Syndromic Surveillance-Based Estimates of Vaccine Efficacy Against COVID-Like Illness from Emerging Omicron and COVID-19 Variants

New infections from the omicron variant of SARS-CoV-2 have been increasing dramatically in South Africa since first identification in November 2021. Despite increasing uptake of COVID-19 vaccine, there are concerns vaccine protection against omicron may be reduced compared to other variants. We sought to characterize a surrogate measure of vaccine efficacy in Gauteng, South Africa by leveraging real-time syndromic surveillance data. The University of Maryland Global COVID Trends and Impact Survey (UMD-CTIS) is an online, cross-sectional survey conducted among users sampled from the Facebook active user base. We derived three COVID-like illness (CLI) definitions (stringent, classic, and broad) using combinations of self-reported symptoms (present or not in the prior 24 hours) that broadly tracked with reported COVID-19 cases during June 18, 2021 - December 14, 2021 (inclusive of the delta wave and up-trend of the omicron wave). We used syndromic-surveillance-based CLI prevalence measures among the vaccinated ( P V ) and unvaccinated ( P U ) respondents to estimate V E CLIP = 1 - ( P V / P U ), a proxy for vaccine efficacy, during the delta (June 18-July 18, N= 9,387 surveys) and omicron (December 4-14, N= 2,389 surveys) wave periods. We assume no waning immunity, CLI prevalence approximates incident infection with each variant, and vaccinated and unvaccinated survey respondents in the two variant wave periods are exchangeable. The vaccine appears to have consistently lower V E CLIP against omicron, compared to delta, regardless of the CLI definition used. Stringent CLI (i.e. anosmia plus fever, cough and/or myalgias) yielded a delta V E CLIP = 0.85 [0.54, 0.95] higher than omicron V E CLIP = 0.62 [0.46, 0.72]. Classic CLI (cough plus anosmia, fever, and/or myalgias) gave lower estimates (delta V E CLIP = 0.76 [0.54, 0.87], omicron V E CLIP = 0.51 [0.42, 0.59]), but omicron was still lower than delta. We acknowledge the potential for measurement, confounding, and selection bias, as well as limitations for generalizability for these self-reported, syndromic surveillance-based V E CLIP measures. Thus V E CLIP as estimates of true, population-level vaccine efficacy should therefore be taken with caution. Nevertheless, these preliminary findings demonstrating declining V E CLIP raise concern for a true decline in vaccine efficacy versus waning immunity as a potential contributor to the omicron variant taking hold in Gauteng and elsewhere.