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The aim of this study is to predict the COVID-19 infection fifth wave in South Africa using the Gaussian mixture model for the available data of the early four waves for March 18, 2020-April 13, 2022. The quantification data is considered, and the time unit is used in days. We give the modeling of COVID-19 in South Africa and predict the future fifth wave in the country. Initially, we use the Gaussian mixture model to characterize the coronavirus infection to fit the early reported cases of four waves and then to predict the future wave. Actual data and the statistical analysis using the Gaussian mixture model are performed which give close agreement with each other, and one can able to predict the future wave. After that, we fit and predict the fifth wave in the country and it is predicted to be started in the last week of May 2022 and end in the last week of September 2022. It is predicted that the peak may occur on the third week of July 2022 with a high number of 19383 cases. The prediction of the fifth wave can be useful for the health authorities in order to prepare themselves for medical setup and other necessary measures. Further, we use the result obtained from the Gaussian mixture model in the new model formulated in terms of differential equations. The differential equations model is simulated for various values of the model parameters in order to determine the disease's possible eliminations. [ABSTRACT FROM AUTHOR]