sFGL2 as a Potential Immunosuppressive Biomarker Associated With COVID‐19 Severity in Kidney Transplant Recipients

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Background SARS‐CoV‐2 infection can induce persistent immunosuppression. Soluble fibrinogen‐like protein 2 (sFGL2) is an emerging immune regulator. However, the correlation between sFGL2 and SARS‐CoV‐2–induced immunosuppression in kidney transplant recipients (KTRs) remains unclear. Materials and Methods sFGL2 levels and peripheral blood lymphocyte subpopulations (PBLSs) were measured simultaneously in 50 KTRs with COVID‐19 on Day 1 and Day 7 after admission. An additional cohort of 15 stable KTRs without COVID‐19 was recruited as the control group. sFGL2 was quantified using enzyme‐linked immunosorbent assay, and PBLSs were analyzed with 6‐Color TBNK Reagent and quantified by flow cytometry. Results sFGL2 levels in the COVID‐19 group were significantly higher than those in the stable group [64.33 ng/mL, interquartile range (IQR) 45.32–111.94 ng/mL vs. 53.82 ng/mL, IQR 31.31–72.63 ng/mL; p = 0.029]. Within the COVID‐19 group, KTRs with pneumonia exhibited markedly higher sFGL2 levels than those without pneumonia (97.29 ng/mL, IQR 74.13–141.82 ng/mL vs. 45.13 ng/mL, IQR 33.07–55.82 ng/mL; p < 0.001). sFGL2 correlated with disease severity ( r = 0.692; p < 0.001), and sFGL2 > 70.58 ng/mL was identified as a risk factor for pneumonia [odds ratio (OR) 128.697; 95% confidence interval (CI) 8.339–1985.665; p < 0.001]. In addition, absolute PBLS counts were decreased in the COVID‐19 group, and CD3 + and CD8 + T‐cell counts were negatively correlated with sFGL2 ( r = –0.241 and –0.278; p = 0.032 and 0.013, respectively). With clinical improvement of COVID‐19, sFGL2 levels decreased while PBLS counts recovered. Conclusion sFGL2 was associated with immunosuppression, disease severity, and prognosis in KTRs with COVID‐19, suggesting that it could serve as a novel biomarker for monitoring immune status.