ABSTRACT: OBJECTIVES:Socio-economic inequalities may affect coronavirus disease 2019 (COVID-19) incidence. The goal of the research was to explore the association between deprivation of socio-economic status (SES) and spatial patterns of COVID-19 incidence in Chennai megacity for unfolding the disease epidemiology. STUDY DESIGN:This is an ecological (or contextual) study for electoral wards (subcities) of Chennai megacity. METHODS:Using data of confirmed COVID-19 cases from May 15, 2020, to May 21, 2020, for 155 electoral wards obtained from the official website of the Chennai Municipal Corporation, we examined the incidence of COVID-19 using two count regression models, namely, Poisson regression (PR) and negative binomial regression (NBR). As explanatory factors, we considered area deprivation that represented the deprivation of SES. An index of multiple deprivations (IMD) was developed to measure the area deprivation using an advanced local statistic, geographically weighted principal component analysis. Based on the availability of appropriately scaled data, five domains (i.e., poor housing condition, low asset possession, poor availability of WaSH services, lack of household amenities and services, and gender disparity) were selected as components of the IMD in this study. RESULTS:The hot spot analysis revealed that area deprivation was significantly associated with higher incidences of COVID-19 in Chennai megacity. The high variations (adjusted R2: 72.2%) with the lower Bayesian Information Criteria (BIC) (124.34) and Akaike's Information Criteria (AIC) (112.12) for NBR compared with PR suggests that the NBR model better explains the relationship between area deprivation and COVID-19 incidences in Chennai megacity. NBR with two-sided tests and P <0.05 were considered statistically significant. The outcome of the PR and NBR models suggests that when all other variables were constant, according to NBR, the relative risk (RR) of COVID-19 incidences was 2.19 for the wards with high housing deprivation or, in other words, the wards with high housing deprivation having 119% higher probability (RR = e0.786 = 2.19, 95% confidence interval [CI] = 1.98 to 2.40), compared with areas with low deprivation. Similarly, in the wards with poor availability of WaSH services, chances of having COVID-19 incidence was 90% higher than in the wards with good WaSH services (RR = e0.642 = 1.90, 95% CI = 1.79 to 2.00). Spatial risks of COVID-19 were predominantly concentrated in the wards with higher levels of area deprivation, which were mostly located in the northeastern parts of Chennai megacity. CONCLUSIONS:We formulated an area-based IMD, which was substantially related to COVID-19 incidences in Chennai megacity. This study highlights that the risks of COVID-19 tend to be higher in areas with low SES and that the northeastern part of Chennai megacity is predominantly high-risk areas. Our results can guide measures of COVID-19 control and prevention by considering spatial risks and area deprivation.