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Background: COVID-19 is a global pandemic leading to high death tolls worldwide day by day. Clinical evidence suggests that COVID-19 patients can be classified as non-severe, severe, and critical cases. In particular, studies have highlighted the relationship between lymphopenia and the severity of the illness, where CD8+ T cells have the lowest levels in critical cases. However, a quantitative understanding of the immune responses in COVID-19 patients is still missing. Objectives: In this work, we aim to elucidate the key parameters that define the course of the disease deviating from severe to critical cases. The dynamics of different immune cells are taken into account in mechanistic models to elucidate those that contribute to the worsening of the disease. Methods: Several mathematical models based on ordinary differential equations are proposed to represent data sets of different immune response cells …