Vaccination and hybrid immunity is associated with SARS-CoV-2 protection but not shedding duration in rural Guatemalan households

Background: Essential agricultural workers in Central America and their households faced a high force of infection during the COVID-19 pandemic. Here, we evaluated if pre-existing seropositivity and vaccination (hybrid immunity) influenced SARS-CoV-2 infection risk and duration of shedding in an agricultural community in rural Guatemala. Methods: Individuals from 70 households were enrolled in a community cohort. From September 2021 to December 2022, all participants reported symptoms twice-weekly and provided saliva weekly for SARS-CoV-2 RNA testing by reverse transcriptase polymerase chain reaction (RT-PCR). Upon SARS-CoV-2 detection, participants submitted saliva three times per week for four weeks, which was tested by RT-PCR, to assess duration of shedding. We selected 119 SARS-CoV-2 PCR-positive individuals and 101 month-matched controls to measure nucleocapsid IgG and Omicron neutralizing antibody (NAb) titers. Results: Compared to uninfected controls, SARS-CoV-2 cases were more frequently female (60.5% vs 48.5%, p=0.08), had fewer vaccine doses (p=0.07), and were less likely to have hybrid immunity (p=0.08). Compared to controls, SARS-CoV-2 cases had lower median titers of nucleocapsid IgG (cutoff index [COI]=9.6 vs 23.6, p=0.12) and Omicron NAb (28.4 vs 50.4, p=0.15). SARS-CoV-2 cases also had lower NAb than controls among those vaccinated with 1 (16.1 vs 182.7, p=0.01), 2 (11.9 vs 87.0, p=0.04), or 3 doses (13.4 vs 232.5, p=0.004), and those considered up-to-date on vaccination (13.1 vs 155.6, p=0.0001). Nucleocapsid IgG and Omicron NAb were similar between individuals with short (<7 days) vs long (>7 days) viral shedding durations. Conclusions: In a household cohort of Guatemalan agricultural workers, cumulative vaccine doses associated with lower odds of infection. Among those previously vaccinated, lower titers of nucleocapsid IgG and Omicron NAb were associated with elevated infection risk, highlighting the importance of hybrid immunity in COVID-19 protection in this population.