Sera containing anti – IFN-I antibodies neutralize IFN-α2 antiviral activity in a reconstituted HAE model of SARS-CoV-2 infection. The effect of APS-1 serum was evaluated in an HAE model of SARS-CoV-2 infection.(A) Nasal HAEs were treated (24 h before and 1 h after SARS-CoV-2 infection) with recombinant IFN-α2 in the presence or absence of APS-1 patient or control serum, as indicated. Apical washes were performed 54 hpi, and viral titers were determined by RT-PCR. Results are representative of three biological replicates and expressed as relative to the mock-treated control. (B) Apical infectious viral titers 54 hpi determined by TCID50 (median tissue culture infectious dose). The dotted line depicts the limit of detection. (C) Relative TEER (Δ TEER) between t = 0 and t = 54 hpi. (D) Relative expression ofIFI44L assessed using FilmArray technology from total cellular RNA extracted after infection. In the figure, bars and error bars represent mean and SD, respectively. A Kruskal–Wallis with uncorrected Dunn’s test was used for statistical analysis of data presented in this figure (multiple comparisons; *, P < 0.05; **, P <0.01; ***, P < 0.001). In A, B, and D, the reference condition was SARS-CoV-2 alone (white bars), and in C, the reference was the mock condition (beige bars).