COVID-19 severity associates with pulmonary redistribution of CD1c+ DC and inflammatory transitional and nonclassical monocytes

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 

1. COVID19 is associated with reductions in almost all myeloid subsets compared to healthy controls 

2. Inflammatory transitional (CD14+CD16+) monocytes are increased in mild patients compared to healthy controls but deceased in severe and critical patients 

3. 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)  

4. Expression of the maturation marker CD40 is decreased in all monocyte subsets in peripheral blood of critical patients 

5. 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 

6. 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:  

• 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: 

• Study Type: cross-sectional comparison of healthy individuals, mild, severe and critical COVID-19 patients 

• Key Techniques: analysis of peripheral blood samples from all participants, bronchoscopy samples from critical patients  

Limitations: 

• Samples were not time matched, which is difficult since severe symptoms develop late when mild patients would already be recovering 

• 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 

• Most patients were on various kinds of treatments that could potentially affect myeloid populations differently  

• Lung samples were only taken from critical patients, it would have been interesting to compare lung infiltrates between the different severity groups