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COVID-19 is a current global health threat caused by the novel coronavirus SARS-CoV-2. Emerging evidence indicates that SARS-CoV-2 elicits a dysregulated immune response and a delayed interferons (IFNs) expression in patients, which contribute largely to the viral pathogenesis and development of COVID-19. However, underlying mechanisms remain to be elucidated. Here, we report the activation and repression of innate immune response by SARS-CoV-2. We show that SARS-CoV-2 RNA activates the RIG-I-MAVS-dependent IFN signaling pathway. We further uncover that ORF9b immediately accumulates and antagonizes the antiviral type I IFN response during SARS-CoV-2 infection on primary human pulmonary alveolar epithelial cells. ORF9b targets the NF-κB essential modulator NEMO and interrupts its K63-linked polyubiquitination upon viral stimulation, thereby inhibiting the canonical IKKα/β/γ-NF-κB signaling and subsequent IFN production. Our findings thus unveil the innate immunosuppression by ORF9b, and provide insights into the host-virus interplay during the early stage of SARS-CoV-2 infection.

Purpose To examine how demographic and geographic variations in US populations from 2011 to 2050 will contribute to estimated numbers of primary open-angle glaucoma (POAG). Design Cross-sectional study Methods Prevalence rates from selected population-based studies were used to estimate the number of persons aged 40 years and older with POAG in the US. For calculation, the age-, sex-, race/ethnicity-specific prevalence rates were multiplied by the US census estimates and projections from 2011–2050. Main outcome measures are estimated numbers of persons with POAG in different age, sex and racial/ethnic groups and total and per-capita POAG rates by state. Results In 2011, 2.71 million persons in the US have POAG, with the highest estimated number among populations aged 70–79 years (31%), women (53%), and non-Hispanic white (44%). The largest demographic group is non-Hispanic white women. In 2050, an estimated 7.32 million persons will have POAG; with the highest number among populations aged 70–79 years (32%), women (50%), and Hispanics (50%). The largest demographic group will shift to Hispanic men. During the next 40 years, the highest per capita POAG rates will double in New Mexico, Texas, and Florida. Conclusions Despite the high prevalence of POAG in African Americans and Hispanics, the largest group in the US is currently among older non-Hispanic white women but is expected to shift to Hispanic men over the next few decades. Given this shift, the greatest yield from screening programs is likely to be in those states with high numbers of non-Hispanic white women and Hispanic men.