Description Type I interferon autoantibodies in patients with COVID-19 are associated with poor interferon responses and increased LAIR1 abundance in leukocytes. Interfering with interferons A subset of patients diagnosed with coronavirus disease 2019 (COVID-19) present with autoantibodies specific to type I interferons (IFNs). However, the systemic impacts of type I IFN–specific autoantibodies are not fully understood. Here, van der Wijst et al. longitudinally evaluated the relationship between type I IFN–specific autoantibody abundance and changes to the immune system of individuals with COVID-19. Using single-cell transcriptomics, the authors found that the presence of type I IFN autoantibodies correlated with reduced type I IFN–stimulated gene (ISG) expression in patients with critical COVID-19. Reduced ISG expression, in turn, correlated with increased expression of the inhibitory receptor, leukocyte-associated immunoglobulin-like receptor 1 (LAIR1), on monocytes. Together, these findings suggest that early evidence of type I IFN autoantibodies and increased LAIR1 expression may help distinguish severe cases of COVID-19. Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.
【초록키워드】 COVID-19, coronavirus disease, Transcriptome, Monocytes, antibodies, SARS-CoV-2, Coronavirus disease 2019, Single-cell transcriptomics, coronavirus, severity, transcriptomics, myeloid cells, interferons, interferon, immune system, severe acute respiratory syndrome Coronavirus, type I interferon, Population, monocyte, Peripheral blood, Prevalence, Immunoglobulin, autoantibodies, response, Patient, Peripheral blood mononuclear cells, Control, severe cases, type I interferons, mechanisms, receptor, respiratory, epitope, longitudinal, expression, interferon response, change, Critical, single-cell, IFNs, dendritic cell, transcriptome sequencing, ISG, Critical disease, leukocytes, Evidence, severe disease, Type I IFN, autoantibody, mononuclear cells, evidence of, in some, leukocyte, mononuclear cell, Support, disease pathogenesis, acute respiratory syndrome, increased expression, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, moderate disease, type I, individual, disease course, help, Severe case, systemic impact, healthy controls, peripheral blood samples, description, myeloid cell, circulating leukocytes, inhibitory receptor, LAIR1, systemic impacts, Effect, Course, lack, caused, diagnosed, the disease, evaluated, elevated, reduced, functional, expressed, correlated, producing, Type, subset, turn, circulating leukocyte, individuals with COVID-19, patients with COVID-19, 【제목키워드】 immune, autoantibody, alteration, Type, patients with COVID-19,