Predicting the severity of COVID-19 patients using the CD24-CSF1R index in whole blood samples

Abstract

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has become one of the most serious public health crises worldwide. Most infected people are asymptomatic but are still able to spread the virus. People with mild or moderate illnesses are likely to recover without hospitalization, while critically ill patients face a higher risk of organ injury or even death. In this study, we aimed to identify a novel biomarker that can predict the severity of COVID-19 patients. Clinical information and RNA-seq data of leukocytes from whole blood samples with and without a COVID-19 diagnosis (n = 100 and 26, respectively) were retrieved from the National Center for Biotechnology Information Gene Expression Omnibus database. Raw data were processed using the Transcripts Per Million (TPM) method and then transformed using log₂ (TPM+1) for normalization. The CD24-CSF1R index was established. Violin plots, Kaplan-Meier curves, ROC curves, and multivariate Cox proportional hazards regression analyses were performed to evaluate the prognostic value of the established index. The CD24-CSF1R index was significantly associated with ICU admission (n = 50 ICU, 50 non-ICU) and ventilatory status (n = 42 ventilation, 58 non-ventilation) with p = 4.186e-11 and p = 1.278e-07, respectively. The ROC curve produced a relatively accurate prediction of ICU admission with an AUC of 0.8524. Additionally, patients with a high index had significantly fewer mechanical ventilation-free days than patients with a low index (p = 6.07e-07). Furthermore, the established index showed a strong prognostic ability for the risk of using a ventilator in the multivariate Cox regression model (p < 0.001). The CD24-CSF1R index was significantly associated with COVID-19 severity. The established index could have potential implications for prognosis, disease severity stratification, and clinical management.

Keywords: Biomarker; CD24-CSF1R index; COVID-19; Immunity; SARS-CoV-2.

Fig. 1

The violin plots of the mRNA expression level of CD24, CSF1R, and CD24-CSF1R index. Violin plots of the mRNA expression levels of CD24 (A, D), CSF1R (B, E), and CD24-CSF1R index (C, F) between non-COVID-19 and COVID-19 patients with or without ICU admission and mechanical ventilation. Differences between two groups were estimated using t-test.

Fig. 2

ROC curve analysis of the CD24-CSF1R index and Charlson score. The red line represents the established index, and the green line represents the Charlson score.

Fig. 3

Kaplan-Meier curves of the CD24-CSF1R index and Charlson score based on ventilation status of COVID-19 patients. KM plots of Charlson score (A) and CD24-CSF1R index (B) of COVID-19 patients. Cut-off values of the CD24-CSF1R index and Charlson score from ROC curve analysis were used to divide COVID-19 patients into two risk groups (low index/score group versus high index/score group). The p-value was calculated by log-rank tests.

Fig. 4

Multivariate Cox proportional hazards regression analysis of clinical variables. N is the number of COVID-19 patients in each group. The hazard ratio in brackets is the value within the 95% CI. The p-value was calculated based on the log-rank test and presented on the right outer side.

Fig. 5

Protein interaction network of CD24 and CSF1R. This protein network was generated by STRING.