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Dynamics of circulating calprotectin accurately predict the outcome of moderate COVID-19 patients
Nicolas Chapuis1, Nusaibah Ibrahimi2, Thibaut Belmondo3
1Laboratory of Hematology, Assistance Publique-Hôpitaux de Paris, Cochin Hospital, Paris, France; Université de Paris, Institut Cochin, CNRS UMR8104, INSERM U1016, Paris, France.
Insights
Serial monitoring of calprotectin, an inflammatory biomarker, can predict poor outcomes in hospitalized COVID-19 patients. This approach refines initial assessments, identifying individuals at high risk for intensive care unit transfer or death.
Area of Science:
- Immunology
- Infectious Diseases
- Clinical Biomarkers
Background:
- Elevated calprotectin (S100A8/S100A9 alarmin) is linked to severe COVID-19.
- Initial calprotectin levels correlate with disease severity.
- Optimal use of calprotectin during COVID-19 requires further study.
Purpose of the Study:
- To evaluate the utility of serial calprotectin measurements in predicting outcomes for moderate COVID-19 patients.
- To identify distinct calprotectin trajectories associated with different risk levels.
Main Methods:
- Analysis of calprotectin levels in plasma and serum from 626 hospitalized moderate COVID-19 patients across three cohorts.
- Longitudinal calprotectin measurements (1461 samples) in 457 patients.
- Application of a joint latent class mixture model to identify risk-predicting calprotectin trajectories.
Main Results:
- Serial calprotectin monitoring refines the predictive value of baseline levels in moderate COVID-19.
- Three calprotectin trajectories were identified, correlating with low, moderate, and high risks of poor outcomes.
- An online algorithm was developed to monitor individual patient risk.
Conclusions:
- Serial calprotectin monitoring in peripheral blood is clinically valuable for anticipating poor outcomes in moderate COVID-19 patients.
- This approach aids in managing patients hospitalized in standard care units.
Background:
Severe COVID-19 is associated with a high circulating level of calprotectin, the S100A8/S100A9 alarmin heterodimer. Baseline calprotectin amount measured in peripheral blood at diagnosis correlates with disease severity. The optimal use of this biomarker along COVID-19 course remains to be delineated.
Methods:
We focused on patients with a WHO-defined moderate COVID-19 requiring hospitalization in a medical ward. We collected plasma and serum from three independent cohorts (N = 626 patients) and measured calprotectin amount at admission. We performed longitudinal measures of calprotectin in 457 of these patients (1461 samples) and used a joint latent class mixture model in which classes were defined by age, body mass index and comorbidities to identify calprotectin trajectories predicting the risk of transfer into an intensive care unit or death.
Findings:
After adjustment for age, sex, body mass index and comorbidities, the predictive value of baseline calprotectin in patients with moderate COVID19 could be refined by serial monitoring of the biomarker. We discriminated three calprotectin trajectories associated with low, moderate, and high risk of poor outcome, and we designed an algorithm available as online software (https://calpla.gustaveroussy.fr:8443/) to monitor the probability of a poor outcome in individual patients with moderate COVID-19.
Interpretation:
These results emphasize the clinical interest of serial monitoring of calprotectin amount in the peripheral blood to anticipate the risk of poor outcomes in patients with moderate COVID-19 hospitalized in a standard care unit.
Funding:
The study received support (research grants) from ThermoFisher immunodiagnostics (France) and Gustave Roussy Foundation.
