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

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. Highlights Antibodies to common coronaviruses (HCoV) were higher in older than younger adults. Antibodies to HCoV can be cross‐reactive between strains. More HCoV‐related respiratory illnesses were detected in younger than older adults, and binding antibodies to HCoV increased with respiratory illness more frequently than neutralizing antibodies. There were correlations between binding and neutralizing antibodies, especially to related HCoV strains in convalescent sera. Pre‐existing antibodies to HCoV may not necessarily be protective against repeated infections and lower rates of neutralizing antibody stimulation may contribute to susceptibility to re‐infection. Assessment of binding antibodies to HCoV may be useful in seroepidemiologic studies of HCoV infections.