Your work is very inspiring, thank you for sharing!!

A huge thank you to my coauthor Pritha Sen, mentor Chloe Villani, colleague Chris Cosgriff, and the whole COVID-19 Severity team for making this study possible and supporting me all these years. I am very grateful to the hundreds of people who created this opportunity to study disease severity.

While many immunologic abnormalities in acute severe COVID-19 resolve during convalescence 3-months post-infection, we observed persistently high ICOS expression in regulatory T cells, potentially linking acute infection to chronic post-COVID syndromes.

We also identify HLA-DQB1 amino acid positions associated with:
- COVID-19 disease severity
- specific TCRs in CD8 T cells
- viral load
- neutralization capacity of serum

We found that tocilizumab eliminates CLU-expressing MDSCs and ISG-positive myeloid subsets, restores antigen presentation, and reactivates productive adaptive immunity.

In myeloid cells, the mRNA signature of tocilizumab treatment appears inverse to the signature of disease severity.

Severe disease is also linked to autoantibodies targeting type I interferons, influenced by specific HLA-DQB1 allelic variants, and strongly correlated with serum IL-6 levels.

Here is a schematic representation of our findings:

Our findings show that myeloid dysfunction, which is marked by impaired antigen presentation, drives a non-productive adaptive immune response, as reflected by reduced expression of B and T cell gene programs involved in antigen recognition, immune synapse formation, and cytotoxicity.

We analyzed 2.5 million immune cells from 428 patients in three contemporaneous SARS-CoV-2 cohorts:
(1) acutely infected patients across severity levels and time points
(2) patients from a trial to study tocilizumab for COVID-19
(3) convalescent patients three months after infection

"After adjusting for smoking and other risk factors, we observed statistically significant and robust associations between air pollution and mortality."

"Air pollution was positively associated with death from lung cancer and cardiopulmonary disease"

pubmed.ncbi.nlm.nih.gov/8179653/

Could you please share the original links or files for the source data you are using in these figures?

Thank you for sharing! Your work is inspiring.