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Authors:Padgett et al.  

Journal/ Pre-PrintBioarchives 

Tags: Bioinformatics, Immunology/Immunity, Inflammation 

Research Highlights 

  1. 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. 

  1. 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. 

  1. 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.  

Summary 

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+ TEMRANon-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 

Study Type  

  • Cohort study 

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 patientsThe 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 

Main limitations:  

  • 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