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

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

Abstract

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.

Publication types

  • Clinical Trial
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • COVID-19 / blood*
  • COVID-19 / pathology
  • COVID-19 / therapy
  • Chemokine CXCL10 / blood*
  • Decision Support Systems, Clinical*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Practice Guidelines as Topic

Substances

  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10

Associated data

  • ClinicalTrials.gov/NCT04389645

Grant support

The funder, MeMed, supplied the measurement platforms and test cartridges. MeMed employees performed the TRAIL, IP-10, CRP, and IL-6 measurements and were involved in analysis and interpretation of data and in writing the manuscript. The roles of the funder employees in patient selection, sample collection, analysis, data interpretation, and manuscript writing are given in the authors’ contributions section in the manuscript file.