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A compartmental, epidemiological, mathematical model was developed in order to analyze the transmission dynamics of Delta and Omicron variant, of SARS-CoV-2, in Greece. The model was parameterized twice during the 4th and 5th wave of the pandemic. The 4th wave refers to the period during which the Delta variant was dominant (approximately July to December of 2021) and the 5th wave to the period during which the Omicron variant was dominant (approximately January to May of 2022), in accordance with the official data from the National Public Health Organization (NPHO). Fitting methods were applied to evaluate important parameters in connection with the transmission of the variants, as well as the social behavior of population during these periods of interest. Mathematical models revealed higher numbers of contagiousness and cases of asymptomatic disease during the Omicron variant period, but a decreased rate of hospitalization compared to the Delta period. Also, parameters related to the behavior of the population in Greece were also assessed. More specifically, the use of protective masks and the abidance of social distancing measures. Simulations revealed that over 5,000 deaths could have been avoided, if mask usage and social distancingwere 20% more efficient, during the short period of the Delta and Omicron outbreak. Furthermore, the spread of the variants was assessed using viral load data. The data were recorded from PCR tests at 417 Army Equity Fund Hospital (NIMTS), in Athens and the Ct values from 746 patients with COVID-19 were processed, to explain transmission phenomena and disease severity in patients. The period when the Delta variant prevailed in the country, the average Ct value was calculated as 25.19 (range: 12.32e39.29), whereas during the period when the Omicron variant prevailed, the average Ct value was calculated as 28 (range: 14.41e39.36). In conclusion, our experimental study showed that the higher viral load, which is related to the Delta variant, may interpret the severity of the disease. However, no correlation was confirmed regarding contagiousness phenomena. The results of the model, Ct analysis and official data from NPHO are consistent. [ABSTRACT FROM AUTHOR]