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Predictive and prognostic value of biomarkers in COVID-19 people receiving tocilizumab

Biomarkers_in_COVID Biomarkers_in_COVID
Biomarkers_in_COVID Biomarkers_in_COVID

This study was carried out to investigate the predictive and prognostic value of previously identified biomarkers regarding clinical outcomes in SARS-CoV-2 pneumonia people after tocilizumab therapy.

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Key take away

Ferritin, as a macrophage activation marker and an acute-phase protein, may have potential as a predictive biomarker for identifying people having severe COVID-19 who respond to tocilizumab therapy.

Background

This study was carried out to investigate the predictive and prognostic value of previously identified biomarkers regarding clinical outcomes in SARS-CoV-2 pneumonia people after tocilizumab therapy.

Method

Utilizing data from a phase 3, multicenter, randomized, double-blind, placebo-controlled trial (COVACTA), this exploratory assessment was carried out. Adults hospitalized with severe COVID-19 pneumonia receiving standard care were recruited and randomly allocated to get either placebo or intravenous 8 mg/kg tocilizumab (anti-interleukin-6 receptor antibody). The candidate biomarkers  were estimated in 142 subjects in the placebo group and 295 subjects in the tocilizumab group.

The effectiveness endpoints evaluated were hospital discharge time, clinical status on a 7-category ordinal scale (1-discharge; 7-death), death, and mechanical ventilation (if not getting it at randomization) through day twenty-eight. Using proportional odds, binomial or fine-gray models, and additional sensitivity assessment, the predictive and prognostic biomarkers (lactate dehydrogenase [LDH], interleukin-6, neutrophils, C-reactive protein, ferritin, platelets, lymphocytes, monocytes, d-dimer) were continuously assessed.

Result

Markers of hyperinflammation, dysregulated immune cells, and macrophage activation seem to be pivotal prognostic biomarkers in COVID-19. The modeling in tocilizumab group illustrated ferritin's predictive value for day twenty-eight clinical outcomes of mortality, mechanical ventilation, and clinical status when compared to placebo.

The modeling in placebo group illustrated all candidate biomarkers with the exception of d-dimer and LDH that were found to be strongly prognostic for day twenty-eight clinical outcomes of hospital discharge time, death, clinical status, and mechanical ventilation.

Conclusion

In COVACTA, numerous biomarkers prognostic for clinical outcomes were substantiated. Ferritin was recognized as a predictive biomarker for tocilizumab's effects in COVACTA patient population. Raised ferritin levels were linked with enhanced clinical outcomes for tocilizumab vs. placebo at day twenty-eight.

Source:

Critical Care Medicine

Article:

Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial

Authors:

Jennifer Tom et al.

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