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

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.

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.

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.

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.