We characterize the overall incidence and risk factors for breakthrough infection among fully vaccinated participants in the North Carolina COVID-19 Community Research Partnership cohort. Among 15,808 eligible participants, 638 reported a positive SARS-CoV-2 test after vaccination. Factors associated with a lower risk of breakthrough in the time-to-event analysis included older age, prior SARS-CovV-2 infection, higher rates of face mask use, and receipt of a booster vaccination. Higher rates of breakthrough were reported by participants vaccinated with BNT162b2 or Ad26.COV2.S compared to mRNA-1273, in suburban or rural counties compared to urban counties, and during circulation of the Delta and Omicron variants.

Coronavirus Disease-2019 (COVID-19) vaccine acceptance is variable. We surveyed participants in the COVID-19 Community Research Partnership from 17 December 2020 to 13 January 2021 to assess vaccine receptiveness. Vaccine uptake was then monitored until 15 May 2021; 20,232 participants responded to the receptiveness survey with vaccination status accessed in 18,874 participants via daily follow-up surveys (participants not completing daily surveys ≥30 days to 15 May 2021, were excluded). In the initial survey, 4802 (23.8%) were vaccine hesitant. Hesitancy was most apparent in women (Adjusted RR 0.93, p < 0.001), Black Americans (Adjusted RR 1.39, 1.41, 1.31 to non-Hispanic Whites, Other, and Hispanic or Latino, respectively p < 0.001), healthcare workers (Adjusted RR 0.93, p < 0.001), suburbanites (ref. Urban Adjusted RR 0.85, 0.90 to urban and rural dwellers, respectively, p < 0.01), and those previously diagnosed with COVID-19 (RR 1.20, p < 0.01). Those <50 years were also less accepting of vaccination. Subsequent vaccine uptake was 99% in non-hesitant participants. For those who were unsure, preferred not to answer, or answered “no”, vaccination rates were 80% (Adjusted RR 0.86, p < 0.0001), 78% (Adjusted RR 0.83, p < 0.0001), and 52.7% (Adjusted RR 0.65, p < 0.0001), respectively. These findings suggest that initial intent did not correlate with vaccine uptake in our cohort.

During the COVID-19 pandemic, longitudinal serological surveillance was critical to accurately assess the cumulative incidence of COVID-19 and monitor population-level immunity among children. We characterized the epidemiology of COVID-19 among North and South Carolina children using remote electronic symptom surveillance and serial at-home antibody testing in 2–17-year-old children from April to December 2021. We estimated accumulation of infection-induced antibodies, defined as seropositivity before vaccination. Reported novel symptoms were characterized for seropositive and seronegative participants. A total of 1058 children (median age 10 years (IQR 7–13)) participated in symptom surveillance. Estimated cumulative prevalence of infection-induced antibody increased from 0% (0–60%) to 85.7% (31.6–97%), 3.1% (0–9.0%) to 61.7% (46.1–72.7%) and 5.6% (0–15.6%) to 75% (59.9–84.4%), respectively, among those aged 2–4, 5–11 and 12–17 years. Determinants of seropositivity included Black race (OR 2.06 (1.19 to 3.47)) and having >5 household members (OR 3.05 (1.21 to 7.45)). Participants seroconverting reported mostly respiratory or systemic symptoms, but 52% (28/52) were asymptomatic. We demonstrate the role of at-home testing in trending SARS-CoV-2 seroprevalence in a community cohort of children. Such regional serological surveillance complements national data for a more complete assessment of SARS-CoV-2 burden and transmission. Future applications of the remote surveillance platform may be leveraged for characterizing the epidemiology of novel pathogens.