Figure 4. SARS-CoV-2 escapes immune surveillance through the DNAM1 paired receptor pathway.

(A) Killing efficiency of SARS-CoV-2–infected Calu-1 cells by primary NK cells with or without TIGIT-Fc from 2 independent experiments (n = 6). Maximums, 75th, 50th, 25th percentiles and minimums for TIGIT-Fc alone were 11.40, 10.43, 7.50, 6.10, 4.90; for NK cells alone were 10.70, 10.48, 8.10, 4.50, 2.40; and for NK cells with TIGIT-Fc were 18.10, 17.28, 14.20, 10.88, 9.60, respectively. P = 0.0130 between TIGIT-Fc alone and NK cells with TIGIT-Fc and P = 0.0076 between NK cells alone and NK cells with TIGIT-Fc; Tukey’s multiple comparison test. (B) Box-and-whisker plots of relative CD155 protein (left) and peptide (right) levels in control sera, sera from patients with mild COVID-19, and sera from patients with severe COVID-19. Maximums, 75th, 50th, 25th percentiles and minimums for control, mild COVID-19, and severe COVID-19 in the protein data set were 0.31, –0.07, –0.23, –0.33, and –0.75; 0.18, 0.02, –0.13, –0.25, and –0.59; and 0.45, 0.33, 0.21, –0.09, and –0.21, respectively (n = 72). Values in the peptide data set were 0.61, 0.27, –0.10, –0.27, and –0.58; 0.87, 0.11, –0.11, –0.20, and –0.44; and 1.09, 0.47, 0.30, 0.08, and –0.21, respectively (n = 61). P = 1.03 × 10^–5 for protein data set and P = 0.00364 for peptide data set; linear regression. (C) Histogram overlays of percentage of the maximum events for DNAM1 and NKp30 in NK cells from 2 healthy donors versus fluorescence intensity. (D) The efficiencies of killing of pseudovirus-infected A549 cells (target, T) by NK cells from 2 healthy donors (effector, E) at 3 effector/target (E-T) ratios. The means ± SEM for NK cells from healthy donor no. 4 (DNAM1^hi and NKp30^hi) and healthy donor no. 5 (DNAM1^lo and NKp30^lo), respectively, were 64.0% ± 1.79% and 34.90% ± 0.40% in 10:1 conditions, 34.78% ± 2.99% and 5.92% ± 1.73% in 2.5:1 conditions, and 14.93% ± 0.93% and 4.91% ± 7.16% in 0.25:1 conditions. P = 0.0225 by linear regression.