Characterizing the antibody repertoires associated with immunocompetence

Viral infectious diseases may cause different clinical outcomes, ranging from asymptomatic infection to life-threatening ones. The extensive heterogeneity in immune responses to natural infections and vaccines can be summarized by the concept of immunocompetence, defined as the overall level of function of the immune system. However, clinical data on infection histories of individuals is currently lacking. To address this, we conducted a clinical trial following 50 individuals over 9 months. Symptom questionnaires and nasopharyngeal swabs were collected weekly, and blood samples were collected monthly. Swabs were used to identify symptomatic and asymptomatic infections by RT-PCR providing detailed infection history of all individuals. We hypothesized that longitudinally characterizing the serological immune responses to common human pathogens can be used to quantify the immunocompetence of an individual as reflected in the number of symptomatic and asymptomatic infections he/she encounters. As proof of concept, we profiled the baseline immune history (BIH) of all 50 subjects to SARS-CoV-2, and used SARS-CoV-2 infection history as a clinical outcome. During the study, n=xx (60%) of the cohort were infected with SARS-CoV-2. We found that ranking individuals based on BIH was significantly associated with risk of SARS-CoV-2 infection, using a quartile based approach. We found that the infection rate within the low-BIH quartile was 83.3%, while only 33.3% of the high-BIH quartile were infected (p=0.03607). We are currently longitudinally profiling the antibody repertoires of the cohort and will compare changes in the antibody repertoire with all symptomatic and asymptomatic viral infections identified during the study.