting of acute respiratory distress syndrome (ARDS) secondary to severe COVID-19, a "differentiation bridge from plasmablasts to developing neutrophils" connected these distantly related cell types. This conclusion is controversial as it appears to violate several basic principles in cell biology relating to cell lineage identity and fidelity. Correctly classifying cells and their developmental history is an important issue in cell biology and we suggest that this conclusion is not supported by the data as we show here that: (1) regressing out covariates such as unique molecular identifiers (UMIs) can lead to overfitting; and (2) that UMAP embeddings may reflect the expression of similar genes but not necessarily direct cell lineage relationships.