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156 Transient Anti-Interferon Auto Antibodies in the Airway Are Associated with Recovery in Mild COVID-19

Program: Oral and Poster Abstracts
Type: Oral
Session: 203. Lymphocytes and Acquired or Congenital Immunodeficiency Disorders: Decoding the Complex Landscape of Human Immunity: Insights From Genetic Mutations to Cellular Heterogeneity
Hematology Disease Topics & Pathways:
Research, Fundamental Science, autoimmune disorders, adult, assays, Diseases, Immune Disorders, immune mechanism, immunology, Biological Processes, emerging technologies, Technology and Procedures, Study Population, Human, Serologic Tests
Saturday, December 9, 2023: 3:15 PM

Benjamin R Babcock, BS1, Astrid Kosters1*, Nadia R Roan2,3*, Sulggi Lee4,5* and Eliver E.B. Ghosn, PhD6*

1Department of Medicine, Division of Immunology, Lowance Center for Human Immunology, Emory University, Atlanta, GA
2Gladstone Institutes, San Francisco
3Department of Urology, University of California San Francisco, San Francisco
4Zuckerberg San Francisco General Hospital, San Francisco
5Department of Medicine, University of California San Francisco, San Francisco
6Department of Medicine, Division of Immunology, Lowance Center for Human Immunology, Emory Vaccine Center, Emory National Primate Research Center, Emory University, Atlanta, GA

Pre-existing blood anti-interferon autoantibodies have been associated with susceptibility to severe COVID-19. However, nothing is known about the autoantibody response in the airway mucosa of mild to severe COVID-19 patients. We profiled longitudinal samples collected from the airway and matching blood of more than 100 donors over >18 months, spanning from mild COVID-19 to hospitalized patients in the ICU. We found that transiently induced anti-type I interferon autoantibodies in the nasal mucosa are a common feature and are associated with recovery from mild and moderate COVID-19.

To quantify the breadth of antibody response in blood and the airway site of infection, we developed flowBEAT, a novel flow cytometry-based assay capable of simultaneously measuring all 8 human antibody isotypes against 22 SARS-CoV-2 structural and non-structural antigens, including autoantigens. We identified the induction of nasal anti-type I interferon autoantibodies within the first two weeks of infection, waning with disease recovery. Notably, there was an inverse association between nasal and blood anti-interferon responses, while nasal anti-interferon was linked to recovery in cases of mild/moderate disease. In contrast, near-ubiquitous anti-interferon in the endotracheal aspirates of critical cases correlated with heightened airway hyper-inflammation. In both blood and mucosa, anti-interferon positively correlated with a broad anti-viral antibody response, including non-structural proteins. While nasal anti-interferon was universally transient, we identified a group of donors sustaining long-term blood anti-interferon autoantibodies who may be at risk for a more severe subsequent viral infection.

Within our longitudinal cohort, we assessed 500 infected-recovered and vaccinated samples and showed that nasal anti-SARS-CoV-2 antibodies are sustained over 18 months by repeated vaccination and boosting. We identified isotype signatures associated with disease severity and an autoantibody signature predictive of vaccine non-response. Thus, our findings emphasize the importance of continued vaccination/boosting to sustain nasal immunity and help prevent ongoing community spread. More importantly, our studies reveal predictive blood markers of protective nasal immunity and highlight a protective role for nasal anti-interferon autoantibodies in the immunopathology of COVID-19.

Disclosures: No relevant conflicts of interest to declare.

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*signifies non-member of ASH