Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19.

Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19.

bioRxiv : the preprint server for biology (2021-03-25)

Monique G P van der Wijst, Sara E Vazquez, George C Hartoularos, Paul Bastard, Tianna Grant, Raymund Bueno, David S Lee, John R Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Sabrina A Mann, Kara L Lynch, Cassandra Yun, Diane V Havlir, Gabriel Chamie, Carina Marquez, Bryan Greenhouse, Michail S Lionakis, Philip J Norris, Larry J Dumont, Kathleen Kelly, Peng Zhang, Qian Zhang, Adrian Gervais, Tom Le Voyer, Alexander Whatley, Yichen Si, Ashley Byrne, Alexis J Combes, Arjun Arkal Rao, Yun S Song, Gabriela K Fragiadakis, Kirsten Kangelaris, Carolyn S Calfee, David J Erle, Carolyn Hendrickson, Matthew F Krummel, Prescott G Woodruff, Charles R Langelier, Jean-Laurent Casanova, Joseph L Derisi, Mark S Anderson, Chun Jimmie Ye

PMID33758859

摘要

Type I interferon (IFN-I) neutralizing autoantibodies have been found in some critical COVID-19 patients; however, their prevalence and longitudinal dynamics across the disease severity scale, and functional effects on circulating leukocytes remain unknown. Here, in 284 COVID-19 patients, we found IFN-I autoantibodies in 19% of critical, 6% of severe and none of the moderate cases. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 COVID-19 patients, 15 non-COVID-19 patients and 11 non-hospitalized healthy controls, revealed a lack of IFN-I stimulated gene (ISG-I) response in myeloid cells from critical cases, including those producing anti-IFN-I autoantibodies. Moreover, surface protein analysis showed an inverse correlation of the inhibitory receptor LAIR-1 with ISG-I expression response early in the disease course. This aberrant ISG-I response in critical patients with and without IFN-I autoantibodies, supports a unifying model for disease pathogenesis involving ISG-I suppression via convergent mechanisms.