Clinical Utility of Corona Virus Disease-19 Immunoglobulin G, M, Spike Protein, and Neutralizing Antibodies in Health, Disease and Post-Vaccination

Abstract

Objective: About 80% of corona virus disease-19 (COVID-19) deaths due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection occur in subject’s ≥ 65 years of age, even though subjects in this age group only account for about 10% of COVID-19 cases. Our objectives were to assess age effects and the clinical utility of COVID-19 antibody levels in health, disease, and post-vaccination. Methods: We measured serum SARS-CoV-2 immunoglobulin M (IgM), IgG and neutralizing antibodies using immunoassay kits obtained from Diazyme (Poway, CA) and spike (S) protein antibodies using immunoassay kits obtained from Roche Diagnostics (Indianapolis, IN). Results: In 79,005 subjects, IgG and IgM levels were positive (≥1.0 arbitrary units [AU]/mL) in 5.29% and 3.25% of subjects, respectively, with median IgG levels being 3.93AU/mL, 10.18 AU/mL, and 10.85 AU/mL in positive subjects <45 years, 45-64 years, and ≥65 years of age, respectively (p<0.0001). IgG antibody testing was found to be valuable for case finding in 1,111 exposed subjects with a wide variability in response. Persistently positive IgM levels were associated with chronic symptoms. Median IgG levels were 0.05 in 100 controls, 14.83 in 129 COVID-19 outpatients, and 30.61AU/mL in 49 COVID-19 hospitalized patients (p<0.0001). Neutralizing antibody levels correlated with IgG levels (r=0.875; p 2 weeks after second vaccine for Moderna, Pfizer, and AstraZeneca) in 105 subjects S protein antibody levels were all >250 U/mL and neutralizing antibodies were positive in all subjects except for 2 patients with chronic lymphocytic leukemia and 1 subject after the Johnson & Johnson vaccine. However, in all subjects, antibodies measured with the Diazyme IgG and IgM antibody and Roche total antibody levels were negative. S protein antibody levels were accurately assessed by fingerstick and micro-testing devices (Seventh Sense) in COVID-19 positive and negative subjects. Conclusions: Our data indicate that: 1) IgG levels are significantly higher in positive older subjects than in younger positive subjects, possibly in order to compensate for the decreased cellular immunity observed in the elderly, 2) IgG levels are important for case finding and there is a wide variability in response, 3) persistently elevated IgM levels are associated with chronic symptoms, 4) IgG levels are correlated with neutralizing antibody levels, both of which are significantly elevated in hospitalized COVID-19 patients, and 5) S protein antibody levels are >250 U/mL after full vaccination except for those with leukemia, and can be accurately assessed by fingerstick or micro-testing technology.