LAUSR

Monoclonal antibodies (MAbs), convalescent plasma (CP) and hyperimmune intravenous immunoglobulins are routinely used to treat COVID19 patients with autoimmune disorders, organ transplant patients and patients on immunosuppressive drugs. The recent emergence of rapidly spreading SARSCoV2 variant of concern (VOC), omicron, contains large number of mutations in the SARSCoV2 spike protein. Some of these mutations are known to increase resistance to antibodies elicited by prior infections or current SARSCoV2 vaccines. The omicron variant is resistant to most of the MAbs, including those approved for treatment of SARSCoV2 exposed individuals. In contrast to individual MAbs, CP from individuals contain a broad array of polyclonal antibodies, some of which may provide protection against currently circulating VOCs. In the hamster model, highly neutralising CP (but not CP with low neutralisation titres) protected animals from virusinduced lung lesions following challenge with ancestral SARSCoV2 strain. Due to large variability in the SARSCoV2 neutralising capacity of CP, the emergency use authorisation for treatment of COVID19 patients was updated to recommend use of only hightitre CP administered early after SARSCoV2 exposure. Hyperimmune SARSCoV2 intravenous immunoglobulins (hCoV2IG) represent a concentrated form of IgG fractionated from many CP units that are prescreened for the presence of high titre antispike antibodies and predetermined SARSCoV2 neutralisation titres (>1:320). The effectiveness of hCoV2 IG products may be hampered by the emergence of new variants, which might be less susceptible to antibodies from recovered COVID19 patients previously infected with ancestral SARSCOV2 strains. To evaluate the therapeutic potential of polyclonal CP and hCoV2IG against currently circulating dominant SARSCoV2 delta and omicron variants, we measured the neutralisation capacity of 7 hCoV2IG lots against the ancestral SARSCoV2 WA1/2020 strain as well as delta and omicron VOCs in a pseudovirus neutralisation assay (PsVNA) (online supplemental appendix 1). For comparison, we also evaluated 10 CP from recovered COVID19 patients and 17 IVIG preparations that were manufactured with prepandemic plasma units. Seventeen prepandemic IVIG lots (2019IGIV) were all negative in the PsVNA against either WA1/2020 or the two VOCs (figure 1A and online supplemental table S1). Ten individual COVID19 CP showed heterogeneity of neutralisation titres against the WA1/2020 strain. One CP was negative, and 50% neutralisation titres (PsVNA50) of the other nine CPs ranged between 1:74 and 1:3177 (geometric mean titre (GMT): 1:282) (figure 1A, online supplemental table S1). For all CPs, the titres against delta were reduced by ~1.8fold. In the case of omicron, only 2/10 CPs (CP2 and CP10) showed minimal neutralising titres (PsVNA50 of 1:29 and 1:67, respectively), with an overall 21fold reduction in neutralisation titres compared with WA1/2020 (figure 1A,B, (online supplemental table S1). In contrast to CPs, the hCoV2IGs demonstrated higher 50% virus neutralisation titres against WA1/2020 strain, ranging Letter