ABSTRACT
BACKGROUND: The outbreak of Coronavirus Disease 2019 (COVID-19) has been increasing rapidly. This disease causes an increase in proinflammatory cytokine production that leads to cytokine storm or cytokine release syndrome (CRS). Autologous activated platelet-rich plasma (aaPRP) contains various types of growth factors and anti-inflammatory cytokines that may have the potential to suppress CRS. This study of phase I/II trial was aimed to evaluate the safety and efficacy of aaPRP to treat severe COVID-19 patients. METHODS: A total of 10 severe COVID-19 patients from Koja Regional Public Hospital (Koja RPH) were admitted to the intensive care unit (ICU). All patients received aaPRP administration three times. Primary outcomes involving the duration of hospitalization, oxygen needs, time of recovery, and mortality were observed. Secondary outcomes involving C-reactive protein (CRP), neutrophil, lymphocyte, and lymphocyte-to-CRP (LCR) and neutrophil-lymphocyte ratio (NLR) were analyzed. RESULTS: All patients were transferred to the ICU with a median duration of 9 days. All patients received oxygen at enrollment and nine of ten patients recovered from the ICU and transferred to the ward room. There was one patient who passed away in the ICU due to heart failure. The results of secondary outcomes showed that CRP value and lymphocytes counts were significantly decreased while neutrophils, LCR, and NLR were slightly increased after aaPRP administration. CONCLUSIONS: Our results of the phase I/II trial demonstrated that the use of aaPRP in severe COVID-19 patients was safe and not associated with serious adverse events, which showed that aaPRP was a promising adjunctive therapy for severe COVID-19 patients.
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-1ß (IL-1ß) 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-1ß 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-1ß 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-1ß concentration was 4.71 pg/mL and 3.095 pg/mL, respectively. After 2 treatments with aaPRP, severe patients' plasma IL-1ß concentration decreased 12.48 pg/mL, while critical patients' plasma IL-1ß 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-1ß concentration and the amelioration of PaO2/FiO2 ratio.
