Hundred-fold increase in SARS-CoV-2 spike antibody levels over three years in a hospital clinical laboratory

ABSTRACT Natural infection with the SARS-CoV-2 virus and vaccination increase the serum spike antibody levels. These levels, which differ among the various commercial assays, are used by the FDA to qualify individuals as potential COVID-19 convalescent plasma (CCP) donors. Over a 3-year period (April 2020–February 2023), we performed a retrospective analysis of spike IgG antibodies measured by a tertiary hospital clinical immunology laboratory using the Euroimmun SARS-CoV-2 IgG ELISA. The 3-year interval was classified into five periods based on the SARS-CoV-2 strain variant epidemiology. A total of 15,820 sera, derived from 11,022 individuals (6,362 females and 4,660 males) ranging from severe immunocompromised state to routine health visits, were tested. Spike IgG levels rose significantly over time, from a median ELISA 0.13 Arbitrary Units (AU) in the first period to 48.7 in the last period ( P < 0.0001). The 80th percentile of the spike IgG distribution was 0.55, 8.1, 9.6, 64.9, and 151 AU in the five periods. Using 3.5 AU, the FDA threshold for qualifying CCP donors with this Euroimmun assay, the percentage of subjects eligible for CCP donation would have been 11%, 44%, 61%, 81%, and 91% in the five time periods. Overall, spike antibody levels have risen more than 100-fold during the pandemic, while SARS-CoV-2 variants have become resistant to monoclonal antibodies. Since CCP containing high titers of spike antibodies is known to be most effective against variants, restricting CCP donors to those with antibody values in the upper two deciles may allow greater therapeutic transfusion protection. IMPORTANCE Despite the evolution of SARS-CoV-2 variants of concern and ongoing transmission, COVID-19 hospitalization and mortality rates continue to decline. Both the percent seropositive and antibody levels have risen over the past 3 years. Here, we observe more than 90% seropositivity as well as more than a hundred-fold increase in spike IgG levels in a tertiary hospital clinical immunology laboratory setting. Antibody effector functions (such as neutralization, opsonization, and complement activation) and cell-mediated immunity all contribute to protection from COVID-19 progression to hospitalization, and all correlate to the total SARS-CoV-2 antibody levels. We recommend therapeutic COVID-19 convalescent plasma be restricted to the top 20% of potential donors to maintain activity against ongoing SARS-CoV-2 variant evolution.