Delayed inflammation decrease is associated with mortality in Tocilizumab-treated critically ill SARS-CoV-2 patients: A retrospective matched-cohort analysis

Innate Immun. 2022 Jan;28(1):3-10. doi: 10.1177/17534259211064602. Epub 2022 Jan 28.

Abstract

Little is known about the immuno-inflammatory response to Tocilizumab and its association with outcome in critically-ill SARS-CoV2 pneumonia. In this multicenter retrospective cohort of SARS-CoV-2 patients admitted to three intensive care units between March and April 2020, we matched on gender and SAPS II 21 Tocilizumab-treated patients to 42 non-treated patients. Need for mechanical ventilation was 76% versus 79%. IL-6, C-reactive protein, and fibrinogen had been collected within the first days of admission (T1), 3 d (T2) and 7 d (T3) later. Tocilizumab-treated patients had persistently higher IL-6 plasma levels and persistently lower C-Reactive protein and fibrinogen levels. Among Tocilizumab-treated patients, baseline levels of inflammatory biomarkers were not different according to outcome. Conversely, C-reactive protein and fibrinogen decrease was delayed in non-survivors. C-Reactive protein decreased at T1 in survivors (45 [30-98] vs 170 [69-204] mg/l, P < 0.001) but only at T2 in non-survivors (37 [13-74] vs 277 [235-288], P = 0.03). Fibrinogen decreased at T2 in survivors (4.11 [3.58-4.69] vs 614 [5.61-7.85] g/l, P = 0.005) but not in non-survivors (4.79 [4.12-7.58] vs 7.24 [6.22-9.24] g/l, P = 0.125). Tocilizumab treatment was thus associated with a persistent both increase in plasma IL-6, and decrease in C-reactive protein and fibrinogen. Among Tocilizumab-treated patients, the decrease in inflammatory biomarkers was delayed in non-survivors.

Keywords: C-reactive protein; SARS-CoV-2; Tocilizumab; cytokine; intensive care unit.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • COVID-19 / mortality*
  • COVID-19 Drug Treatment*
  • Cohort Studies
  • Critical Illness
  • Female
  • Fibrinogen / analysis
  • Humans
  • Inflammation / drug therapy*
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Respiration, Artificial
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antiviral Agents
  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • Fibrinogen
  • C-Reactive Protein
  • tocilizumab