PLoS One

. 2021 Jan 12;16(1):e0245296.
doi: 10.1371/journal.pone.0245296. eCollection 2021.
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

Shaul Lev 1 2 , Tamar Gottesman 2 3 , Gal Sahaf Levin 1 2 , Doron Lederfein 4 , Evgeny Berkov 5 , Dror Diker 5 , Aliza Zaidman 5 , Amir Nutman 2 6 , Tahel Ilan Ber 7 , Alon Angel 7 , Lior Kellerman 7 , Eran Barash 7 , Roy Navon 7 , Olga Boico 7 , Yael Israeli 7 , Michal Rosenberg 7 , Amir Gelman 7 , Roy Kalfon 7 , Einav Simon 7 , Noa Avni 7 , Mary Hainrichson 7 , Oren Zarchin 7 , Tanya M Gottlieb 7 , Kfir Oved 7 , Eran Eden 7 , Boaz Tadmor 4



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:, NCT04389645, retrospectively registered on May 15, 2020.