SERPINA3 in Diabetic Retinopathy: A Pilot Study Assessing the Impact of Prior COVID-19 Infection on Patients

Purpose: SERine Protease INhibitor clade A member 3 (SERPINA3), a protease inhibitor involved in the acute phase response, is regulated by interleukin 6 trans-signaling, a pro-inflammatory pathway associated with diabetic retinopathy (DR) pathogenesis. We hypothesized that SERPINA3 may serve as a biomarker to distinguish DR patients from diabetic patients without retinopathy. Methods: We measured serum SERPINA3 levels in DR patients and demographically matched diabetic patients without retinopathy to assess the biomarker potential of SERPINA3. History of COVID-19 infection was included as a demographic variable. Results: Our results showed that SERPINA3 levels did not vary between cases and controls, nor was there any correlation with disease severity as measured by hemoglobin A1c and diabetic retinopathy stage. We found that excluding patients with a history of COVID-19 infection increased the predictive value of SERPINA3, and that SERPINA3 levels were significantly increased in those subjects hospitalized due to COVID-19. The predictive value of SERPINA3 for hospitalization was similar to age, duration of diabetes, and HbA1c in our cohort. Conclusions: Overall, SERPINA3 had poor sensitivity and specificity for identifying DR patients, and COVID-19 infection history significantly increased variance in SERPINA3 levels. Further investigation into the potential of SERPINA3 as DR biomarker should be sufficiently powered to account for the potentially confounding effects of COVID-19 infection.