The proteomic analysis of 101 plasma proteins of 40 hospitalized COVID-19 patients who did or did not require Intensive Care Unit (ICU) admission revealed that the sustained variations found over the disease course were in Caspase 8 (CASP8), TNF Superfamily Member 14 (TNFSF14), Transforming Growth Factor Beta 1 (TGFB1), and Hepatocyte growth factor (HGF), which were associated with apoptotic pathways and inflammation. Here, CASP8 is linked to COVID-19.