Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19
By
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 M 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,
Yun S. Song,
Gabriela K. Fragiadakis,
UCSF COMET consortium,
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
Posted 10 Mar 2021
bioRxiv DOI: 10.1101/2021.03.09.434529
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.
Download data
- Downloaded 2,088 times
- Download rankings, all-time:
- Site-wide: 11,163
- In immunology: 429
- Year to date:
- Site-wide: 9,352
- Since beginning of last month:
- Site-wide: 10,246
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!