Neutralisation of circulating SARS-CoV-2 delta and omicron variants by convalescent plasma and SARS-CoV-2 hyperimmune intravenous human immunoglobulins for treatment of COVID-19
Authors: Fatema Tuz Zahra, Lorenza Bellusci, Gabrielle Grubbs, Hana Golding, Surender Khurana
Journal: Annals of the Rheumatic Diseases (2022)

Neutralisation of circulating SARS-CoV-2 delta and omicron variants by convalescent plasma and SARS-CoV-2 hyperimmune intravenous human immunoglobulins for treatment of COVID-19 Monoclonal antibodies (MAbs), convalescent plasma (CP) and hyperimmune intravenous immunoglobulins are routinely used to treat COVID-19 patients with autoimmune disorders, organ transplant patients and patients on immunosuppressive drugs.The recent emergence of rapidly spreading SARS-CoV-2 variant of concern (VOC), omicron, contains large number of mutations in the SARS-CoV-2 spike protein. 1 Some of these mutations are known to increase resistance to antibodies elicited by prior infections or current SARS-CoV-2 vaccines. 2The omicron variant is resistant to most of the MAbs, including those approved for treatment of SARS-CoV-2 exposed individuals. 2In 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 virus-induced lung lesions following challenge with ancestral SARS-CoV-2 strain. 3Due to large variability in the SARS-CoV-2 neutralising capacity of CP, the emergency use authorisation for treatment of COVID-19 patients was updated to recommend use of only high-titre CP administered early after SARS-CoV-2 exposure.Hyperimmune SARS-CoV-2 intravenous immunoglobulins (hCoV-2IG) represent a concentrated form of IgG fractionated from many CP units that are prescreened for the presence of high titre antispike antibodies and predetermined SARS-CoV-2 neutralisation titres (>1:320). 4The effectiveness of hCoV-2 IG products may be hampered by the emergence of new variants, which might be less susceptible to antibodies from recovered COVID-19 patients previously infected with ancestral SARS-COV-2 strains.To evaluate the therapeutic potential of polyclonal CP and hCoV-2IG against currently circulating dominant SARS-CoV-2 delta and omicron variants, we measured the neutralisation capacity of 7 hCoV-2IG lots against the ancestral SARS-CoV-2 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 COVID-19 patients and 17 IVIG preparations that were manufactured with prepandemic plasma units. 5eventeen prepandemic IVIG lots (2019-IGIV) were all negative in the PsVNA against either WA1/2020 or the two VOCs (figure 1A and online supplemental table S1).Ten individual COVID-19 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 ~1.8-fold.In the case of omicron, only 2/10 CPs (CP-2 and CP-10) showed minimal neutralising titres (PsVNA50 of 1:29 and 1:67, respectively), with an overall 21-fold reduction in neutralisation titres compared with WA1/2020 (figure 1A,B, (online supplemental table S1).In contrast to CPs, the hCoV-2IGs demonstrated higher 50% virus neutralisation titres against WA1/2020 strain, ranging