Convalescent plasma with a high level of virus-specific antibody effectively neutralizes SARS-CoV-2 variants of concern

Abstract

The ongoing evolution of SARS-Co-V2 variants to omicron severely limits available effective monoclonal antibody therapies. Effective drugs are also supply limited. Covid-19 convalescent plasma (CCP) qualified for high antibody levels effectively reduces immunocompetent outpatient hospitalization. The FDA currently allows outpatient CCP for the immunosuppressed. Viral specific antibody levels in CCP can range ten- to hundred-fold between donors unlike the uniform viral specific monoclonal antibody dosing. Limited data are available on the efficacy of polyclonal CCP to neutralize variants. We examined 108 pre-delta/pre-omicron donor units obtained before March 2021, 20 post-delta COVID-19/post-vaccination units and one pre-delta/pre-omicron hyperimmunoglobulin preparation for variant specific virus (vaccine-related isolate (WA-1), delta and omicron) neutralization correlated to Euroimmun S1 IgG antibody levels. We observed a 2- to 4-fold and 20- to 40-fold drop in virus neutralization from SARS-CoV-2 WA-1 to delta or omicron, respectively. CCP antibody levels in the upper 10% of the 108 donations as well as 100% of the post-delta COVID-19/post-vaccination units and the hyperimmunoglobulin effectively neutralized all three variants. High-titer CCP neutralizes SARS-CoV-2 variants despite no previous donor exposure to the variants.

Omicron Severe Acute Respiratory Syndrome Coronavirus 2 Neutralization by Immunoglobulin Preparations Manufactured From Plasma Collected in the United States and Europe

“…In line with a previous report for Wuhan SARS-CoV-2 WT virus [ 8 ], IG fractionated from plasma collected prior to the COVID-19 pandemic also did not neutralize the Omicron SARS-CoV-2 variant ( Figure 1 ). COVID-19 HIG preparations, fractionated from COVID-19 convalescent donor plasma collected at the beginning of the pandemic and therefore representative of the antibody response to infection only, provided for some Wuhan as well as Omicron neutralization, with the latter, however, considerably lower than against the Wuhan SARS-CoV-2 WT, in line with previous reports of 16-fold and up to 40-fold lower neutralization of the Omicron versus Wuhan strain by post–COVID-19 sera or convalescent plasma [ 9 , 10 ].…”

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma

“…There are several advantages of CCP, especially as SARS-CoV-2 evolves and new variants of concern (VOCs) emerge. In vitro data suggest that high-titer CCP continues to be effective against the Omicron VOC ( 66 , 67 ), which has many mutations in the spike glycoprotein. However, data indicate that the Omicron VOC and 2 sublineages of Omicron can evade most available monoclonal antibodies ( 68 ).…”

Multi-center matched cohort study of convalescent plasma for hospitalized patients with COVID-19

“…The results should be interpreted in the context of both strengths and limitations of this study, which, while reflecting real-word use of CCP, include a heterogeneous hospitalized patient population largely requiring oxygen support, a lack of data on the antibody titer in the transfused CCP and on the serostatus of patients prior to transfusion. These results can help prioritize future studies and inform the potential role of CP in future pandemics, or in the context of emerging variants, where the rapid availability of CCP, some with ability to cross-neutralize variants [ 47 ], supports the importance of continuing to evaluate data from both randomized and observational studies to guide future studies and clinical practices, and optimize patient selection and plasma qualification for CP therapy.…”