The Effect of Intravenous Autologous Activated Platelet-Rich Plasma Therapy on "profibrotic Cytokine" IL-1 β Levels in Severe and Critical COVID-19 Patients: A Preliminary Study

Abstract

Introduction. Elevated concentration of proinflammatory cytokines followed by hyperinflammation is one of the hallmarks of severe and critical COVID-19. In the short term, this may result in ARDS and lung injury; subsequently, this may cause pulmonary fibrosis - a disease with poor prognosis - in the long run. Among the cytokines, interleukin-1β (IL-1β) is one of the most overexpressed in COVID-19. We speculate that administration of intravenous activated autologous platelet-rich plasma (aaPRP), which contains interleukin-1 receptor antagonist (IL-1RA), would lower IL-1β levels and benefit the severe and critical COVID-19 patients. Methods. After acquiring ethical clearance, we recruited 12 adult COVID-19 patients of both sexes from the Koja Regional Hospital (Jakarta, Indonesia) ICU. After selection, seven patients were included and divided into two groups, severe and critical. In addition to three doses of aaPRP, both groups received the same treatment of antiviral, steroid, and antibiotics. Quantification of plasma IL-1β levels was performed by beads multiplex assay a day before the first aaPRP administration and a day after the second and third aaPRP administration. PaO2/FiO2 ratio and lung injury scores were evaluated a day before and a day after each aaPRP administration. Results. Severe and critical patients' initial plasma IL-1β concentration was 4.71 pg/mL and 3.095 pg/mL, respectively. After 2 treatments with aaPRP, severe patients' plasma IL-1β concentration decreased 12.48 pg/mL, while critical patients' plasma IL-1β concentration increased to 18.77 pg/mL. Furthermore, after 3 aaPRP treatments, significant amelioration of patients' PaO2/FiO2 ratio from 71.33 mmHg at baseline to 144.97 mmHg was observed (p<0.05). However, no significant improvement in lung injury score was observed in severe and critical groups. All severe patients and one critical patient recovered. Conclusion. The use of aaPRP may prevent pulmonary fibrosis in severe COVID-19 patients through the reduction of patients' plasma IL-1β concentration and the amelioration of PaO2/FiO2 ratio.