Diminished Neutralization Capacity of SARS-CoV-2 Omicron BA.1 in Donor Plasma Collected from January to March 2021.

The 50% plaque reduction neutralization assay (PRNT50) has been previously used to assess the neutralization capacity of donor plasma against wild-type and variant of concern (VOC) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging data suggest that plasma with an anti-SARS-CoV-2 level of ≥2 × 104 binding antibody units/mL (BAU/mL) protects against SARS-CoV-2 Omicron BA.1 infection. Specimens were collected using a cross-sectional random sampling approach. For PRNT50 studies, 63 previously analyzed specimens by PRNT50 versus SARS-CoV-2 wild-type, Alpha, Beta, Gamma, and Delta were analyzed by PRNT50 versus Omicron BA.1. The 63 specimens plus 4,390 specimens (randomly sampled regardless of serological evidence of infection) were also tested using the Abbott SARS-CoV-2 IgG II Quant assay (anti-spike [S]; Abbott, Chicago, IL, USA; Abbott Quant assay). In the vaccinated group, the percentages of specimens with any measurable PRNT50 versus wild-type or VOC were wild type (21/25 [84%]), Alpha (19/25 [76%]), Beta (18/25 [72%]), Gamma (13/25 [52%]), Delta (19/25 [76%]), and Omicron BA.1 (9/25 [36%]). In the unvaccinated group, the percentages of specimens with any measurable PRNT50 versus wild type or VOC were wild-type SARS-CoV-2 (16/39 [41%]), Alpha (16/39 [41%]), Beta (10/39 [26%]), Gamma (9/39 [23%]), Delta (16/39 [41%]), and Omicron BA.1 (0/39) (Fisher's exact tests, vaccinated versus unvaccinated for each variant, P < 0.05). None of the 4,453 specimens tested by the Abbott Quant assay had a binding capacity of ≥2 × 104 BAU/mL. Vaccinated donors were more likely than unvaccinated donors to neutralize Omicron when assessed by a PRNT50 assay. IMPORTANCE SARS-CoV-2 Omicron emergence occurred in Canada during the period from November 2021 to January 2022. This study assessed the ability of donor plasma collected earlier (January to March 2021) to generate any neutralizing capacity against Omicron BA.1 SARS-CoV-2. Vaccinated individuals, regardless of infection status, were more likely to neutralize Omicron BA.1 than unvaccinated individuals. This study then used a semiquantitative binding antibody assay to screen a larger number of specimens (4,453) for individual specimens that might have high-titer neutralizing capacity against Omicron BA.1. None of the 4,453 specimens tested by the semiquantitative SARS-CoV-2 assay had a binding capacity suggestive of a high-titer neutralizing capacity against Omicron BA.1. These data do not imply that Canadians lacked immunity to Omicron BA.1 during the study period. Immunity to SARS-CoV-2 is complex, and there is still no wide consensus on correlation of protection to SARS-CoV-2.

Utilization of the Abbott SARS-CoV-2 IgG II Quant Assay To Identify High-Titer Anti-SARS-CoV-2 Neutralizing Plasma against Wild-Type and Variant SARS-CoV-2 Viruses.

