Viral Clearance

"We first conducted the ADCC assay to elucidate the relationship between plasma ADCC activity and the rate of viral clearance, symptom severity, antibody neutralizing capacity, titers of IgG antibodies against full-length (FL) WT S protein, WT S protein subunits, or the maximum viral load in individuals recovering from WT SARS-CoV-2 infection. ADCC activity was determined by measuring the release of Calcein AM from labeled S protein-expressing 293T cells, which were killed by NK-92 MI-FcR cells in the presence of convalescent plasma. The plasma samples were obtained from 38 donors who were primarily infected with SARS-CoV-2 (WT, WH01) between February and June 2020 in Taiwan. Plasma samples were collected when their viral loads turned negative in hospitals, and sputum samples were collected at multiple time points during hospitalization. Some donors had higher levels of plasma ADCC activity than others. ADCC activity was positively associated with both IgG titers against FL WT S protein and neutralization capacity, but not with disease severity. However, ADCC activity was negatively associated with the Ct value of maximum viral RNA levels, suggesting that convalescent donors with higher plasma ADCC activity tended to experience higher maximum viral loads during infection. Additionally, the duration of detectable SARS-CoV-2 genome was positively correlated with ADCC activity. These results imply that ADCC is negatively linked with SARS-CoV-2 clearance. Pneumonia patients exhibited higher neutralizing activity and IgG titers against the WT S1 protein, but they did not show increased ADCC activity or IgG titers against the WT S, RBD, and S2 proteins. Plasma from the slow-clearance group had higher ADCC activity, while neutralization capacity, symptom severity, and IgG titers against FL WT S protein, WT S1 subunit, WT RBD subunit, and WT S2 subunit were comparable between the fast- and slow-clearance groups. In the fast-clearance group, ADCC activity was positively correlated with neutralization capacity and with IgG titers against FL WT S protein and WT S1 subunit. In contrast, no such correlations were observed in the slow-clearance group. Taken together, these findings suggest that plasma ADCC activity is associated with slow viral clearance."