PT  - JOURNAL ARTICLE
AU  - Monique G.P. van der Wijst
AU  - Sara E. Vazquez
AU  - George C. Hartoularos
AU  - Paul Bastard
AU  - Tianna Grant
AU  - Raymund Bueno
AU  - David S. Lee
AU  - John R. Greenland
AU  - Yang Sun
AU  - Richard Perez
AU  - Anton Ogorodnikov
AU  - Alyssa Ward
AU  - Sabrina A. Mann
AU  - Kara L. Lynch
AU  - Cassandra Yun
AU  - Diane V. Havlir
AU  - Gabriel Chamie
AU  - Carina Marquez
AU  - Bryan Greenhouse
AU  - Michail S. Lionakis
AU  - Philip J. Norris
AU  - Larry J. Dumont
AU  - Kathleen Kelly
AU  - Peng Zhang
AU  - Qian Zhang
AU  - Adrian Gervais
AU  - Tom Le Voyer
AU  - Alexander Whatley
AU  - Yichen Si
AU  - Ashley Byrne
AU  - Alexis J. Combes
AU  - Arjun Arkal Rao
AU  - Yun S. Song
AU  - UCSF COMET consortium
AU  - Gabriela K. Fragiadakis
AU  - Kirsten Kangelaris
AU  - Carolyn S. Calfee
AU  - David J. Erle
AU  - Carolyn Hendrickson
AU  - Matthew F. Krummel
AU  - Prescott G. Woodruff
AU  - Charles R. Langelier
AU  - Jean-Laurent Casanova
AU  - Joseph L. Derisi
AU  - Mark S. Anderson
AU  - Chun Jimmie Ye
TI  - Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19
AID  - 10.1101/2021.03.09.434529
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.09.434529
4099  - http://biorxiv.org/content/early/2021/03/10/2021.03.09.434529.short
4100  - http://biorxiv.org/content/early/2021/03/10/2021.03.09.434529.full
AB  - 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.Competing Interest StatementJ.R.G. has consulted for Boehringer Ingelheim and has consulted for and received research support from Theravance Biopharma, Inc. J.L.D. is a SAB member for The Public Health Company, and a consultant for Allen & Company. C.J.Y. is a SAB member for and hold equity in Related Sciences and ImmunAI, a consultant for and hold equity in Maze Therapeutics, and a consultant for TRex Bio. C.J.Y. has received research support from Chan Zuckerberg Initiative, Chan Zuckerberg Biohub and Genentech.