Differential Redistribution of Activated Monocyte and Dendritic Cell Subsets to the Lung Associates with Severity of COVID-19
cell biology immunology/immunity inflammation
Authors: Sanchez-Cerillo et al
Journal/ Pre-Print: medRxiv
Tags: Immunology/Immunity, Cell Biology, Inflammation
1. Frequencies of various myeloid cells in the blood of COVID patients are lower compared to healthy controls
2. Inflammatory transitional and non-classical (T and NC) monocytes and CD1c+ cDCs preferentially migrate into the lungs in severe COVID patients.
3. Critical patients had enriched frequency of CD38+CXCR5+CD8+ T cells among the total T cells in the lungs and this was negatively correlated with infiltration of inflammatory monocytes
This study characterises myeloid cells and CD8+ T cells in COVID-19 patients (G1-mild, G2-severe and G3-critical) compared to healthy controls. Patient blood shows reduced frequency of classical (C Mo), transitional (T Mo) and non-classical monocytes (NC Mo) and all DC subsets (cDC1+, 141+ cDCs and 123+ pDCs and increased granulocytes (apart from G3, which had decreased frequency). Paired bronchoscopy samples showed enrichment of CD1+ cDCs, T and NC Mo compared to the blood which indicates migration, and associated with increased IL-6, PCT and CRP. However, most abundant cells in the lung were granulocytes. Critical patients had enriched CD38+CXCR5+CD8+ T cell levels in the lungs among the total CD8+ cells.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19. Characterised differences in monocyte infiltration in severe COVID patients compared to mild cases and healthy controls.
Clinical symptoms and pathogenesis of SARS-Cov2/COVID19.
· Patient Case study
Strengths and limitations of the paper
Novelty: Reduced blood frequencies of monocyte subsets and CD1c+DCs paired with examination of bronchoscopies indicates accumulation of these cells in the lungs of COVID19 patients and is associated (particularly monocytes) with disease severity.
Standing in the field: Increased granulocyte frequencies in the patient blood (G1, G2) confirms the existing literature, although critical patients (G3) had lower granulocyte frequency which is somewhat controversial. Decreased frequencies of blood Mo are also at odds with previous reports that find Mo expansion in the blood of COVID patients. Higher Mo frequency in the patient lung compared to blood is in line with the current understanding of COVID19, and higher levels of CCL-2 and -7 were found in the diseased BALF previously supporting the notion of Mo recruitment.
Appropriate statistics: Yes
Viral model used: SARS-CoV-2 (COVID-19 patient study)
· It would have been good to see the correlation of inflammatory monocyte infiltration with neutrophil infiltration into the lung as this is associated with severe disease
· Only frequencies reported, no counts
· Many patients had a bacterial or fungal superinfection in the lung and blood potentially confounding the results
· Patients have been receiving therapy already
· No statistical difference
· Very limited phenotyping to denote T cell exhaustion
· Small sampling