Geospatial variations in socioeconomic conditions and health outcomes in COVID-19 era: insights from South Africa (2020–2022)

South Africa also has the highest burden of coronavirus disease 2019 (COVID-19) related comorbidities in Africa. We aimed to quantify the temporal and geospatial changes in unemployment, food insecurity, and their combined impact on depressive symptoms among South Africans who participated into several rounds of national surveys. We estimated the population-attributable risk percent ([Formula: see text] ) for the combinations of the risk factors after accounting for their correlation structure in multifactorial setting. Our study provided compelling evidence for immediate and severe effect of the pandemic where 60% of South Africans reported household food insecurity or household hunger, shortly after the pandemic emerged in 2020. Despite the grants provided by the government, these factors were also identified as the most influential risk factors (adjusted odds ratios (aORs) ranged from 2.06 to 3.10, p < 0.001) for depressive symptoms and collectively associated with 62% and 53% of the mental health symptoms in men and women, respectively. Similar pattern was observed among pregnant women and 41% of the depressive symptoms were exclusively associated with those who reported household hunger. However, aORs associated with the concerns around pandemic and vaccine were mostly not significant and ranged from 1.12 to 1.26 which resulted substantially lower impacts on depressive symptoms (PAR%:7%-and-14%). Our findings suggest that South Africa still has unacceptably high rates of hunger which is accelerated during the pandemic. These results may have significant clinical and epidemiological implications and may also bring partial explanation for the low vaccine coverage in the country, as priorities and concerns are skewed towards economic concerns and food insecurity.