Clinical Evaluation of the Abbott Alinity SARS-CoV-2 Spike-Specific Quantitative IgG and IgM Assays among Infected, Recovered, and Vaccinated Groups

Abstract

The COVID-19 pandemic continues to impose a significant burden on global health infrastructure. While identification and containment of new cases remains important, laboratories must now pivot and consider an assessment of SARS-CoV-2 immunity in the setting of the recent availability of multiple COVID-19 vaccines. Here we have utilized the latest Abbott Alinity semi-quantitative IgM and quantitative IgG spike protein (SP) serology assays (IgMSP and IgGSP) in combination with Abbott Alinity IgG nucleocapsid (NC) antibody test (IgGNC) to assess antibody responses in a cohort of 1236 unique participants comprised of naïve, SARS-CoV-2 infected, and vaccinated (including both naïve and recovered) individuals. The IgMSP and IgGSP assays were highly specific (100%) with no cross-reactivity to archived samples collected prior to the emergence of SARS-CoV-2, including those from individuals with seasonal coronavirus infections. Clinical sensitivity was 96% after 15 days for both IgMSP and IgGSP assays individually. When considered together, the sensitivity was 100%. A combination of NC- and SP-specific serologic assays clearly differentiated naïve, SARS-CoV-2-infected, and vaccine-related immune responses. Vaccination resulted in a significant increase in IgGSP and IgMSP values, with a major rise in IgGSP following the booster (second) dose in the naïve group. In contrast, SARS-CoV-2 recovered individuals had several fold higher IgGSP responses than naïve following the primary dose, with a comparatively dampened response following the booster. This work illustrates the strong clinical performance of these new serological assays and their utility in evaluating and distinguishing serological responses to infection and vaccination.

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines

“…Two Index values of ≥1.4 (IgG NC ), ≥1.0 (IgM SP ), and ≥50 AU/mL (IgG SP ) were interpreted as positive per the manufacturer’s recommended threshold. IgG NC positivity informs natural SARS-CoV-2 infection, while IgG SP /IgM SP positivity strongly correlates with the emergence of natural or vaccine-driven neutralizing immunity [ 5 , 7 ]. CD4+ T-cell activity was assessed as a marker of immune competence using the ImmuKnow ® assay (Viracor-IBT, Lee’s Summit, MO, USA).…”

“…We and others have demonstrated that the serological assessment of IgG and IgM against SARS-CoV-2 nucleocapsid (NC) and spike (SP) proteins is reliable in differentiating humoral responses to infection versus vaccination [ 2 , 3 , 4 , 5 , 6 ]. A recent study has evaluated a conservative IgG Spike-Receptor Binding Domain (S-RBD) level (Abbott assay) as a surrogate measure of antibody neutralization and identified that at or above 4160 AU/mL, the IgG (S-RBD) titer estimates consistently corresponded to a 0.95 probability of the plaque reduction neutralization test (PRNT; the gold standard) proportion at a 50-stringency threshold for 1/250 dilution.…”

Long-term Specific IgG Response to SARS-CoV-2 Nucleocapsid Protein in Recovered COVID-19 Patients

“…The protein has several epitopes that stimulate B and T cell responses and are suitable for vaccine formulations [10]. Moreover, as most SAR-CoV-2 vaccines used in humans are based on the spike antigen, the detection of antibody responses against nucleocapsid protein may be useful for distinguishing between serologic responses to infection and vaccination [11,12].…”

Poor Humoral Response in Solid Organ Transplant Recipients Following Complete mRNA SARS-CoV-2 Vaccination

“…Notably, a serological study revealed 39 391.2 AU/mL of anti-S IgG 17 days after the positive PCR test (30 days after complete vaccination), a value significantly higher than that of most SOT recipients (36 of 37) but comparable with those of fully vaccinated immunocompetent or previously infected control groups ( Fig. 1 ) ( 4 ). This finding indicates that subsequent infection may function as an additional stimulus to boost antibody response and induce higher levels of anti-S IgG in SOT recipients.…”

“…The seroconversion rate of SOT recipients (40.5%) was significantly lower than the 100% positive antibody response in fully vaccinated immunocompetent individuals and patients with past COVID-19 infection ( Fig. 1 ) ( 4 ). In addition, the median value of anti-S IgG in SOT recipients (1.4 AU/mL) was approximately 10 000-fold lower than median values observed in vaccinated immunocompetent individuals (13 951.5 AU/mL) and patients with past infection (16 532.5 AU/mL) ( t -test; P < 0.005) ( Fig.…”