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

• DOI: 10.1101/2021.03.09.434529
• Publication Date: 2021-03-10T22:45:14Z
• Authors: Monique G.P. van ...; Sara E. Vazquez; George C. Hartoul...; 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. Fragi...; Kirsten Kangelaris; Carolyn S. Calfee; David J. Erle; Carolyn Hendrickson; Matthew F. Krummel; Prescott G. Woodruff; Charles R. Langelier; Jean-Laurent Casa...; Joseph L. Derisi; Mark S. Anderson; Chun Jimmie Ye
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

AbstractType 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.