COVID-19
Elevated levels of IL-6 and CRP predict the need for mechanical ventilation in COVID-19

https://doi.org/10.1016/j.jaci.2020.05.008Get rights and content

Background

Coronavirus disease 2019 (COVID-19) can manifest as a viral-induced hyperinflammation with multiorgan involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available.

Objective

We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation.

Methods

Patients with COVID-19 who were hospitalized from February 29 to April 9, 2020, were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n = 40) followed by a temporally separated validation cohort (n = 49).

Results

We identified markers of inflammation, lactate dehydrogenase, and creatinine as the variables most predictive of respiratory failure in the evaluation cohort. Maximal IL-6 level before intubation showed the strongest association with the need for mechanical ventilation, followed by maximal CRP level. The respective AUC values for IL-6 and CRP levels in the evaluation cohort were 0.97 and 0.86, and they were similar in the validation cohort (0.90 and 0.83, respectively). The calculated optimal cutoff values during the course of disease from the evaluation cohort (IL-6 level > 80 pg/mL and CRP level > 97 mg/L) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure.

Conclusion

The maximal level of IL-6, followed by CRP level, was highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP level to guide escalation of treatment in patients with COVID-19–related hyperinflammatory syndrome.

Key words

IL-6
CRP
COVID-19
respiratory failure
mechanical ventilation
prediction
hyperinflammation

Abbreviations used

AUC
Area under the curve
BAL
Bronchoalveolar lavage
CORKUM
COVID-19 Registry of the Ludwig Maximilian University Hospital Munich
COVID-19
Coronavirus disease 2019
CRP
C-Reactive protein
NPV
Negative predictive value
PPV
Positive predictive value
SARS
Severe acute respiratory syndrome
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2

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Disclosure of potential conflict of interest: B. Lipworth reports grants and personal fees from Sanofi, AstraZeneca, and Teva; personal fees from Cipla, Glenmark, and Lupin; and research grants, consulting, advisory board, personal fees from Chiesi, outside the submitted work; in addition, he reports that his son is an employee of AstraZeneca. M. von Bergwelt-Baildon is the local principal investigator of the COVACTA-Trial (A Study to Evaluate the Safety and Efficacy of Tocilizumab in Patients with Severe COVID-19 Pneumonia [NCT04320615]; sponsored by Hoffmann-La Roche), which is currently being conducted, and he has previously received honoraria and research funding from Hoffman-La Roche unrelated to this project. M. Klein has received speaker fees from BioMerieux and served on the advisory board of BioMerieux. The rest of the authors declare that they have no relevant conflicts of interest.

These authors contributed equally.

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