Antibodies to coronaviruses are higher in older compared with younger adults and binding antibodies are more sensitive than neutralizing antibodies in identifying coronavirus-associated illnesses

Abstract

Human coronaviruses (HCoV) are common causes of respiratory illnesses (RI) despite preexisting humoral immunity. Sera were obtained near the onset of RI and 3 to 4 weeks later as part of a prospective study of 200 subjects evaluated for RI from 2009 to 2013. Antibodies against common HCoV strains were measured by enzyme-linked immunosorbent assay and neutralization assay comparing older adults with cardiopulmonary diseases (99 subjects) to younger, healthy adults (101 subjects). Virus shedding was detected in respiratory secretions by polymerase chain reaction. Of 43 HCoV-associated illnesses, 15 (35%) occurred in 14 older adults (aged ≥60 years) and 28 (65%) in 28 younger adults (aged 21-40 years). Binding and neutralizing antibodies were higher in older adults. Only 16 (35.7%) of RI with increases in binding antibodies also had increases in neutralizing antibodies to HCoV. Increases in binding antibodies with RI were more frequent than increased neutralizing antibodies and virus shedding, and more frequent in younger compared to older adults. Functional neutralizing antibodies were not stimulated as often as binding antibodies, explaining in part a susceptibility to reinfection with HCoV. Monitoring binding antibodies may be more sensitive for the serologic detection of HCoV infections.

Keywords: antibody; coronavirus; immunity; neutralization; respiratory illness.

Figure 1

Geometric mean titers (GMT) of antibodies by two methods to human coronaviruses (HCoV) ‐229E, ‐NL63, ‐OC43, and ‐HKU1 are shown by age group (15 serum pairs from group 1 subjects who were 60‐85 years of age and 28 serum pairs from group 2 subjects who were 21‐40 years of age) and by time of serum collection (acute, collected within five days of onset of acute respiratory illness, and convalescent, collected 3‐4 weeks later). “All visits” refer to the GMT of both acute and convalescent sera together by the patient subject group. The tick marks at the ends of the vertical lines show the corresponding 25th and 75th percentile antibody levels above and below the GMT to indicate a measure of interpatient variability, IgG binding antibody GMT measured by enzyme‐linked immunosorbent assay (ELISA) are shown in panel A and neutralizing antibody GMT are shown in panel B, categorized by reactivity to the respective HCoV strains. IgG, immunoglobulin G