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Longitudinal single-cell epitope and RNA-sequencing reveals the immunological impact of type 1 interferon autoantibodies in critical COVID-19: Anti-IFN antibodies in critical COVID-19 correlate with poor ISG response and upregulation of LAIR1 surface protein in PBMCs #MMPMID33758859
van der Wijst MGP; Vazquez SE; Hartoularos GC; Bastard P; Grant T; Bueno R; Lee DS; Greenland JR; Sun Y; Perez R; Ogorodnikov A; Ward A; Mann SA; Lynch KL; Yun C; Havlir DV; Chamie G; Marquez C; Greenhouse B; Lionakis MS; Norris PJ; Dumont LJ; Kelly K; Zhang P; Zhang Q; Gervais A; Le Voyer T; Whatley A; Si Y; Byrne A; Combes AJ; Rao AA; Song YS; Fragiadakis GK; Kangelaris K; Calfee CS; Erle DJ; Hendrickson C; Krummel MF; Woodruff PG; Langelier CR; Casanova JL; Derisi JL; Anderson MS; Ye CJ
bioRxiv 2021[Mar]; ä (ä): ä PMID33758859show ga
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.