Efficacy of Licensed Monoclonal Antibodies and Antiviral Agents against the SARS-CoV-2 Omicron Sublineages BA.1 and BA.2.

Newly emerging SARS-CoV-2 variants may escape monoclonal antibodies (mAbs) and antiviral drugs. By using live virus assays, we assessed the ex vivo inhibition of the B.1 wild-type (WT), delta and omicron BA.1 and BA.2 lineages by post-infusion sera from 40 individuals treated with bamlanivimab/etesevimab (BAM/ETE), casirivimab/imdevimab (CAS/IMD), and sotrovimab (SOT) as well as the activity of remdesivir, nirmatrelvir and molnupiravir. mAbs and drug activity were defined as the serum dilution (ID 50 ) and drug concentration (IC 50 ), respectively, showing 50% protection of virus-induced cytopathic effect. All pre-infusion sera were negative for SARS-CoV-2 neutralizing activity. BAM/ETE, CAS/IMD, and SOT showed activity against the WT (ID 50 6295 (4355-8075) for BAM/ETE; 18,214 (16,248-21,365) for CAS/IMD; and 456 (265-592) for SOT) and the delta (14,780 (ID 50 10,905-21,020) for BAM/ETE; 63,937 (47,211-79,971) for CAS/IMD; and 1103 (843-1334) for SOT). Notably, only SOT was active against BA.1 (ID 50 200 (37-233)), whereas BA.2 was neutralized by CAS/IMD (ID 50 174 (134-209) ID 50 ) and SOT (ID 50 20 (9-31) ID 50 ), but not by BAM/ETE. No significant inter-variant IC 50 differences were observed for molnupiravir (1.5 ± 0.1/1.5 ± 0.7/1.0 ± 0.5/0.8 ± 0.01 μM for WT/delta/BA.1/BA.2, respectively), nirmatrelvir (0.05 ± 0.02/0.06 ± 0.01/0.04 ± 0.02/0.04 ± 0.01 μM) or remdesivir (0.08 ± 0.04/0.11 ± 0.08/0.05 ± 0.04/0.08 ± 0.01 μM). Continued evolution of SARS-CoV-2 requires updating the mAbs arsenal, although antivirals have so far remained unaffected.