Background: An excessive immune response during coronavirus disease (COVID-19) can induce cytokine release syndrome (CRS), which is associated with life-threatening complications and disease progression.
Methods: This study was aimed to investigate the differences and similarities between CRS induced by COVID-19 and CAR-T therapy, then provide valuable experiences for early identification and controlling CRS progression in COVID-19. We retrospectively evaluated the clinical characteristics of severe CRS (sCRS, grade 3-4) induced by COVID-19 (40 patients) or chimeric antigen receptor T-cell (CAR-T) therapy as a comparator (41 patients).
Results: Grade 4 CRS was significantly more common in the COVID-19 group (15/40 [35.7%] vs. 5/41 [12.2%], P=0.008). CAR-T group had more more dramatic increase in cytokine than COVID-19 group (Figure1), including IL-2 (7.3pg/mL [IQR: 2.0-12.7] vs.1.7 [0.7-2.7], P<0.001), IL-6 (7120.6 pg/mL [1066.8-15 136.4] vs. 110.3 [41.7-728.1], P<0.001), IL-10 (174.5pg/mL [61.7, 434.6] vs. 10.1 [6.3-20.6], P<0.001) and IFN-γ (1308.5pg/mL [296.6, 3108.2] vs .35.0 [16.9-60.8], P<0.001). Interestingly, COVID-19 group had significantly higher levels for TNF-α (31.1 pg/ml [16.1-70.0] vs. 3.3 [1.8-9.6], P<0.001).The correlations between viral load/ tumor burden and various cytokine levels were shown in Figure 2. Lg viral loads were correlated with lg IL-6 (R2=0.101; P<0.001) and lg IL-10 (R2=0.105; P<0.001) .In CAR-T group, LDH was a common indicator related to tumor burden among patients with ALL, NHL, and MM. The lg LDH concentration was correlated with the lg serum concentration of IL-6 (R2=0.161; P=0.01). The independent risk factors for COVID-19-related sCRS were hypertension history (OR: 7.167, 95% CI: 2.345-21.903; P=0.001) and minimum platelets <100×109 /L during disease course (OR: 9.237, 95% CI: 2.544-33.546; P=0.001).
Conclusion: Our study demonstrated that there were similar processes but different intensity of inflammatory responses of sCRS in COVID-19 and CAR-T group. The diagnose and management of COVID-19 related sCRS can learn lessons from treatment of sCRS induced by CAR-T therapy.
Keywords: Cytokine release syndrome, COVID-19, Chimeric antigen receptor T-cell therapy
Figure 1
Disclosures
No relevant conflicts of interest to declare.
Using JAK inhibitor to treat cytokine release syndrome developed after chimeric antigen receptor T cell therapy for patients with refractory acute lymphoblastic leukemia