Observational cohort study of IP-10’s potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19

Lev, Shaul; Gottesman, Tamar; Sahaf Levin, Gal; Lederfein, Doron; Berkov, Evgeny; Diker, Dror; Zaidman, Aliza; Nutman, Amir; Ilan Ber, Tahel; Angel, Alon; Kellerman, Lior; Barash, Eran; Navon, Roy; Boico, Olga; Israeli, Yael; Rosenberg, Michal; Gelman, Amir; Kalfon, Roy; Simon, Einav; Avni, Noa; Hainrichson, Mary; Zarchin, Oren; Gottlieb, Tanya M.; Oved, Kfir; Eden, Eran; Tadmor, Boaz

BACKGROUND: Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking. METHODS: In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation. RESULTS: Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications. CONCLUSIONS: Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.