There is evidence that COVID-19 convalescent plasma may improve outcomes of patients with impaired immune systems; however, more clinical trials are required. Although we have previously used a 50% plaque reduction/neutralization titer (PRNT50) assay to qualify convalescent plasma for clinical trials and virus-like particle (VLP) assays to validate PRNT50 methodologies, these approaches are time-consuming and expensive. Here, we characterized the ability of the Abbott severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2 characterized by both VLP assays and PRNT50. Plasma specimens previously tested in wild-type, Alpha, Beta, Gamma, and Delta VLP neutralization assays were selected based on availability. Selected specimens were evaluated by the Abbott SARS-CoV-2 IgG II Quant assay [Abbott anti-Spike (S); Abbott, Chicago, IL], and values in units per milliliter were converted to binding antibody units (BAU) per milliliter. Sixty-three specimens were available for analysis. Abbott SARS-CoV-2 IgG II Quant assay values in BAU per milliliter were significantly different between high- and low-titer specimens for wild-type (Mann-Whitney U = 42, P < 0.0001), Alpha (Mann-Whitney U = 38, P < 0.0001), Beta (Mann-Whitney U = 29, P < 0.0001), Gamma (Mann-Whitney U = 0, P < 0.0001), and Delta (Mann-Whitney U = 42, P < 0.0001). A conservative approach using the highest 95% confidence interval (CI) values from wild-type and variant of concern (VOC) SARS-CoV-2 experiments would identify a potential Abbott SARS-CoV-2 IgG II Quant assay cutoff of ≥7.1 × 103 BAU/mL. IMPORTANCE The United States Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the use of COVID-19 convalescent plasma (CCP) to treat hospitalized patients with COVID-19 in August 2020. However, by 4 February 2021, the FDA had revised the convalescent plasma EUA. This revision limited the authorization for high-titer COVID-19 convalescent plasma and restricted patient groups to hospitalized patients with COVID-19 early in their disease course or hospitalized patients with impaired humoral immunity. Traditionally our group utilized 50% plaque reduction/neutralization titer (PRNT50) assays to qualify CCP in Canada. Since that time, the Abbott SARS-CoV-2 IgG II Quant assay (Abbott, Chicago IL) was developed for the qualitative and quantitative determination of IgG against the SARS-CoV-2. Here, we characterized the ability of the Abbott SARS-CoV-2 IgG II Quant assay to identify high- and low-titer plasma for wild-type and variant (Alpha, Beta, Gamma, and Delta) SARS-CoV-2.

A Qualitative Comparison of the Abbott SARS-CoV-2 IgG II Quant Assay against Commonly Used Canadian SARS-CoV-2 Enzyme Immunoassays in Blood Donor Retention Specimens, April 2020 to March 2021.

Our group has previously used laboratory and commercially developed assays to understand the IgG responses to SARS-CoV-2 antigens, including nucleocapsid (N), spike (S), and receptor binding domain (RBD), in Canadian blood donors. In this current study, we analyzed 17,428 available and previously characterized retention samples collected from April 2020 to March 2021. The analysis compared the characteristics of the Abbott SARS-CoV-2 IgG II Quant assay (Abbott anti-spike [S], Abbott, Chicago, IL) against four other IgG assays. The Abbott anti-S assay has a qualitative threshold of 50 AU/mL. The four comparator assays were the Abbott anti-nucleocapsid (N) assay and three commonly used Canadian in-house IgG enzyme-linked immunosorbent assays (ELISAs) recognizing distinct recombinant viral antigens, full-length spike glycoprotein, glycoprotein RBD, and nucleocapsid. The strongest qualitative relationship was between Sinai RBD and the Abbott anti-S assay (kappa, 0.707; standard error [SE] of kappa, 0.018; 95% confidence interval, 0.671 to 0.743). We then scored each previously characterized specimen as positive when two anti-SARS-COV-2 assays identified anti-SARS-CoV-2 IgG in the specimen. Using this composite reference standard approach, the sensitivity of the Abbott anti-S assay was 95.96% (95% confidence interval [CI], 93.27 to 97.63%). The specificity of the Abbott anti-S assay was 99.35% (95% CI, 99.21 to 99.46%). Our study provides context on the use of commonly used SARS-CoV-2 serologies in Canada and identifies how these assays qualitatively compare to newer commercial assays. Our next steps are to assess how well the Abbott anti-S assays quantitatively detect wild-type and SARS-CoV-2 variants of concern. IMPORTANCE We describe the qualitative test characteristics of the Abbott SARS-CoV-2 IgG II Quant assay against four other anti-SARS-CoV-2 IgG assays commonly used in Canada. Although there is no gold standard for identifying anti-SARS-CoV-2 seropositivity, aggregate standards can be used to assess seropositivity. In this study, we used a specimen bank of previously well-characterized specimens collected between April 2020 and March 2021. The Abbott anti-S assay showed the strongest qualitative relationship with a widely used laboratory-developed IgG assay for the SARS-CoV-2 receptor binding domain. Using the composite reference standard approach, we also showed that the Abbott anti-S assay was highly sensitive and specific. As new anti-SARS-CoV-2 assays are developed, it is important to compare their test characteristics against other assays that have been extensively used in prior research.