The linkage of individuals with obesity and COVID-19 is controversial and lacks systematic reviews. After a systematic search of the Chinese and English language literature on COVID-19, 75 studies were used to conduct a series of meta-analyses on the relationship of individuals with obesity-COVID-19 over the full spectrum from risk to mortality. A systematic review of the mechanistic pathways for COVID-19 and individuals with obesity is presented. Pooled analysis show individuals with obesity were more at risk for COVID-19 positive, >46.0% higher (OR = 1.46; 95% CI, 1.30-1.65; p < 0.0001); for hospitalization, 113% higher (OR = 2.13; 95% CI, 1.74-2.60; p < 0.0001); for ICU admission, 74% higher (OR = 1.74; 95% CI, 1.46-2.08); and for mortality, 48% increase in deaths (OR = 1.48; 95% CI, 1.22-1.80; p < 0.001). Mechanistic pathways for individuals with obesity are presented in depth for factors linked with COVID-19 risk, severity and their potential for diminished therapeutic and prophylactic treatments among these individuals. Individuals with obesity are linked with large significant increases in morbidity and mortality from COVID-19. There are many mechanisms that jointly explain this impact. A major concern is that vaccines will be less effective for the individuals with obesity.