The outbreak of highly contagious and deadly SARS-CoV-2, also known asCoronavirus Disease 2019 (COVID-19) has posed a serious threat to public healthacross the globe, calling for the development of effective diagnostic markersand therapeutics. Here, we report a highly reliable severity diagnosticbiomarker, acetylated 676th lysine transforming growth factor beta-inducedprotein (TGFBIp K676Ac). The TGFBIp K676Ac was consistently elevated in theblood of SARS-CoV-2 pneumonia patients (n=113); especially in patients ofintensive care unit (ICU) than non-ICU. Patients’ blood samples showedincreased cytokines and lymphopenia, which are exemplary evidences of SARS-CoV-2pneumonia. Treatment of TGFBIp neutralizing antibodies suppressed the cytokinestorm. The increased level of TGFBIp K676 Ac in ICU patients implies that it canbe used as a reliable severity diagnostic biomarker for SARS-CoV-2.