A new study found raised levels of transforming growth factor beta-induced protein (TGFBIp) in blood sampled from roughly 100 people hospitalized for COVID-19, and further found that elevated levels of both the normal and acetylated forms of TGFBIp correlated with the severity of disease symptoms in these patients. While more work will be required to determine whether heightened levels of acetylated TGFBIp can serve as an exclusive, specific, and reliable diagnostic indicator for the severity of COVID-19, the research also suggests that TGFBIp could be a viable therapeutic target to treat severe inflammation - including deadly "cytokine storms" - in patients suffering from severe cases of the disease. While much work has been done to characterize the immune responses of patients with COVID-19, the inflammatory markers and cytokines known to be induced by SARS-CoV-2 infection are often short-lived. Hee Ho Park and colleagues set out to investigate whether increased levels of both the normal and acetylated forms of TGFBIp, a more stable molecule known to activate the immune-regulating transcription factor NF-κB, might serve as a more lasting signal of SARS-CoV-2 infection. The researchers analyzed blood samples from healthy controls and two cohorts of COVID-19 patients: those admitted to a hospital for treatment with relatively mild symptoms, and those who required ICU care to treat acute respiratory distress syndrome (ARDS) and/or sepsis. Compared with the healthy controls, both patient cohorts exhibited elevated levels of TGFBIp, as well as higher levels of acetylated TGFBIp, with the ICU patients exhibiting even greater levels of both protein forms. Upon treating immune cells taken from these patients with antibodies that neutralize TGFBIp, the researchers also observed a decrease in the production of inflammatory cytokines. While further work will be required to validate these results and assess the safety of the neutralizing antibodies, the finding nonetheless suggests that TGFBIp could be targeted to help treat severe inflammation in COVID-19 patients.