Interplay of Monocytes and T Lymphocytes in COVID-19 Severity
bioinformatics immunology/immunity inflammation
Authors:Padgett et al.
Journal/ Pre-Print: Bioarchives
Tags: Bioinformatics, Immunology/Immunity, Inflammation
This study examined convalescent COVID-19 patients using an in depth 41 marker CyTOF panel. Intermediate and non-classical monocytes together with CD4 stem cell memory (TSCM) correlated with severity during the illness, coagulation factor levels, and/or inflammatory indicators.
Non-classical monocytes clustered in two groups distinguished by the expression of a sugar residue (Slan), Slanlo was depleted in hospitalised patients, while Slanhi increased with disease severity and was linked to CD4+ T effector memory (TEM) cell frequencies, coagulation factors, and inflammatory indicators.
Intermediate monocytes tightly correlated with T cell subsets that delineate disease severity; loss of naive T cells and an increased abundance of effector memory T cells expressing the exhaustion marker PD-1.
Padgett et al. aimed to characterise the interplay between the myeloid and T cell compartments by CyTOF in PBMCs from 30 convalescent COVID-19 patients stratified by their previous illness severity. Most classical monocytes were found to increase with disease severity but not linked to any clinical parameter. Intermediate monocytes showed the strongest correlation with T cell subsets that delineated disease severity, loss of naïve T cells and increase of CD4+ TEMRA. Non-classical monocytes clustered in two groups distinguished by the expression of a sugar residue (6-Sulfo LacNac (Slan)). Slanlo was depleted in hospitalised patients, while Slanhi subset increased with disease severity and was linked to CD4+ T effector memory (TEM) cell frequencies, coagulation factors, and inflammatory indicators. Also, it showed increased expression of HLA-DR, CD45RA, PDL1 and PD-L2; which the authors associated to the inability to mount an effective immune response and to contribute to T cell exhaustion. In the T cell compartment, CD4+ TSCM was the sole differentially-expressed subset between moderate and severe and Th1 subset appeared lost in moderate disease. CD8+ TSCM cell frequencies were reduced in moderate versus severe although non-significantly. The authors suggest that both intermediate and non-classical monocyte subsets shape the adaptive immune response to SARS-CoV-2.
Impact for SARS-CoV2/COVID19 research efforts
Understand the immune response to SARS-CoV2/COVID19 by examining the immune phenotype in the peripheral blood of convalescent patients
Strengths and limitations of the paper
Novelty: The study interrogates the immunoprofile for non-classical and intermediate monocytes in relation to T cells in the development of the adaptive immune response in convalescent COVID-19 patients. The data on nMo2 monocytes may be relevant for understanding the coagulopathy that develops with COVID-19.
Standing in the field:In line with current literature
Appropriate statistics: Yes
Viral model used:N/A. PBMCs from clinical samples from SARS-CoV-2-infected individuals
Translatability:This study does not aim for translatability
The role of the innate response is key to mounting a specific response during the acute infection and this study evaluates monocytes in convalescent patients
The mild group has a significantly lower age (as expected) which may bias the immune phenotype which is known to change with age
DCs and NK cells are not discussed