Similar changes were observed for a study on bacterial sepsis, and treatment techniques targeting T cell activity, such as recombinant human interleukin 7 (rhIL-7), were proposed in this clinical setting. For a study, the researchers sought to describe T lymphocyte response over time in severe COVID-19 patients and to examine the effect of ex vivo delivery of rhIL-7 because COVID-19 was viral sepsis. COVID-19 patients in the intensive care unit (ICU) had peripheral blood mononuclear cells taken at admission and after 20 days. NanoString technology was used to assess the transcriptomic profile. Flow cytometry was used to detect the expression of inhibitory immunological checkpoints. After ex vivo stimulation in the presence or absence of rhIL-7, T cell proliferation, and IFN- production was assessed. At the time of admission, COVID-19 ICU patients were severely lymphopenic. Mononuclear cells had a suppressed transcriptome profile associated with poor T cell activation pathways. Overexpression of co-inhibitory molecules PD-1, PD-L1, CTLA-4, and TIM-3 was seen in CD4 + and CD8 + T cells. CD4 + and CD8 + T cell proliferation and IFN- production were significantly altered in ICU admission samples. These changes, indicative of T cell exhaustion, were more noticeable at ICU admission and lessened over time. Ex vivo treatment with rhIL-7 increased T cell proliferation and IFN-production in COVID-19 patient cells. On ICU admission, severe COVID-19 patients showed signs of significant T cell fatigue, which could be restored ex vivo by rhIL-7. The outcomes add to investigators’ understanding of severe COVID-19 pathogenesis and open up new treatment options for treating critically ill patients based on immunomodulation techniques. To corroborate the ex vivo outcomes mentioned thus far, it was now necessary to define the right period for commencing such immune-adjuvant therapy in a clinical environment and the relevant markers for carefully selected patients.