Combining IL-6 and SARS-CoV-2 RNAaemia-based risk stratification for fatal outcomes of COVID-19

PLoS One. 2021 Aug 11;16(8):e0256022. doi: 10.1371/journal.pone.0256022. eCollection 2021.

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality.

Objective: We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19.

Methods: Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR.

Results: Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/μL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively).

Conclusions: Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • COVID-19 / mortality*
  • COVID-19 / pathology
  • COVID-19 / virology
  • Female
  • Hospital Mortality
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Oxygen Consumption
  • Prognosis
  • Prospective Studies
  • RNA, Viral / metabolism*
  • ROC Curve
  • Respiration, Artificial
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / isolation & purification
  • Viral Load

Substances

  • Interleukin-6
  • RNA, Viral

Grants and funding

This study was funded by the Japan Agency for Medical Research and Development (JP19fk0108169). This funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and did not provide financial support in the form of authors' salaries. This funding only provided financial support in the form of research materials. YM, a contributor is employed by Kanto Chemical Co provided support in the form of salaries, but the Kanto Chemical Co did not have any role in this study, including study design, data collection and analysis, decision to publish, provision of financial support in the form of authors' salaries and research materials, and preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.