<p>Summary of the population characteristics.</p>

Given limited data on SARS‑CoV‑2 transmission and immunity in rural, low‑vaccine‑coverage settings, we evaluated infection rates and population‑level neutralizing antibody increase in a rural community in western Kenya. The study was conducted at the KEMRI/WRAIR-Africa Health Demographic Surveillance System that has a population of 160,000. Clusters of households that had representative demographics were identified and individuals invited to participate in six cross-sectional surveys that targeted 234 participants at each survey, two months apart, conducted between April 2021 and March 2022, during which time, the Alpha, Delta and Omicron waves dominated. At each survey, participants provided naso-pharyngeal samples for SARS-CoV-2 detection and serum for measuring neutralizing antibodies (NAbs) using surrogate virus neutralizing test which assessed inhibition of RBD–ACE2 binding. 69% (917/1329) of the participants were females. By RT-qPCR, SARS-CoV-2 increased from 3% (7/224) at survey one (April 2021) to 24% (55/229) by survey two (June 2021), and thereafter decreased to zero, only to rise to 10% (23/234) during the January 2022 Omicron wave. NAbs increased from 18% (40/224) at survey one to 86% (202/234) by end of the study. The quantity of NAbs rose from geometric mean of 0.42 U/mL at survey one to 9.4 U/mL by survey six. Females had higher NAbs (3.73U/mL, 95% CI), compared to 1.98 U/mL, 95% CI (p = 0.0146) for males. NAbs quantities increased with age: 2.1 U/mL for <9 years, 2.6 U/mL for 10 – 19 years, 3.4 U/mL for 20 – 39 years, 3.8 U/mL for 40 – 59 years and 4.9 U/mL for >60 years. The increase in population-level NAbs is consistent with widespread exposure to the virus during the study period. As caveat, causality of NAbs for the decline in SARS‑CoV‑2 infections cannot be inferred with confidence, because other factors such as the use of non‑pharmaceutical interventions and other individual-level variables were not measured.