COVID-19 severity associates with pulmonary redistribution of CD1c+ DC and inflammatory transitional and nonclassical monocytes
Cardiff University review immunology/immunity
First Author: Ildefonso Sánchez-Cerrillo
Journal/preprint name: The Journal of Clinical Investigation
Paper DOI: 10.1172/JCI140335
Tags: acute respiratory distress syndrome, myeloid cells, DCs
Summary
The authors investigate myeloid cell populations in COVID-19, linking certain monocyte and DC subsets with disease progression. They suggest that increased levels of transitional monocytes in peripheral blood could be a marker of mild disease, while decreases in transitional and non classical monocytes as well as CD1c+ DCs could be associated with severe disease.
The authors further point out potential differences in myeloid cell activation status and a link between increased lung infiltration with inflammatory transitional and non classical monocytes/CD1c+ cDCs and decreased effector CXCR5+CD38+CD8+T cells in the lungs of critical patients.
Research Highlights
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COVID19 is associated with reductions in almost all myeloid subsets compared to healthy controls
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Inflammatory transitional (CD14+CD16+) monocytes are increased in mild patients compared to healthy controls but deceased in severe and critical patients
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Depletion of classical and transitional monocytes from the blood as observed in severe and critical patients correlates with high plasma levels of inflammatory markers (PCT, CRP, IL-6)
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Expression of the maturation marker CD40 is decreased in all monocyte subsets in peripheral blood of critical patients
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In critical patients, transitional and non classical monocytes as well as CD1c+cDCs are enriched in the lungs, expressing higher CD40 than those circulating in the blood
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High ratios of inflammatory transitional and non classical monocytes /CD1c+ cDCs are negatively associated with proportions of CXCR5+CD38+CD8+T cells in the lungs of critical patients
Impact for COVID-19 research:
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At this point it is unclear whether myeloid dysregulation drives severity or is an effect of superinfection. If levels of myeloid cells are found to be dysregulated early in COVID-19 infection, this could be useful for early detection of severe disease.
Methodologies:
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Study Type: cross-sectional comparison of healthy individuals, mild, severe and critical COVID-19 patients
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Key Techniques: analysis of peripheral blood samples from all participants, bronchoscopy samples from critical patients
Limitations:
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Samples were not time matched, which is difficult since severe symptoms develop late when mild patients would already be recovering
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Between 80.95% and 100% of critical patients displayed microbial superinfection at the time of sample collection, it would be interesting to know whether changes in myeloid cell populations are due to superinfections or severe COVID-19 alone
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Most patients were on various kinds of treatments that could potentially affect myeloid populations differently
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Lung samples were only taken from critical patients, it would have been interesting to compare lung infiltrates between the different severity groups