Corticosteroids such as dexamethasone and IL6 receptor blockers such as tocilizumab (Actemra) are known to be effective for managing patients with the earlier strains of severe COVID-19. The impact on the effectiveness of other treatments was being assessed in 2021. Relating to monoclonal antibodies (mAbs) treatments, similar testing and research is ongoing. Preclinical data on in vitro pseudotyped virus data demonstrate that some mAbs designed to use highly conserved epitopes retain neutralizing activity against key mutations of<unk>  substitutions. Similar results are confirmed by cryo-electron microscopy and X-ray data, also providing the structural approach and molecular basis for the evasion of humoral immunity exhibited by<unk>  antigenic shift as well as the importance of targeting conserved epitopes for vaccine and therapeutics design. While 7 clinical mAbs or mAb cocktails experienced loss of neutralizing activity of 1-2 orders of magnitude or greater relative to the prototypic virus, the S309 mAb, the parent mAb of sotrovimab, neutralized<unk>  with only 2-3-fold reduced potency. Further data suggest<unk>  would cause significant humoral immune evasion, while neutralizing antibodies targeting the sarbecovirus conserved region remain most effective. Indeed, most receptor-binding motif (RBM)-directed monoclonal antibodies lost in vitro neutralizing activity against<unk> , with only 3 out of 29 mAbs examined in another study retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized<unk>  through recognition of antigenic sites outside the RBM, including sotrovimab (VIR-7831), S2X259 and S2H97. In particular, sotrovimab is not fully active against the BA.2<unk>  sublineage, and in early 2022 the office of the U.S. ASPR stopped distributing the antibody treatment to states where BA.2 was dominant.
SARS-CoV-2 Omicron variant
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