The blood levels of ORF8 protein in COVID-19 patients correlate with the disease outcome, and the ORF8/NLRP3 axis is targetable with NLRP3 inhibitor MCC950
(A) Representative western blot images showing ORF8 protein but not NSP9 or NSP10 were detectable in as little as 4.0 μL of serum samples from newly infected COVID-19 patients. ORF8 protein in patient sera shown as glycosylated by size estimation.
(B) Kaplan-Meier curve showing fatality in hospitalized patients is associated with higher serum level of ORF8. p=0.0146.
(C) Western images showing ORF8 levels at different time points correlate with disease course in two patients with prolonged clinical courses, and in one patient with long-covid.
(D) Targetability of ORF8 mediated IL1β expression with various NLRP3 inhibitors in THP1 cells and human primary PBMCs. The data shown are representative of three independent experiments. Abbreviations: Dx = diagnosis; ED = emergency department; ICU = intensive care unit.